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Supporting Information for
Base-catalyzed controllable reaction of 3-ylideneoxindoles and O-Boc
hydroxycarbamates for the synthesis of amidoacrylates and spiroaziridine
oxindoles
Yi-Yin Liu,a Shu-Wen Duan,a Rui Zhang,a Yun-Hang Liu,a Jia-Rong Chen*a and Wen-Jing Xiaoa a Key Laboratory of Pesticide & Chemical Biology, Ministry of Education; College of Chemistry, Central
China Normal University, 152 Luoyu Road, Wuhan, Hubei 430079, China.
E-mail: [email protected], Fax: +86 27 67862041; Tel: +86 27 67862041.
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2016
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Table of Contents
1. General information…………………………………………………………………....S3
2. Preparation of substrates …………………………………….……..………………….S4
2.1 General Procedure for the preparation of 3-ylideneoxindoles……………..….………………… S4
2.2 General Procedure for the preparation of O-Boc hydroxycarbamates…………...……………… S4
3. Representative procedure for preparation of the products………………...…..….….………… S5
3.1 Representative procedure for preparation of the amidoacrylates 3……….…….…...……… S5
3.2 Representative procedure for preparation of the spiroaziridine 4.……….……..…...……… S5
3.3 Representative procedure for preparation of the bispirooxindole 5……….…....…...……… S6
4. Control experiments………………..…...…………………….…….………………… S6
5. Spectral data of products ………………..………………..……….…….…….…………………S7
6. X-Ray structures of 3a, 4a, 4a’ and 5...………………………..……...…………….. S14
7. Copies of 1H NMR and 13C NMR spectra……………………………………………S16
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1. General information
Unless otherwise noted, materials were purchased from commercial suppliers and used
without further purification. All the solvents were treated according to general methods.
Flash column chromatography was performed using 200-300 mesh silica gel. 1H NMR
spectra were recorded on 400 or 600 MHz spectrometers. Chemical shifts were reported
on the delta (δ) scale in parts per million (ppm) relative to the singlet (0 ppm) for
tetramethylsilane (TMS). Data are reported as follows: chemical shift, multiplicity (s =
singlet, d = doublet, t = triplet, dd = doublet of doublets, m = multiplet), coupling
constants (Hz) and integration. 13C NMR spectra were recorded at 100 MHz with complete
proton decoupling. Chemical shifts are reported in ppm relative to the central line of the
triplet at 77.0 ppm for CDCl3. Mass spectra were measured on a MS spectrometer (EI).
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2. Preparation of substrates
2.1 General procedure for the preparation of 3-ylideneoxindoles
Step 1: To a 250 mL 3-necked-round bottom flask equipped with a silicone oil bubbler was added
commercially available isatin (7.7 g, 50 mmol) and anhydrous DMF (80 mL). And the mixture was
cooled down to 0 oC. To this solution was added NaH (1.32 g, 55 mmol), then CH3I was added 10 min
later (without gas bubbling), and stirred at 0 oC for 15 min. Upon completion of the reaction
(monitored by TLC), the mixture was diluted with saturated NH4Cl solution and extracted with ethyl
acetate, the ethyl acetate layer was washed with water and brine. The combined organic layer was then
dried over MgSO4, filtered, and concentrated to yield the crude N-methylindoline-2, 3-dione ( 7.6 g,
94% yield), which was used directly in the next step[1].
Step 2: To a stirred solution of ethyl 2-(triphenylphosphoranylidene) acetate (18.0 g, 51.7 mmol) in
anhydrous THF (100 mL), the N-methylindoline-2, 3-dione (7.58 g, 47 mmol) was added at 0 oC. The
mixture was stirred at the same temperature until the reaction was completed monitored by TLC
analysis. The crude product was purified by flash chromatography on silica gel (petroleum ether/ ethyl
acetate 5:1). Compound 1a was obtained as a red solid (9.45 g, 87% yield)[2].
The other 3-ylideneoxindoles were prepared according to the above procedure.
2.2 General procedure for the preparation of O-Boc hydroxycarbamates
Step 1: Sodium bicarbonate (21.0 g, 250 mmol) was added to a 500 mL round bottom flask and
dissolved in H2O (120 mL). Then, hydroxylamine hydrochloride (13.9 g, 200 mmol) was added into
this solution. After this, the solution of benzyl chloroformate (8.8 g, 50 mmol) in CH2Cl2 (60 mL) was
added to the mixture dropwisely and the mixture stirred at room temperature. Upon completion of the
reaction (monitored by TLC), the system was acidized to pH 4-5 with 1M HCl solution. The aqueous
layer was extracted with CH2Cl2. The combined organic layer was then dried over MgSO4, filtered,
and concentrated to yield the crude white solid benzyl hydroxycarbamate ( 8.3 g, 99% yield), which
was used directly in the next step.
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Step 2: benzyl hydroxycarbamate (8.3 g, 49.6 mmol) and ditertbutyl dicarbonate (10.8 g, 49.6 mmol)
were dissolved into THF (60 mL) and the mixture stirred vigorously at RT. Then, aqueous NaOH
solution (1M, 60 mL) was added to the mixture dropwise. Upon completion of the reaction, the crude
product was diluted with ether and brine, the aqueous layer was extracted with ether, the combined
organic layer was washed with brine and dried over MgSO4. The crude product was purified by flash
chromatography on silica gel (petroleum ether/ ethyl acetate 10:1 to 5:1). Compound 2a was obtained
as a colorless oil (4.64 g, 35% yield)[3].
The other N-protected carbamates were prepared according to the above procedure.
References:
[1] B. M. Trost, Y. Zhang. J. Am. Chem. Soc., 2007, 129, 14548.
[2] S.W. Duan, Y. Li, Y. Y. Liu, Y. Q. Zou, D. Q. Shi, and W. J. Xiao. Chem. Commun., 2012, 48, 5160.
[3] S.-F. Lu, D.-M. Du, J.-X. Xu, Org. Lett., 2006, 8, 2115.
3. Representative procedure for preparation of the products.
3.1 Representative procedure for preparation of the amidoacrylates 3.
+ NH
R4BocO
2
DABCO (20 mol%)
DCM (2 mL), RT.
1
NR1
O
R2O2C
R3
NR1
O
R2
R3NH
R4
4 The compound 2 (xx mg, 0.24 mmol) and DABCO (4.5 mg, 0.04 mmol) were dissolved in CH2Cl2
(1 mL). Then, compound 1 (xx mg, 0.20 mmol) was added to the mixture. Upon the completion of the
reaction (monitored by TLC), the crude product was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate 8:1 to 5:1) to give the desired product 3 as a yellow or red solid.
3.2 Representative procedure for preparation of the spiroaziridine 4.
The compound 2 (xx mg, 0.36 mmol) and TMG (6.9 mg, 0.06 mmol) were dissolved in CH2Cl2 (5
mL). Then, compound 1 (0.30 mmol) was added to the mixture at 0 oC. Upon the completion of the
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reaction (monitored by TLC), The crude product was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate 5:1 to 3:1) to give the desired product 4 as a white solid.
3.3 Representative procedure for preparation of the bispirooxindole 5.
The compound 2 (91.3 mg, 0.24 mmol) and DBU (6.1 mg, 0.04 mmol) were dissolved in CH2Cl2 (1
mL). Then compound 1 (46.3 mg, 0.20 mmol) was added to the mixture and stirred at room temperature,
Upon the completion of the reaction (monitored by TLC), The crude product was purified by flash
chromatography on silica gel (petroleum ether/ethyl acetate 3:1 to 2:1), Compound 5 was obtained as a
white solid (91.7 mg, 75% yield, 1.6:1 dr.) .
The compound 1 (46.3 mg, 0.20 mmol) and compound 4a (91.3 mg, 0.24 mmol) were dissolved in
CH2Cl2 (1 mL). Then DBU (6.1 mg, 0.04 mmol) was added to the mixture. Upon the completion of the
reaction (monitored by TLC), The crude product was purified by flash chromatography on silica gel
(petroleum ether/ethyl acetate 3:1 to 2:1), Compound 5 was obtained as a white solid (73.4 mg, 60%
yield, 1.6:1 dr.) .
4. Control experiments.
The compound 3a (76.1 mg, 0.20 mmol) was dissolved in CH2Cl2 (1 mL). And either DABCO (4.5
mg, 0.04 mmol) or TMG (4.6 mg, 0.04 mmol) was added. The mixture were allowed to stirred at room
temperature for 48 h, and no transformation was observed, and substrate 3a was fully remained. This
result proves the amidoacrylate is not the intermidate for the generation of spiroaziridine 4a.
S7
The compound 4a (76.1 mg, 0.20 mmol) was dissolved in CH2Cl2 (1 mL). And DABCO (4.5 mg,
0.04 mmol) or TMG (4.6 mg, 0.04 mmol) was added. The mixture were allowed to stirred at room
temperature for 48 h, however, no amidoacrylate 3a; instead, the isomer 4a’ was isolated in 30% and
64% yield, respectively. This result rules out the possibility that the amidoacrylate product 3a was formed
through the spiroaziridine oxindole 4a.
5. Spectral data of products
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(1-methyl-2-oxoindolin-3-ylidene)acetate (3a)
yellow solid; 99% yield in 24 h, mp 112-114 oC. 1H NMR (600 MHz, CDCl3): δ = 11.27 (s, 1H), 7.42 – 7.31 (m, 5H), 7.27 – 7.19 (m, 2H), 7.01 (t, J = 7.7 Hz, 1H), 6.86 (d, J = 7.5 Hz, 1H), 5.22 (s, 2H), 4.52 (s, 2H), 3.26 (d, J = 4.1 Hz, 3H), 1.42 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.5, 162.4, 152.1, 140.6, 137.9, 134.8, 128.4,
128.2, 127.6, 122.1, 120.0, 119.6, 108.3, 104.1, 68.1, 62.6, 25.6, 13.7; HRMS (ESI): for C21H20N2O5 [M]+: calcd 380.1372, found 380.1370. (Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(2-oxoindolin-3-ylidene)acetate (3b)
yellow solid; 98% yield in 24 h, mp 155-157 oC. 1H NMR (600 MHz, CDCl3): δ = 11.13 (d, J = 19.5 Hz, 1H), 8.43 (s, 1H), 7.39 (d, J = 6.1 Hz, 3H), 7.37 (d, J = 4.0 Hz, 1H), 7.21 (d, J = 7.8 Hz, 1H), 7.17 (t, J = 7.7 Hz, 1H), 6.99 (t, J = 7.7 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 5.23 (s, 2H), 4.52 (s, 2H), 1.41 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 170.8, 162.5, 152.2, 138.6, 138.2, 134.8, 128.6, 128.5, 127.8, 122.3,
120.4, 120.4, 110.3, 104.5, 68.4, 62.9, 13.8; HRMS (ESI): for C20H18N2O5 [M]+: calcd 366.1216, found 366.1215.
(Z)-ethyl 2-(1-acetyl-2-oxoindolin-3-ylidene)-2-(((benzyloxy)carbonyl)amino)acetate (3c)
yellow solid; 95% yield in 24 h, mp 104-107 oC. 1H NMR (600 MHz, CDCl3): δ = 11.01 (s, 1H), 8.27 (d, J = 8.2 Hz, 1H), 7.40 (s, 4H), 7.36 (d, J = 2.4 Hz, 1H), 7.29 (d, J = 7.3 Hz, 1H), 7.23 (d, J = 7.7 Hz, 1H), 7.16 (d, J = 7.5 Hz, 1H), 5.24 (s, 2H), 4.54 (d, J = 6.3 Hz, 2H), 2.71 (d, J = 1.8 Hz, 3H), 1.42 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 170.4, 169.7, 162.0, 151.8, 139.8, 137.0, 134.4, 128.8, 128.6, 128.2,
124.9, 120.4, 119.3, 116.5, 102.9, 68.74, 63.1, 26.9, 13.7; HRMS (ESI): for C22H20N2O6 [M]+: calcd 408.1321, found 408.1321. (Z)-tert-butyl 3-(1-(((benzyloxy)carbonyl)amino)-2-ethoxy-2-oxoethylidene)-2-oxoindoline-1-carboxylate (3d)
yellow solid; 94% yield in 24 h, mp 99-102 oC. 1H NMR (600 MHz, CDCl3): δ = 11.17 (s, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.42 – 7.33 (m, 5H), 7.30 – 7.25 (m, 2H), 7.22 (d, J = 7.7 Hz, 1H), 7.11 (t, J = 7.6 Hz, 1H), 5.22 (s, 2H), 4.53 (d, J = 5.7 Hz, 2H), 1.65 (s, 9H), 1.42 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.0, 162.2, 151.9, 148.7, 139.4, 136.8, 134.6, 128.6, 128.5, 128.3, 127.9, 124.2, 120.0, 119.5,
114.9, 103.0, 84.6, 68.5, 63.0, 28.0, 13.7; HRMS (ESI): for C25H26N2O7 [M]+: calcd 466.1740, found 466.1741. (Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(1-(4-methoxybenzyl)-2-oxoindolin-3-ylidene)acetate(3e)
yellow solid; 98% yield in 24 h, mp 97-100 oC. 1H NMR (600 MHz, CDCl3): δ =11.31 (s, 1H), 7.41 – 7.31 (m, 5H), 7.21 (dd, J = 17.7, 8.1 Hz, 3H), 7.13 (t, J = 7.7 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 6.80 (dd, J = 11.8, 8.4 Hz, 3H), 5.26 – 5.17 (m, 2H), 4.90 (d, J = 17.3 Hz, 2H), 4.53 (s, 2H), 3.78 – 3.68 (m, 3H), 1.41 (t, J = 6.7 Hz, 3H); 13C NMR
N O
EtO2C
NH
Cbz
N O
EtO2C
NH
Cbz
H
NAc
O
EtO2C
NH
Cbz
NBoc
O
EtO2C
NH
Cbz
NPMB
O
EtO2C
NH
Cbz
S8
(100 MHz, CDCl3): δ = 168.8, 162.5, 159.0, 152.2, 140.0, 138.3, 134.8, 128.6, 128.4, 127.7, 127.6, 122.3, 120.2, 120.0, 114.1, 109.2, 104.0, 68.3, 62.8, 55.2, 42.8, 13.8; HRMS (ESI): for C28H26N2O6 [M]+: calcd 486.1791, found 486.1787.
(Z)-ethyl 2-(1-benzyl-2-oxoindolin-3-ylidene)-2-(((benzyloxy)carbonyl)amino)acetate (3f)
yellow solid; 98% yield in 24 h, mp 118-121 oC. 1H NMR (600 MHz, CDCl3): δ=11.31 (s, 1H), 7.43 – 7.30 (m, 5H), 7.30 – 7.19 (m, 6H), 7.12 (t, J = 7.6 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 6.76 (d, J = 7.9 Hz, 1H), 5.21 (s, 2H), 4.94 (s, 2H), 4.53 (s, 2H), 1.41 (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ =168.7, 162.4, 152.1, 139.8, 138.3, 135.5, 134.7, 128.7, 128.5, 128.3, 127.6, 127.6, 127.0, 122.3, 120.2,
119.9, 109.2, 103.9, 68.2, 62.8, 43.2, 13.7; HRMS (ESI): for C27H24N2O5 [M]+: calcd 456.1685, found 456.1681.
(Z)-ethyl 2-(1-allyl-2-oxoindolin-3-ylidene)-2-(((benzyloxy)carbonyl)amino)acetate (3g)
yellow solid; 99% yield in 24 h, mp 80-83 oC. 1H NMR (600 MHz, CDCl3): δ=11.27 (s, 1H), 7.38 – 7.32 (m, 5H), 7.24 (d, J = 7.7 Hz, 1H), 7.20 (td, J = 7.8, 0.8 Hz, 1H), 7.00 (dd, J = 17.2, 9.5 Hz, 1H), 6.87 – 6.81 (m, 1H), 5.86 – 5.75 (m, 1H), 5.20 (d, J = 4.7 Hz, 2H), 5.20 – 5.14 (m, 2H), 4.52 (s, 2H), 4.42 – 4.33 (m, 2H), 1.41 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ= 168.5, 162.5, 152.2, 139.9, 138.3, 134.8, 131.0,
128.5, 128.3, 127.7, 122.3, 120.2, 119.9, 117.5, 109.1, 104.0, 68.2, 62.8, 41.9, 13.8; HRMS (ESI): for C23H22N2O5 [M]+: calcd 406.1529, found 406.1526.
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(4-bromo-1-methyl-2-oxoindolin-3-ylidene)acetate (3h)
yellow solid; 98% yield in 24 h, mp 118-120 oC. 1H NMR (600 MHz, CDCl3): δ= 11.96 (s, 1H), 7.43 – 7.32 (m, 5H), 7.23 (d, J = 8.1 Hz, 1H), 7.09 (s, 1H), 6.82 (d, J = 7.8 Hz, 1H), 5.21 (s, 2H), 4.46 (d, J = 7.2 Hz, 2H), 3.28 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.9, 162.5, 152.2, 142.5, 140.8, 134.8, 128.5, 128.4, 128.2, 127.9, 120.6, 116.1, 107.0, 105.2, 68.1, 62.8, 26.0, 13.5; HRMS
(ESI): for C21H19BrN2O5 [M]+: calcd 458.0477, found 458.0475.
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(5-bromo-1-methyl-2-oxoindolin-3-ylidene)acetate (3i)
yellow solid; 98% yield in 24 h, mp 121-124 oC. 1H NMR (600 MHz, CDCl3): δ=11.23 (s, 1H), 7.41 – 7.30 (m, 6H), 7.29 (s, 1H), 6.70 (d, J = 8.3 Hz, 1H), 5.22 (s, 2H), 4.54 (s, 2H), 3.22 (s, 3H), 1.44 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.3, 162.1, 152.1, 139.6, 139.3, 134.7, 130.2, 128.7, 128.6, 128.4, 123.2, 121.7,
115.1, 109.6, 103.1, 68.4, 63.1, 25.9, 13.8; HRMS (ESI): for C21H19BrN2O5 [M]+: calcd 458.0477, found 458.0461.
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(6-bromo-1-methyl-2-oxoindolin-3-ylidene)acetate (3j)
yellow solid; 99% yield in 24 h, mp 130-132 oC. 1H NMR (600 MHz, CDCl3): δ=11.18 (s, 1H), 7.45 – 7.30 (m, 5H), 7.15 (d, J = 8.2 Hz, 1H), 7.07 (d, J = 8.2 Hz, 1H), 7.02 (s, 1H), 5.22 (s, 2H), 4.51 (s, 2H), 3.26 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ= 168.4, 162.3, 152.0, 141.7, 138.6, 134.7, 128.5, 128.4,
128.3, 128.2, 125.0, 121.1, 118.7, 111.7, 103.3, 68.3, 62.9, 25.8, 13.7; HRMS (ESI): for C21H19BrN2O5 [M]+: calcd 458.0477, found 458.0477.
NBn
O
EtO2C
NH
Cbz
N
Allyl
O
EtO2C
NH
Cbz
N O
EtO2C
NH
CbzBr
N O
EtO2C
NH
CbzBr
N O
EtO2C
NH
Cbz
Br
S9
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(4-chloro-1-methyl-2-oxoindolin-3-ylidene)acetate (3k)
yellow solid; 99% yield in 24 h, mp 129-131oC. 1H NMR (600 MHz, CDCl3): δ = 12.15 (s, 1H), 7.43 – 7.32 (m, 5H), 7.18 (t, J = 8.0 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.79 (d, J = 7.6 Hz, 1H), 5.21 (s, 2H), 4.44 (d, J = 7.2 Hz, 2H), 3.29 (s, 3H), 1.38 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 167.0, 162.6, 152.1, 142.1, 141.6,
134.8, 128.5, 128.4, 128.3, 128.2, 127.8, 124.5, 118.5, 106.6, 103.5, 68.1, 62.5, 26.1, 13.6; HRMS (ESI): for C21H19ClN2O5 [M]+: calcd 414.0982, found 414.0967.
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(5-chloro-1-methyl-2-oxoindolin-3-ylidene)acetate (3l)
yellow solid; 98% yield in 24 h, mp 152-155 oC. 1H NMR (600 MHz, CDCl3): δ= 11.16 (s, 1H), 7.45 – 7.31 (m, 5H), 7.13 (d, J = 8.3 Hz, 1H), 6.98 (dd, J = 8.3, 1.8 Hz, 1H), 6.86 (d, J = 1.6 Hz, 1H), 5.22 (s, 2H), 4.51 (s, 2H), 3.25 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ= 168.7, 162.3, 152.1, 141.7, 138.5, 134.7,
133.4, 128.6, 128.4, 122.2, 121.0, 118.3, 108.9, 103.4, 68.4, 62.9, 25.9, 13.8; HRMS (ESI): for C21H19ClN2O5 [M]+: calcd 414.0982, found 414.0974.
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(5-fluoro-1-methyl-2-oxoindolin-3-ylidene)acetate (3m)
yellow solid; 98% yield in 24 h, mp 123-125 oC. 1H NMR (600 MHz, CDCl3): δ =11.29 (s, 1H), 7.38 (d, J = 8.5 Hz, 5H), 6.96 (d, J = 7.4 Hz, 2H), 6.82 – 6.73 (m, 1H), 5.23 (s, 2H), 4.53 (s, 2H), 3.26 (s, 3H), 1.42 (t, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.5, 162.1, 160.0, 157.6, 152.0, 139.1, 136.8, 134.7, 128.5, 128.3,
120.9, 114.0, 113.8, 108.6, 108.6, 108.0, 107.7, 103.8, 68.3, 62.9, 25.8, 13.7; HRMS (ESI): for C21H19FN2O5 [M]+: calcd 398.1278, found 398.1266.
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(7-fluoro-1-methyl-2-oxoindolin-3-ylidene)acetate (3n)
yellow solid; 98% yield in 24 h, mp 131-134 oC. 1H NMR (600 MHz, CDCl3): δ = 11.32 (s, 1H), 7.44 – 7.31 (m, 5H), 6.96 (ddd, J = 13.0, 12.4, 6.2 Hz, 3H), 5.23 (s, 2H), 4.52 (s, 2H), 3.49 (d, J = 2.4 Hz, 3H), 1.41 (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.3, 162.2, 152.0, 149.1, 146.7, 139.2, 134.6, 128.5, 128.39, 128.3,
127.3, 127.2, 122.7, 122.6, 115.9, 115.2, 115.0, 103.4, 68.3, 62.9, 28.2, 13.7; HRMS (ESI): for C21H19FN2O5 [M]+: calcd 398.1278, found 398.1271. (Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(1,5-dimethyl-2-oxoindolin-3-ylidene)acetate(3o)
yellow solid; 98% yield in 24 h, mp 98-101 oC. 1H NMR (600 MHz, CDCl3): δ = 11.28 (s, 1H), 7.38 (d, J = 3.8 Hz, 3H), 7.36 (t, J = 3.6 Hz, 2H), 7.16 – 6.92 (m, 2H), 6.75 (d, J = 7.9 Hz, 1H), 5.22 (d, J = 3.1 Hz, 2H), 4.53 (d, J = 6.4 Hz, 2H), 3.25 (s, 3H), 2.32 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.7,
162.6, 152.3, 138.7, 137.7, 134.9, 131.6, 128.5, 128.3, 128.2, 120.9, 119.8, 108.0, 104.4, 68.2, 62.7, 25.8, 21.3, 13.8; HRMS (ESI): for C22H22N2O5 [M]+: calcd 394.1529, found 394.1512.
(Z)-ethyl 2-(((benzyloxy)carbonyl)amino)-2-(1-methyl-2-oxo-5-(trifluoromethoxy)indolin-3-ylidene)acetate (3p)
yellow solid; 98% yield in 24 h, mp 77-80 oC. 1H NMR (600 MHz, CDCl3): δ 11.23 (s, 1H), 7.46 – 7.33 (m, 5H), 7.17 – 7.06 (m, 2H), 6.85 (d, J = 8.5 Hz, 1H), 5.23 (s, 2H), 4.51 (s, 2H), 3.29 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.7, 162.1, 152.1, 144. 4, 139.7, 139.2, 134.7, 128.6, 128.4, 121.8, 121.0, 120.7, 119.2, 113.9, 108.6, 103.3, 68.5, 63.1, 26.0, 13.7. HRMS (ESI): for
C22H19F3N2O6 [M]+: calcd 464.1195, found 464.1189.
N O
EtO2C
NH
CbzCl
N O
EtO2C
NH
Cbz
Cl
N O
EtO2C
NH
CbzF
N O
EtO2C
NH
Cbz
F
N O
EtO2C
NH
CbzMe
N O
EtO2C
NH
CbzF3CO
S10
(Z)-benzyl (1-(1-methyl-2-oxoindolin-3-ylidene)-2-oxopropyl)carbamate (3q)
yellow solid; 98% yield in 24 h, mp 139-141 oC. 1H NMR (600 MHz, CDCl3): δ = 11.39 (s, 1H), 7.37 (d, J = 8.9 Hz, 5H), 7.24 (d, J = 7.7 Hz, 1H), 7.18 (d, J = 7.7 Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H), 6.87 (d, J = 7.8 Hz, 1H), 5.22 (s, 2H), 3.29 (s, 3H), 2.61 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 196.8, 186.2, 168.9, 152.8, 145.8, 140.7,
134.7, 128.6, 128.6, 128.4, 127.6, 122.4, 120.3, 119.6, 108.3, 102.1, 68.4, 30.0, 25.7; HRMS (ESI-TOF) for C20H18N2NaO4 [M+Na]+: calcd 373.1159, found 373.1161.
(Z)-benzyl (1-(1-methyl-2-oxoindolin-3-ylidene)-2-oxo-2-phenylethyl)carbamate (3r)
red solid; 98% yield in 24 h, mp 165-167 oC. 1H NMR (600 MHz, CDCl3): δ = 11.65 (s, 1H), 8.05 (s, 2H), 7.62 (s, 1H), 7.50 (s, 2H), 7.33 – 7.25 (m, 5H), 7.15 (s, 1H), 6.89 – 6.75 (m, 3H), 5.10 (d, J = 12.5 Hz, 2H), 3.31 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 189.7, 168.7, 152.3, 144.5, 140.6, 134.9, 134.7, 134.3, 129.12, 128.7, 128.5, 128.3,
127.4, 122.2, 121.0, 119.8, 108.2, 104.3, 68.3, 25.8; HRMS (ESI-TOF) for C25H20N2NaO4 [M+Na]+: calcd 435.1315, found 435.1304.
(Z)-benzyl (1-(1-methyl-2-oxoindolin-3-ylidene)-2-oxo-2-(thiophen-2-yl)ethyl)carbamate (3s)
yellow solid; 99% yield in 24 h, mp 146-148 oC. 1H NMR (600 MHz, CDCl3): δ = 11.56 (s, 1H), 7.78 (d, J = 4.7 Hz, 1H), 7.70 (d, J = 3.5 Hz, 1H), 7.33 (d, J = 3.3 Hz, 5H), 7.17 (t, J = 7.7 Hz, 1H), 7.12 – 7.08 (m, 1H), 7.01 (d, J = 7.5 Hz, 1H), 6.85 (t, J = 7.3 Hz, 2H), 5.14 (s, 2H), 3.31 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 186.2, 181.5, 168.7, 152.1, 143.6, 142.0, 140.7, 135.8, 134.5, 128.6, 128.5, 128.3, 127.5, 122.3, 121.1, 119.7, 108.2,
104.5, 68.3, 25.8; HRMS (ESI-TOF) for C23H18N2NaO4S [M+Na]+: calcd 441.0879, found 441.0879.
(Z)-ethyl 2-((benzoyloxy)amino)-2-(1-methyl-2-oxoindolin-3-ylidene)acetate (3t)
yellow solid; 99% yield in 24 h. 1H NMR (600 MHz, CDCl3): δ = 11.54 (s, 1H), 7.39 (t, J = 8.0 Hz, 2H), 7.29 – 7.23 (m, 4H), 7.23 – 7.19 (m, 2H), 7.05 (d, J = 7.6 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 4.51 (q, J = 7.2 Hz, 2H), 3.31 (s, 3H), 1.39 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.7, 162.2, 150.8, 150.0, 140.9, 137.5, 129.4, 128.0, 126.1, 122.4, 121.2, 120.3, 119.6, 108.4, 105.1, 62.9, 25.8, 13.8; HRMS (ESI-
TOF) for C20H18N2NaO5 [M+Na]+: calcd 389.1108, found 389.1105.
(Z)-ethyl 2-(1-methyl-2-oxoindolin-3-ylidene)-2-(((4-methylbenzoyl)oxy)amino)acetate (3u)
yellow solid; 99% yield in 24 h. 1H NMR (600 MHz, CDCl3): δ = 11.51 (s, 1H), 7.29 – 7.25 (m, 2H), 7.18 (d, J = 8.2 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 7.04 (s, 1H), 6.89 (d, J = 7.8 Hz, 1H), 4.50 (q, J = 7.2 Hz, 2H), 3.31 (s, 3H), 2.34 (s, 3H), 1.39 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.8, 162.3, 151.0, 147.9, 141.0, 137. 7, 135.8, 129.9, 128.0, 122.4, 120.9, 120.4, 119.7, 108.4, 105.0, 62.9, 25.8, 20.8, 13.8; HRMS
(ESI-TOF) for C21H20N2NaO5 [M+Na]+: calcd 403.1264, found 403.1257.
1-benzyl 3-ethyl 1'-methyl-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4a)
white solid; 82% yield in 2.5 h, >95:5 d.r. mp 120-122 oC. 1H NMR (600 MHz, CDCl3):
δ = 7.38 – 7.24 (m, 5H), 7.16 (dd, J = 7.7 Hz, 1.6, 2H), 6.92 – 6.83 (m, 2H), 6.55 (d, J = 7.4 Hz, 1H), 5.18 – 5.03 (m, 2H), 4.32 (dd, J = 7.2 Hz, 4.6, 2H), 3.88 (s, 1H), 3.24 (s, 4H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 167.8, 164.1, 158.3, 144.8, 134.51, 130.4, 128.7, 128.5, 128.3, 122.5, 120.7, 119.8, 109.0, 69.0, 62.1, 48.7,
46.8, 26.6, 14.0; HRMS (ESI-TOF) for C21H20N2NaO5 [M+Na]+: calcd 402.1264, found 402.1259.
N O
MeOC
NH
Cbz
N O
PhOC
NH
Cbz
N O
NH
CbzS
O
N O
EtO2C
NH
O
O
N O
EtO2C
NH
O
O
N O
N Cbz
EtO2C
S11
1-benzyl 3-methyl 1'-methyl-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4b)
white solid; 75% yield in 2 h, >95:5 d.r. mp 130-132oC. 1H NMR (600 MHz, CDCl3): δ = 7.42 – 7.21 (m, 4H), 7.17 (s, 2H), 6.87 (t, J = 8.6 Hz, 2H), 6.55 (d, J = 7.3 Hz, 1H), 5.10 (dd, J = 28.5, 11.7 Hz, 2H), 3.91 (s, 1H), 3.84 (s, 3H), 3.21 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 167.8, 164.6, 158.2, 144.8, 134.5, 130.4, 128.7, 128.5, 128.4, 122.6, 120.7, 119.7, 109.1, 69.1, 52.8, 48.7, 46.7, 26.6; HRMS (ESI-TOF) for C20H18N2NaO5
[M+Na]+: calcd 389.1108, found 389.1104.
1-benzyl 3-tert-butyl 1'-methyl-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4c)
white solid; 74% yield in 2 h, >95:5 d.r. mp 139-142 oC. 1H NMR (600 MHz, CDCl3): δ = 7.28 (dt, J = 12.8, 6.8Hz, 5H), 7.20 – 7.11 (m, 2H), 6.92 – 6.82 (m, 2H), 6.54 (d, J =7.4 Hz, 1H), 5.08 (dd, J = 28.4, 12.0 Hz, 2H), 3.80 (s, 1H), 3.23 (d, J = 8.3 Hz, 3H), 1.54 – 1.49 (m, 9H); 13C NMR (100 MHz, CDCl3): δ = 168.0, 162.9, 158.5, 157.8, 144.9, 134.7, 130.2, 128.6, 128.4, 128.3, 122.4, 120.7, 120.3, 108.9, 83.2, 68.9, 48.7, 47.5, 27.9, 26.6;
HRMS (ESI-TOF) for C23H24N2NaO5 [M+Na]+: calcd 431.1577, found 431.1559.
1-benzyl 3-methyl 1'-benzyl-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4d)
white solid; 84% yield in 2 h, >95:5 d.r. mp 112-114 oC. 1H NMR (600 MHz, CDCl3): δ = 7.31 – 7.22 (m, 9H), 7.11 (d, J = 7.6 Hz, 2H), 6.84 (t, J = 7.6 Hz, 1H), 6.76 (d, J = 7.9 Hz, 1H), 6.57 (d, J = 7.5 Hz, 1H), 5.10 (dd, J = 43.7, 12.0 Hz, 2H), 4.94 (d, J = 10.5 Hz, 2H), 3.97 (s, 1H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 168.3, 164.6, 158.2, 144.0, 134.8, 134.5, 130.4, 128.8, 128.5, 128.5, 128.4, 127.7, 127.1, 122.7, 120.8,
119.9, 110.2, 69.1, 52.9, 48.8, 46.9, 44.2; HRMS (ESI-TOF) for C26H22N2NaO5 [M+Na]+: calcd 465.1421, found 465.1421.
1-benzyl 3-tert-butyl 1'-benzyl-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4e)
white solid; 95% yield in 2 h, >95:5 d.r. mp 108-110 oC. 1H NMR (600 MHz, CDCl3): δ = 7.31 – 7.21 (m, 10H), 7.12 (d, J = 7.4 Hz, 2H), 6.83 (s, 1H), 6.75 (d, J = 7.9 Hz, 1H), 6.57 (d, J = 7.5Hz, 1H), 5.11 (dd, J = 44.0, 12.2 Hz, 2H), 4.95 (dd, J = 105.6, 15.9 Hz, 2H), 3.86 (s, 1H), 1.51 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 168.3, 162.7, 158.5, 144.0, 135.1, 134.7, 130.1, 128.7, 128.5, 128.4, 128.3, 127.6, 127.0, 122.6, 120.8, 120.4,
110.0, 83.3, 68.9, 48.7, 47.8, 44.0, 27.9, 27.5; HRMS (ESI-TOF) for C29H28N2NaO5 [M+Na]+: calcd 507.1890, found 507.1866.
1-benzyl 3-tert-butyl 1'-benzyl-5'-methyl-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4f)
white solid; 96% yield in 2 h, >95:5 d.r. mp 122-124 oC. 1H NMR (600 MHz, CDCl3): δ = 7.25 (d, J = 5.2 Hz, 9H), 7.13 (d, J = 6.8 Hz, 2H), 6.99 (d, J = 7.6 Hz, 1H), 6.63 (d, J = 8.0 Hz, 1H), 6.40 (s, 1H), 5.13 (dd, J = 30.6, 12.1 Hz, 2H), 4.94 (dd, J=73.8, 15.8 Hz, 2H), 3.82 (s, 1H), 2.11 (s, 3H), 1.51 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 168.2, 162.7, 158.4, 141.6, 135.2, 134.8, 132.3, 130.5, 128.7, 128.4, 128.3, 127.6,
127.0, 121.5, 120.4, 109. 8, 83.2, 68.8, 48.8, 47.8, 44.0, 27.9, 20.9; HRMS (ESI-TOF) for C30H30N2NaO5 [M+Na]+: calcd 521.2047, found 521.2036.
1-benzyl 3-tert-butyl 1'-benzyl-5'-methoxy-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4g)
white solid; 98% yield in 6 h, >95:5 d.r. mp 136-138 oC. 1H NMR (600 MHz, CDCl3): δ = 7.27 – 7.24 (m, 6H), 7.23 (s, 2H), 7.13 (s, 1H), 7.11 (s, 1H), 6.72 (dd, J = 8.6, 2.4,
N O
N Cbz
MeO2C
N O
N Cbz
tBuO2C
N
BnO
N Cbz
MeO2C
NBn
O
N Cbz
tBuO2C
NBn
O
N Cbz
tBuO2C
Me
NBn
O
N Cbz
tBuO2C
MeO
S12
1H), 6.64 (d, J = 8.6 Hz, 1H), 6.26 (d, J = 2.4 Hz, 1H), 5.13 (dd, J = 28.7, 12.1 Hz, 2H), 4.93 (dd, J = 65.6, 15.8 Hz, 2H), 3.84 (s, 1H), 3.57 (s, 3H), 1.51 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 168.0, 162.7, 158.4, 137.2, 135.2, 134.7, 128.7, 128.4, 128.3, 128.1, 127.6, 127.0, 121.6, 114.8, 110.6, 107.9, 83.3, 68.8, 55.6, 48.9, 47.8, 44.1, 27.9; HRMS (ESI-TOF) for C30H30N2NaO6 [M+Na]+: calcd 537.1996, found 537.1983.
1-benzyl 3-tert-butyl 1'-benzyl-4'-bromo-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4h)
white solid; 93% yield in 15 min, >95:5 d.r. mp 159-161 oC. 1H NMR (600 MHz, CDCl3): δ = 7.26 (dd, J =12.2, 5.8 Hz, 10H), 7.08 (d, J = 5.9 Hz, 2H), 6.71 (dd, J = 6.0, 2.5 Hz, 1H), 5.17 (s, 2H), 5.05 (d, J = 15.9 Hz, 1H), 4.86 (s, 1H), 4.83 (d, J = 16.0 Hz, 1H), 1.52 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 168.0, 163.2, 156.9, 146.4, 134.8, 134.6, 131.2, 128.8, 128.4, 128.3, 128.3, 127.8, 127.2, 126.9, 118.2,
118.1, 109.2, 83.4, 69.0, 48.9, 44.2, 43.1, 28.0; HRMS (ESI-TOF) for C29H27BrN2NaO5 [M+Na]+: calcd 585.0996, found 585.0992.
1-benzyl 3-tert-butyl 1'-benzyl-5'-bromo-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4i)
white solid; 92% yield in 15 min, >95:5 d.r. mp 123-126 oC. 1H NMR (600 MHz, CDCl3): δ = 7.32 – 7.24 (m, 8H), 7.21 (d, J = 10.1 Hz, 4H), 6.77 (s, 1H), 6.60 (d, J = 8.3 Hz, 1H), 5.15 (dd, J = 44.1, 12.1 Hz, 2H), 4.93 (dd, J = 81.3, 15.8 Hz, 2H), 3.84 (s, 1H), 1.51 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 167.7, 162.3, 158.0, 142.9, 134.6, 134.5, 133.0, 128.8, 128.7, 128.6, 128.4, 127.8, 126.9, 124.1, 122.5, 115.2, 111.4,
83.5, 69.2, 48.0, 44.1, 27.9; HRMS (ESI-TOF) for C29H27BrN2NaO5 [M+Na]+: calcd 585.0996, found 585.0990.
1-benzyl 3-tert-butyl 1'-benzyl-6'-bromo-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4j)
white solid; 90% yield in 15 min, >95:5 d.r. mp 72-74 oC. 1H NMR (600 MHz, CDCl3): δ = 7.32 – 7.24 (m, 8H), 7.16 (d, J = 7.5 Hz, 2H), 6.88 (d, J = 6.5 Hz, 2H), 6.31 (d, J = 8.4 Hz, 1H), 5.12 (s, 2H), 5.01 (d, J = 15.8 Hz, 1H), 4.83 (d, J = 15.9 Hz, 1H), 3.82 (s, 1H), 1.51 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 168.1, 162.4, 158.2, 145.2, 134.7, 134.6, 128.9, 128.7, 128.6, 128.4, 127.9, 127.0, 125.4, 123.9,
122.0, 119.3, 113.3, 83.5, 69.0, 48.2, 47.8, 44.2, 27.9; HRMS (ESI-TOF) for C29H27BrN2NaO5 [M+Na]+: calcd 585.0996, found 585.0993. 1-benzyl 3-tert-butyl 1'-benzyl-4'-chloro-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4k)
white solid; 99% yield in 15 min, >95:5 d.r. mp 149-152 oC. 1H NMR (600 MHz, CDCl3): δ = 7.28 (s, 3H), 7.23 (d, J = 6.7 Hz, 5H), 7.18 – 7.12 (m, 2H), 6.90 (d, J = 8.2 Hz, 1H), 6.68 (d, J = 7.9 Hz, 1H), 5.16 (s, 2H), 5.06 (d, J = 15.9 Hz, 1H), 4.83 (d, J = 15.9 Hz, 1H), 4.71 (s, 1H), 1.52 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 168.0, 163.1, 157.3, 146.1, 134.8, 134.6, 131.0, 130.0, 128.8, 128.4, 128.3, 127.8, 127.0, 124.0, 116.6, 108.7, 83.4,
69.0, 48.5, 44.2, 43.4, 28.0; HRMS (ESI-TOF) for C29H27ClN2NaO5 [M+Na]+: calcd 541.1501, found 541.1509.
1-benzyl 3-tert-butyl 1'-benzyl-5'-chloro-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4l)
white solid; 90% yield in 15 min, >95:5 d.r. mp 128-131 oC. 1H NMR (600 MHz, CDCl3): δ = 7.26 (s, 6H), 7.19 (dd, J = 16.0, 9.9 Hz, 5H), 6.65 (d, J = 8.4 Hz, 1H), 6.60 (s, 1H), 5.15 (dd, J = 38.5, 12.0 Hz, 2H), 4.93 (dd, J = 79.2, 15.9 Hz, 2H), 3.83 (s, 1H), 1.51 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 167.8, 162.3, 158.0, 142.4, 134.6, 134.5,
130.1, 128.8, 128.61, 128.5, 128.4, 128.2, 127.8, 127.0, 122.2, 121.4, 111.0, 83.6, 69.2, 48.0, 44.2, 27.9;
N
Bn
O
N Cbz
tBuO2CBr
N
Bn
O
N Cbz
tBuO2C
Br
N
Bn
O
N Cbz
tBuO2C
Br
N
BnO
N Cbz
tBuO2CCl
N
BnO
N Cbz
tBuO2C
Cl
S13
HRMS (ESI-TOF) for C29H27ClN2NaO5 [M+Na]+: calcd 541.1501, found 541.1500.
1-benzyl 3-tert-butyl 1'-benzyl-7'-fluoro-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4m)
white solid; 90% yield in 15 min, >95:5 d.r. mp 92-95oC. 1H NMR (600 MHz, CDCl3): δ = 7.31 – 7.19 (m, 10H), 7.15 (d, J = 6.7 Hz, 2H), 7.00 – 6.92 (m, 1H), 6.75 (d, J = 4.2 Hz, 1H), 6.31 (s, 1H), 5.19 – 5.11 (m, 2H), 5.05 (dd, J = 20.6, 13.7 Hz, 2H), 3.82 (s, 1H), 1.50 (s, 9H); 13C NMR (100 MHz, CDCl3): δ = 178.2, 174.2, 168.0, 162.3, 158.1, 148.9, 146.4, 136.3, 134.6, 130.6, 128.6, 128.5, 128.4, 127.6, 127.2, 123.3, 118.4, 118.2, 116.7, 83.4,
69.0, 48.4, 48.2, 45.7, 27.9; HRMS (ESI-TOF) for C29H27FN2NaO5 [M+Na]+: calcd 525.1796, found 525.1784. 1-benzyl 3-ethyl 1'-methyl-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (4a')
white solid; >95:5 d.r. mp 120-122 oC. 1H NMR (600 MHz, CDCl3): δ = 7.41-7.33 (m,
7H), 7.06 (t, J = 7.4 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 5.18 (dd, J = 38.1, 12.0 Hz, 2H),
4.22 (dt, J = 17.8, 10.8 Hz, 2H), 3.90 (s, 1H), 3.26 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ =168.1, 164.3, 157.9, 144.6, 134.5, 130.0, 128.2, 128.0,
128.0, 123.8, 122.6, 120.1, 108.6, 68.8, 61.9, 48.8, 47.8, 26.6, 14.0; HRMS (ESI-TOF) for C21H20N2NaO5
[M+Na]+: calcd 402.1264, found 402.1259.
1-benzyl 3-tert-butyl 1'-benzyl-5'-bromo-2'-oxospiro[aziridine-2,3'-indoline]-1,3-dicarboxylate (5)
white solid; 75% yield, 1.6:1 d.r. mp 156-159 oC. 1H NMR (600 MHz, CDCl3): δ =
8.08 (d, J = 6.9 Hz, 1H), 7.95 (d, J = 7.1 Hz, 1H), 7.50 (d, J = 7.8 Hz, 2H), 7.30 (s,
4H), 7.16 (dd, J = 15.1, 7.3 Hz, 5H), 7.09 (t, J = 7.5 Hz, 2H), 6.77 – 6.66 (m, 4H),
6.43 (d, J = 7.1 Hz, 1H), 5.39 (d, J = 9.2 Hz, 2H), 5.05 (dd, J = 39.4, 12.0 Hz, 1H), 4.79 (dd, J = 30.2,
11.5 Hz, 2H), 4.38 (dd, J = 15.0, 7.2 Hz, 2H), 4.29 (dd, J = 17.7, 9.0 Hz, 2H), 4.06 (s, 1H), 3.91 (s, 1H),
3.84 (s, 2H), 3.79 (d, J = 7.6 Hz, 2H), 3.48 (d, J = 6.5 Hz, 1H), 2.98 (d, J = 9.6 Hz, 7H), 2.30 (s, 3H), 1.62
(d, J = 6.9 Hz, 3H), 1.38 (t, J = 6.4 Hz, 3H), 1.21 (t, J = 7.1 Hz, 1H), 1.10 (s, 2H), 0.81 (d, J = 6.1 Hz,
5H); 13C NMR (100 MHz, CDCl3) δ = 171.4, 171.1, 170.8, 170.5, 166.1, 152.2, 151.7, 142.6, 141.9,
136.9, 134.9, 134.1, 129.8, 129.1, 127.9, 127.6, 127.2, 126.7, 126.2, 125.2, 122.9, 121.5, 121.1, 107.5,
72.0, 71.3, 67.5, 61.4, 60.8, 60.2, 59.4, 53.5, 52.7, 26.1, 25.5, 13.6, 13.4, 13.0; HRMS (ESI-TOF) for
C34H34N3O8 [M+H]+: calcd 612.2268, found 612.2337.
N
BnO
N Cbz
tBuO2C
F
N O NO
N
CO2EtEtO2C Cbz
N O
N Cbz
EtO2C
S14
6. X-Ray single crystal diffraction structures of 3a, 4a, 4a’and 5.
N O
NO
O
O
O
4a
S15
N O NO
N
O
O
OO
O
O
5
N O
N
O
O
O
O
4a'
S16
7. Copies of 1H NMR and 13C NMR spectra 1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of 3a
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
3.14
1.99
2.20
1.08
1.10
2.25
5.08
1.01
-0.00
0.00
1.40
1.42
1.43
3.25
3.26
4.52
5.22
6.85
6.86
7.00
7.01
7.03
7.22
7.24
7.25
7.34
7.34
7.35
7.35
7.36
7.36
7.38
7.38
7.39
11.27
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.6
8
25.5
8
62.6
2
68.0
8
76.6
877
.00
77.3
2
104.
11
108.
19
119.
6312
0.01
122.
1212
7.63
128.
1912
8.39
134.
7513
7.86
140.
65
152.
10
162.
36
168.
49
S17
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3b
-3-2-1012345678910111213f1 (ppm)
3.00
1.95
2.08
1.01
1.02
1.05
1.00
1.02
3.61
0.95
0.95
-0.00
1.40
1.41
1.43
1.48
4.52
5.23
6.90
6.91
6.98
6.99
7.00
7.16
7.17
7.18
7.21
7.22
7.25
7.37
7.37
7.39
7.40
8.43
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
9
62.8
8
68.4
0
76.6
877
.00
77.3
2
104.
54
110.
31
120.
3912
0.44
122.
2712
7.81
128.
4812
8.60
134.
8013
8.21
138.
59
152.
19
162.
48
170.
81
S18
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3c
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
3.00
2.00
2.00
1.09
1.11
1.05
0.93
4.08
1.05
1.03
0.00
1.39
1.41
1.42
1.43
2.70
2.71
4.53
4.54
5.24
7.15
7.16
7.22
7.23
7.26
7.26
7.27
7.28
7.29
7.36
7.36
7.38
7.40
8.26
8.27
11.01
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
4
26.9
2
63.1
3
68.7
3
76.6
877
.00
77.3
2
102.
89
116.
4711
9.33
120.
3912
4.91
128.
1912
8.63
128.
78
134.
3713
7.04
139.
81
151.
84
162.
04
169.
6817
0.38
178.
22
194.
76
S19
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3d
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
9.07
2.05
2.21
1.05
1.03
1.57
5.19
1.11
1.18
-0.00
1.41
1.42
1.43
1.65
4.53
4.54
5.22
7.10
7.11
7.12
7.21
7.22
7.26
7.27
7.28
7.36
7.37
7.37
7.38
7.39
7.87
7.88
11.17
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
1
27.9
8
62.9
7
68.4
6
76.6
877
.00
77.3
2
84.6
3
102.
95
114.
9411
9.53
120.
0412
4.15
127.
8912
8.34
128.
5412
8.60
134.
5613
6.77
139.
39
148.
67
151.
94
162.
16
167.
97
S20
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3e
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
2.98
3.08
2.01
2.09
2.07
3.07
1.05
1.11
3.19
5.03
1.03
1.40
1.41
1.42
3.74
4.53
4.89
5.22
6.79
6.80
6.81
6.82
6.96
6.97
6.99
7.12
7.13
7.15
7.19
7.20
7.22
7.23
7.34
7.35
7.36
7.37
7.38
11.31
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.8
0
55.1
8
62.8
5
68.3
0
76.6
877
.00
77.3
2
104.
04
109.
24
114.
08
119.
9712
0.23
122.
3112
7.62
128.
3912
8.55
134.
8013
8.32
139.
96
152.
23
159.
00
162.
54
168.
77
S21
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3f
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
2.09
2.20
2.13
1.10
1.22
1.27
6.19
4.71
1.09
1.40
1.41
1.42
4.53
4.94
5.21
6.75
6.76
6.96
6.97
6.99
7.10
7.12
7.13
7.21
7.22
7.24
7.25
7.26
7.28
7.29
7.32
7.32
7.33
7.33
7.34
7.34
7.34
7.36
7.37
7.38
11.31
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
4
43.2
4
62.7
8
68.2
2
76.6
877
.00
77.3
2
103.
89
109.
1711
9.86
122.
2912
7.04
127.
5512
7.64
128.
3012
8.47
128.
66
134.
7113
5.49
138.
3213
9.85
152.
14
162.
44
168.
72
S22
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3g
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
2.14
1.95
2.17
1.89
1.08
1.05
1.04
1.08
1.08
4.93
0.99
0.00
1.40
1.41
1.43
4.37
4.38
4.52
5.15
5.15
5.18
5.19
5.20
5.21
5.79
5.80
5.81
5.82
5.83
5.84
6.83
6.85
6.99
7.00
7.02
7.18
7.18
7.20
7.20
7.21
7.21
7.23
7.25
7.32
7.33
7.34
7.34
7.34
7.35
7.36
7.36
7.37
7.38
11.27
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
9
41.9
1
62.8
3
68.2
5
76.6
877
.00
77.3
2
103.
98
109.
10
117.
4811
9.88
120.
2412
2.30
127.
6712
8.31
128.
5313
1.04
134.
7913
8.28
139.
94
152.
20
162.
51
168.
47
S23
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3h
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
3.00
3.01
2.04
2.11
1.04
1.08
1.02
4.96
0.95
-0.00
1.35
1.36
1.37
3.28
4.45
4.46
5.21
6.82
6.83
7.09
7.23
7.24
7.26
7.37
7.38
7.39
11.96
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
13.5
1
26.0
3
62.8
1
68.0
9
76.6
877
.00
77.3
2
105.
1510
6.98
116.
12
120.
64
127.
8812
8.23
128.
4012
8.43
134.
83
140.
7714
2.46
152.
19
162.
54
168.
87
S24
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3i
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
3.03
2.14
2.12
1.01
0.96
6.01
0.97
1.43
1.44
1.45
3.22
4.54
5.22
6.69
6.70
7.25
7.29
7.31
7.33
7.34
7.35
7.36
7.38
7.38
11.23
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.8
0
25.8
8
63.0
6
68.4
5
76.6
877
.00
77.3
2
103.
05
109.
60
115.
06
121.
6812
3.15
128.
4012
8.57
130.
1813
4.67
139.
3013
9.55
152.
07
162.
11
168.
28
S25
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3j
-3-2-1012345678910111213f1 (ppm)
3.00
3.08
1.99
2.15
1.02
0.99
1.03
1.03
3.94
0.87
0.00
1.39
1.40
1.41
3.26
4.49
4.51
5.22
7.02
7.07
7.08
7.14
7.15
7.26
7.36
7.37
7.38
7.39
11.17
3j
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
3
25.8
1
62.8
7
68.3
2
76.6
877
.00
77.3
2
103.
31
111.
68
118.
6712
1.13
124.
9912
8.16
128.
3212
8.43
128.
49
134.
6613
8.55
141.
70
152.
05
162.
27
168.
44
S26
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3k
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
3.00
2.98
2.04
2.08
1.00
0.98
1.00
4.82
0.91
0.00
1.36
1.38
1.39
3.29
4.42
4.44
4.45
4.46
5.21
6.78
6.79
7.03
7.04
7.16
7.18
7.19
7.26
7.35
7.37
7.38
7.39
7.40
12.15
-100102030405060708090100110120130140150160170180190200f1 (ppm)
13.5
7
26.1
0
62.5
4
68.1
4
76.6
877
.00
77.3
2
103.
50
106.
55
118.
46
124.
48
127.
80
128.
4713
4.83
141.
5714
2.12
152.
08
162.
57
168.
95
S27
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3l
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
3.07
2.11
2.14
1.08
1.09
1.06
5.07
0.97
-0.00
1.39
1.40
1.42
3.25
4.50
4.51
5.22
6.86
6.86
6.98
6.98
6.99
6.99
7.12
7.13
7.26
7.35
7.35
7.36
7.37
7.38
7.39
11.16
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
8
25.8
7
62.9
0
68.3
6
76.6
977
.00
77.3
2
103.
39
108.
94
118.
2812
0.95
122.
16
128.
3612
8.55
133.
3913
4.74
138.
4714
1.71
152.
11
162.
33
168.
68
S28
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3m
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
3.23
2.00
2.18
1.11
2.10
5.11
0.92
-0.00
1.41
1.42
1.44
1.60
3.26
4.53
4.54
5.23
6.77
6.78
6.79
6.95
6.97
7.26
7.37
7.39
11.29
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
3
25.8
0
62.9
4
68.3
2
76.6
877
.00
77.3
2
103.
7510
7.72
107.
9810
8.58
108.
6511
3.79
114.
03
120.
88
128.
3112
8.50
134.
6813
6.76
139.
07
152.
04
157.
6216
0.00
162.
08
168.
47
S29
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3n
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
3.11
2.11
2.16
3.07
5.05
0.99
-0.00
1.40
1.41
1.42
3.49
3.50
4.52
5.23
6.92
6.93
6.94
6.94
6.95
6.97
6.99
7.00
7.26
7.36
7.37
7.37
7.39
7.39
11.32
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
1
28.2
2
62.8
6
68.3
2
76.6
877
.00
77.3
2
103.
41
115.
0511
5.24
115.
8912
2.62
122.
6912
8.32
128.
3912
8.49
134.
65
139.
22
146.
6814
9.09
152.
02
162.
19
168.
28
S30
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3o
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
3.04
2.99
1.84
2.02
0.90
1.96
1.92
2.95
0.85
-0.00
1.41
1.43
1.45
2.32
3.25
4.52
4.54
5.22
5.23
6.74
6.76
7.04
7.04
7.06
7.26
7.35
7.36
7.37
7.38
7.39
11.28
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.8
0
21.2
7
25.7
7
62.7
0
68.1
7
76.6
877
.00
77.3
2
104.
40
108.
02
119.
8012
0.93
128.
2512
8.30
128.
5213
1.64
134.
8713
7.72
138.
68
152.
28
162.
59
168.
70
S31
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3p
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
3.00
3.06
2.03
2.09
1.09
2.10
4.97
0.98
0.00
1.40
1.41
1.43
3.29
4.51
5.23
6.84
6.86
7.10
7.12
7.13
7.26
7.36
7.37
7.38
7.39
7.40
11.23
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.6
7
25.9
5
63.1
0
68.5
2
76.6
877
.00
77.3
2
103.
26
108.
63
113.
9111
9.23
120.
6612
0.98
121.
7812
8.43
128.
60
134.
6613
9.19
139.
6614
4.44
152.
06
162.
08
168.
66
S32
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3q
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.0f1 (ppm)
2.87
2.83
2.00
0.96
1.10
1.04
0.99
4.86
0.85
-0.00
2.61
3.29
5.22
6.86
6.88
6.98
7.00
7.02
7.17
7.19
7.23
7.25
7.36
7.39
11.39
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
25.7
4
29.9
5
68.4
2
76.6
877
.00
77.3
1
102.
07
108.
32
119.
6312
0.28
122.
3612
8.37
128.
5612
8.59
134.
72
140.
69
145.
81
152.
71
168.
89
186.
23
196.
81
S33
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3r
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
3.04
2.00
3.08
1.09
5.01
2.08
0.98
1.96
0.77
-0.00
3.31
5.08
5.11
6.79
6.82
6.85
7.15
7.26
7.30
7.33
7.50
7.62
8.05
11.65
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
25.7
5
68.2
9
76.6
877
.00
77.3
2
104.
27
108.
17
119.
8312
0.95
122.
2212
8.27
128.
48
134.
2713
4.67
134.
9014
0.62
144.
54
152.
31
168.
67
189.
66
S34
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3s
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
3.00
2.00
1.91
1.07
1.02
1.22
5.14
1.05
1.06
0.75
0.00
3.31
5.14
6.83
6.85
6.87
7.00
7.02
7.09
7.10
7.11
7.15
7.17
7.19
7.26
7.33
7.34
7.69
7.70
7.77
7.78
11.56
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
25.7
6
68.2
6
76.6
977
.00
77.3
2
104.
46
108.
19
119.
7212
1.12
122.
3112
8.27
128.
47
134.
5213
4.70
135.
8414
0.68
142.
0114
3.56
152.
13
168.
69
181.
54
S35
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3t
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.5f1 (ppm)
3.00
3.05
2.06
1.08
1.10
2.09
3.66
2.37
0.91
0.00
1.38
1.39
1.41
3.28
3.31
4.49
4.50
4.51
4.52
5.11
6.88
6.90
7.04
7.05
7.20
7.21
7.21
7.25
7.26
7.26
7.27
7.27
7.38
7.39
7.40
11.54
S36
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 3u
3.00
3.08
2.95
1.97
0.99
1.11
1.98
2.05
2.38
0.95
0.00
1.38
1.39
1.40
2.34
3.31
4.48
4.49
4.50
4.52
6.41
6.88
6.90
7.04
7.07
7.08
7.17
7.18
7.26
7.27
7.27
11.5
1
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
13.7
9
20.8
0
25.8
3
62.8
9
76.6
877
.00
77.3
2
105.
03
108.
39
119.
7112
0.38
120.
8912
2.39
128.
0112
9.91
135.
8313
7.67
140.
95
147.
90
151.
01
162.
26
168.
76
N O
EtO2C
NH
O
O
N O
EtO2C
NH
O
O
S37
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4a
S38
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4b
S39
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4c
N O
N Cbz
tBuO2C
N O
N Cbz
tBuO2C
S40
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4d
S41
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4e
N
Bn
O
N Cbz
tBuO2C
N
Bn
O
N Cbz
tBuO2C
S42
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4f
S43
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4g
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
9.18
3.00
1.00
2.41
2.16
1.06
1.15
1.08
1.00
1.16
2.07
5.98
-0.00
1.51
3.55
3.57
3.84
4.83
4.87
4.99
5.03
5.07
5.11
5.15
5.18
6.25
6.26
6.63
6.65
6.71
6.71
7.11
7.13
7.20
7.21
7.23
7.25
7.25
7.26
-100102030405060708090100110120130140150160170180190200210220230f1 (ppm)
27.9
3
44.0
8
47.8
448
.87
55.6
2
68.8
4
76.6
877
.00
77.3
2
83.2
6
107.
9311
0.57
114.
75
121.
6012
6.98
128.
1412
8.36
134.
7213
5.15
137.
25
155.
8015
8.39
162.
66
168.
03
S44
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4h
S45
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4i
S46
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4j
S47
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4k
S48
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4l
S49
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4m
S50
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 4a’
S51
1H NMR (600 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) spectra of product 5 (d.r. = 1.6:1)
N O NO
N
CO2EtEtO2C Cbz
N O NO
N
CO2EtEtO2C Cbz
