Reinventing Hydroacylation: A Redox-Neutral Synthesis of

doi.org/10.26434/chemrxiv.7265519.v1

Reinventing Hydroacylation: A Redox-Neutral Synthesis of Ketones byCoupling of Alkenes and AmidesJing Li, Rik Oost, Nuno Maulide

Submitted date: 29/10/2018 • Posted date: 30/10/2018Licence: CC BY 4.0Citation information: Li, Jing; Oost, Rik; Maulide, Nuno (2018): Reinventing Hydroacylation: A Redox-NeutralSynthesis of Ketones by Coupling of Alkenes and Amides. ChemRxiv. Preprint.

Herein, we present a new concept for the hydroacylation of alkenes employing amides in a metal-free regime,proceeding by an entirely new mechanism and offering orthogonal reactivity to the conventional,metal-catalysed alternatives.

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Reinventing Hydroacylation: A Redox-Neutral Synthesis of Ketones by Coupling of Alkenes and Amides

Authors: Jing Li†, Rik Oost† and Nuno Maulide*

Institute of Organic Chemisty, University of Vienna, Währinger Strasse 38, 1090 Vienna, Austria

† These authors contributed equally to this work.

Abstract: The direct synthesis of ketones via carbon–carbon bond formation represents one of the

most important challenges in organic synthesis. Hydroacylation of alkenes offers perhaps the most

efficient and atom-economical approach for the preparation of ketones employing carbonyl

compounds and alkenes as feedstocks. State-of-the-art hydroacylation is typically achieved by a

transition metal-catalyzed coupling of an aldehyde and an alkene but is plagued by competing

decarbonylation, requiring the installation of directing groups in the aldehyde reactant. Herein, we

present a new concept for the hydroacylation of alkenes employing amides in a metal-free regime,

proceeding by an entirely new mechanism and offering orthogonal reactivity to the conventional,

metal-catalysed alternatives.

Ketones and aldehydes are perhaps the quintessential functional groups of organic chemistry. Their

unique ability to mediate C–C bond forming reactions serving as either electrophiles (by direct

nucleophilic addition to the carbonyl) or nucleophiles (by virtue of enolate or enamine formation)

remains one of the cornerstones of the past 4 decades of organic synthesis. An overabundance of

ketone syntheses rely on the direct, one-step 1,2-addition of organometallic reagents to suitable

electrophilic carboxylic acid derivatives.[1,2] Unfortunately, these nucleophilic substitutions can

suffer from a number of limitations including overaddition, poor chemoselectivity regarding the

presence of other carbonyl groups, excessive use of acylating reagents or tedious procedures. The

advent of the venerable Weinreb amides and related derivatives[3,4] offered a robust solution to the

overaddition issue and triggered the development of related procedures relying on amide

activation/organometallic addition.[5] The recent breakthrough of Garg, Szostak and others on

achieving ketone synthesis from activated amides via Ni-catalyzed cross-coupling is perhaps the

corollary of these developments.[6-8] Nevertheless, both the Weinreb family of reactions and these

elegant cross-coupling processes still rely on stoichiometric amounts of main group

organometallics or organoboron reagents.

Figure 1. | Paradigms for ketone synthesis in modern organic chemistry and new hydroacylation concept using secondary amides. a, 1,2- monoaddition of organometallic reagents to Weinreb amides. b, Ni-catalyzed cross-coupling of activated amides. c, challenges in contemporary olefin hydroacylation. d, The present study: novel concept for intermolecular hydroacylation of olefins and amides.

Alkenes would constitute highly appealing alternatives to conventional organometallic reagents

for addition to carbonyl groups en route to ketone synthesis.[9-11] Hydroacylation of olefins has

therefore emerged as a robust method for the preparation of ketones, typically achieved by the

atom-economical, catalytic addition of an aldehyde C−H bond across an alkene.[12,13] However,

contemporary transition metal-catalyzed hydroacylation presents several challenges, the most

notable of which is the competing decarbonylation of the aldehyde partner prior to coupling with

the alkene counterpart. Therefore, while intramolecular olefin hydroacylation has reached high

levels of efficiency and selectivity, intermolecular hydroacylation still typically relies on (a)

aldehydes equipped with directing groups designed to minimize decarbonylation as well as on (b)

activated alkene partners.

Aiming to address these challenges and guided by previous work on amide activation,[5,14-18] we

herein report a conceptually novel approach to olefin hydroacylation relying on an intermolecular

coupling of secondary amides and alkenes, which requires neither a transition metal catalyst nor

directing groups and which delivers ketones with high levels of chemo- and regioselectivity.

Table 1. Reaction discovery and optimizationa

entry R

yield (%)

1

1a 12

2

1b 50

3

1c 40

4 1d 50

5

1e <5

6 1f 86

7b 1f 81

aFor detailed reaction conditions, see the Supplementary Information. bCH3CN instead of CH2Cl2.

In initial experiments, a range of secondary amides 1 was activated prior to the addition of

commercially available alkene 2a. From the outset, trace amounts of ketone could be detected

using the simple N-propyl amide 1a (Table 1, entry 1). Encouraged by this result, we noted that

the amide N-substituent critically affects the efficiency of this transformation (entries 1–6).

Eventually, we found that N-allylamides afforded high (80-90%) and reproducible yields of the

ketone 3a, a formal hydroacylation product. Additional screening of base (see Supporting

Information, pages S2) and solvent effects revealed that CH2Cl2 and CH3CN afforded the desired

ketone product in similar yields. (cf. entry 6 and entry 7)

Table 2. Scope of the metal-free hydroacylation of alkenes.

aFor reaction conditions and further substrates, see the Supplementary Information.

With optimized conditions in hand, we assessed the scope of the methodology. The functional

group tolerance and substrate scope on the amide component of this transformation were

investigated first. Different aromatic amides bearing valuable substituents for downstream

reactions (such as -CN, -NO2, -COOMe, -Cl and –Br) were tolerated. Functional groups which are

unlikely to tolerate organometallic reagents, such as a ketone 3a, an aldehyde 3f or a boronic ester

3i also afforded the desired ketone selectively in moderate to good yields. In addition, the

orthogonality of this process in respect to hydroacylation of alkenes/alkynes becomes apparent

when examining aliphatic amides 3u–3v, whereby alkene and alkyne moieties entailed in the

amide partner behaved as spectators in this process.

At this juncture we turned our attention to the scope of alkenes. Different -substituted styrenes

were tested and it was observed that steric hindrance doesn’t affect reactivity in a pronounced

manner (4a–4e ). Electron-withdrawing substituents such as –CF3 or -CN (4j, 4k) still afforded

the desired ketone in good chemical yield. More importantly, a simple 1,3-diene (4f) was also a

suitable substrate for this transformation. The use of an allyl silane led to what could be termed an

“interrupted allylation”, delivering a product (4h) where silicon is retained. The methodology was

also applied with success to heterocyclic and more complex amides with a drug-like

framework[19,20] containing Lewis basic pyrimidine moieties (3w) or the late-stage

functionalization of dehydrocholic acid (3x).

We then sought to obtain experimental information on the reaction mechanism (Figure 2). The use

of deuterated amide d1-1b led to selective deuterium incorporation at the carbon -to the ketone

carbonyl (Fig. 2a). This is suggestive of a hydride transfer event. On the other hand, the use of

bisdeuterated -methylstyrene d2-3a led to deuterium incorporation in the α-position of ketone 3

(Fig. 2b). Finally, quenching the reaction with H218O (20 equiv.) generated a ketone product

whereby the incorporation of 18O is > 90% (Fig. 2c). These observations allow us to put forth a

mechanistic proposal as depicted in Fig. 2d. Thus, activation of the amide starting material is likely

to generate an N-allyl nitrilium species 6,[21] for which we also have obtained in situ NMR evidence

(see Supporting Information for details, pages S23). This electrophile is captured by the alkene

partner, setting up the stage for intramolecular 1,5-hydride delivery. This step simultaneously

achieves reduction of the transient carbocation 7 and formation of an azoniaallene intermediate 8,

the hydrolysis of which results in the hydroacylation products.[22]

a

NC

O

NH Ph

CH3 1) Tf2O, 2-F-pyridineMeCN, 0 °C to r.t.

NC

O

Ph

CH3

75% yield(89% D)

+ 2) H2OD

DD D

O

NH Ph

CH3 1) Tf2O, 2-F-pyridineMeCN, 0 °C to r.t.

O

Ph

CH3

55% yield(> 95% D)

+ 2) H2O

D

D

b

c

NC

O

NH

Ph

CH3

1) Tf2O, 2-F-pyridineMeCN, 0 °C to r.t.

NC

18O

Ph

CH3

88% yield

(> 90% 18O)

+2) H2

18O (20 equiv., 97%18O)

d1-1b(> 95% D)

2o

2o

3a

d2-3a(> 95% D)

R NH

O

R

H2O

R

O

R'

H

Tf2O

2-F-Py

R

N R

R

N H

R

R' R

N

R'

H

6 7 8

OTf

OTfOTf

d

R

Figure 2 | Control studies and proposed mechanism.

The herein presented approach to olefin hydroacylation is a novel concept whereby ketone

synthesis can be achieved by the direct, metal-free coupling of secondary amides and alkenes. This

obviates the need for transition metal catalysis and proceeds by an entirely new mechanism that

neither requires directing groups nor suffers from deleterious decarbonylation. This work also

showcases the potential of carefully designed internal hydride transfer events to provide unique

solutions for fundamental, contemporary challenges in organic synthesis.

Funding. We acknowledge funding by the Austrian Science Fund (FWF, Grant P30226) and the

European Research Council (CoG 682202, VINCAT). Continued support of our research programs

by the University of Vienna is gratefully acknowledged.

References and Notes:

1. Dieter, R. K. Reaction of acyl chlorides with organometallic reagents: a banquet table of metals for ketone synthesis.

Tetrahedron 55, 4177–4236 (1999). 2. Katritzky, A. R., Le, K. N. B., Khelashvili, L. & Mohapatra, P. P. Alkyl, unsaturated, (hetero)aryl, and N protected a-

amino ketones by acylation of organometallic reagents. J. Org. Chem. 71, 9861–9864 (2006). 3. Balasubramaniam, S. & Aiden, I. S. The growing synthetic utility of the Weinreb amide. Synthesis, 3707–3738 (2008). 4. Sengupta, S., Mondal, S. & Das, D. Amino acid derived morpholine amides fornucleophilica-amino acylation reactions:

a new synthetic route to enantiopurea-amino ketones. Tetrahedron Lett. 40, 4107–4110 (1999).

5. Bechara, W. S., Pelletier, G. & Charette, A. B. Chemoselective synthesis of ketones and ketimines by addition of organometallic reagents to secondary amides. Nat. Chem. 4, 228-234 (2012).

6. Dander, J. E. & Garg, N. K. Breaking Amides using Nickel Catalysis. ACS Catal. 7, 1413-1423 (2017).

7. Weires, N. A., Baker, E. L. & Garg, N. K. Nickel-Catalysed Suzuki–Miyaura Coupling of Amides. Nat. Chem. 8, 75–79 (2016).

8. Shi, S., Meng, G. & Szostak, M. Synthesis of Biaryls through Nickel‐Catalyzed Suzuki–Miyaura Coupling of Amides by Carbon–Nitrogen Bond Cleavage. Angew. Chem. Int. Ed. 55, 6959-6963 (2016).

9. Nguyen, K. D., Park, B. Y., Luong, T., Sato, H., Garza, V. J. & Krische, M. J. Metal-catalyzed reductive coupling of olefin-derived nucleophiles: Reinventing carbonyl addition. Science 354, 300-306 (2016).

10. Hong, Y.-T., Barchuk, A., Krische, M. J. Branched-Selective Intermolecular Hydroacylation: Hydrogen-Mediated Coupling of Anhydrides to Styrenes and Activated Olefins. Angew. Chem. Int. Ed., 128, 6885 (2006).

11. Yujing Zhou, Jeffrey S. Bandar, and Stephen L. Buchwald,Enantioselective CuH-Catalyzed Hydroacylation Employing Unsaturated Carboxylic Acids as Aldehyde Surrogates, J. Am. Chem. Soc., 139, 8126–8129 (2017).

12. Ghosh, A., Johnson, K. F., Vickerman, K. L., Walker Jr. J. A. & Stanley L. M. Recent advances in transition metal-catalysed hydroacylation of alkenes and alkynes. Org. Chem. Front. 3, 639-644 (2016).

13. Willis, M. C. Transition Metal Catalyzed Alkene and Alkyne Hydroacylation. Chem. Rev. 110, 725–748 (2010).

14. Kaiser, D. & Maulide, N. Making the Least Reactive Electrophile the First in Class: Domino Electrophilic Activation of Amides. J. Org. Chem. 81, 4421-4428 (2016).

15. Movassaghi, M. & Hill, M. D. Single-Step Synthesis of Pyrimidine Derivatives. J. Am. Chem. Soc. 128, 14254-14255 (2006).

16. Movassaghi, M. Hill, M. D. & Ahmad, O. K. Direct Synthesis of Pyridine Derivatives, J. Am. Chem. Soc. 129, 10096–10097 (2007).

17. Huang, P.-Q., Huang, Y.-H., Geng, H. & Ye, J.-L. Metal-Free C–H Alkyliminylation and Acylation of Alkenes with Secondary Amides. Sci. Rep. 6, 28801 (2016).

18. Jochims, J. C., Hehl, S. & Herzberger, S. Preparation and Beckman rearrangement of o-(chiorooxalyl)oximes. Synthesis 1128–1133 (1990).

19. Anderson, N. A., Bandyopadhyay, D., Daugan, A. C.-M., Donche, F. G., Eidam, P. M., Faucher, N. E., George, N. S., Harris, P. A., Jeong, J. U., King, B. W., Sehon, C. A., White, G. V & Wisnoski, D. D. Preparation of heterocyclic amides as RIP1 kinase inhibitors for therapy. PCT Int. Appl. 177 (2016). CODEN:PIXXD2; WO2016185423.

20. Fang, J., Tang, J., Carpenter, A. J., Peckham, G., Conlee, C. R., Du, K. S. & Katamreddy, S. R. Preparation of piperidine derivatives as GPR119 agonists for treating metabolic disorders. PCT Int. Appl. 224 (2008) CODEN:PIXXD2; WO2008070692.

21. van Dijk, T. Slootweg, J. C. & Lammertsma, K. Nitrilium ions–synthesis and applications. Org. Biomol. Chem. 15, 10134-10144 (2017).

22. Abu-El-Halawa, R. & Jochims, J. C. On the Reaction of N-Alkylnitrilium Salts with Acetylenes: A New Synthesis of 2-Azoniaallene Salts. Synthesis, 9, 871-874 (1992).

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S-1

Reinventing Hydroacylation: A Redox-neutral Synthesis of Ketones by Coupling of Alkenes and Amides

Authors: Jing Li†, Rik Oost† and Nuno Maulide*

Institute of Organic Chemisty, University of Vienna, Währinger Strasse 38, 1090 Vienna, Austria

† These authors contributed equally to this work.

Contents

1. General informations S-2

2. Optimization S-2

3. Synthesis of amide S-3

4. Character of ketones S-9

5. Mechanistic studies S-23

6. References S-28

7. NMR Spectra S-29

S-2

1. General informations

All reactions were carried out under an argon atmosphere using oven-dried glassware and

using standard Schlenk techniques. All starting materials were purchased from Aldrich or TCI

and used without further purification. Chromatography was performed on silica gel (230–400

mesh). Thin-layer chromatography was performed on silica plates. Compounds were

visualized by UV and cerium/molybdenum or potassium permanganate staining. Mass spectra

were recorded on a mass spectrometer using an Orbitrap analyzer. 1H, 13C and 19F spectra

were recorded on 400 and 100.59 MHz using CDCl3 as solvent. Chemical shift values are

reported in ppm with the solvent resonance as the internal standard (CHCl3: δ 7.26 for 1H, δ

77.16 for 13C). Data are reported as follows: chemical shifts, multiplicity (s = singlet, d =

doublet, t = triplet, q = quartet, p = pentet, br = broad, m = multiplet), coupling constants

(Hz), and integration. Optical rotations were measured on a Perkin Elmer 341

polarimeter using a 100 mm path-length cell at 589 nm (c given in g/100 mL).

2. Optimization

We used amides 1a/1b and styrene to further study the effect of base and temperature.

entry 1 base solvent

(temperature) yield (%)

1 1a 2-F-Pyridine CH3CN

(r.t.) 60

2 1 2,6-Lutidine CH3CN

(r.t.) No reaction

3

1a

DTBP CH3CN

(r.t.) trace

4

1a

2-F-Pyridine (1.5 equiv)

CH3CN (r.t.)

40

5 1a 2-F-Pyridine CH3CN (0 °C)

30

6 1a 2-F-Pyridine CH3CN

(0 °C to r.t.) 60

7 1b 2-F-Pyridine CH3CN

(0 °C to r.t.) 78

S-3

3. General procedure for the synthesis of amides 1a-1w

To a solution of amine (5.5 mmol) in 10 mL DCM was added Et3N (0.84 mL, 6 mmol). The

mixture was cooled to 0°C and added dropwise acyl chloride (5 mmol). The reaction was

stirred for 2h at 0°C and quenched with 1M HCl. The layers were separated and the organic

layer was extracted with DCM (2x 20 mL). The combined organic layers were dried on

MgSO4, filtered and the solvent was evaporated in vacuo to afford the pure amide.

N-allylbenzamide (1a)1

Following the general procedure, the product was obtained as a

colorless oil (96%). 1H-NMR (400 MHz, CDCl3) δ 4.08 (t, J = 5.7 Hz,

2H), 5.22 (ddq, J = 1.5, 11.3, 35.9 Hz, 2H), 5.94 (ddd, J = 5.7, 10.8,

16.0 Hz, 1H), 6.29 (br.s, 1H), 7.38–7.41 (m, 2H), 7.47–7.50 (m, 1H), 7.76–7.80 (m, 2H); 13C-

NMR δ 42.3, 116.2, 126.9, 128.3, 131.4, 134.2, 134.4, 167.5; All spectroscopic data was in

good accordance with those reported in literature.1

N-allyl-4-cyanobenzamide (1b)2


white solid (66%). 1H-NMR (400 MHz, CDCl3) δ 4.10 (tt, J = 1.5,

5.8 Hz, 2H), 5.25 (ddq, J = 1.5, 10.2, 18.9 Hz, 2H), 5.93 (ddt, J =

5.8, 10.2, 17.1 Hz, 1H), 6.25 (br.s, 1H), 7.72–7.76 (m, 2H), 7.85–7.90 (m, 2H); 13C-NMR δ

42.6, 115.1, 117.2, 117.9, 127.7, 132.4, 133.5, 138.3, 165.5. All spectroscopic data was in

good accordance with those reported in literature.2

N-allyl-4-nitrobenzamide (1c)3



5.8 Hz, 2H), 5.26 (ddq, J = 1.5, 10.2, 19.4 Hz, 2H), 5.95 (ddt, J =

S-4

5.8, 10.2, 17.1 Hz, 1H), 6.26 (br.s, 1H), 7.93–7.97 (m, 2H), 8.25–8.30 (m, 2H); 13C-NMR δ

42.8, 117.4, 123.9, 128.2, 133.4, 140.0, 149.6, 165.3. All spectroscopic data was in good

accordance with those reported in literature.3

Methyl 4-(allylcarbamoyl)benzoate (1d)4


white solid (99%). 1H-NMR (400 MHz, CDCl3) δ 3.94 (s, 3H),

4.11 (tt, J = 1.5, 5.8 Hz, 2H), 5.25 (ddq, J = 1.4, 10.2, 24.1 Hz,

2H), 5.95 (ddt, J = 5.8, 10.2, 17.1 Hz, 1H), 6.22 (br.s, 1H),

7.82–7.86 (m, 2H), 8.07–8.12 (m, 2H); 13C-NMR δ 44.7, 52.8, 127.5, 128.2, 128.4, 129.2,

130.2, 133.2, 138.3, 138.7, 166.7, 166.9. All spectroscopic data was in good accordance with

those reported in literature.4

4-acetyl-N-allylbenzamide (1e)5


white solid (96%). 1H-NMR (400 MHz, CDCl3) δ 2.63 (s, 3H),

4.11 (tt, J = 1.5, 5.8 Hz, 2H), 5.24 (ddq, J = 1.4, 10.2, 24.3 Hz, 2H),

5.95 (ddt, J = 5.8, 10.2, 17.1 Hz, 1H), 6.30 (br.s, 1H), 7.85–7.88

(m, 2H), 8.00–8.03 (m, 2H); 13C-NMR δ 26.8, 42.6, 116.9, 127.3, 128.5, 133.8, 138.4, 139.1,

166.4, 197.5. All spectroscopic data was in good accordance with those reported in literature.5

N-allyl-4-formylbenzamide (1f)


colorless oil (72%). 1H-NMR (400 MHz, CDCl3) δ 4.12 (tt, J =

1.5, 5.8 Hz, 2H), 5.26 (ddq, J = 1.4, 2.7, 10.2, 22.7 Hz, 2H), 5.95

(ddt, J = 5.7, 10.1, 16.8 Hz, 1H), 6,25 (br.s, 1H), 7.85–8.02 (m,

4H), 10.08 (s, 1H); 13C-NMR δ 42.6, 117.2, 127.6, 129.9, 133.7, 138.3, 139.6, 166.2, 191.5;

IR (neat): 3323, 3086, 3012, 2985, 2924, 2850, 2737, 1703, 1650, 1634, 1543, 1502, 1421,

1317, 1298, 1207, 1159, 1005; HRMS (ESI): [M+Na]+ calculated for C11H11O2NNa+

212.0682, found 212.0680.

N-allyl-4-chlorobenzamide (1g)7


colorless oil (44%). 1H-NMR (400 MHz, CDCl3) δ 4.09 (tt, J = 1.5,

S-5

5.8 Hz, 2H), 5.24 (ddq, J = 1.4, 2.8, 10.2, 22.6 Hz, 2H), 5.94 (ddt, J = 5.7, 10.2, 17.1 Hz, 1H),

6.10 (br.s, 1H), 7.36–7.50 (m, 2H), 7.69–7.80 (m, 2H); 13C-NMR δ 42.7, 117.1, 128.5, 129.0,

133.0, 134.1, 137.9, 166.4. All spectroscopic data was in good accordance with those reported

in literature.7

N-allyl-4-bromobenzamide (1h)6


colorless oil (67%). 1H-NMR (400 MHz, CDCl3) δ 4.08 (tt, J = 1.3,

5.7 Hz, 2H), 5.15–5.32 (m, 2H), 5,93 (ddt, J = 5.7, 10.3, 16.0 Hz,

1H), 6,15 (br.s, 1H), 7.52–7.73 (m, 4H); 13C-NMR δ 42.7, 117.1,

126.4, 128.7, 132.0, 133.5, 134.1, 166.5; All spectroscopic data was in good accordance with


N-allyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (1i)

Following the general procedure, the product was obtained as a colorless

oil (67%). 1H-NMR (400 MHz, CDCl3) δ 1.36 (s, 12H), 4.10 (tt, J = 1.5,

5.8 Hz, 2H), 5.23 (ddq, J = 1.5, 10.2, 29.0 Hz, 2H), 5.95 (ddt, J = 5.8,

10.2, 17.0 Hz, 1H), 6.26 (br.s, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.94 (dt, J =

1.1, 7.4 Hz, 1H), 7.99 (dt, J = 1.6, 7.7 Hz, 1H), 8.09 (s, 1H); 13C-NMR δ 25.0, 42.6, 84.3,

116.9, 128.4, 130.8, 132.2, 134.0, 134.4, 138.0, 167.3; IR (neat): 3308, 2979, 2926, 2855,

1641, 1604, 1536, 1484, 1419, 1360, 1320, 1275, 1166, 1143, 1081; HRMS (ESI): [M+Na]+

calculated for C16H22O3BNNa+ 310.1585, found 310.1585.

N-allyl-3-(methylthio)benzamide (1j)

Following the general procedure, the product was obtained as a white

solid (75%). 1H-NMR (400 MHz, CDCl3) δ 2.50 (s, 3H), 4.06 (tt, J =

1.5, 5.7 Hz, 2H), 5.21 (ddq, J = 1.4, 10.2, 25.6 Hz, 2H), 5.92 (ddt, J =

5.7, 10.2, 17.0 Hz, 1H), 6.31 (br.s, 1H), 7.28–7.38 (m, 2H), 7.48 (dt, J =

1.5, 7.3 Hz, 1H), 7.68 (t, J = 1.5 Hz, 1H); 13C-NMR δ 15.8, 42.6, 116.9, 123.3, 125.1, 129.0,

129.4, 134.2, 135.3, 139.8, 167.1; IR (neat): 3313, 3073, 3008, 2987, 2921, 1638, 1568, 1535,

1472, 1426, 1298, 1275; HRMS (ESI): [M+Na]+ calculated for C11H13ONSNa+, 230.0610;

found 230.0607.

N-allyl-2-naphthamide (1k)6

S-6



5.7 Hz, 2H), 5.27 (ddq, J = 1.4, 10.2, 32.9 Hz, 2H), 5.99 (ddt, J =

5.7, 10.2, 17.0 Hz, 1H), 6.36 (br.s, 1H), 7.54–7.57 (m, 2H), 7.85–

7.88 (m, 4H), 8.30 (s, 1H); 13C-NMR δ 42.7, 117.0, 123.7, 126.9, 127.5, 127.8, 127.9, 128.6,

129.1, 131.9, 132.8, 134.4, 134.9, 167.5; All spectroscopic data was in good accordance with


N-allylthiophene-2-carboxamide (1l)


solid (90%). 1H-NMR (600 MHz, CDCl3) δ 4.06–4.09 (m, 2H), 5.18–

5.30 (m, 2H), 5.58–5.97 (m, 1H), 6.28 (s, 1H), 7.08–7.10 (m, 1H), 7.48 –

7.50 (m, 1H), 7.55–7.56 (m, 1H). 13C-NMR δ 42.4, 116.8, 127.6, 128.1, 129.9, 134.0, 138.8,

161.8. IR (neat): 1619, 1548, 1514, 1419, 1304, 1277, 1261, 1144, 750; HRMS (ESI):

[M+Na]+ calculated for C8H9ONSNa+, 190.0297; found 190.0298.

N-allylcinnamamide (1m)4


solid (84%). 1H-NMR (600 MHz, CDCl3) δ 4.04–4.06 (m, 2H), 5.18-

5.28 (m, 2H), 5.90 (s, 1H), 5.91–5.95 (m, 1H), 6.45 (d, J = 16 Hz, 1H),

7.37–7.39 (m, 3H), 7.51–7.53 (m, 2H), 7.67 (d, J = 15.6 Hz, 1H); 13C-NMR (150 MHz,

CDCl3) δ 42.2, 116.7, 120.5, 127.8, 128.8, 129.7, 134.1, 134.8, 141.3, 165.7. All

spectroscopic data was in good accordance with those reported in literature.4

N-allyl-3-phenylpropanamide (1n)10


solid (91%). 1H-NMR (600 MHz, CDCl3) δ 2.52 (t, J = 7.8 Hz, 2H),

3.00 (t, J = 7.7 Hz, 2H), 3.86–3.88 (m, 2H), 5.07–5.11 (m, 2H), 5.54 (s,

1H), 5.76–5.82 (m, 1H), 7.22–7.23 (m, 3H), 7.29–7.32 (m, 2H); 13C-NMR δ 37.7, 38.5, 41.9,

116.3, 126.3, 128.4, 128.5, 134.2, 140.8, 171.9. All spectroscopic data was in good

accordance with those reported in literature.10

N-allylcyclohexanecarboxamide (1p)11



S-7

1.48 (m, 2H), 1.66–1.68 (m, 1H), 1.78–1.81 (m, 2H), 1.86–1.89 (m, 2H), 2.07–2.12 (m, 1H),

3.86–3.89 (m, 1H), 5.11–5.18 (m, 2H), 5.49 (s, 1H), 5.80–5.87 (m, 1H), 13C-NMR δ 25.8,

29.8, 41.7, 45.6, 116.2, 134.5, 175.8. All spectroscopic data was in good accordance with


N-allyltetrahydro-2H-pyran-4-carboxamide (1q)


colorless oil (45%). 1H-NMR (400 MHz, CDCl3) δ 1.75–1.87 (m, 4H),

2.30–2.40 (m, 1H), 3.41 (td, J = 3.2, 11.4 Hz, 2H), 3.89 (tt, J = 1.5, 5.7

Hz, 2H), 4.02 (ddd, J = 2.5, 3.4, 6.6 Hz, 2H), 5.12–5.21 (m, 2H), 5.54 (br.s, 1H), 5.84 (ddt, J

= 5.7, 10.2, 17.1 Hz, 1H); 13C-NMR δ 29.5, 42.0, 42.4, 67.4, 116.6, 134.4, 174.1; IR (neat):

3291, 3007, 2989, 2954, 2924, 2842, 1636, 1550, 1275, 1261; HRMS (ESI): [M+Na]+

calculated for C9H15O2NNa+ 192.0995, found 192.0991.

N-allyl-2-ethylbutanamide (1r)4



1.53 (m, 2H), 1.61–1.67 (m, 2H), 1.84–1.93 (m, 1H), 3.93 (ddd, J = 8.9,

5.7, 1.6 Hz, 2H), 5.02–5.29 (m, 2H), 5.57 (s, 1H), 5.75–5.99 (m, 1H); 13C-NMR δ 12.1, 25.8,

41.7, 51.6, 116.2, 134.6, 175.5. All spectroscopic data was in good accordance with those

reported in literature.

N-allyl-4-chlorobutanamide (1s)


colorless oil (85%). 1H-NMR (400 MHz, CDCl3) δ 2.12 (p, J = 6.2

Hz, 2H), 2.38 (t, J = 7.1 Hz, 2H), 3.61 (t, J = 6.2 Hz, 2H), 3.88 (tt, J

= 1.5, 5.7 Hz, 2H), 5.16 (m, 2H), 5.69 (br.s, 1H), 5.83 (ddt, J = 5.7, 10.3, 17.1 Hz, 1H); 13C-

NMR δ 28.2, 33.3, 42.1, 44.6, 116.6, 134.3, 171.5; IR (neat): 3285, 3080, 2962, 2921, 1639,

1542, 1421, 1377, 1325, 1302, 1249, 1196, 1149; HRMS (ESI): [M+Na]+ calculated for

C7H12NOClNa+, 184.0500, found 184.0498.

Methyl 9-(allylamino)-9-oxononanoate (1t)

S-8

Following the general procedure, the product was

obtained as a colorless oil (66%). 1H-NMR (600

MHz, CDCl3) δ 1.32 (t, J = 20.2 Hz, 7H), 1.64 (dt, J

= 13.7, 6.9 Hz, 5H), 2.20 (t, J = 7.6 Hz, 2H), 2.43–2.28 (m, 2H), 3.68 (d, J = 1.3 Hz, 3H),

4.05–3.85 (m, 2H), 5.17 (ddd, J = 13.7, 11.5, 1.3 Hz, 2H), 5.54 (s, 1H), 5.95–5.76 (m, 1H);

13C-NMR δ 24.9, 25.6, 28.9, 28.9, 29.0, 34.0, 36.7, 41.9, 51.5, 116.3, 134.4, 172.8, 174.3; IR

(neat): 1735, 1640, 1539, 1435, 1364, 1260; HRMS (ESI): [M+Na]+ calculated for

C12H23O3NNa+, 241.1678; found: 241.1676.

N-allylhex-5-ynamide (1u)


sticky oil (83%). 1H-NMR (600 MHz, CDCl3) δ 1.77–1.93 (m 2H),

1.93–1.99 (m, 1H), 2.19–2.30 (m, 2H), 2.36 (dt, J = 14.7, 7.2 Hz,

2H), 3.66–3.96 (m, 2H), 5.00–5.28 (m, 2H), 5.54 (s, 1H), 5.75–6.00 (m, 1H); 13C- NMR δ

17.8, 24.1, 35.0, 41.9, 69.2, 83.5, 116.4, 134.2, 172.0; IR (neat): 1638, 1540, 1422, 1375,

1257, 630; HRMS (ESI): [M+Na]+ calculated for C9H13ONNa+, 174.0889; found 174.0893.

N-allyl-2-ethylbutanamide (1v)


obtained as a white solid (44 %). 1H-NMR (700 MHz,

CDCl3) δ 1.14–1.53 (m, 12H), 1.53–1.72 (m, 2H),

2.03 (q, J = 7.1 Hz, 2H), 2.12–2.28 (m, 2H), 3.88 (t, J = 5.6 Hz, 2H), 4.95 (ddd, J = 13.6,

11.1, 1.2 Hz, 4H), 5.15 (dd, J = 33.8, 13.7 Hz, 1H), 5.50 (s, 1H), 5.64–5.95 (m, 2H); 13C-

NMR (176 MHz, CDCl3) δ 25.7, 28.9, 29.0, 29.3, 29.3, 33.8, 36.8, 41.8, 76.8, 77.0, 77.2,

114.1, 116.3, 134.4, 139.2, 172.9; IR (neat): 1638, 1548, 1466, 1420, 1276, 1259; HRMS

(ESI): [M+Na]+ calculated for C14H25ONNa+, 246.1828; found 246.1823.

N-allyl-8-cyanooctanamide (1w)

N-allyl-8-chlorooctanamide (5 mmol) was dissolved in DMSO (10 mL), then NaCN was

added in one-portion and transferred the flask to 100 °C oil bath for 1 hour. Then 50 mL sat.

NaS2O3 solution was added, and extracted with 50 mL AcOEt, the organic phase was washed

with sat. NH4Cl (30 ml) solution and dried with MgSO4, filtered and the solvent was

S-9

evaporated in vacuo to afford the crude, which further purified via silica gel to afford pure

amide as a sticky oil (70%). 1H-NMR (600 MHz, CDCl3) δ 1.13–1.52 (m, 6H), 1.55–1.78 (m,

1H), 2.05 (q, J = 7.1 Hz, 1H), 2.10–2.31 (m, 1H), 3.91 (t, J = 5.7 Hz, 1H), 5.07–4.77 (m, 1H),

5.17 (ddd, J = 13.7, 11.4, 1.3 Hz, 1H), 5.45–5.68 (m, 1H), 5.71–6.04 (m, 1H); 13C-NMR δ

17.1, 25.3, 25.5, 28.5 (2C), 28.9, 36.6, 41.9, 116.4, 119.8, 134.4, 172.7; IR (neat): 2246,

1642, 1640, 1462, 1424, 1361, 1260, 1147; HRMS (ESI): [M+Na]+ calculated for

C12H20N2NaO+, 231,1468; found 231.1473.

N-allyl-1-(5-fluoropyrimidin-2-yl)piperidine-4-carboxamide (1w)

Following the general procedure, the product was obtained as

a white solid (54%). 1H-NMR (600 MHz, CDCl3) δ 1.72 (qd,

J = 4.2, 12.1 Hz, 2H), 1.92 (dd, J = 2.2, 12.8 Hz, 2H), 2.37

(tt, J = 3.8, 11.7 Hz, 1H), 2.92 (td, J = 2.7, 13.4 Hz, 2H), 3.90

(tt, J = 1.4, 5.7 Hz, 2H), 4.71 (dt, J = 2.7, 10.7 Hz, 2H), 5.14 (dq, J = 1.3, 10.2 Hz, 1H), 5.18

(dq, J = 1.5, 17.2 Hz, 2H), 5.53 (br.s, 1H), 5.84 (ddt, J = 5.7, 10.3, 15.9 Hz, 1H), 8.18 (s, 2H);

13C-NMR δ 28.6, 42.0, 43.8, 44.2, 116.7, 134.3, 145.3 (d, J = 21.5 Hz), 151.6 (d, J = 248.1

Hz), 158.9, 174.4; 19F-NMR δ -157.2; IR (neat): 3287, 2929, 2859, 1633, 1610, 1553, 1511,

1456, 1443, 1400, 1362, 1322, 1289, 1261, 1238, 1218, 1177, 1167, 1123; HRMS (ESI):

[M+Na]+ calculated for C13H17ON4FNa+, 287.1279, found 287.1276.

(R,S,S,R,S,R)-N-allyl-4-(10,13-dimethyl-3,7,12-trioxohexadecahydro-1H-cyclopenta

[a]phenanthren-17-yl)pentanamide


obtained as a white solid (77%). 1H-NMR (600 MHz,

CDCl3) δ 0.88 (d, J = 6.6 Hz, 3H), 1.09 (s, 3H), 1.21–1.47

(m, 8H), 1.63 (td, J = 14.5, 4.6 Hz, 2H), 1.81–2.10 (m,

6H), 2.09 – 2.19 (m, 3H), 2.19–2.42 (m, 7H), 2.79 –3.03

(m, 3H), 3.90 (tt, J = 5.8, 1.5 Hz, 2H), 5.06–5.26 (m, 2H), 5.54 (s, 1H), 5.86 (ddt, J = 17.1,

10.3, 5.7 Hz, 1H); 13C-NMR δ 11.8. 18.9, 21.9, 25.1, 27.6, 31.1, 33.6, 35.3, 35.5, 36.0, 36.5,

38.7, 41.9, 42.8, 45.0, 45.5, 45.6, 46.8, 49.0, 51.8, 56.9, 116.3, 134.4, 173.0, 208.7, 209.0,

NH

O

O

HO

HO

S-10

212.0; IR (neat): 1735, 1640, 1539, 1364, 1260, 1198, 1173, 1147, 1063; HRMS (ESI):

[M+Na]+ calculated for C27H39O4NNa+, 441.2879; found 441.2873.

4. General reaction conditions for the metal-free hydroacylation.

A flame dried Schlenk under argon was charged with the allyl amide 1 (0.2 mmol), and 2-

fluoropyridine (0.22 mmol) in 1 mL dry solvent. The mixture was cooled to 0°C and added

freshly distilled Tf2O (0.22 mmol) dropwise and stirred for 15 minutes, then α-methyl styrene

(0.4 mmol) was added, the reaction was stirred for 2 hours at 0°C and warmed up to room

temperature. After stirring for 12 hours, the reaction was quenched with 10 mL 1M HCl. The

layers were separated and the aqueous layer was extracted with DCM (3x10 mL). The

combined organic layers were dried on MgSO4, filtered and evaporated in vacuo. The product

was purified on column chromatography (Heptane/MTBE = 99:1 to 8:2).

Characterization of ketone products:

1,3-diphenylbutan-1-one (3a)9

Following the general procedure in DCM as solvent, the product was

obtained as a white solid (38.7 mg, 86%). 1H-NMR (400 MHz, CDCl3) δ

1.34 (d, J = 6.9 Hz, 3H), 3.25 (ddd, J = 6.9, 16.4, 24.7 Hz, 2H), 3.51 (m,

1H), 7.18–7.21 (m, 1H), 7.23–7.31 (m, 4H), 7.41–7.46 (m, 2H), 7.52–7.54 (m, 1H), 7.93 (m,

2H); 13C-NMR δ 22.0, 35.7, 47.2, 126.4, 127.0, 128.2, 128.68, 128.71, 133.1, 137.4, 146.7,

199.2. All spectroscopic data was in good accordance with those reported in literature.9

4-(3-phenylbutanoyl)benzonitrile (3b)

Following the general procedure in MeCN as solvent, the product

was obtained as a slightly yellow oil (45.4 mg, 91%). 1H-NMR (400

MHz, CDCl3) δ 1.28 (d, J = 6.9 Hz, 3H), 3.10 (dd, J = 7.8, 16.6 Hz,

1H), 3.24 (dd, J = 6.1, 16.6 Hz, 1H), 3.41 (sext, J = 6.9 Hz, 1H), 7.10–7.25 (m, 5H), 7.62–

7.66 (m, 2H), 7.87–7.90 (m, 2H); 13C-NMR δ 22.0, 35.7, 47.4, 116.4, 118.0, 126.6, 126.9,

128.6, 128.8, 132.6, 140.2, 146.0, 197.9; IR (neat): 3061, 3027, 2962, 2925, 2230, 1689,

1604, 1566, 1494, 1452, 1403, 1365, 1289, 1270, 1201, 1175, 1107, 1084, 1063, 1016;

HRMS (ESI): [M+Na]+ calculated for C16H15NONa+, 272.1046; found 272.1043.

S-11

1-(4-nitrophenyl)-3-phenylbutan-1-one (3c)


was obtained as a colorless oil (47.4 mg, 88%). 1H-NMR (400

MHz, CDCl3) δ 1.37 (d, J = 9.5 Hz, 3H), 3.22 (dd, J = 7.7, 16.7

Hz, 1H), 3.35 (dd, J = 6.2, 16.7 Hz, 1H), 3.50 (sext, J = 7.0 Hz, 1H), 7.17–7.33 (m, 5H),

8.02–8.05 (m, 2H), 8.26–8.29 (m, 2H); 13C-NMR δ 22.0, 35.8, 47.7, 123.9, 126.7, 126.9,

128.8, 129.2, 141.7, 146.0, 150.4, 197.7; IR (neat): 3027, 2962, 2926, 1690, 1602, 1522,

1494, 1452, 1405, 1343, 1317, 1268, 1214, 1196, 1108; HRMS (ESI): [M+Na]+ calculated

for C16H15NO3Na+, 292.0944; found 292.0938.

Methyl 4-(3-phenylbutanoyl)benzoate (3d)

Activation at -40°C in DCM, following the general procedure

the product was obtained as a white solid (34.5 mg, 61%). 1H-

NMR (400 MHz, CDCl3) δ 1.36 (d, J = 6.9 Hz, 3H), 3.20 (dd, J

= 8.1, 16.6 Hz, 1H), 3.33 (dd, J = 5.8, 16.6 Hz, 1H), 3.50 (sext,

J = 6.9 Hz, 1H), 3.94 (s, 3H), 7.15–7.35 (m, 5H), 7.92–7.97 (m, 2H), 8.08–8.12 (m, 2H); 13C-

NMR δ 22.0, 35.7, 47.5, 52.6, 126.5, 127.0, 128.1, 128.7, 129.9, 133.9, 140.5, 146.4, 166.3,

198.7; IR (neat): 3060, 3027, 2955, 2928, 1722, 1686, 1495, 1452, 1435, 1405, 1311, 1273,

1216, 1193, 1106, 1016; HRMS (ESI): [M+Na]+ calculated for C18H18O3Na+, 305.1148;

found 305.1153.

1-(4-acetylphenyl)-3-phenylbutan-1-one (3e)


was obtained as a white solid (38.2 mg, 72%). 1H-NMR (400 MHz,

CDCl3) δ 1.36 (d, J = 6.9 Hz, 3H), 2.63 (s, 3H), 3.20 (dd, J = 8.0,

16.6 Hz, 1H), 3.33 (dd, J = 5.9, 16.6 Hz, 1H), 3.50 (sext, J = 6.9 Hz,

1H), 7.20–7.22 (m, 1H), 7.24–7.31 (m, 4H), 7.97–8.01 (m, 4H); 13C-NMR δ 22.0, 27.0, 35.8,

47.6, 126.6, 127.0, 128.4, 128.6, 128.7, 140.2, 140.5, 146.4, 197.6, 198.7; IR (neat): 3060,

3027, 2961, 2922, 1681, 1496, 1452, 1401, 1356, 1306, 1261, 1217, 1200, 1075; HRMS

(ESI): [M+Na]+ calculated for C18H18O2Na+, 289.1199; found 289.1207.

S-12

4-(3-phenylbutanoyl)benzaldehyde (3f)


was obtained as a yellow oil (15.2 mg, 30%). 1H-NMR (400 MHz,

CDCl3) δ 1.36 (d, J = 6.9 Hz, 3H), 3.22 (dd, J = 8.0, 16.6 Hz, 1H),

3.35 (dd, J = 6.0, 16.6 Hz, 1H), 3.51 (sext, J = 6.9 Hz, 1H), 7.18–

7.21 (m, 1H), 7.24–7.34 (m, 4H), 7.93–7.97 (m, 2H), 8.02–8.05 (m, 2H), 10.09 (s, 1H); 13C-

NMR δ 22.0, 35.7, 47.7, 126.6, 127.0, 128.7, 128.8, 129.9, 139.1, 141.6, 146.3, 191.7, 198.7;

IR (neat): 3060, 3027, 2962, 2925, 2873, 2849, 2735, 1686, 1604, 1574, 1496, 1452, 1413,

1382, 1304, 1105; HRMS (ESI): [M+Na]+ calculated for C17H16O2Na+, 275.1043; found

275.1042.

1-(4-chlorophenyl)-3-phenylbutan-1-one (3g)


obtained as a colorless oil (40.0 mg, 77%). 1H-NMR (400 MHz,


3.27 (dd, J = 5.9, 16.4 Hz, 1H), 3.49 (sext, J = 6.9 Hz, 1H), 7.18–7.22 (m, 1H), 7.24–7.33 (m,

4H), 7.39–7.42 (m, 2H), 7.82–7.87 (m, 2H); 13C-NMR δ 22.0, 35.8, 47.1, 126.5, 127.0, 128.7,

129.0, 129.6, 135.7, 139.6, 146.5, 198.0; IR (neat): 3084, 3061, 3028, 2962, 2927, 2874,

1682, 1587, 1491, 1453, 1399, 1363, 1311, 1269, 1201, 1175, 1090, 1012, 990, 908, 816, 759,

699; HRMS (ESI): [M+Na]+ calculated for C16H15OClNa+, 281.0704; found 281.0706.

1-(4-bromophenyl)-3-phenylbutan-1-one (3h)




3.26 (dd, J = 5.9, 16.5 Hz, 1H), 3.49 (sext, J = 6.9 Hz, 1H), 7.20 (m, 1H), 7.24–7.35 (m, 4H),

7.56–7.59 (m, 2H), 7.77–7.79 (m, 2H); 13C-NMR δ 22.0, 35.7, 47.1, 126.5, 127.0, 128.3,

128.7, 129.7, 132.0, 136.1, 146.4, 198.1; IR (neat): 3084, 3060, 3027, 2962, 2925, 1682,

1583, 1493, 1452, 1395, 1361, 1309, 1270, 1216, 1200, 1175, 1102, 1070, 1021, 812, 756,

699; HRMS (ESI): [M+Na]+ calculated for C16H15OBrNa+, 325.0198; found 325.0192.

3-phenyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)butan-1-one (3i)

Following the general procedure in DCM as solvent, the product


S-13

MHz, CDCl3) δ 1.34 (d, J = 7.1 Hz, 3H), 1.36 (s, 12H), 3.22 (d, J = 8.3, 16.7 Hz, 1H), 3.33

(dd, J = 5.6, 16.7 Hz, 1H), 3.53 (sext, J = 7.1 Hz, 1H), 7.19–7.21 (m, 1H), 7.27–7.35 (m, 4H),

7.45 (t, J = 7.6 Hz, 1H), 7.97 (dt, J = 1.1, 7.3 Hz, 1H), 8.02 (dt, J = 1.6, 7.8 Hz, 1H), 8.32 (s,

1H); 13C-NMR δ 21.9, 25.0, 25.1, 35.6, 47.3, 84.3, 126.4, 127.1, 128.2, 128.7, 130.8, 134.5,

136.8, 139.4, 146.9, 199.3; IR (neat): 3060, 3028, 2976, 2928, 1685, 1600, 1579, 1485, 1453,

1418, 1358, 1322, 1265, 1213, 1198, 1166, 1142, 1112, 1076; HRMS (ESI): [M+Na]+

calculated for C22H27O3BNa+, 373.1942; found 373.1955.

1-(3-(methylthio)phenyl)-3-phenylbutan-1-one (3j)



MHz, CDCl3) δ 1.35 (d, J = 6.9 Hz, 3H), 2.51 (s, 3H), 3.16 (dd, J =

8.1, 16.5 Hz, 1H), 3.29 (dd, J = 5.8, 16.5 Hz, 1H), 3.50 (sext, J = 6.9 Hz, 1H), 7.18–7.22 (m,

1H), 7.25–7.35 (m, 4H), 7.35 (t, J = 7.8 Hz, 1H), 7.42 (ddd, J = 1.2, 1.8, 7.8 Hz, 1H), 7.66 (dt,

J = 1.3, 7.8 Hz, 1H), 7.79 (t, J = 1.7 Hz, 1H); 13C-NMR δ 15.8, 22.0, 35.7, 47.2, 124.8, 125.7,

126.5, 127.0, 128.7, 129.0, 130.9, 137.9, 139.8, 146.6, 198.8; IR (neat): 3060, 3027, 2961,

2922, 2872, 1681, 1602, 1569, 1494, 1452, 1413, 1362, 1311, 1265, 1201, 1082, 1026, 1008;

HRMS (ESI): [M+Na]+ calculated for C17H18OSNa+, 293.0971; found 293.0969.

1-(naphthalen-2-yl)-3-phenylbutan-1-one (3k)




1H), 3.44 (dd, J = 5.7, 16.3 Hz, 1H), 3.58 (sext, J = 6.9 Hz, 1H), 7.19–7.22 (m, 1H), 7.32 (d, J

= 4.3 Hz, 4H), 7.52–7.63 (m, 2H), 7.88 (dd, J = 4.2, 8.3 Hz, 2H), 7.95 (d, J = 8.0 Hz, 1H),

8.01 (dd, J = 1.7, 8.6 Hz, 1H), 8.43 (s, 1H); 13C-NMR δ 22.0, 35.9, 47.3, 124.1, 126.5, 126.9,

127.1, 127.9, 128.5, 128.6, 128.7, 129.7, 129.8, 132.7, 134.7, 135.7, 146.8, 199.2; IR (neat):

3058, 3026, 2961, 2926, 2873, 1676, 1627, 1597, 1494, 1467, 1452, 1407, 1358, 1277, 1235,

1211, 1180, 1124, 1086, 1018; HRMS (ESI): [M+Na]+ calculated for C20H18ONa+, 297.1250;

found 297.1248.

3-phenyl-1-(thiophen-2-yl)butan-1-one (3l)


obtained as a colorless oil (26.7 mg, 58%). 1H-NMR (600 MHz, CDCl3)

S-14

δ 1.35 (d, J = 6.6 Hz, 3H), 3.11 (dd, J = 8.4, 15.6 Hz, 1H), 3.21 (dd, J = 5.4, 15.6 Hz, 1H),

3.48–3.52 (m, 1H), 7.10 (dd, J = 3.8, 4.9 Hz, 1H), 7.18–7.21 (m, 1H), 7.26–7.32 (m, 4H),

7.61 (dd, J = 1.1, 4.9 Hz, 1H), 7.67 (dd, J = 1.1, 3.8 Hz, 1H); 13C-NMR δ 21.7, 36.0, 47.9,

126.4, 126.9, 128.1, 128.6, 131.9, 133.6, 144.7, 146.3, 192.0; IR (neat): 3085, 2929, 2873,

1654, 1354, 1271, 1232, 1057; HRMS (ESI): [M+Na]+ calculated for C14H14OSNa+,

253.0658; found 253.0660.

(E)-1,5-diphenylhex-1-en-3-one (3m)




1H), 2.91 (dd, J = 6.0, 15.6 Hz, 1H), 3.33–3.38 (m, 1H), 6.61 (d, J = 16 Hz, 1H), 7.10–7.44

(m, 5H); 13C-NMR δ 21.9, 35.8, 49.4, 126.3, 126.5, 126.9, 128.3, 128.5, 128.9, 130.4, 134.5,

142.6, 146.4, 199.1; IR (neat): 1660, 1576, 1494, 1364, 1333, 1203, 1173, 1121, 1074, 1013;

HRMS (ESI): [M+Na]+ calculated for C18H18ONa+, 273.1250; found 273.1251.

1,5-diphenylhexan-3-one (3n)



MHz, CDCl3) δ 1.28 (d, J = 8.8 Hz, 3H), 2.59–2.71 (m, 4H), 2.75

(dd, J = 13.2, 16.2 Hz, 1H), 2.81–2.89 (m, 1H), 3.31–3.36 (m, 1H), 7.13–7.15 (m, 2H), 7.19–

7.24 (m, 4H), 7.27–7.33 (m, 4H); 13C-NMR δ 22.0, 29.6, 35.5, 45.0, 51.4, 126.1, 126.3,

126.8, 128.3, 128.5, 128.6, 141.0, 146.1, 208.9; IR (neat): 2930, 1690, 1326, 1261, 1117;

HRMS (ESI): [M+Na]+ calculated for C18H21ONa+, 253.1587; found 253.1563.

1-cyclohexyl-3-phenylbutan-1-one (3o)



δ 1.07–1.25 (m, 5H), 1.17 (d, J = 8.0 Hz, 3H), 1.52–1.72 (m, 5H), 2.12–

2.18 (m, 1H), 2.58 (dd, J = 8.0, 16.0 Hz, 1H), 2.67 (dd, J = 4.0, 16 Hz, 1H), 3.22–3.30 (m,

1H), 7.08–7.14 (m, 3H), 7.17–7.22 (m, 2H); 13C-NMR δ 21.9, 25.6, 25.7, 25.9, 28.1, 28.3,

35.1, 49.2, 51.3, 126.2, 126.8, 128.5, 146.6, 212.8; IR (neat): 2927, 2854, 1706, 1494, 1450,

1144, 1070; HRMS (ESI): [M+Na]+ calculated for C16H22ONa+ 253.1563; found: 253.1563.

3-phenyl-1-(tetrahydro-2H-pyran-4-yl)butan-1-one (3p)

S-15



δ 1.26 (d, J = 7.0 Hz, 3H), 1.51–1.75 (m, 4H), 2.41 (sept, J = 4.5 Hz,

1H), 2.66 (dd, J = 7.7, 16.5 Hz, 1H), 2.77 (dd, J = 6.5, 16.5 Hz, 1H), 3.29–3.43 (m, 3H), 3.94

(m, 2H), 7.19 (m, 3H), 7.28 (m, 2H); 13C-NMR δ 22.0, 27.9, 28.1, 35.3, 48.1, 49.0, 67.3,

67.3, 126.4, 126.9, 128.6, 146.4, 210.8; IR (neat): 2954, 2843, 1705, 1602, 1494, 1446, 1406,


C15H20O2Na+, 255.1356; found 255.1356.

5-ethyl-2-phenylheptan-4-one (3q)



δ 0.65 (t, J = 8.0 Hz, 3H), 0.72 (t, J = 8.0 Hz, 3H), 1.19 (d, J = 4.0 Hz,

3H), 1.24–1.39 (m, 2H), 1.41–1.53 (m, 2H), 2.13–2.20 (m, 1H), 2.57 (dd, J = 8.0, 16.0 Hz,

1H), 2.67 (dd, J = 8.0, 16.0 Hz, 1H), 3.25–3.34 (m, 1H), 7.08–7.23 (m, 5H); 13C-NMR δ

11.6, 11.7, 21.9, 23.8, 24.0, 34.8, 50.8, 55.8, 126.2, 126.9, 128.4, 146.7, 213.2; IR (neat):

1692, 1494, 1276, 1262, 1008; HRMS (ESI): [M+Na]+ calculated for C15H22ONa+, 241.1563;

found: 241.1562.

9-oxo-11-phenyldodecanenitrile (3r)

Following the general procedure in DCM as solvent, the

product was obtained as a colorless oil (40.0 mg, 74%).

1H-NMR (600 MHz, CDCl3) δ 1.28 (d, J = 7.7 Hz, 3H), 1.16–1.26 (m, 1H), 1.26–1.35 (m,

2H), 1.39–1.47 (m, 1H), 1.51 (dt, J = 14.9, 7.4 Hz, 2H), 1.62–1.67 (m, 2H), 2.26–2.36 (m,

4H), 2.64 (dd, J =, 7.7, 16.1 Hz, 1H), 2.74 (dd, J = 6.7, 16.1 Hz, 1H), 3.34 (sext, J = 7.0 Hz,

1H), 7.18–7.26 (m, 3H), 7.26–7.36 (m, 2H), 13C-NMR δ 17.1, 22.0, 23.4, 25.3, 28.4, 28.5,

28.8, 35.5, 43.4, 51.2, 119.8, 126.3, 126.8, 128.5, 128.5, 146.2, 209.9; IR (neat): 2932, 2863,


C18H25ONNa+, 294,1828; found 294.1832.

1-chloro-6-phenylheptan-4-one (3s)



CDCl3) δ 1.27 (d, J = 1.27 Hz, 3H), 1.96 (p, J = 6.6 Hz, 2H), 2.49 (qt, J = 6.9, 17.9 Hz, 2H),

S-16

2.65 (dd, J = 7.6, 16.0 Hz, 1H), 2.76 (dd, J = 6.9, 16.0 Hz, 1H), 3.32 (sext, J = 7.1 Hz, 1H),

3.49 (m, 2H), 7.17–7.22 (m, 3H), 7.25–7.30 (m, 2H); 13C-NMR δ 22.2, 26.3, 35.8, 40.2, 44.5,

51.4, 126.5, 126.9, 128.7, 146.1, 208.8; IR (neat): 3028, 2961, 2924, 1710, 1494, 1451, 1409,


C13H17OClNa+, 247.0860; found 247.0864.

Methyl 9-oxo-11-phenyldodecanoate (3t)

Following the general procedure in DCM as solvent,

the product was obtained as a colorless oil (36.5 mg,

60%). 1H-NMR (400 MHz, CDCl3) δ 1.09–1.29 (m, 6H), 1.18 (d, J = 6.8 Hz, 3H), 1.38–1.56

(m, 4H), 2.14–2.28 (m, 4H), 2.54 (dd, J = 7.2, 16 Hz, 1H), 2.64 (dd, J = 6.8, 16 Hz, 1H),

3.20–3.29 (m, 1H), 3.59 (s, 3H), 7.09–7.31 (m, 5H); 13C-NMR δ 22.0, 23.5, 24.9, 28.9 (2C),

29.0, 34.0, 35.5, 43.5, 51.1, 51.4, 126.3, 126.8, 128.5, 146.3, 174.2, 210.0; IR (neat): 2926,


C19H28NaO3+, 327.1931; found 327.1933.

2-phenylnon-8-yn-4-one (3u)



MHz, CDCl3) δ 1.27 (d, J = 7.0 Hz, 3H), 1.70–1.75 (m, 2H), 1.93 (t, J = 6.8 Hz, 1H), 2.14–

2.17 (m, 2H), 2.40–2.44 (m, 1H), 2.47–2.51 (m, 1H), 2.65 (dd, J = 7.7, 16.1 Hz, 1H), 2.75

(dd, J = 7.0, 16.1 Hz, 1H), 3.30–3.35 (m, 1H), 7.18–7.21 (m, 2H), 7.26–7.30 (m, 3H); 13C-

NMR δ 17.7, 21.9, 22.0, 35.5, 41.8, 51.2, 69.0, 83.6, 126.3, 126.8, 128.5, 146.1, 209.2; IR

(neat): 3027, 2958, 1710, 1492, 1452, 1368, 1111; HRMS (ESI): [M+Na]+ calculated for

C15H18ONa+ 237.1250; found: 237.1249.

2-phenyltetradec-13-en-4-one (3v) Following the general procedure in DCM as solvent,


60%). 1H-NMR (700 MHz, CDCl3) δ 1.29 (d, J = 7.0 Hz, 3H), 1.13–1.37 (m, 9H), 1.39 (dq, J

= 7.6, 15.0 Hz, 1H), 1.49–1.56 (m, 2H), 2.01–2.13 (m, 2H), 2.25–2.39 (m, 2H), 2.65 (dd, J =

16.2, 7.9 Hz, 1H), 2.74 (dd, J = 16.2, 6.5 Hz, 1H), 3.28–3.42 (m, 1H), 4.87–5.07 (m, 2H),

5.84 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 7.17–7.26 (m, 3H), 7.28–7.38 (m, 2H); 13C-NMR δ

22.0, 23.6, 28.9, 29.0, 29.1, 29.3, 29.3, 33.8, 35.5, 43.6, 51.1, 114.2, 126.3, 126.8, 128.5,

S-17

139.2, 146.3, 210.1; IR (neat): 2926, 2855, 1712, 1494, 1452, 1374; HRMS (ESI): [M+Na]+

calculated for C20H30ONa+, 309.2189; found 309.2190.

1-(1-(5-fluoropyrimidin-2-yl)piperidin-4-yl)-3-phenylbutan-1-one (3w)


reaction was quenched with 1M NaOH and extracted with

DCM. The product was obtained as a colorless oil (32.1 mg,

49%). 1H-NMR (600 MHz, CDCl3) δ 1.26 (d, J = 7.0 Hz,

3H), 1.48–1.54 (m, 2H), 1.71–1.76 (m, 1H), 1.80–1.86 (m, 1H), 2.46 (tt, J = 3.7, 11.4 Hz,

1H), 2.70 (dd, J = 7.8, 16.6 Hz, 1H), 2.80 (dd, J = 6.5, 16.6 Hz, 1H), 2.87–2.92 (m, 2H), 3.35

(sext, J = 7.0 Hz, 1H), 4.58–4.63 (m, 2H), 7.18–7.22 (m, 3H), 7.29 (t, J = 7.6 Hz, 2H), 8.16

(s, 2H); 13C-NMR δ 22.0, 27.0, 27.2, 35.3, 44.1, 44.1, 49.3, 49.4, 126.5, 126.9, 128.7, 145.2

(d, J = 21.5 Hz), 146.4, 151.6 (d, J = 248.1 Hz), 158.8, 211.3; 19F-NMR δ -157.2; IR (neat):

3028, 2924, 2854, 1705, 1608, 1554, 1492, 1447, 1399, 1361, 1309, 1287, 1237, 1209, 1171,

1156, 1128, 1070, 1003; HRMS (ESI): [M+Na]+ calculated for C19H22ON3FNa 350.1639;

found 350.1642.

(5S,9S,10S,13R,14S,17R)-10,13-dimethyl-17-((2R)-5-oxo-7-phenyloctan-2-yl)dodecahydr

o-3H-cyclopenta[a]phenanthrene-3,7,12(2H,4H)-trione (3x)

Following the general procedure in DCM as solvent,


70%, 1:1 d.r.). 1H-NMR (600 MHz, CDCl3) δ 0.76–

0.79 (m, 3H), 1.05 (s, 3H), 1.18–1.35 (m, 3H), 1.28 (d,

J = 2.4, 3H), 1.21–1.30 (m, 4H), 1.41 (s, 3H), 1.60–

1.67 (m, 1H), 1.71–1.76 (m, 1H), 1.81–1.87 (m, 1H), 1.93–2.06 (m, 4H), 2.12–2.16 (m, 2H),

2.22–2.42 (m, 8H), 2.62–2.68 (m, 1H), 2.72–2.78 (m, 1H), 2.82–2.95 (m, 3H), 3.30–3.36 (m,

1H), 7.19–7.34 (m, 5H). 13C-NMR δ 11.9, 11.9, 18.7, 18.7, 21.9, 22.0, 22.1, 25.1, 25.1, 27.5,

27.6, 28.9, 28.9, 35.2, 35.2, 35.3, 35.5, 35.6, 36.0, 36.5, 38.6, 40.4, 40.5, 42.8, 45.0, 45.5,

45.6, 45.6, 46.8, 49.0, 51.2, 51.8, 126.3, 126.8, 128.5, 146.2, 208.7, 209.0, 210.3, 212.0; IR

(neat): 3082, 2958, 2926, 2871, 1701, 1697, 1492, 1424, 1385, 1277; HRMS (ESI): [M+Na]+

calculated for C33H44O4Na+, 527.3132; found 527.3132.

4-(4-methyl-3-phenylpentanoyl)benzonitrile (4a)

S-18



CDCl3) δ 0.71 (d, J = 6.8 Hz, 3H), 0.92 (d, J = 6.4 Hz, 3H), 1.83–

1.92 (m, 1H), 2.99–3.05 (m, 1H), 3.22–3.23 (m, 2H), 7.05–7.09 (m,

3H), 7.14–7.19 (m, 2H), 7.61–7.63 (m, 2H), 7.81–7.83 (m, 2H); 13C-NMR δ 20.4, 20.9, 33.3,

43.0, 48.2, 116.1, 118.0, 126.4, 128.2, 128.4, 132.4, 140.4, 143.1, 198.4; IR (neat): 3027,

2958, 2926 2231, 1685, 1492, 1452, 1289, 1258, 1016; HRMS (ESI): [M+Na]+ calculated for

C19H19NONa+, 300.1359; found 300.1359.

4-(3,3-diphenylpropanoyl)benzonitrile (4b)



MHz, CDCl3) δ 3.66 (d, J = 8.0 Hz, 2H), 4.72 (t, J = 4.0 Hz, 1H),

7.09–7.22 (m, 10H), 7.65–7.67 (m, 2H), 7.89–7.91 (m, 2H); 13C-NMR δ 45.1, 46.0, 116.4,

117.9, 126.6, 127.7, 128.4, 128.7, 132.5, 140.0, 143.6, 196.9; IR (neat): 3027, 2923, 2231,


C22H17NONa+, 334.1202; found 334.1203.

4-(2-(1,2,3,4-tetrahydronaphthalen-1-yl)acetyl)benzonitrile (4c)

Following the general procedure in MeCN as solvent, the

product was obtained as a colorless oil (44.6 mg, 81%). 1H-

NMR (400 MHz, CDCl3) δ 1.57–1.64 (m, 1H), 1.67–1.81 (m,

2H), 1.85–1.93 (m, 1H), 2.65–2.79 (m, 2H), 3.22 (d, J = 6.8 Hz, 2H), 3.51–3.58 (m, 1H),

7.00–7.05 (m, 4H), 7.68–7.70 (m, 2H), 7.96–7.98 (m, 2H); 13C-NMR δ 19.7, 28.3, 29.5, 33.4,

46.6, 116.4, 117.9, 126.0, 126.1, 128.3, 128.5, 129.4, 132.6, 137.3, 139.5, 140.2, 198.0; IR

(neat): 2930, 2863, 1689, 1491, 1451, 1403, 1356, 1288, 1237, 1202; HRMS (ESI): [M+Na]+

calculated for C19H17NONa+, 298.1202; found 298.1197.

4-(3,4-diphenylbutanoyl)benzonitrile (4d)


was obtained as a colorless oil (54.0 mg, 83%). 1H-NMR (400 MHz,

CDCl3) δ 2.86–2.97 (m, 2H), 3.17 (dd, J = 16.4, 6.0 Hz, 1H), 3.25

(dd, J = 16.8, 7.2 Hz, 1H), 3.52–3.59 (m, 1H), 7.00–7.02 (m, 2H),

7.07–7.18 (m, 8H), 7.59–7.61 (m, 2H), 7.76–7.78 (m, 2H); 13C-NMR δ 43.0, 43.2, 44.4,

S-19

116.2, 117.9, 126.3, 126.7, 127.6, 128.3, 128.4, 128.5, 129.3, 132.4, 139.5, 140.1, 143.6,

197.7; IR (neat): 3026, 2926, 2231, 1690, 1603, 1495, 1453, 1369, 1331, 1178, 1016; HRMS

(ESI): [M+Na]+ calculated for C23H19NNaO+, 348.1359; found 348.1355.

4-(3-(o-tolyl)butanoyl)benzonitrile (4e)



MHz, CDCl3) δ 1.33 (d, J = 6.8 Hz, 3H), 2.40 (s, 3H), 3.22 (dd, J

= 16.8, 8.0 Hz, 1H), 3.34 (dd, J = 16.8, 5.6 Hz, 1H), 3.73–3.82 (m, 1H), 7.10–7.28 (m, 4H),

7.75–7.77(m, 2H), 8.00–8.02 (m, 2H); 13C-NMR δ 19.5, 21.5, 30.4, 46.6, 116.3, 117.9, 125.1,

126.2, 126.4, 128.4, 130.6, 132.5, 135.3, 140.1, 144.1, 197.8; IR (neat): 2967, 2929, 2231,


for C18H17NONa+, 286.1202; found 286.1202.

2-phenylnon-8-yn-4-one (4f)



MHz, CDCl3) δ 1.11 (d, J = 4.4 Hz, 3H), 2.87–2.93 (m, 2H), 3.02–

3.06 (m, 1H), 4.96–5.04 (m, 2H), 5.79–5.85 (m, 1H), 7.76–7.78 (m, 2H), 8.02–8.03 (m, 2H);

13C-NMR δ 19.8, 33.5, 45.4, 113.5, 116.3, 117.9, 128.5, 132.5, 140.2, 142.5, 197.9; IR

(neat): 2963, 2231, 1693, 1455, 1360, 1276, 1177; HRMS (ESI): [M+Na]+ calculated for

C13H13ONNa+, 222.0889; found 222.0882.

4-(4-(triisopropylsilyl)butanoyl)benzonitrile (4g)



NMR (400 MHz, CDCl3) δ 0.56–0.60 (m, 2H), 0.95–0.99 (m,

3H), 0.97 (s, 18H), 1.71–1.78 (m, 2H), 2.94 (t, J = 4.0 Hz, 2H), 7.69–7.71 (m, 2H), 7.95–7.98

(m, 2H); 13C-NMR δ 9.5, 10.9, 18.8, 19.3, 43.2, 116.2, 118.0, 128.4, 132.5, 140.1, 198.9; IR

(neat): 2940, 2889, 2865, 2232, 1692, 1464, 1403, 1290; HRMS (ESI): [M+Na]+ calculated

for C20H31ONSiNa+, 352.2067; found 352.2061.

4-(tert-butyldiphenylsilyl)-1-cyclohexylbutan-1-one (4h)

S-20


was obtained as a colorless oil (470 mg, 72%). 1H-NMR (400

MHz, CDCl3) δ 1.09 (s, 9H), 1.14–1.39 (m, 7H), 1.62–1.84 (m,

7H), 2.24–2.33 (m, 1H), 2.49 (t, J = 4.0 Hz, 2H), 7.40–7.46 (m, 6H), 7.67–7.70 (m, 4H); 13C-

NMR δ 10.4, 18.1, 18.6, 25.7, 25.9, 27.9, 28.5, 44.1, 50.7, 127.6, 129.0, 134.7, 136.0, 214.1;

IR (neat): 2926, 2855, 1701, 1149, 1362, 1104; HRMS (ESI): [M+Na]+ calculated for

C26H36OSiNa+, 415.2428; found 415.2432.

4-(3-(naphthalen-1-yl)butanoyl)benzonitrile (4i)



NMR (400 MHz, CDCl3) δ 1.41 (d, J = 8.0 Hz, 3H), 3.26 (dd,

J = 8.8, 17.2, 1H), 3.35 (dd, J = 4.4, 17.2 Hz, 1H), 4.29–4.34 (m, 1H), 7.34–7.47 (m, 4H),

7.62–7.66 (m, 3H), 7.77–7.79 (m, 1H), 7.89–7.92 (m, 2H), 8.05–8.07 (m, 1H); 13C-NMR δ

21.1, 29.6, 47.0, 116.3, 117.9, 122.6, 122.9, 125.5, 125.6, 126.2, 127.1, 128.4, 129.1, 131.1,

132.5, 134.0, 140.1, 142.0, 197.8; IR (neat): 2960, 2230, 1691, 1598, 1510, 1455, 1402, 1378,

1278, 1254, 1208, 1006; HRMS (ESI): [M+Na]+ calculated for C21H17NONa+, 322.1202;

found 322.1203.

4-(3-(4-(trifluoromethyl)phenyl)butanoyl)benzonitrile (4j)



NMR (600 MHz, CDCl3) δ 1.30 (d, J = 8.0 Hz, 3H), 3.16

(dd, J = 8.0, 20.0 Hz, 1H ), 3.26 (dd, J = 4.0, 16.0 Hz, 1H), 3.48–3.53 (m, 1H), 7.29–7.31 (m,

2H), 7.47–7.49 (m, 2H), 7.67–7.72 (m, 2H), 7.90–7.92 (m, 2H); 13C-NMR δ 21.8, 35.2, 46.8,

116.5, 117.8, 125.6 (q, J = 5.0 Hz), 127.2, 128.4, 128.9 (q, J = 16.3 Hz), 132.5, 139.8, 150.0,

197.0; IR (neat): 2960, 2232, 1693, 1619, 1405, 1326, 1274, 1203, 1164, 1119, 1063, 1017;

HRMS (ESI): [M+Na]+ calculated for C18H14OF3NNa+ 340.0920; found: 340.0917.

4,4'-(1-oxobutane-1,3-diyl)dibenzonitrile (4k)



NMR (400 MHz, CDCl3) δ 1.30 (d, J = 8.0 Hz, 3H), 3.17

(dd, J = 8.0, 20 Hz, 1H), 3.25 (dd, J = 8.0, 20 Hz, 1H), 3.48–3.54 (m, 1H), 7.29–7.31 (m,

S-21

2H), 7.52–7.54 (m, 2H), 7.68–7.70 (m, 2H), 7.90–7.93 (m, 2H); 13C-NMR δ 21.7, 35.4, 46.6,

110.5, 116.6, 117.8, 118.8, 127.8, 128.4, 132.5, 132.6, 139.7, 151.4, 196.6; IR (neat): 2969,


for C18H14ON2Na+ 297.0998; found: 297.0998.

4-(3-phenylpropanoyl)benzonitrile (4l)



MHz, CDCl3) δ 3.09–3.12 (m, 2H), 3.33–3.35 (m, 2H), 7.23–7.34

(m, 5H), 7.77–7.79 (m, 2H), 8.04–8.06 (m, 2H); 13C-NMR δ 29.9, 40.8, 116.4, 117.9, 126.4,

128.4, 128.4, 128.6, 132.5, 139.8, 140.7, 197.8; IR (neat): 2231, 1692, 1605, 1453, 1365,

1233, 1178; HRMS (ESI): [M+Na]+ calculated for C16H13ONNa+, 258.0889; found:

258.0893.

4-(3-(p-tolyl)propanoyl)benzonitrile (4m)



NMR (600 MHz, CDCl3) δ 2.32 (s, 3H), 3.04 (t, J = 6.0 Hz,

2H), 3.29 (t, J = 6.0 Hz, 2H), 7.11–7.14 (m, 4H), 7.75–7.76 (m, 2H), 8.01–8.03 (m, 2H); 13C-

NMR δ 21.0, 29.4, 40.9, 116.3, 117.9, 128.3, 128.4, 129.3, 132.5, 135.9, 137.6, 139.8, 197.9;

IR (neat): 3028, 2230, 1689, 1576, 1494, 1363, 1332, 1276, 1204, 1173; HRMS (ESI):

[M+Na]+ calculated for C17H15ONNa+, 272.1046; found 272.1048..

4-(3-(4-chlorophenyl)propanoyl)benzonitrile (4n)



NMR (400 MHz, CDCl3) δ 2.98 (t, J = 8.0 Hz, 2H), 3.22 (t, J

= 8.0 Hz, 2H), 7.09–7.11 (m, 2H), 7.18–7.21 (m, 2H), 7.68–7.72 (m, 2H), 7.94–7.96 (m, 2H);

13C-NMR δ 29.1, 40.5, 116.5, 117.8, 128.4, 128.7, 129.8, 132.2, 132.6, 139.1, 139.7, 197.4;

IR (neat): 2923, 2233, 1691, 1608, 1514, 1443, 1404, 1363, 1292, 1268, 1205, 1177; HRMS

(ESI): [M+Na]+ calculated for C16H12OClNNa+, 292.0500; found 292.0500.

4-(3-(4-(chloromethyl)phenyl)propanoyl)benzonitrile (4o)

S-22



NMR (400 MHz, CDCl3) δ 3.01 (t, J = 8.0 Hz, 2H), 3.23

(t, J = 8.0 Hz, 2H), 4.50 (s, 2H), 7.15–7.19 (m, 2H), 7.24–7.26 (m, 2H), 7.67–7.72 (m, 2H),

7.94–7.96 (m, 2H); 13C-NMR δ 29.5, 40.5, 46.0, 116.5, 117.9, 128.4, 128.8, 128.9, 132.6,

135.7, 139.7, 141.1, 197.6; IR (neat): 2231, 1695, 1567, 1446, 1364, 1277, 1262, 1177;

HRMS (ESI): [M+Na]+ calculated for C17H14OClNNa+, 306.0656; found 306.0653.

S-23

5. Mechanistic studies:

A flame dried Schlenk under argon was charged with the allyl amide 1 (0.2 mmol), and 2-fluoropyridine (0.22 mmol) in 1 mL dry CDCl3. The mixture was cooled to 0°C and added freshly distilled Tf2O (0.22 mmol) dropwise and stirred for 5 minutes, then monitor the reaction with 1H NMR. The 1H NMR was consistent with previous report.[13]

Synthesis of d1-1e

Step 1:[12] To a solution of ketone-d1 (5 mmol) and hydroxyaminhydrochloride (11.5 mmol,

2.3 equiv.) in 10 mL of MeOD, sodiumacetate trihydrate (12.5 mmol, 2.5 equiv.) was added

at room temperature, and the mixture was refluxed for 12 hours. The mixture was neutralized

with sat. aq. NaHCO3, and diluted with ether. The organic layer was separated, washed with

S-24

brine and dried over anhydrous MgSO4. The solvent was removed in vacuo, and the obtained

product was purified over silica gel.

Step 2: The mixture of ketoxime (2 mmol) and 5 mol% of cyanuricchloride (18.41 mg, 0.1

mmol) in dry MeCN (4 mL) was refluxed for 12 hours. The reaction was quenched with sat.

aq. NaHCO3. The organic layer was extracted with ethyl acetate, dried over anhydrous

MgSO4, and concentrated in vacuo. The crude product was purified by column

chromatography on silica gel to afford the corresponding amide as a white solid (40% yield).

N-(propan-2-yl-2-d)benzamide-d1 (d1-1e)

1H-NMR (600 MHz, CDCl3) δ 1.26 (s, 3H), 5.89 (s, 1H), 7.43 (tt, J =

6.7, 1.4 Hz, 1H), 7.45–7.56 (m, 1H), 7.75 (dt, J = 8.5, 1.7 Hz, 1H); 13C-

NMR δ 22.8, 41.6 (t, J = 22.7 Hz), 126.8, 128.5, 131.3, 135.0, 166.7;

HRMS (ESI): [M+H]+ calculated for C10H13DON+, 165.1133; found: 165.1133.

1,3-diphenylbutan-1-one-3-d (d1-3a)

Following the general procedure in MeCN as solvent, the product was


CDCl3) δ 1.26 (s, 3H), 3.11 (d, J = 16.5 Hz, 1H), 3.22 (d, J = 16.4 Hz,

1H), 7.07–7.15 (m, 1H), 7.16–7.26 (m, 4H), 7.33 – 7.41 (m, 2H), 7.42 – 7.52 (m, 1H), 7.85

(dd, J = 8.3, 1.2 Hz, 2H); 13C-NMR δ 21.8, 35.1, 35.2, 35.3, 126.3, 126.9, 128.1, 128.5,

128.6, 133.0, 137.2, 146.6, 199.1; HRMS (ESI): [M+Na]+ calculated for C16H15DONa+,

248,1156; found 248.1162.

S-25

3.00

1.03

1.03

1.15

4.30

1.98

0.99

1.91

1.26

3.10

3.12

3.20

3.23

7.11

7.11

7.11

7.12

7.12

7.13

7.13

7.13

7.18

7.19

7.20

7.21

7.21

7.22

7.23

7.24

7.24

7.35

7.36

7.37

7.38

7.45

7.46

7.46

7.47

7.48

7.48

7.48

7.84

7.85

7.86

7.86

21.7

8

35.0

635

.19

35.3

3

46.9

5

76.8

277

.03

77.2

5

126.

2912

6.86

128.

0912

8.55

128.

5813

2.99

137.

22

146.

55

199.

12

S-26

Following the general procedure in MeCN as solvent, the product was obtained as a colorless

oil (27.5 mg, 55%).

3.00

0.11

0.11

1.00

4.98

1.94

2.15

1.35

1.36

3.15

3.17

3.19

3.21

3.29

3.30

3.33

3.34

3.44

3.46

3.48

3.49

7.20

7.20

7.22

7.22

7.23

7.25

7.25

7.26

7.28

7.30

7.32

7.72

7.73

7.74

7.74

7.95

7.96

7.96

7.97

7.98

S-27

CH318O

Ph

O

NH

Tf2O 1.1 equiv.2-F-pyridine 1.1 equiv.

MeCN, 0 °C to rt, 14 hThen H2

18O

CH3

Ph+

NCNC

88% yield> 90% 18O

Following the general procedure in MeCN as solvent, the product was obtained as a colorless

oil (27.5 mg, 55%). HRMS (ESI): [M+Na]+ calculated for C17H15NNa18O+ 274,1088; found:

274.1087.

S-28

6. References

1. J. S. Quesnel, A. Fabrikant, B. A. Arndtsen, Chem. Sci. 2016, 7, 295–300.

2. K. S. Goh, C.-H. Tan, RSC Advances 2012, 2, 5536–5538.

3. B. Nammalwar, N. P. Muddala, F. M. Watts, R. A. Bunce, Tetrahedron 2015, 71, 9101-

9111.

4. S. De Sarkar, A. Studer, Org. Lett. 2010, 12, 1992–1995.

5. M. Pilo, A. Porcheddu, L. De Luca, Org. Biomol. Chem. 2013, 11, 8241–8246.

6. G. N. Papadopoulos, C. G. Kokotos, J. Org. Chem. 2016, 81, 7023–7028.

7. P. Prediger, L. Ferreira Barbosa, Y. Génisson, C. R. Duarte Correira, J. Org. Chem. 2011,

76, 7737–7749.

8. P. Baburajan, K. P. Elango, Tetrahedron Lett. 2014, 52, 1006–1010.

9. N. Kalutharage, C. S. Yi, Angew. Chem. Int. Ed. 2013, 52, 13651–13655.

10. M. R. Tremblay, M. Nevalainen, S. J. Nair, J. R. Porter, A. C. Castro, M. L. Behnke, L.-C.

Yu, M. Hagel, K. White, K. Faia, L. Grenier, M. J. Campbell, J. Cushing, C. N. Woodward,

J. Hoyt, M. A. Foley, M. A. Read, J. R. Sydor, J. K. Tong, V. J. Palombella, K. .Govern, J.

Adams, J. Med. Chem. 2008, 51,6646–6649.

11. B. Thiedemann, C. M. L. Schmitz, A. Staubitz, J. Org. Chem., 2014, 79, 10284–10295. 12. Y. Furuya, K. Ishihara, H. Yamamoto, J. Am. Chem. Soc., 2005, 127, 11240–11241. 13. T. van Dijk, S. Burck, M. K. Rong, A. J. Rosenthal, M. Nieger, J. C. Slootweg, K. Lammertsma, Angew. Chem. Int. Ed. 2014, 53, 9068–9071.

S-29

6. NMR spectra

2.17

2.13

1.00

0.97

4.21

1.02

4.06

4.06

4.07

4.08

5.16

5.18

5.19

5.23

5.25

5.89

5.90

5.90

5.91

5.92

5.93

6.67

7.89

7.91

7.92

7.93

10.0

4

42.7

117.

1

127.

812

9.9

133.

813

8.3

139.

7

166.

4

191.

7

S-30

12.0

0

2.00

1.00

1.00

1.00

1.00

1.00

0.97

1.00

1.00

1.36

4.08

4.08

4.09

4.09

4.10

4.10

4.11

4.11

4.12

5.17

5.18

5.20

5.20

5.25

5.29

5.29

5.91

5.94

5.95

5.98

6.26

7.44

7.46

7.48

7.93

7.93

7.94

7.95

7.98

7.99

8.00

8.09

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-40000

-30000

-20000

-10000

0

10000

20000

30000

40000

50000

60000

S-31

3.00

2.01

2.04

1.00

1.00

2.00

1.00

1.00

2.50

4.05

4.05

4.05

4.06

4.06

4.07

4.07

4.08

4.08

5.16

5.16

5.19

5.19

5.22

5.27

5.27

5.89

5.91

5.91

5.93

5.95

6.31

7.29

7.31

7.33

7.34

7.35

7.35

7.36

7.37

7.37

7.47

7.47

7.47

7.48

7.49

7.49

7.67

7.68

7.68

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-30000

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

S-32

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

S-33

2.02

2.00

2.00

2.00

2.01

0.94

1.01

2.09

2.11

2.11

2.12

2.13

2.14

2.14

2.16

2.36

2.38

2.40

3.59

3.61

3.62

3.87

3.87

3.88

3.88

3.89

3.89

3.90

3.90

5.12

5.12

5.15

5.15

5.16

5.20

5.21

5.64

5.78

5.80

5.81

5.81

5.82

5.83

5.84

5.84

5.85

5.86

5.87

5.88

-100102030405060708090100110120130140150160170180190200210f1 (ppm)

-10000

-5000

0

5000

10000

15000

20000

25000

S-34

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

0102030405060708090100110120130140150160170180190200210220

-5E+05

0

5E+05

1E+06

2E+06

2E+06

2E+06

3E+06

4E+06

4E+06

4E+06

5E+06

6E+06

6E+06

6E+06

S-35

2.00

1.97

1.01

2.00

1.93

2.00

1.98

1.00

1.01

1.79

1.68

1.69

1.70

1.71

1.72

1.73

1.74

1.75

1.91

1.91

1.93

1.93

2.35

2.36

2.37

2.90

2.91

2.92

2.93

2.94

3.89

3.89

3.89

3.90

3.90

3.90

3.91

4.70

4.70

4.72

4.72

5.13

5.15

5.15

5.19

5.53

5.81

5.81

5.82

5.82

5.83

5.84

5.85

5.85

5.86

5.87

8.18

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-15000

-10000

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

S-36

-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010f1 (ppm)

-100

-50

0

50

100

150

200

250

300

350

400

450

500

550

600

650

700

750

800

S-37

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

S-38

3.07

1.01

1.03

1.00

5.09

1.95

1.95

1.35

1.37

3.15

3.17

3.19

3.21

3.29

3.30

3.33

3.35

3.45

3.46

3.48

3.50

3.52

3.53

7.18

7.18

7.18

7.19

7.20

7.20

7.21

7.22

7.22

7.24

7.25

7.26

7.26

7.28

7.29

7.30

7.31

7.32

7.72

7.72

7.72

7.74

7.74

7.96

7.97

7.98

7.98

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-50000

-40000

-30000

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

S-39

3.01

1.00

1.00

1.00

5.26

2.00

2.00

1.37

1.38

3.19

3.21

3.23

3.25

3.33

3.34

3.37

3.38

3.46

3.48

3.50

3.51

3.53

3.55

7.18

7.20

7.22

7.22

7.25

7.26

7.27

7.29

7.30

7.32

8.02

8.05

8.26

8.28

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-40000

-30000

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

S-40

3.00

1.00

1.00

1.00

3.00

0.98

4.51

1.97

1.97

1.35

1.36

3.17

3.19

3.21

3.23

3.30

3.31

3.34

3.35

3.46

3.47

3.49

3.51

3.53

3.54

3.94

7.18

7.18

7.19

7.19

7.20

7.20

7.21

7.21

7.22

7.25

7.26

7.27

7.27

7.28

7.29

7.30

7.32

7.32

7.94

7.95

7.96

7.96

8.08

8.09

8.10

8.11

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-20000

-15000

-10000

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

S-41

3.00

3.00

0.98

0.99

1.00

0.99

4.27

3.80

1.35

1.36

2.63

3.17

3.19

3.21

3.23

3.30

3.32

3.34

3.36

3.46

3.48

3.49

3.51

3.53

3.54

7.18

7.19

7.20

7.20

7.20

7.21

7.21

7.22

7.26

7.26

7.27

7.28

7.29

7.29

7.30

7.32

7.32

7.96

7.97

7.97

7.98

7.99

7.99

8.00

8.01

8.01

8.02

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-18000

-16000

-14000

-12000

-10000

-8000

-6000

-4000

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

S-42

3.00

1.00

1.00

1.00

1.02

4.23

2.00

2.00

1.00

1.36

1.37

3.19

3.21

3.23

3.25

3.32

3.33

3.36

3.37

3.46

3.48

3.50

3.52

3.53

3.55

7.18

7.19

7.20

7.21

7.22

7.22

7.26

7.26

7.27

7.28

7.29

7.29

7.30

7.32

7.32

7.94

7.94

7.95

7.96

8.03

8.05

10.0

9

22.0

35.7

47.7

126.

612

7.0

128.

712

8.8

129.

9

139.

114

1.6

146.

3

191.

7

198.

7

S-43

3.00

1.00

1.00

1.00

1.00

4.25

1.98

1.98

1.34

1.35

3.12

3.14

3.16

3.18

3.24

3.26

3.28

3.30

3.44

3.46

3.48

3.50

3.51

3.53

7.18

7.18

7.18

7.19

7.20

7.20

7.21

7.21

7.22

7.25

7.26

7.27

7.27

7.29

7.29

7.30

7.32

7.32

7.39

7.40

7.40

7.42

7.42

7.43

7.84

7.84

7.85

7.86

7.87

7.87

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-60000

-50000

-40000

-30000

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

1E+05

1E+05

S-44

3.00

1.00

1.00

1.00

1.00

4.17

2.00

2.01

1.34

1.35

3.11

3.13

3.15

3.17

3.24

3.25

3.28

3.29

3.44

3.46

3.48

3.50

3.51

3.53

7.18

7.19

7.19

7.20

7.20

7.21

7.22

7.22

7.25

7.26

7.27

7.27

7.29

7.29

7.30

7.32

7.32

7.56

7.57

7.57

7.58

7.59

7.59

7.76

7.77

7.77

7.78

7.79

7.79

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-60000

-50000

-40000

-30000

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

1E+05

1E+05

1E+05

S-45

2.94

12.1

3

1.00

1.00

1.00

1.12

4.14

1.02

1.96

0.97

1.34

1.35

1.36

3.19

3.21

3.24

3.26

3.30

3.32

3.35

3.36

3.48

3.50

3.52

3.54

3.55

3.57

7.17

7.18

7.19

7.19

7.20

7.21

7.22

7.22

7.28

7.29

7.30

7.31

7.32

7.33

7.43

7.45

7.46

7.96

7.98

8.01

8.03

8.32

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-20000

-15000

-10000

-5000

0

5000

10000

15000

20000

25000

S-46

3.00

3.00

1.00

1.00

1.00

1.00

5.27

1.00

1.00

1.00

1.34

1.35

2.51

3.13

3.15

3.17

3.19

3.26

3.27

3.30

3.31

3.46

3.47

3.49

3.51

3.53

3.54

7.18

7.19

7.19

7.20

7.20

7.20

7.21

7.22

7.22

7.26

7.27

7.28

7.28

7.29

7.30

7.31

7.32

7.33

7.35

7.37

7.41

7.41

7.41

7.41

7.43

7.43

7.43

7.43

7.65

7.65

7.66

7.67

7.67

7.68

7.78

7.79

7.79

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-80000

-70000

-60000

-50000

-40000

-30000

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

1E+05

1E+05

1E+05

S-47

3.00

1.00

1.00

1.00

1.00

3.89

2.00

1.97

1.02

1.00

0.99

1.39

1.40

3.29

3.31

3.33

3.35

3.41

3.43

3.45

3.47

3.54

3.56

3.57

3.58

3.59

3.59

3.59

3.61

3.62

7.20

7.21

7.22

7.23

7.32

7.33

7.53

7.53

7.55

7.55

7.57

7.57

7.58

7.58

7.59

7.60

7.60

7.61

7.62

7.86

7.87

7.88

7.89

7.94

7.96

8.00

8.00

8.02

8.02

8.43

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-50000

-40000

-30000

-20000

-10000

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

S-48

3.00

0.86

0.84

0.84

0.86

0.90

3.64

1.58

1.34

61.

357

3.09

33.

107

3.11

93.

133

3.19

13.

201

3.21

83.

227

7.09

37.

100

7.10

27.

108

7.18

47.

186

7.18

97.

194

7.19

87.

200

7.20

77.

210

7.21

27.

260

7.26

77.

270

7.27

77.

281

7.28

37.

292

7.29

57.

304

7.31

47.

317

7.60

57.

607

7.61

37.

615

7.66

37.

665

7.66

97.

671

21.7

36.0

47.9

126.

412

6.9

128.

112

8.6

131.

813

3.6

144.

714

6.3

192.

0

S-49

3.00

1.02

0.99

1.04

0.97

1.28

4.88

3.25

2.97

1.24

71.

265

2.78

32.

804

2.82

32.

843

2.88

72.

902

2.92

62.

941

3.32

63.

343

3.36

23.

379

6.58

76.

627

7.09

97.

103

7.11

57.

121

7.12

67.

134

7.13

87.

142

7.18

27.

193

7.19

97.

203

7.21

67.

221

7.23

37.

248

7.25

27.

292

7.29

87.

307

7.31

17.

314

7.32

37.

404

7.41

97.

425

7.42

87.

431

7.43

67.

443

21.8

5

35.8

2

49.3

8

76.7

077

.02

77.3

4

126.

3212

6.48

126.

8612

8.27

128.

5512

8.93

130.

4513

4.54

142.

6214

6.42

199.

12

S-50

3.00

3.96

1.97

0.96

0.97

1.80

3.68

3.93

1.27

01.

281

1.59

52.

634

2.65

32.

666

2.67

12.

730

2.74

12.

844

2.84

72.

855

2.85

8

3.31

43.

325

3.33

73.

349

3.36

1

7.13

47.

135

7.14

77.

148

7.19

47.

206

7.21

27.

216

7.21

97.

223

7.22

57.

235

7.23

67.

272

7.28

57.

294

7.29

77.

301

7.30

47.

309

7.31

77.

327

7.33

0

22.0

29.6

35.5

45.0

51.4

76.8

77.0

77.2

126.

112

6.3

126.

812

8.3

128.

512

8.6

141.

0

146.

1

208.

9

S-51

8.69

5.56

1.02

2.06

1.00

5.31

1.09

1.10

1.12

1.14

1.16

1.18

1.19

1.19

1.22

1.52

1.57

1.58

1.61

1.61

1.62

1.64

1.66

1.66

1.67

1.70

3.22

3.23

3.25

3.27

3.29

3.30

7.08

7.08

7.09

7.10

7.10

7.11

7.12

7.12

7.14

7.14

7.14

7.18

7.19

7.19

7.21

7.22

7.22

21.8

25.6

25.7

25.9

28.1

28.3

35.1

49.2

51.3

76.7

77.0

77.3

126.

212

6.8

128.

5

146.

6

212.

8

S-52

3.00

4.01

1.00

1.00

1.00

3.00

2.00

2.96

2.02

1.26

1.27

1.58

1.59

1.60

1.61

1.68

2.41

2.65

2.67

2.69

2.74

2.76

2.80

3.34

3.35

3.37

3.38

3.90

3.91

3.92

3.93

3.94

3.95

3.96

3.97

3.98

3.99

7.17

7.17

7.19

7.19

7.21

7.21

7.26

7.27

7.27

7.29

7.30

7.31

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-1E+05

-80000

-60000

-40000

-20000

0

20000

40000

60000

80000

1E+05

1E+05

1E+05

2E+05

S-53

3.00

3.05

3.14

2.29

2.26

1.01

2.07

0.99

5.50

0.73

0.75

0.77

0.81

0.82

0.84

2.23

2.24

2.25

2.26

2.26

2.27

2.28

2.28

2.30

2.68

2.70

2.74

2.75

3.37

3.39

3.41

3.42

7.18

7.18

7.19

7.20

7.20

7.21

7.22

7.22

7.22

7.24

7.24

7.24

7.25

7.26

7.26

7.27

7.28

7.29

7.30

7.31

7.32

7.33

11.6

11.7

21.9

23.8

24.0

34.8

50.8

55.8

76.7

77.0

77.3

126.

212

6.9

128.

4

146.

7

213.

2

S-54

2.51

4.92

2.13

1.98

2.33

4.05

0.97

0.89

3.00

2.22

1.22

1.24

1.27

1.29

1.30

1.41

1.43

1.44

1.50

1.51

1.53

1.63

1.64

1.65

2.30

2.32

2.32

2.33

2.34

2.66

2.73

3.31

3.32

3.33

3.34

3.35

3.36

7.19

7.20

7.20

7.21

7.22

7.23

7.28

7.28

7.30

7.30

7.31

7.32

7.32

17.1

022

.01

23.3

525

.27

28.4

428

.52

28.7

5

35.5

0

43.3

5

51.1

5

119.

7812

6.28

126.

8012

8.51

128.

54

146.

24

209.

90

S-55

3.02

2.04

2.09

1.14

1.03

1.00

2.08

2.85

2.02

1.26

1.28

1.94

1.95

1.95

1.97

1.98

2.00

2.47

2.52

2.66

2.68

2.73

2.74

3.28

3.29

3.31

3.33

3.35

3.37

3.44

3.45

3.46

3.48

3.49

3.50

3.51

3.52

3.54

7.18

7.18

7.20

7.21

7.26

7.28

7.28

7.29

7.31

7.31

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-35000

-30000

-25000

-20000

-15000

-10000

-5000

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

50000

55000

60000

S-56

10.2

5

4.89

3.92

2.05

0.85

3.00

6.38

1.09

01.

098

1.10

61.

119

1.12

71.

142

1.15

41.

158

1.17

61.

193

1.22

31.

249

1.26

01.

376

1.39

51.

413

1.43

11.

450

1.48

21.

488

1.50

01.

519

1.53

71.

556

2.15

82.

182

2.19

42.

200

2.21

32.

218

2.23

12.

237

2.24

72.

260

2.45

62.

467

2.47

02.

511

2.53

02.

551

2.57

02.

615

2.63

22.

655

2.67

23.

215

3.23

23.

250

3.26

83.

590

7.08

57.

089

7.09

27.

096

7.10

17.

105

7.11

07.

115

7.11

97.

121

7.12

97.

131

7.13

97.

143

7.15

07.

157

7.17

67.

179

7.18

97.

195

7.20

07.

213

7.21

57.

228

7.23

27.

294

7.29

97.

306

7.31

2

22.0

23.5

24.9

28.9

29.0

34.0

35.5

43.5

51.1

51.4

126.

312

6.8

128.

5

146.

3

174.

2

210.

0

S-57

3.00

1.86

0.79

1.88

0.94

0.95

0.96

1.03

0.90

2.75

2.23

1.16

1.22

1.26

1.27

1.72

1.72

1.93

1.93

2.15

2.15

2.16

2.16

2.66

2.67

2.74

3.31

3.32

3.33

3.34

7.18

7.18

7.18

7.19

7.20

7.20

7.21

7.26

7.26

7.28

7.28

7.29

7.30

7.30

-20-100102030405060708090100110120130140150160170180190200210f1 (ppm)

-1E+09

0

1E+09

2E+09

3E+09

4E+09

5E+09

6E+09

7E+09

8E+09

9E+09

1E+10

1E+10

1E+10

1E+10

1E+10

2E+10

2E+1017.6

521

.96

22.0

3

35.4

7

41.7

8

51.2

4

68.9

5

76.7

977

.00

77.2

183

.55

126.

2912

6.75

128.

51

146.

14

209.

17

S-58

12.6

11.

742.

17

2.00

2.15

1.06

1.05

1.00

1.47

0.66

3.16

2.03

1.21

91.

223

1.22

91.

239

1.24

01.

245

1.25

21.

260

1.26

71.

274

1.28

21.

292

1.38

01.

391

1.40

01.

509

1.52

01.

530

1.66

51.

667

1.67

01.

672

1.67

42.

045

2.04

72.

055

2.06

62.

076

2.27

92.

291

2.29

32.

303

2.31

42.

317

2.32

82.

338

2.35

12.

632

2.64

32.

655

2.66

62.

728

2.73

72.

751

2.76

03.

333

3.34

33.

354

3.36

44.

949

4.95

14.

952

4.96

44.

965

4.96

74.

968

5.00

65.

008

5.03

05.

033

5.81

65.

830

5.84

05.

855

7.20

27.

204

7.21

27.

221

7.22

37.

224

7.22

97.

230

7.24

07.

283

7.30

27.

305

7.31

37.

322

7.32

4

21.9

723

.63

28.9

029

.06

29.1

329

.28

29.3

333

.80

35.4

543

.56

51.1

3

114.

15

126.

2612

6.80

128.

50

139.

17

146.

33

210.

14

S-59

3.02

2.13

1.03

1.02

0.99

1.01

1.00

1.99

0.97

2.00

2.90

1.87

1.85

1.26

1.27

1.47

1.47

1.47

1.49

1.49

1.51

1.51

1.53

1.53

1.53

1.55

1.56

1.72

1.72

1.73

1.74

1.75

1.75

1.82

1.82

1.83

1.84

1.84

1.85

2.44

2.45

2.46

2.46

2.47

2.68

2.69

2.70

2.72

2.78

2.79

2.81

2.82

2.86

2.87

2.89

2.89

2.89

2.90

2.90

2.91

2.91

2.92

2.92

2.92

2.94

2.94

3.33

3.35

3.36

3.37

4.56

4.56

4.57

4.58

4.59

4.59

4.60

4.61

4.61

4.63

4.63

4.64

7.18

7.19

7.20

7.20

7.21

7.26

7.27

7.29

7.30

8.16

22.0

27.0

27.2

35.3

44.1

44.1

49.3

49.4

126.

512

6.6

126.

912

8.7

128.

7

145.

214

5.3

146.

415

0.8

152.

4

158.

8

211.

3

S-60

-157

.23

S-61

S-62

3.00

2.77

1.12

0.92

1.87

5.34

2.00

1.97

0.71

0.72

0.92

0.93

1.76

1.83

1.85

1.86

1.88

1.90

1.92

1.97

2.99

3.01

3.01

3.03

3.03

3.05

3.24

3.26

3.26

3.28

3.28

7.05

7.06

7.07

7.07

7.09

7.09

7.10

7.14

7.14

7.16

7.16

7.17

7.18

7.18

7.19

7.61

7.62

7.63

7.63

7.64

7.81

7.82

7.83

7.83

20.4

20.9

33.3

43.0

48.2

76.7

77.0

77.3

116.

111

8.0

126.

412

8.2

128.

413

2.4

140.

414

3.1

198.

4

S-63

2.00

0.99

9.98

1.98

1.90

3.65

3.67

4.70

4.72

4.73

7.09

7.10

7.11

7.11

7.12

7.12

7.13

7.13

7.16

7.16

7.17

7.18

7.19

7.19

7.20

7.21

7.22

7.22

7.65

7.65

7.66

7.67

7.72

7.89

7.90

7.91

7.91

45.0

46.0

76.7

77.0

77.3

116.

411

7.9

126.

612

7.7

128.

412

8.7

132.

5

140.

014

3.6

196.

9

S-64

1.08

2.13

1.09

2.22

2.04

1.03

4.18

1.99

2.00

1.62

1.63

1.71

1.71

1.72

1.72

1.73

1.74

1.74

1.75

1.86

1.86

1.87

1.88

1.90

1.90

2.70

2.72

2.73

2.75

2.77

3.22

3.23

3.51

3.53

3.54

3.56

3.57

7.00

7.01

7.02

7.03

7.04

7.05

7.18

7.68

7.68

7.69

7.70

7.96

7.96

7.97

7.98

19.7

28.3

29.5

33.4

46.6

76.7

77.0

77.4

116.

411

7.9

126.

012

6.1

128.

312

8.5

129.

413

2.6

137.

313

9.5

140.

2

198.

0

S-65

2.00

2.01

1.04

10.8

3

2.12

2.07

2.86

2.88

2.90

2.90

2.92

2.92

2.93

2.95

3.14

3.16

3.18

3.20

3.22

3.24

3.26

3.28

3.52

3.54

3.56

3.57

3.59

7.00

7.01

7.02

7.07

7.07

7.08

7.09

7.09

7.10

7.12

7.14

7.14

7.15

7.16

7.16

7.17

7.18

7.18

7.59

7.59

7.60

7.61

7.69

7.76

7.77

7.78

7.78

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

30000

3200043.0

43.2

44.4

76.7

77.1

77.4

116.

211

7.9

127.

612

8.3

128.

412

8.5

129.

313

2.4

139.

514

0.1

143.

6

197.

7

S-66

3.58

3.06

1.96

0.97

4.39

2.00

2.00

1.32

51.

342

2.39

83.

189

3.20

93.

231

3.25

13.

301

3.31

63.

358

3.72

93.

746

3.76

33.

780

3.79

73.

815

7.10

27.

106

7.12

27.

124

7.13

87.

142

7.16

17.

179

7.19

87.

215

7.21

97.

239

7.24

27.

258

7.28

37.

752

7.75

67.

769

7.77

38.

002

8.00

68.

019

8.02

3

19.5

021

.47

30.4

4

46.6

1

76.7

277

.03

77.3

5

116.

2811

7.92

125.

0812

6.19

126.

3812

8.43

130.

6013

2.47

135.

2614

0.14

144.

13

197.

81

S-67

2.03

1.67

0.96

1.79

1.16

2.13

2.00

1.10

31.

114

2.86

82.

879

2.89

12.

896

2.89

92.

902

2.91

82.

929

3.01

63.

021

3.02

53.

031

3.04

73.

057

3.06

2

4.96

24.

964

4.97

94.

981

5.00

95.

011

5.01

35.

038

5.04

05.

792

5.80

35.

809

5.82

05.

831

5.83

75.

848

7.26

07.

763

7.76

67.

774

7.77

78.

016

8.01

98.

028

8.03

1

19.8

29.7

30.3

33.5

45.4

76.8

77.0

77.2

113.

511

6.3

117.

9

128.

5

132.

5

140.

214

2.5

197.

9

S-68

2.13

22.2

0

2.10

2.04

2.06

2.00

0.56

0.58

0.58

0.59

0.60

0.97

0.97

0.98

0.99

1.48

1.71

1.72

1.73

1.74

1.74

1.75

1.75

1.76

1.77

2.93

2.94

2.96

7.19

7.69

7.69

7.70

7.71

7.71

7.95

7.96

7.97

7.98

9.5

10.9

18.8

19.3

43.2

76.7

77.0

77.3

116.

211

8.0

128.

413

2.5

140.

1

198.

9

S-69

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

-1000

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

11000

12000

13000

14000

15000

16000

17000

18000

19000

20000

9.02

7.54

7.37

1.02

1.97

5.99

4.00

1.09

1.15

1.16

1.17

1.17

1.18

1.19

1.25

1.26

1.28

1.28

1.29

1.31

1.31

1.34

1.36

1.55

1.60

1.62

1.62

1.63

1.64

1.64

1.64

1.65

1.66

1.67

1.68

1.70

1.72

1.72

1.73

1.81

1.82

1.83

1.84

2.29

2.30

2.31

2.33

2.47

2.49

2.50

7.32

7.40

7.40

7.41

7.41

7.42

7.42

7.43

7.43

7.43

7.44

7.44

7.45

7.46

7.67

7.68

7.68

7.69

7.69

7.70

7.70

0102030405060708090100110120130140150160170180190200210f1 (ppm)

-2000

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

20000

22000

24000

26000

28000

30000

32000

34000

36000

38000

40000

10.4

18.1

18.6

25.7

25.9

27.9

28.5

44.1

50.7

76.7

77.0

77.3

127.

612

9.0

134.

713

6.0

214.

1

S-70

3.08

2.13

1.00

4.38

3.52

1.15

2.17

1.02

1.40

1.42

3.22

3.24

3.26

3.28

3.30

3.32

3.33

3.36

3.37

4.27

4.29

4.30

4.31

4.31

4.32

4.33

4.33

4.34

4.36

7.17

7.34

7.35

7.36

7.37

7.38

7.40

7.40

7.41

7.42

7.42

7.43

7.43

7.44

7.45

7.45

7.46

7.47

7.62

7.63

7.64

7.65

7.66

7.66

7.77

7.78

7.80

7.89

7.90

7.91

7.91

8.05

8.07

21.1

29.6

47.0

116.

311

7.9

122.

612

2.9

125.

512

5.6

126.

212

7.1

128.

412

9.1

131.

113

2.5

134.

014

0.1

142.

0

197.

8

S-71

3.00

1.97

0.99

1.89

2.10

2.55

2.09

1.29

1.31

3.12

3.14

3.17

3.19

3.23

3.24

3.27

3.28

3.48

3.50

3.52

3.53

7.19

7.29

7.31

7.47

7.49

7.67

7.67

7.68

7.69

7.69

7.72

7.90

7.91

7.92

7.92

21.8

35.2

46.8

76.7

77.0

77.3

116.

511

7.8

125.

612

5.6

127.

212

8.4

132.

5

139.

8

150.

0

197.

0

S-72

3.20

2.00

1.04

1.92

1.96

1.86

1.87

1.29

1.31

3.13

3.15

3.18

3.20

3.22

3.23

3.26

3.28

3.48

3.50

3.52

3.54

7.19

7.29

7.31

7.52

7.52

7.53

7.54

7.68

7.68

7.69

7.70

7.90

7.91

7.92

7.93

21.7

35.4

46.6

76.7

77.0

77.3

110.

5

116.

611

7.8

118.

8

127.

812

8.4

132.

513

2.6

139.

7

151.

4

196.

6

S-73

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)

-200

0

200

400

600

800

1000

1200

1400

1600

1800

2000

2200

2400

2600

2800

3000

1.02

0.98

2.84

1.01

1.00

3.09

3.11

3.11

3.12

3.33

3.33

3.34

3.35

3.35

7.23

7.25

7.26

7.27

7.29

7.32

7.32

7.33

7.34

7.34

7.77

7.77

7.78

7.79

7.79

8.04

8.04

8.05

8.06

8.06

29.8

7

40.7

7

76.8

177

.02

77.2

4

116.

3811

7.92

126.

3712

8.40

128.

4412

8.64

132.

5313

9.75

140.

66

197.

81

S-74

3.00

1.83

1.82

3.51

1.73

1.77

2.32

3.03

3.04

3.05

3.28

3.29

3.30

7.11

7.12

7.13

7.13

7.14

7.14

7.26

7.74

7.75

7.75

7.76

7.76

7.76

8.01

8.01

8.02

8.03

8.03

8.03

21.0

29.4

40.9

76.8

77.0

77.3

116.

311

7.9

128.

312

8.4

129.

313

2.5

135.

913

7.6

139.

8

197.

9

S-75

2.00

1.92

1.99

3.53

2.43

2.39

2.96

2.98

3.00

3.20

3.22

3.24

7.09

7.11

7.18

7.18

7.19

7.20

7.20

7.21

7.68

7.68

7.69

7.70

7.72

7.94

7.94

7.95

7.96

29.1

40.5

116.

511

7.8

128.

412

8.7

129.

813

2.2

132.

6

197.

4

S-76

2.00

2.00

2.42

5.26

2.20

2.18

2.99

3.01

3.03

3.21

3.23

3.25

4.50

7.15

7.17

7.19

7.24

7.26

7.67

7.68

7.69

7.70

7.72

7.94

7.94

7.95

7.96

29.4

8

40.5

3

46.0

2

76.7

077

.01

77.3

3

116.

4711

7.87

128.

4212

8.82

128.

9213

2.55

135.

6513

9.70

141.

06

197.

55

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