Institute of Materia Medica and College of Pharmaceutical ...Institute of Materia Medica and College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P.R.China E-mail:

Supporting Information for

Rh(III)-Catalyzed C−H Activation/[4+3] Cycloaddition of Benzamides and Vinylcarbenoids: Facile Synthesis of Azepinones

Sunliang Cui,* Yan Zhang, Dahai Wang and Qifan Wu Institute of Materia Medica and College of Pharmaceutical Sciences,

Zhejiang University, Hangzhou 310058, P.R.China E-mail: [email protected]

Contents

General Considerations S2

General Procedure for the Synthesis of 3 - 4 S3

Characterization of 3 - 4 S3-S19

Synthesis of Pyrazole 5 S20

Derivation of Product 3m to 6 and 7 S20-S22

Kinetic Isotope Effect Study S22-S23

References S23

Copies of NMR Spectra S24-S184

S1

Electronic Supplementary Material (ESI) for Chemical ScienceThis journal is © The Royal Society of Chemistry 2013

General Information:

Infrared spectra were obtained on a FTIR spectrometer. 1H NMR and 13C NMR

spectra were recorded on BRUKER AVANCE III 500 or BRUKER AVANCE III 400

spectrometer. CDCl3 was used as solvent and tetramethylsilane (TMS) as internal

standard. Chemical shifts were referenced relative to residual solvent signal (1H NMR:

δ 7.26 ppm, 13C NMR: δ 77.0 ppm). The following abbreviations are used to describe

peak patterns where appropriate: b = broad, s = singlet, d = doublet, t = triplet, q =

quartet, m = multiplet. Coupling constants (J) are reported in Hertz (Hz). HRMS

were performed on Waters GCT Premier Time of Flight Mass Spectrometer (EI) or

Agilent Technologies 6224 TOF LC/MS apparatus (ESI). Melting points were

measured with micro melting point apparatus.

The N-pivaloyloxybenzamides 1, vinyldiazoacetates and ketone 2, were prepared

according to the literature. 1, 2 [Cp*RhCl2]2, CsOAc, anhydrous CH3CN and

d5-benzoic acid were commercial available.

NHOPiv

O

1a

NHOPiv

O

1bMe

NHOPiv

O

1cPh

NHOPiv

O

1dNC

NHOPiv

O

1eF3C

NHOPiv

O

1fMeO

NHOPiv

O

1gCl

NHOPiv

O

1hBr

NHOPiv

O

1iI

NHOPiv

O

1jO2N

NHOPiv

O

1k

MeNHOPiv

O

1l

Me

O2N

NHOPiv

O

1mCl

ClNHOPiv

O

1n

O

O

NHOPiv

O

1o

N2O

O2a

tBu

N2O

O2b

Me

N2O

O2c

BrN2

O

O2d

EtMe

N2O

O2e

EtPh

N2O

O2f

Et

Br

N2O

O2g

Et

O

N2O

O2h

Et

S

N2

O2i

N2O

OH3C

2j

Ph

S2


General Procedure:

Typical procedure for synthesis of azepinone: [Cp*RhCl2]2 (2.5 mg, 2 mol%),

benzamide 1a (44.2 mg, 0.2 mmol), CsOAc (38.4 mg, 0.2 mmol) were added to a vial.

CH3CN (1.0 mL) was added, followed by micro-syringe addition of tert-butyl

vinyldiazoacetate 2a (50.4 mg, 0.3 mmol). The micro-syringe was washed with an

additional 0.5 mL CH3CN and added to the reaction solution. The mixture was kept at

room temperature under air. After completion within 6 hours, it was diluted with

CH2Cl2 and transferred to a round bottom flask. Silica was added to the flask and

volatiles were evaporated under vacuum. The purification was performed by flash

column chromatography on silica gel using ethyl acetate/petroleum ether (v/v, 1:1) as

eluent to give product 3a as a white solid (49 mg, 95% yield). White solid; mp.

204-205 oC; 1H NMR (CDCl3, 500 MHz) δ 8.38 (b, 1H), 7.95 (d, J = 7.5 Hz, 1H),

7.50 (m, 2H), 7.45 (m, 1H), 7.28 (m, 1H), 3.51 (t, J = 7.0 Hz, 2H), 1.51 (s, 9H) ppm; 13C NMR (CDCl3, 125 MHz) δ 171.7, 165.2, 138.9, 137.6, 134.7, 132.3, 129.8, 129.6,

129.5, 128.3, 81.7, 37.4, 28.0 ppm; IR (KBr) v 3180, 1703, 1650, 1286, 1177, 1160,

785 cm-1; HRMS (EI) (m/z): calcd for C15H17NO3 [M+] 259.1208; found 259.1208.

Characterization of Products 3-4:

tert-Butyl 1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3a). White solid;

mp. 204-205 oC; 1H NMR (CDCl3, 500 MHz) δ 8.38 (b, 1H), 7.95 (d, J = 7.5 Hz, 1H),

7.50 (m, 2H), 7.45 (m, 1H), 7.28 (m, 1H), 3.51 (t, J = 7.0 Hz, 2H), 1.51 (s, 9H) ppm; 13C NMR (CDCl3, 125 MHz) δ 171.7, 165.2, 138.9, 137.6, 134.7, 132.3, 129.8, 129.6,

S3

NH

O

OtBuO3a


129.5, 128.3, 81.7, 37.4, 28.0 ppm; IR (KBr) v 3180, 1703, 1650, 1286, 1177, 1160,

785 cm-1; HRMS (EI) (m/z): calcd for C15H17NO3 [M+] 259.1208; found 259.1208.

tert-Butyl 7-methyl-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3b).

Pale yellow solid; mp. 163-165 oC; 1H NMR (CDCl3, 400 MHz) δ 8.33 (b, 1H), 7.85

(d, J = 8.0 Hz, 1H), 7.32 (s, 1H), 7.26 (m, 2H), 3.51 (t, J = 6.4 Hz, 2H), 2.42 (s, 3H),

1.52 (s, 9H) ppm; 13C NMR (CDCl3, 125 MHz) δ 165.3, 140.1, 138.6, 137.6, 132.2,

132.1, 129.9, 129.7, 129.2, 81.6, 37.5, 28.0, 21.4 ppm; IR (KBr) v 3176, 3047, 1710,

1652, 1283, 1158 cm-1; HRMS (EI) (m/z): calcd for C16H19NO3 [M+] 273.1365; found

273.1358. tert-Butyl 1-oxo-7-phenyl-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3c).

White solid; mp. 222-224 oC; 1H NMR (CDCl3, 400 MHz) δ 8.04 (d, J = 8.0 Hz, 1H),

7.98 (b, 1H), 7.76 (d, J = 1.6 Hz, 1H), 7.68 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 7.63 (m,

2H), 7.47 (m, 2H), 7.36 (m, 2H), 3.58 (t, J = 6.4 Hz, 2H), 1.53 (s, 9H) ppm; 13C NMR

(CDCl3, 100 MHz) δ 171.5, 165.2, 142.7, 139.9, 139.0, 137.8, 133.4, 132.7, 130.3,

128.9, 128.3, 128.0, 127.2, 127.1, 81.8, 37.6, 28.1 ppm; IR (KBr) v 3187, 1702, 1651,

1411, 1280, 1160 cm-1; HRMS (EI) (m/z): calcd for C21H21NO3 [M+] 335.1521; found

335.1523.

S4

NH

O

OtBuO3b

Me

NH

O

OtBuO

3c

Ph


tert-Butyl 7-cyano-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3d).

Yellow solid; mp. 204-205 oC; 1H NMR (CDCl3, 400 MHz) δ 8.04 (d, J = 8.0 Hz, 1H),

7.92 (d, J = 1.6 Hz, 1H), 7.71 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.43 (m, 1H), 7.20 (b,

1H), 3.56 (t, J = 7.2 Hz, 2H), 1.54 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz) δ 169.3,

163.9, 140.6, 138.4, 136.2, 133.8, 133.0, 131.2, 130.8, 117.9, 114.0, 82.8, 37.5, 28.0

ppm; IR (KBr) v 2964, 2227, 1703, 1653, 1474, 1288, 1261, 1092, 801 cm-1; HRMS

(EI) (m/z): calcd for C16H16N2O3 [M+] 284.1161; found 284.1161. tert-Butyl 1-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzo[c]azepine-5-carboxy

late (3e). White solid; mp. 210-211 oC; 1H NMR (CDCl3, 400 MHz) δ 8.07 (d, J = 8.0

Hz, 1H), 7.84 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.48 (b, 1H), 7.42 (m, 1H), 3.56 (t, J =

6.4 Hz, 2H), 1.51 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz) δ 170.3, 164.3, 140.4,

137.7, 136.9, 132.9, 131.8 (q, J = 32 Hz), 130.5, 127.0 (q, J = 4 Hz), 124.8 (q, J = 3

Hz), 123.6 (d, J = 272 Hz), 82.5, 37.5, 28.0 ppm; IR (KBr) v 3345, 2960, 1690, 1655,

1316, 1158, 1080 cm-1; HRMS (EI) (m/z): calcd for C16H16F3NO3 [M+] 327.1082;

found 327.1092.

S5

NH

O

OtBuO3d

NC

NH

O

OtBuO3e

F3C

NH

O

OtBuO3f

MeO


tert-Butyl 7-methoxy-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3f).


(d, J = 8.4 Hz, 1H), 7.27 (m, 1H), 7.01 (m, 2H), 3.86 (s, 3H), 3.52 (t, J = 6.4 Hz, 2H),


134.0, 131.6, 127.4, 114.6, 114.2, 81.7, 55.3, 37.4, 28.0 ppm; IR (KBr) v 3167, 1710,

1649, 1280, 1246, 1170 cm-1; HRMS (EI) (m/z): calcd for C16H19NO4 [M+] 289.1314;

found 289.1317. tert-Butyl 7-chloro-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3g).


(d, J = 8.4 Hz, 1H), 7.56 (d, J = 2.4 Hz, 1H), 7.42 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H),

7.34 (m, 1H), 3.53 (d, J = 7.0 Hz, 2H), 1.52 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz)

δ 170.7, 164.5, 139.9, 136.7, 136.2, 133.7, 133.1, 131.2, 129.6, 128.6, 82.2, 37.4, 28.0

ppm; IR (KBr) v 3180, 2986, 1705, 1653, 1292, 1165, 846 cm-1; HRMS (EI) (m/z):

calcd for C15H16ClNO3 [M+] 293.0819; found 293.0808.

tert-Butyl 7-bromo-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3h).


(d, J = 8.4 Hz, 1H), 7.73 (d, J = 2.0 Hz, 1H), 7.58 (dd, J = 8.4 Hz, J = 2.0 Hz, 1H),

7.35 (m, 1H), 3.54 (t, J = 6.8 Hz, 2H), 1.53 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz)

δ 170.7, 164.4, 140.0, 136.6, 133.9, 133.5, 132.6, 131.5, 131.3, 124.6, 82.2, 37.4, 28.0

S6

NH

O

OtBuO3g

Cl

NH

O

OtBuO

3h

Br


ppm; IR (KBr) v 3183, 2983, 1708, 1654, 1290, 1163 cm-1; HRMS (EI) (m/z): calcd

for C15H16BrNO3 [M+] 337.0314; found 337.0314.

tert-Butyl 7-iodo-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3i). White

solid; mp. 202-204 oC; 1H NMR (CDCl3, 400 MHz) δ 7.93 (m, 2H), 7.79 (dd, J1 = 8.4

Hz, J2 = 1.6 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.34 (m, 1H), 3.53 (t, J = 6.4 Hz, 2H),


136.5, 134.1, 133.8, 131.1, 96.7, 82.2, 37.4, 28.0 ppm; IR (KBr) v 3180, 2924, 1699,

1652, 1578, 1280, 1158 cm-1; HRMS (EI) (m/z): calcd for C15H16INO3 [M+] 385.0175;

found 385.0174. tert-Butyl 7-nitro-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3j).

White solid; mp. 202-203 oC; 1H NMR (CDCl3, 400 MHz) δ 8.49 (d, J = 2.4 Hz, 1H),

8.26 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.54 (b, 1H), 7.48 (m,

1H), 3.59 (t, J = 6.8 Hz, 2H), 1.54 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz) δ 169.3,

163.8, 148.3, 140.9, 139.8, 136.4, 133.6, 131.4, 125.1, 122.7, 82.9, 37.5, 28.0 ppm; IR

(KBr) v 3201, 2925, 1710, 1665, 1524, 1346, 1279, 1155 cm-1; HRMS (EI) (m/z):

calcd for C15H16N2O3 [M+] 304.1059; found 304.1056.

S7

NH

O

OtBuO3i

I

NH

O

OtBu3j

O2N

O


tert-Butyl 8-methyl-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3k).

Yellow solid; mp. 198-200 oC; 1H NMR (CDCl3, 400 MHz) δ 7.67 (m, 2H), 7.40 (d, J

= 8.0 Hz, 1H), 7.31 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 7.22 (m, 1H), 3.51 (t, J = 6.4

Hz, 2H), 2.42 (s, 3H), 1.50 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz) δ 171.4, 165.4,

138.5, 138.0, 137.7, 134.5, 131.0, 130.0, 129.6, 129.5, 81.7, 37.6, 28.0, 21.1 ppm; IR

(KBr) v 2964, 2925, 1706, 1649, 1262, 1095, 802 cm-1; HRMS (EI) (m/z): calcd for

C16H19NO3 [M+] 273.1365; found 273.1366. tert-Butyl 8-methyl-7-nitro-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(3l). Pale yellow solid; mp. 214-215 oC; 1H NMR (CDCl3, 400 MHz) δ 8.22 (s, 1H),

7.93 (s, 1H), 7.41 (m, 1H), 7.23 (b, 1H), 3.58 (t, J = 6.4 Hz, 2H), 2.66 (s, 3H), 1.53 (s,

9H) ppm; 13C NMR (CDCl3, 100 MHz) δ 169.5, 164.0, 149.6, 140.2, 138.2, 136.3,

134.2, 133.2, 131.2, 126.2, 82.8, 37.5, 28.0, 20.0 ppm; IR (KBr) v 2960, 1710, 1661,

1520, 1342, 1157 cm-1; HRMS (EI) (m/z): calcd for C16H18N2O5 [M+] 318.1216;

found 318.1211.

tert-Butyl 6,8-dichloro-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (3m).

White solid; mp. 151-153 oC; 1H NMR (CDCl3, 400 MHz) δ 7.86 (d, J = 2.0 Hz

S8

NH

O

OtBuO

Me

3k

NH

O

OtBuO

3l

O2N

Me

NH

O

3m

Cl

ClO OtBu


, 1H), 7.57 (d, J = 2.4 Hz, 1H), 7.32 (b, 1H), 7.27 (m, 1H), 3.55 (m, 2H), 1.47 (s, 9H)

ppm; 13C NMR (CDCl3, 100 MHz) δ 168.8, 164.2, 139.5, 137.7, 136.9, 135.1, 134.8,

131.8, 130.3, 128.3, 82.3, 37.6, 27.8 ppm; IR (KBr) v 3425, 2978, 1719, 1656, 1285,

1159 cm-1; HRMS (EI) (m/z): calcd for C15H15Cl2N2O3 [M+] 327.0429; found

327.0429. tert-Butyl 6-oxo-7,8-dihydro-6H-[1,3]dioxolo[4',5':3,4]benzo[1,2-c]azepine-10-

carboxylate (3n). White solid; mp. 203-205 oC; 1H NMR (CDCl3, 400 MHz) δ 7.75

(b, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.17 (m, 1H), 6.93 (d, J = 8.4 Hz, 1H), 6.05 (s, 2H),

3.56 (t, J = 6.8 Hz, 2H), 1.47 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz) δ 170.7,

164.7, 149.1, 144.6, 138.9, 134.8, 128.2, 124.9, 115.8, 108.9, 101.6, 81.6, 37.6, 27.9

ppm; IR (KBr) v 2975, 2925, 1715, 1654, 1445, 1282, 1251, 1160 cm-1; HRMS (EI)

(m/z): calcd for C16H17NO5 [M+] 303.1107; found 303.1108. tert-Butyl 1-oxo-2,3-dihydro-1H-naphtho[1,2-c]azepine-5-carboxylate (3o).


7.88 (m, 2H), 7.57 (m, 3H), 7.42 (m, 1H), 7.34 (b, 1H), 3.54 (m, 2H), 1.53 (s, 9H)

ppm; 13C NMR (CDCl3, 100 MHz) δ 170.2, 165.1, 140.1, 138.5, 133.1, 131.7, 130.8,

130.6, 129.3, 127.9, 127.3, 127.1, 127.0, 125.8, 82.0, 37.9, 28.1 ppm; IR (KBr) v

2974, 2926, 1710, 1654, 1276, 1162, 1086 cm-1; HRMS (EI) (m/z): calcd for

C19H19NO3 [M+] 309.1365; found 309.1366.

S9

NH

O

3nO OtBu

OO

NH

O

OtBuO

3o


Methyl 1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (4a). White solid;

mp. 172-174 oC; 1H NMR (CDCl3, 500 MHz) δ 7.96 (m, 1H), 7.75 (b, 1H), 7.49 (m,

3H), 7.39 (m, 1H), 3.82 (s, 3H), 3.54 (m, 2H) ppm; 13C NMR (CDCl3, 125 MHz) δ

171.2, 166.5, 139.9, 136.3, 134.7, 131.8, 130.2, 129.8, 129.4, 128.6, 52.4, 37.5 ppm;

IR (KBr) v 3186, 3071, 1715, 1659, 1264, 1245, 788 cm-1; HRMS (EI) (m/z): calcd

for C12H11NO3 [M+] 217.0739; found 217.0741. 3-Bromopropyl 1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (4b). White

solid; mp. 95-97 oC; 1H NMR (CDCl3, 400 MHz) δ 8.10 (b, 1H), 7.96 (d, J = 7.6 Hz,

1H), 7.50 (m, 3H), 7.38 (m, 1H), 4.37 (t, J = 8.4 Hz, 2H), 3.55 (t, J = 6.4 Hz, 2H),

3.43 (t, J = 6.4 Hz, 2H), 3.21 (m, 2H) ppm; 13C NMR (CDCl3, 100 MHz) δ 171.4,

165.8, 140.2, 136.2, 134.7, 131.7, 130.1, 129.8, 129.3, 128.7, 63.0, 37.5, 31.3, 29.3

ppm; IR (KBr) v 3177, 1716, 1649, 1241, 783 cm-1; HRMS (EI) (m/z): calcd for

C14H14BrNO3 [M+] 323.0157; found 323.0150. 3-Bromopropyl 1-oxo-7-phenyl-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

S10

NH

O

OMeO4a

NH

O

OOBr

3

4b

NH

O

OOBr

3

Ph

4c


(4c). White solid; mp. 173-174 oC; 1H NMR (CDCl3, 400 MHz) δ 8.05 (d, J = 8.0 Hz,

1H), 7.80 (b, 1H), 7.73 (m, 2H), 7.63 (m, 2H), 7.43 (m, 4H), 4.40 (t, J = 6.0 Hz, 2H),

3.62 (t, J = 6.8 Hz, 2H), 3.42 (t, J = 6.4 Hz, 2H), 3.22 (m, 2H) ppm; 13C NMR (CDCl3,

100 MHz) δ 171.2, 165.8, 143.0, 140.3, 139.6, 136.2, 133.4, 132.1, 130.5, 128.9,

128.1, 128.0, 127.3, 63.1, 37.6, 31.5, 29.3 ppm; IR (KBr) v 2962, 1717, 1648, 1418,

1263, 1094, 1025 cm-1; HRMS (EI) (m/z): calcd for C20H18BrNO3 [M+] 399.0470;

found 399.0464. 3-Bromopropyl 1-oxo-2,3-dihydro-1H-naphtho[1,2-c]azepine-5-carboxylate (4d).


7.89 (m, 3H), 7.59 (m, 2H), 7.51 (m, 2H), 4.40 (m, 2H), 3.63 (m, 1H), 3.47 (m, 3H),

2.22 (m, 2H) ppm; 13C NMR (CDCl3, 100 MHz) δ 170.3, 165.8, 141.7, 136.6, 133.1,

131.8, 130.5, 130.1, 129.5, 128.0, 127.5, 127.11, 127.08, 125.5, 63.0, 37.8, 31.3, 29.4

ppm; IR (KBr) v 2963, 1718, 1652, 1262, 1237, 1088 cm-1; HRMS (EI) (m/z): calcd

for C18H16BrNO3 [M+] 373.0314; found 373.0318.

Ethyl 4-methyl-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (4e).

White solid; mp. 159-161 oC; 1H NMR (CDCl3, 400 MHz) δ 7.97 (m, 2H), 7.44 (m,

2H), 7.28 (m, 1H), 4.26 (q, J = 7.2 Hz, 2H), 3.49 (d, J = 6.0 Hz, 2H), 2.21 (s, 3H),

1.26 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 171.1, 168.2, 144.7,

134.0, 133.8, 132.0, 130.4, 129.9, 127.9, 127.7, 61.1, 44.8, 21.1, 14.1 ppm; IR (KBr)

S11

NH

O

OO4d

Br3

NH

O

OEt

MeO

4e


v 3177, 1713, 1655, 1475, 1097, 817 cm-1; HRMS (EI) (m/z): calcd for C14H15NO3

[M+] 245.1052; found 245.1049.

Ethyl 4-methyl-1-oxo-7-(trifluoromethyl)-2,3-dihydro-1H-benzo[c]azepine-5-

carboxylate (4f). White solid; mp. 126-128 oC; 1H NMR (CDCl3, 400 MHz) δ 8.23

(b, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.57 (b, 1H), 4.27 (q, J =

7.2 Hz, 2H), 3.50 (d, J = 6.0 Hz, 2H), 2.27 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H) ppm; 13C

NMR (CDCl3, 100 MHz) δ 169.9, 167.2, 147.7, 136.8, 134.8, 132.2 (q, J = 32 Hz),

130.8, 130.6, 125.2 (q, J = 4 Hz), 124.4 (q, J = 4 Hz), 123.4 (d, J = 271 Hz), 61.4,

45.1, 21.3, 14.0 ppm; IR (KBr) v 3335, 1725, 1625, 1334, 1304, 1220, 1131, 1083

cm-1; HRMS (EI) (m/z): calcd for C15H14F3NO3 [M+] 313.0926; found 313.0930.

Ethyl 7-methoxy-4-methyl-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4g). White solid; mp. 129-131 oC; 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, J = 8.8 Hz,

1H), 7.64 (b, 1H), 6.95 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 6.95 (d, J = 2.4 Hz, 1H),

4.25 (q, J = 7.2 Hz, 2H), 3.82 (s, 3H), 3.48 (d, J = 6.4 Hz, 2H), 2.17 (s, 3H), 1.27 (t, J

= 7.2 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 170.8, 168.2, 160.9, 144.1, 135.7,

132.04, 131.98, 126.5, 114.2, 112.2, 61.1, 55.4, 44.8, 21.1, 14.1 ppm; IR (KBr) v 3171,

2919, 1726, 1650, 1296, 1229 cm-1; HRMS (EI) (m/z): calcd for C15H17NO4 [M+]

275.1158; found 275.1153.

S12

NH

O

OEt

MeO

F3C

4f

NH

O

OEt

MeO

MeO

4g


Ethyl 7-iodo-4-methyl-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4h). White solid; mp. 178-180 oC; 1H NMR (CDCl3, 400 MHz) δ 8.15 (b, 1H), 7.73

(dd, J1 = 8.0 Hz, J2= 1.6 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 4.27 (q, J = 7.2 Hz, 2H),

3.46 (d, J = 6.4 Hz, 2H), 2.20 (s, 3H), 1.27 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3,

100 MHz) δ 170.5, 167.5, 146.5, 136.9, 136.8, 135.6, 133.2, 131.3, 130.6, 97.2, 61.3,

44.8, 21.2, 14.1 ppm; IR (KBr) v 3283, 1717, 1620, 1222, 1045 cm-1; HRMS (EI)

(m/z): calcd for C14H14INO3 [M+] 371.0018; found 371.0020.

Ethyl 4,8-dimethyl-7-nitro-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4i). Pale yellow solid; mp. 192-194 oC; 1H NMR (CDCl3, 400 MHz) δ 7.94 (s, 1H),

7.93 (s, 1H), 7.77 (b, 1H), 4.29 (q, J = 7.2 Hz, 2H), 3.52 (d, J = 6.4 Hz, 2H), 2.64 (s,

3H), 2.28 (s, 3H), 1.29 (t, J = 6.8 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 169.1,

166.9, 149.8, 147.7, 137.3, 134.4, 133.1, 132.8, 130.3, 124.5, 61.6, 45.2, 21.4, 19.9,

14.1 ppm; IR (KBr) v 2925, 1724, 1667, 1519, 1343, 1215, 1066 cm-1; HRMS (EI)

(m/z): calcd for C15H16N2O3 [M+] 304.1059; found 304.1059.

S13

NH

O

OEt

MeO

I

4h

4i

NH

O

OEt

MeO

O2N

Me

NH

O

Me

4j

Cl

ClOEtO


Ethyl 6,8-dichloro-4-methyl-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carbo

xylate (4j). Pale yellow solid; mp. 198-200 oC; 1H NMR (CDCl3, 400 MHz) δ 8.51

(b, 1H), 7.80 (d, J = 2.0 Hz, 1H), 7.51 (d, J = 2.0 Hz, 1H), 4.15 (m, 2H), 3.57 (m, 1H),

3.37 (m, 1H), 2.37 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz)

δ 169.1, 165.9, 151.8, 137.3, 134.8, 134.4, 132.4, 131.6, 127.9, 127.8, 61.2, 46.1, 20.5,

13.8 ppm; IR (KBr) v 3334, 1725, 1623, 1228, 1092, 812 cm-1; HRMS (EI) (m/z):

calcd for C14H13Cl2NO3 [M+] 313.0272; found 313.0276.

Ethyl 1-oxo-4-phenyl-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (4k). White

solid; mp. 205-207 oC; 1H NMR (CDCl3, 400 MHz) δ 8.02 (d, J = 7.6 Hz, 1H), 7.64

(b, 1H), 7.49 (m, 3H), 7.35 (m, 5H), 4.02 (q, J = 6.8 Hz, 2H), 3.87 (d, J = 6.4 Hz, 2H),


139.4, 134.0, 133.9, 133.5, 130.8, 130.4, 128.6, 128.5, 128.4, 127.7, 127.3, 61.2, 45.0,


calcd for C19H17NO3 [M+] 307.1208; found 307.1211.

Ethyl 7-methyl-1-oxo-4-phenyl-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4l). White solid; mp. 200-202 oC; 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, J = 8.4 Hz,

1H), 7.33 (m, 8H), 4.02 (q, J = 7.2 Hz, 2H), 3.85 (d, J = 6.4 Hz, 2H), 2.41 (s, 3H),


141.2, 139.5, 134.0, 133.4, 131.3, 130.5, 129.6, 129.5, 128.3, 128.0, 127.3, 61.2, 45.0,

S14

NH

O

OEt

PhO

4k

NH

O

OEt

PhO

Me

4l


21.5, 13.6 ppm; IR (KBr) v 3177, 2924, 1719, 1659, 1227, 1084, 1022 cm-1; HRMS

(EI) (m/z): calcd for C20H19NO3 [M+] 321.1365; found 321.1367.

Ethyl 7-cyano-1-oxo-4-phenyl-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4m). White solid; mp. 188-190 oC; 1H NMR (CDCl3, 400 MHz) δ 8.10 (d, J = 9.4 Hz,

1H), 7.90 (d, J = 1.6 Hz, 1H), 7.79 (b, 1H), 7.71 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.40

(m, 3H), 7.33 (m, 2H), 4.03 (q, J = 7.2 Hz, 2H), 3.88 (d, J = 6.4 Hz, 2H), 0.92 (t, J =

6.8 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 168.9, 167.6, 147.4, 138.9, 137.6,

134.4, 131.8, 131.32, 131.25, 128.9, 128.7, 127.2, 117.7, 114.8, 61.7, 44.9, 13.5 ppm;

IR (KBr) v 3315, 2958, 2925, 2230, 1716, 1661, 1623, 1461, 1264, 1088, 1029 cm-1;

HRMS (EI) (m/z): calcd for C20H16N2O3 [M+] 332.1161; found 332.1161.

Ethyl 7-methoxy-1-oxo-4-phenyl-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4n). White solid; mp. 181-183 oC; 1H NMR (CDCl3, 400 MHz) δ 7.99 (d, J = 8.4 Hz,

1H), 7.38 (m, 6H), 7.01 (m, 2H), 4.01 (q, J = 7.2 Hz, 2H), 3.86 (m, 5H), 0.95 (t, J =


135.1, 133.7, 132.5, 128.5, 128.4, 127.3, 126.7, 114.8, 112.3, 61.2, 55.4, 45.0, 13.6

ppm; IR (KBr) v 3173, 1720, 1656, 1604, 1294, 1239, 1041, 771 cm-1; HRMS (EI)

(m/z): calcd for C20H19NO4 [M+] 337.1314; found 337.1310.

S15

NH

O

OEt

PhO

NC

4m

NH

O

OEt

PhO

MeO

4n


Ethyl 7-chloro-1-oxo-4-phenyl-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4o). Pale red solid; mp. 168-170 oC; 1H NMR (CDCl3, 400 MHz) δ 7.96 (d, J = 8.4

Hz, 1H), 7.59 (b, 1H), 7.54 (d, J = 1.6 Hz, 1H), 7.43 (dd, J = 8.8 Hz, J = 2.0 Hz, 1H),

7.35 (m, 5H), 4.03 (q, J = 7.2 Hz, 2H), 3.86 (d, J = 6.4 Hz, 2H), 0.94 (t, J = 6.8 Hz,


132.7, 132.4, 132.0, 128.8, 128.6, 127.6, 1273, 61.5, 44.9, 13.5 ppm; IR (KBr) v 3178,

3062, 1722, 1662, 1588, 1452, 1201, 1024 cm-1; HRMS (EI) (m/z): calcd for

C19H16ClNO3 [M+] 341.0819; found 341.0820.

Ethyl 8-methyl-1-oxo-4-phenyl-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4p). Pale yellow solid; mp. 177-179 oC; 1H NMR (CDCl3, 400 MHz) δ 7.84 (s, 1H),

7.34 (m, 7H), 7.11 (b, 1H), 4.02 (q, J = 6.8 Hz, 2H), 3.86 (d, J = 6.4 Hz, 2H), 2.44 (s,

3H), 0.95 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 170.4, 168.6, 143.8,

139.5, 138.9, 134.0, 133.7, 131.8, 130.8, 128.6, 128.3, 127.8, 127.3, 61.2, 45.0, 21.2,


calcd for C20H19NO3 [M+] 321.1365; found 321.1361.

S16

NH

O

OEt

PhO

Cl

4o

4p

NH

O

OEt

PhO

Me

NH

O

OEtO

Br4q


Ethyl 4-(4-bromophenyl)-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4q). White solid; mp. 177-179 oC; 1H NMR (CDCl3, 400 MHz) δ 8.02 (dd, J1= 7.2

Hz, J2 = 1.2 Hz, 1H), 7.49 (m, 5H), 7.32 (b, 1H), 7.22 (d, J = 8.4 Hz, 2H), 4.05 (q, J =

7.2 Hz, 2H), 4.83 (d, J = 6.4 Hz, 2H), 1.01 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3,

100 MHz) δ 170.3, 168.1, 143.4, 138.2, 134.5, 133.9, 133.2, 131.8, 131.0, 130.5,

129.0, 128.9, 127.7, 122.7, 61.5, 44.8, 13.7 ppm; IR (KBr) v 2930, 1721, 1657, 1462,

1261, 1205, 800 cm-1; HRMS (EI) (m/z): calcd for C19H16BrNO3 [M+] 385.0314;

found 385.0318.

Ethyl 4-(4-bromophenyl)-7-chloro-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-

carboxylate (4r). White solid; mp. 228-230 oC; 1H NMR (CDCl3, 400 MHz) δ 7.96

(d, J = 8.4 Hz, 1H), 7.52 (m, 3H), 7.45 (dd, J1= 8.4 Hz, J2= 1.6 Hz, 1H), 7.42 (b, 1H),

7.20 (d, J = 8.4 Hz, 2H), 4.06 (q, J = 7.2 Hz, 2H), 3.83 (d, J = 6.4 Hz, 2H), 1.01 (t, J =


134.7, 133.3, 132.3, 132.1, 131.9, 129.1, 128.9, 127.7, 122.9, 61.7, 44.8, 13.6 ppm; IR

(KBr) v 2960, 2925, 1720, 1656, 1461, 1261, 1082, 1024 cm-1; HRMS (EI) (m/z):

calcd for C19H15BrClNO3 [M+] 418.9924; found 418.9917.

S17

NH

O

OEtO

O

4s

NH

O

OEtO

Br4r

Cl


Ethyl 4-(furan-2-yl)-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate (4s).

Red solid; mp. 78-80 oC; 1H NMR (CDCl3, 400 MHz) δ 8.01 (d, J = 7.2 Hz, 1H), 7.78

(b, 1H), 7.47 (m, 4H), 6.65 (d, J = 3.2 Hz, 1H), 6.46 (m, 1H), 4.32 (q, J = 6.8 Hz, 2H),

3.87 (m, 2H), 1.27 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 170.7,

168.7, 150.2, 144.0, 133.8, 133.3, 131.0, 130.7, 129.9, 129.7, 128.6, 127.1, 112.0,

111.4, 61.7, 40.8, 14.0 ppm; IR (KBr) v 1722, 1655, 1259, 1234, 1203, 1025 cm-1;

HRMS (EI) (m/z): calcd for C17H15NO4 [M+] 297.1001; found 297.1002.

Ethyl 4-(furan-2-yl)-7-methyl-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carbo

xylate (4t). Red solid; mp. 83-85 oC; 1H NMR (CDCl3, 400 MHz) δ 7.91 (d, J = 8.0

Hz, 1H), 7.67 (b, 1H), 7.45 (d, J = 1.2 Hz, 1H), 7.27 (m, 2H), 6.63 (d, J = 3.6 Hz, 1H),

6.45 (m, 1H), 4.32 (q, J = 7.2 Hz, 2H), 3.86 (m, 2H), 2.39 (s, 3H), 1.28 (t, J = 6.8 Hz,


131.1, 130.8, 129.8, 129.63, 129.56, 127.4, 112.0, 111.3, 61.6, 40.9, 21.5, 14.0 ppm;

IR (KBr) v 3396, 1721, 1654, 1235, 1026 cm-1; HRMS (EI) (m/z): calcd for

C18H17NO4 [M+] 311.1158; found 311.1153.

Ethyl 4-(furan-2-yl)-7-iodo-1-oxo-2,3-dihydro-1H-benzo[c]azepine-5-carboxylate

(4u). Red solid; mp. 88-90 oC; 1H NMR (CDCl3, 400 MHz) δ 7.87 (d, J = 1.6 Hz, 1H),

7.78 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.63 (b, 1H), 7.46 (d, J

= 1.6 Hz, 1H), 6.66 (d, J = 3.2 Hz, 1H), 6.48 (m, 1H), 4.34 (q, J = 7.2 Hz, 2H),

S18

NH

O

OEtO

O

Me

4t

NH

O

OEtO

O

I

4u


3.87 (m, 2H), 1.29 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ 170.0,

168.2, 149.9, 144.3, 137.6, 135.9, 134.9, 133.1, 132.1, 130.9, 128.2, 112.2, 112.0,

98.0, 61.9, 40.8, 14.0 ppm; IR (KBr) v 3404, 1721, 1655, 1578, 1251, 1022, 742 cm-1;

HRMS (EI) (m/z): calcd for C17H14INO4 [M+] 422.9968; found 422.9966.

Ethyl 6-oxo-9-(thiophen-2-yl)-7,8-dihydro-6H-[1,3]dioxolo[4',5':3,4]benzo[1,2-c]

azepine-10-carboxylate (4v). White solid; mp. 220-222 oC; 1H NMR (CDCl3, 400

MHz) δ 7.62 (d, J = 8.4 Hz, 1H), 7.41 (dd, J1 = 4.2 Hz, J2 = 1.2 Hz, 1H), 7.15 (m, 1H),

7.04 (m, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.81 (b, 1H), 6.04 (s, 2H), 4.14 (q, J = 6.8 Hz,

2H), 3.95 (m, 2H), 1.12 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3, 100 MHz) δ

169.4, 167.3, 149.3, 145.0, 139.9, 138.8, 128.5, 128.2, 127.8, 127.6, 127.4, 125.7,

116.9, 109.1, 102.0, 61.4, 46.7, 13.7 ppm; IR (KBr) v 2923, 1720, 1652, 1442, 1247,

1035 cm-1; HRMS (EI) (m/z): calcd for C18H15NO5S [M+] 357.0671; found 357.0668.

7-Iodo-5-pentanoyl-2,3-dihydro-1H-benzo[c]azepin-1-one (4w). White solid; mp.

167-169 oC; 1H NMR (CDCl3, 400 MHz) δ 7.81 (dd, J1= 8.4 Hz, J2 = 1.6 Hz, 1H),

7.68 (m, 2H), 7.26 (b, 1H), 7.13 (m, 1H), 3.57 (t, J = 6.8 Hz, 2H), 2.71 (t, J = 7.2 Hz,

2H), 1.63 (m, 2H), 1.36 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (CDCl3, 100

MHz) δ 200.7, 170.3, 143.7, 138.1, 137.8, 134.1, 133.5, 131.5, 97.1, 39.4, 37.6, 26.4,

22.3, 13.9 ppm; IR (KBr) v 2956, 2926, 1654, 1578, 1147, 1079 cm-1; HRMS (EI)

(m/z): calcd for C15H16INO2 [M+] 369.0226; found 369.0222.

S19

4v

NH

O

OO

O OEt S

NH

O

BuO

I

4w


Synthesis of Pyrazole 5:

When styryldiazoacetate 2j was subject to the standard reaction condition, pyrazole 5

was obtained exclusively in 83% yield.

methyl 5-phenyl-1H-pyrazole-3-carboxylate (5). Yellow solid; mp. 183-185 oC; 1H

NMR (CDCl3, 500 MHz) δ 12.0 (b, 1H), 7.73 (t, J = 7.5 Hz, 2H), 7.42 (t, J = 7.0 Hz,

2H), 7.35 (t, J = 7.0 Hz, 1H), 7.08 (s, 1H), 3.87 (s, 3H) ppm; 13C NMR (CDCl3, 100

MHz) δ 161.1, 149.4, 130.6, 128.9, 128.4, 125.7, 105.6, 52.2 ppm; HRMS (ESI) (m/z):

calcd for C11H10N2O2 [M+H] + 203.0821; found 203.0813.

Derivation of Product 3m to 6 and 7:

Azepinone 3m (0.12 mmol, 40 mg) was added to Schlenk tube, vacuumed and refilled

with argon for three times. Anhydrous DCM (2 mL) was added and the solution was

stirred for 10 mins at RT. Then the reaction solution was cooled -78 oC, and DIBAL-H

(0.24 mL, 1.5 M in toluene) was added. The reaction solution was stirred for 20 mins

and poured into aqueous solution of Rochelle’s salt (2 mL). The organic layer was

separated and the aqueous layer was extracted with DCM. The combined organic

S20

NH

O

3m

Cl

ClO OtBu

DIBAL-H

DCM-78 oC

NH

OCl

ClO OtBu

6

82%

CsOAc ( 1 equiv)

CH3CN, RT2j 5, 83%

CO2CH3

N2

PhHN N

PhCO2CH3

[Cp*RhCl2]2 (2 mol%)

5

HN N

PhCO2CH3


layer was washed with brine, dried over MgSO4. The solvent was removed by rotary

evaporation. The residue was subject to flash chromatography on silica gel using ethyl

acetate/petroleum ether (v/v, 1:2) as eluent to give product 6 (33 mg, 82%) as a white

solid.

tert-Butyl 6,8-dichloro-1-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepine-5-carbo

xylate (6). White solid; mp. 150-151 oC; 1H NMR (CDCl3, 400 MHz) δ 7.65 (d, J =

2.0 Hz, 1H), 7.54 (d, J = 2.4 Hz, 1H), 6.54 (b, 1H), 4.52 (d, J = 7.6 Hz, 1H), 3.24 (m,

1H), 2.97 (m, 2H), 1.97 (m, 1H), 1.33 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz) δ

171.0, 170.4, 138.0, 134.6, 133.9, 132.5, 131.4, 128.2, 82.4, 43.8, 38.9, 31.8, 27.9

ppm; IR (KBr) v 2925, 1730, 1672, 1251, 1153 cm-1; HRMS (EI) (m/z): calcd for

C15H17Cl2NO3 [M+] 329.0585; found 329.0577.

Azepinone 3m (0.2 mmol, 65.6 mg) was added to flask, DCM (10 mL) was added and

the solution was stirred for 5 min, aqueous NaHCO3 solution (0.5 M, 10 mL) was

added afterward. m-CPBA (69 mg, 0.4 mmol) was added to the biphasic solution and

the solution was kept at RT for 24 h. Then the mixture was poured into separatory

funnel, the organic layer was separated and the aqueous layer was extracted with

DCM. The combined organic layer was washed with NaHCO3 solution, brine, dried

over MgSO4. The solvent was removed by rotary evaporation. The residue was

subject to flash chromatography on silica gel using ethyl acetate/petroleum ether (v/v,

1:1) as eluent to give product 7 (65 mg, 95%) as white solid.

S21

NH

OCl

ClO OtBu

6

NH

O

3m

Cl

ClO OtBu

m-CPBANaHCO3

DCM

NH

OCl

ClO OtBu

O

795%


tert-Butyl 6,8-dichloro-4-oxo-2,3,4,8b-tetrahydro-1aH-benzo[c]oxireno[2,3-e]

azepine-8b-carboxylate (7). White solid; mp. 69-71 oC; 1H NMR (CDCl3, 400

MHz) δ 7.73 (d, J = 2.0 Hz, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.47 (b, 1H), 3.94 (m, 1H),

3.83 (m, 1H), 2.91 (m, 1H), 1.38 (s, 9H) ppm; 13C NMR (CDCl3, 100 MHz) δ 169.0,

166.2, 137.6, 136.3, 135.5, 132.1, 128.9, 128.7, 83.9, 61.4, 57.6, 43.4, 27.6 ppm; IR

(KBr) v 2980, 1735, 1666, 1370, 1163 cm-1; HRMS (EI) (m/z): calcd for

C15H15Cl2NO4 [M+] 343.0378; found 343.0379.

Kinetic Isotope Effect Study

[D4]-3a was prepared according to general procedure in 70% yield.

White solid; mp. 203-205 oC; 1H NMR (CDCl3, 400 MHz) δ 7.28 (m, 1H), 6.96 (b,

1H), 3.53 (m, 2H), 1.51 (s, 9H) ppm; 13C NMR (CDCl3, 125 MHz) δ 171.1, 165.2,

138.4, 138.1, 134.5, 132.1, 81.9, 37.6, 28.0 ppm; IR (KBr) v 2924, 2853, 1713, 1656,

1461, 1274, 1148 cm-1; HRMS (EI) (m/z): calcd for C15H13D4NO3 [M+] 263.1460;

found 263.1460.

S22

NH

O

OtBuO[D4]-3a

D4

NHOPiv

O[Cp*RhCl2]2 (2 mol%)

CsOAc (1 equiv)CH3CN, RT, 20 min[D5]-1a/1a

NH

O

OtBuO

H5/D5H4/D4

2a (1.5 equiv)

KIE = 2.8 [D4]-3a/3aparallel experiments

NH

OCl

ClO OtBu

O

7


Following general procedure, [Cp*RhCl2]2 (0.6 mg, 2 mol%), benzamide 1a (22.1 mg,

0.1 mmol), CsOAc (20 mg, 0.1 mmol) were added to a vial. CH3CN (0.6 mL) was

added, followed by micro-syringe addition of vinyldiazoacetate 2a (25.2 mg, 0.15

mmol). The micro-syringe was washed with an additional 0.15 mL CH3CN and added

to the reaction solution. In another reaction vial, [D5]-1a (22.6 mg, 0.1 mmol, 1.0

equiv) was used instead of 1a. The two reactions were allowed to stir at RT for 20 min.

Afterwards, the reactions were quenched with water, combined and extracted with

CH2Cl2. The organic layer was washed with brine, dried over Na2SO4. The product

(15.6 mg, 30% combined yield) was isolated by flash chromatography. The value of

KH/KD was obtained based on 1HNMR.

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

9.00

1.98

0.74

1.01

1.74

1.82

1.50

5

3.50

33.

520

3.53

6

7.26

07.

280

7.29

87.

439

7.44

77.

454

7.45

87.

467

7.49

57.

499

7.50

87.

511

7.92

37.

933

7.95

2

Reference:

1 H. Wang, F. Glorius, Angew. Chem., Int. Ed., 2012, 51, 7318-7322.

2 (a) H. M. L. Davies, B. Hu, E. Saikali, P. R. Bruzinski, J. Org. Chem., 1994, 59,

4535-4541; (b) V. V. Pagar, A. M. Jdhav, R.-S. Liu, J. Am. Chem. Soc., 2011, 133,

20728-20731.

S23

NH

O

OtBuO

[D4]-3a/3a

D4/H4


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

9.00

1.98

1.07

0.98

1.96

0.95

0.95

1.50

7

3.50

23.

514

3.52

8

7.26

77.

270

7.28

17.

296

7.43

17.

435

7.44

67.

459

7.46

37.

482

7.49

87.

511

7.52

37.

940

7.95

5

8.37

5

NH

O

OtBuO3a

S24


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

9.00

1.98

1.07

0.98

1.96

0.95

0.95

1.50

7

3.50

23.

514

3.52

8

7.26

77.

270

7.28

17.

296

7.43

17.

435

7.44

67.

459

7.46

37.

482

7.49

87.

511

7.52

37.

940

7.95

5

8.37

5

NH

O

OtBuO3a

S25


3.23.64.04.44.85.25.66.06.46.87.07.27.47.67.88.28.69.09.4f1 (ppm)

1.98

1.07

0.98

1.96

0.95

0.95

3.50

23.

514

3.52

8

7.26

77.

270

7.28

17.

296

7.43

17.

435

7.44

67.

459

7.46

37.

482

7.49

87.

511

7.52

37.

940

7.95

5

8.37

5

NH

O

OtBuO3a

S26


-100102030405060708090100110120130140150160170180f1 (ppm)

27.9

5

37.4

2

76.7

577

.00

77.2

581

.70

128.

2512

9.45

129.

5612

9.83

132.

2913

4.71

137.

6313

8.87

165.

17

171.

71

NH

O

OtBuO3a

S27


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

9.00

2.96

1.94

2.05

0.96

0.96

0.91

1.52

0

2.42

2

3.49

23.

507

3.52

3

7.24

07.

258

7.27

77.

323

7.84

17.

861

8.33

0

NH

O

OtBuO3b

Me

S28


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

9.00

2.96

1.94

2.05

0.96

0.96

0.91

1.52

0

2.42

2

3.49

23.

507

3.52

3

7.24

07.

258

7.27

77.

323

7.84

17.

861

8.33

0

NH

O

OtBuO3b

Me

S29


2.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

2.96

1.94

2.05

0.96

0.96

0.91

2.42

2

3.49

23.

507

3.52

3

7.24

07.

258

7.27

77.

323

7.84

17.

861

8.33

0

NH

O

OtBuO3b

Me

S30


0102030405060708090100110120130140150160170f1 (ppm)

21.4

3

27.9

8

37.4

5

76.7

577

.00

77.2

581

.57

129.

2012

9.65

129.

8913

2.07

132.

2213

7.62

138.

6114

0.05

165.

25

NH

O

OtBuO3b

Me

S31


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

9.00

1.96

1.96

2.01

1.98

0.99

0.95

0.90

0.99

1.53

1

3.56

63.

583

3.59

9

7.26

07.

317

7.33

57.

354

7.37

07.

389

7.39

37.

407

7.44

97.

469

7.48

27.

487

7.61

97.

636

7.64

07.

670

7.67

47.

690

7.69

57.

754

7.75

87.

964

7.97

88.

025

8.04

5

NH

O

OtBuO

3c

Ph

S32


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

9.00

1.96

1.96

2.01

1.98

0.99

0.95

0.90

0.99

1.53

1

3.56

63.

583

3.59

9

7.26

07.

317

7.33

57.

354

7.37

07.

389

7.39

37.

407

7.44

97.

469

7.48

27.

487

7.61

97.

636

7.64

07.

670

7.67

47.

690

7.69

57.

754

7.75

87.

964

7.97

88.

025

8.04

5

NH

O

OtBuO

3c

Ph

S33


3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.28.48.6f1 (ppm)

1.96

1.96

2.01

1.98

0.99

0.95

0.90

0.99

3.56

63.

583

3.59

9

7.26

07.

317

7.33

57.

354

7.37

07.

389

7.39

37.

407

7.44

97.

469

7.48

27.

487

7.61

97.

636

7.64

07.

670

7.67

47.

690

7.69

57.

754

7.75

87.

964

7.97

88.

025

8.04

5

NH

O

OtBuO

3c

Ph

S34


6.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.3f1 (ppm)

1.96

2.01

1.98

0.99

0.95

0.90

0.99

7.26

0

7.31

77.

335

7.35

47.

370

7.38

97.

393

7.40

77.

449

7.46

97.

482

7.48

7

7.61

97.

636

7.64

07.

670

7.67

47.

690

7.69

5

7.75

47.

758

7.96

47.

978

8.02

58.

045

NH

O

OtBuO

3c

Ph

S35


-100102030405060708090100110120130140150160170180f1 (ppm)

28.0

8

37.5

5

76.6

877

.00

77.3

281

.82

127.

0712

7.21

127.

9612

8.27

128.

8713

0.30

132.

6913

3.43

137.

8013

8.97

139.

9214

2.68

165.

19

171.

49

NH

O

OtBuO

3c

Ph

S36


124126128130132134136138140142144146148150152154156158160162164166168170172174176f1 (ppm)

127.

0712

7.21

127.

9612

8.27

128.

87

130.

30

132.

6913

3.43

137.

8013

8.97

139.

92

142.

68

165.

19

171.

49

NH

O

OtBuO

3c

Ph

S37


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

9.00

1.92

0.91

0.97

0.96

0.99

0.93

1.53

5

3.54

53.

561

3.57

9

7.20

37.

260

7.41

17.

429

7.44

87.

699

7.70

37.

720

7.72

37.

913

7.91

78.

031

8.05

1

NH

O

OtBuO3d

NC

S38


6.46.56.66.76.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.38.4f1 (ppm)

0.91

0.97

0.96

0.99

0.93

7.20

3

7.26

0

7.41

17.

429

7.44

8

7.69

97.

703

7.72

07.

723

7.91

37.

917

8.03

18.

051

NH

O

OtBuO3d

NC

S39


-100102030405060708090100110120130140150160170180f1 (ppm)

28.0

3

37.4

7

76.6

877

.00

77.3

2

82.7

8

114.

02

117.

87

130.

7613

1.17

133.

0213

3.80

136.

2313

8.36

140.

57

163.

91

169.

34

NH

O

OtBuO3d

NC

S40


100105110115120125130135140145150155160165170175f1 (ppm)

114.

02

117.

87

130.

7613

1.17

133.

0213

3.80

136.

23

138.

36

140.

57

163.

91

169.

34

NH

O

OtBuO3d

NC

S41


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

9.00

2.02

0.99

0.95

0.97

0.95

0.98

1.51

4

3.54

63.

563

3.57

9

7.26

07.

404

7.42

27.

441

7.48

07.

687

7.70

87.

841

8.05

68.

076

NH

O

OtBuO3e

F3C

S42


3.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.2f1 (ppm)

2.02

0.99

0.95

0.97

0.95

0.98

3.54

63.

563

3.57

9

7.26

0

7.40

47.

422

7.44

17.

480

7.68

77.

708

7.84

1

8.05

68.

076

NH

O

OtBuO3e

F3C

S43


-100102030405060708090100110120130140150160170180f1 (ppm)

27.9

6

37.4

5

76.6

877

.00

77.3

2

82.5

0

122.

2012

4.75

124.

7812

4.82

124.

9212

6.89

126.

9312

6.97

127.

0113

0.45

131.

3113

1.63

131.

9613

2.28

132.

8613

6.86

137.

7014

0.37

164.

26

170.

31

NH

O

OtBuO3e

F3C

S44


100105110115120125130135140145150155160165170f1 (ppm)

122.

2012

4.78

124.

8212

4.92

126.

8912

6.93

126.

97

130.

4513

1.31

131.

6313

1.96

132.

2813

2.86

136.

8613

7.70

140.

37

164.

26

170.

31

NH

O

OtBuO3e

F3C

S45


-100102030405060708090100110120130140150160f1 (ppm)

27.9

6

37.4

6

124.

7612

4.79

124.

8212

4.85

126.

9112

6.94

126.

9712

7.00

130.

46

140.

33

NH

O

OtBuO3e

F3C

S46


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

9.00

1.93

3.01

1.92

1.08

0.95

0.94

1.51

8

3.50

73.

524

3.54

0

3.86

2

6.98

36.

989

7.00

57.

011

7.02

87.

034

7.25

07.

268

7.28

17.

286

7.90

67.

927

8.15

48.

168

8.18

2

NH

O

OtBuO3f

MeO

S47


3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.28.4f1 (ppm)

1.93

3.01

1.92

1.08

0.95

0.94

3.50

73.

524

3.54

0

3.86

2

6.98

36.

989

7.00

57.

011

7.02

87.

034

7.25

07.

268

7.28

17.

286

7.90

67.

927

8.15

48.

168

8.18

2

NH

O

OtBuO3f

MeO

S48


0102030405060708090100110120130140150160170180f1 (ppm)

28.0

0

37.4

4

55.2

9

76.7

577

.00

77.2

581

.71

114.

2011

4.57

127.

4413

1.59

133.

9913

7.52

138.

83

160.

39

165.

20

171.

53

NH

O

OtBuO3f

MeO

S49


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

9.00

1.97

0.97

1.00

0.91

0.96

0.93

1.51

6

3.50

93.

527

3.54

2

7.26

07.

322

7.34

07.

359

7.40

57.

410

7.42

67.

432

7.55

37.

559

7.87

17.

892

7.99

0

NH

O

OtBuO3g

Cl

S50


3.54.04.55.05.56.06.57.07.58.0f1 (ppm)

1.97

0.97

1.00

0.91

0.96

0.93

3.50

93.

527

3.54

2

7.26

07.

322

7.34

07.

359

7.40

57.

410

7.42

67.

432

7.55

37.

559

7.87

17.

892

7.99

0

NH

O

OtBuO3g

Cl

S51


0102030405060708090100110120130140150160170180f1 (ppm)

28.0

0

37.4

4

76.6

877

.00

77.3

2

82.2

1

128.

5912

9.59

131.

2413

3.10

133.

7413

6.21

136.

6713

9.91

164.

45

170.

70

NH

O

OtBuO3g

Cl

S52


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

9.00

1.97

0.97

1.00

0.92

0.99

0.98

1.52

7

3.51

83.

535

3.55

2

7.27

07.

332

7.35

17.

369

7.57

17.

576

7.59

27.

597

7.72

57.

730

7.80

57.

826

7.92

0

NH

O

OtBuO

3h

Br

S53


3.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.2f1 (ppm)

1.97

0.97

1.00

0.92

0.99

0.98

3.51

83.

535

3.55

2

7.27

07.

332

7.35

17.

369

7.57

67.

592

7.59

7

7.72

57.

730

7.80

57.

826

7.92

0

NH

O

OtBuO

3h

Br

S54


0102030405060708090100110120130140150160170180f1 (ppm)

28.0

1

37.4

3

76.6

877

.00

77.3

282

.23

124.

56

131.

3113

1.49

132.

5513

3.53

133.

8813

6.61

139.

98

164.

42

170.

73

NH

O

OtBuO

3h

Br

S55


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

9.00

1.95

0.97

0.96

1.00

1.88

1.52

5

3.51

33.

530

3.54

6

7.27

07.

322

7.34

17.

359

7.64

07.

661

7.77

77.

781

7.79

87.

802

7.92

07.

924

7.94

2

NH

O

OtBuO3i

I

S56


3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.28.48.6f1 (ppm)

1.95

0.97

0.96

1.00

1.88

3.51

33.

530

3.54

6

7.27

07.

322

7.34

17.

359

7.64

07.

661

7.77

77.

781

7.79

87.

802

7.92

07.

924

7.94

2

NH

O

OtBuO3i

I

S57


-100102030405060708090100110120130140150160170180f1 (ppm)

28.0

0

37.3

9

76.6

877

.00

77.3

282

.19

96.7

0

131.

1213

3.76

134.

0613

6.50

137.

3013

8.57

139.

98

164.

42

170.

91

NH

O

OtBuO3i

I

S58


130135140145150155160165170175f1 (ppm)

131.

12

133.

7613

4.06

136.

50

137.

30

138.

57

139.

98

164.

42

170.

91

NH

O

OtBuO3i

I

S59


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

9.00

1.97

0.97

0.91

0.95

0.96

0.93

1.54

0

3.57

03.

587

3.60

4

7.26

07.

459

7.47

87.

496

7.52

17.

536

7.55

08.

104

8.12

58.

248

8.25

48.

270

8.27

68.

490

8.49

6

NH

O

OtBu3j

O2N

O

S60


3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.28.48.68.8f1 (ppm)

1.97

0.97

0.91

0.95

0.96

0.93

3.57

03.

587

3.60

4

7.26

07.

459

7.47

87.

496

7.52

17.

536

7.55

0

8.10

48.

125

8.24

88.

254

8.27

08.

276

8.49

08.

496

NH

O

OtBu3j

O2N

O

S61


0102030405060708090100110120130140150160170180f1 (ppm)

28.0

2

37.4

8

76.6

877

.00

77.3

2

82.9

3

122.

6712

5.11

131.

3613

3.58

136.

4013

9.84

140.

85

148.

27

163.

82

169.

33

NH

O

OtBu3j

O2N

O

S62


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

9.00

3.10

2.04

1.05

1.09

1.00

2.06

1.50

3

2.41

8

3.49

33.

510

3.52

6

7.20

27.

220

7.23

87.

260

7.29

77.

300

7.31

77.

321

7.39

17.

411

7.75

5

NH

O

OtBuO

Me

3k

S63


3.03.54.04.55.05.56.06.57.07.5f1 (ppm)

2.04

1.05

1.09

1.00

2.06

3.49

33.

510

3.52

6

7.20

27.

220

7.23

87.

260

7.29

77.

300

7.31

77.

321

7.39

17.

411

7.75

5

NH

O

OtBuO

Me

3k

S64


-100102030405060708090100110120130140150160170180f1 (ppm)

21.1

4

28.0

3

37.6

2

76.6

877

.00

77.3

281

.73

129.

4812

9.59

130.

0113

0.95

134.

4513

7.70

138.

0113

8.53

165.

40

171.

42

NH

O

OtBuO

Me

3k

S65


128130132134136138140142144146148150152154156158160162164166168170172f1 (ppm)

129.

4812

9.59

130.

0113

0.95

134.

45

137.

7013

8.01

138.

53

165.

40

171.

42

NH

O

OtBuO

Me

3k

S66


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

9.00

3.03

2.06

1.07

1.16

0.95

0.92

1.53

2

2.65

9

3.55

93.

577

3.59

3

7.21

67.

230

7.24

57.

260

7.39

47.

413

7.43

1

7.92

8

8.21

8

NH

O

OtBuO

3l

O2N

Me

S67


2.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.28.4f1 (ppm)

3.03

2.06

1.07

1.16

0.95

0.92

2.65

9

3.55

93.

577

3.59

3

7.21

67.

230

7.24

57.

260

7.39

47.

413

7.43

1

7.92

8

8.21

8

NH

O

OtBuO

3l

O2N

Me

S68


0102030405060708090100110120130140150160170180f1 (ppm)

19.9

9

28.0

1

37.5

1

76.6

877

.00

77.3

2

82.7

5

126.

16

131.

1513

3.23

134.

2213

6.28

138.

1514

0.18

149.

58

163.

97

169.

45

NH

O

OtBuO

3l

O2N

Me

S69


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

9.00

2.08

2.47

0.89

0.88

1.46

5

3.47

33.

493

3.51

13.

526

3.56

73.

585

3.60

33.

622

7.24

77.

265

7.28

57.

318

7.56

97.

575

7.86

27.

867

NH

O

3m

Cl

ClO OtBu

S70


3.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.08

2.47

0.89

0.88

3.47

33.

493

3.51

13.

526

3.56

73.

585

3.60

33.

622

7.24

77.

265

7.28

57.

318

7.56

97.

575

7.86

27.

867

NH

O

3m

Cl

ClO OtBu

S71


0102030405060708090100110120130140150160170180f1 (ppm)

27.7

5

37.6

1

76.6

877

.00

77.3

2

82.2

9

128.

2713

0.26

131.

7513

4.82

135.

1113

6.88

137.

7013

9.50

164.

21

168.

80

NH

O

3m

Cl

ClO OtBu

S72


122124126128130132134136138140142144146148150152154156158160162164166168170172174f1 (ppm)

128.

27

130.

26

131.

75

134.

8213

5.11

136.

88

137.

70

139.

50

164.

21

168.

80

NH

O

3m

Cl

ClO OtBu

S73


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

9.00

1.97

2.13

0.95

1.00

0.98

0.92

1.47

2

3.54

63.

562

3.57

9

6.04

7

6.92

06.

941

7.15

17.

169

7.18

77.

275

7.55

67.

576

7.75

0

NH

O

3nO OtBu

OO

S74


3.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.0f1 (ppm)

1.97

2.13

0.95

1.00

0.98

0.92

3.54

63.

562

3.57

9

6.04

7

6.92

06.

941

7.15

17.

169

7.18

77.

275

7.55

67.

576

7.75

0

NH

O

3nO OtBu

OO

S75


0102030405060708090100110120130140150160170180f1 (ppm)

27.8

5

37.5

8

76.6

877

.00

77.3

281

.55

101.

62

108.

90

115.

75

124.

88

128.

24

134.

76

138.

88

144.

64

149.

09

164.

65

170.

72

NH

O

3nO OtBu

OO

S76


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)

9.00

2.00

0.95

1.01

3.03

2.07

0.93

1.53

4

3.43

63.

454

3.47

33.

491

3.50

93.

569

3.58

73.

604

3.62

43.

641

7.26

07.

324

7.34

07.

356

7.40

57.

423

7.44

07.

517

7.53

97.

554

7.55

77.

574

7.57

77.

579

7.59

67.

599

7.61

37.

616

7.85

37.

857

7.88

17.

903

8.47

68.

496

NH

O

OtBuO

3o

S77


3.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.00

0.95

1.01

3.03

2.07

0.93

3.43

63.

454

3.47

33.

491

3.50

93.

569

3.58

73.

604

3.62

43.

641

7.26

07.

324

7.34

07.

356

7.40

57.

423

7.44

07.

517

7.53

97.

554

7.55

77.

574

7.57

77.

579

7.59

67.

599

7.61

37.

616

7.85

37.

857

7.88

17.

903

8.47

68.

496

NH

O

OtBuO

3o

S78


-100102030405060708090100110120130140150160170180190f1 (ppm)

28.0

6

37.9

2

76.6

877

.00

77.3

282

.01

125.

8012

6.95

127.

0612

7.34

127.

9312

9.29

130.

5613

0.76

131.

6513

3.06

138.

4814

0.07

165.

09

170.

23

NH

O

OtBuO

3o

S79


122123124125126127128129130131132133134135136137138139140141142f1 (ppm)

125.

80

126.

9512

7.06

127.

34

127.

93

129.

29

130.

5613

0.76

131.

65

133.

06

138.

48

140.

07

NH

O

OtBuO

3o

S80


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

2.04

3.00

1.00

2.98

0.95

0.96

3.53

73.

549

3.55

13.

564

3.82

1

7.26

07.

375

7.38

97.

404

7.45

87.

467

7.47

57.

481

7.48

37.

491

7.49

97.

508

7.51

57.

516

7.52

47.

527

7.75

47.

948

7.95

07.

963

7.96

5

NH

O

OMeO4a

S81


6.76.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.3f1 (ppm)

1.00

2.98

0.95

0.96

7.26

0

7.37

57.

389

7.40

47.

458

7.46

77.

475

7.48

17.

483

7.49

17.

499

7.50

87.

515

7.51

67.

524

7.52

7

7.75

4

7.94

87.

950

7.96

37.

965

NH

O

OMeO4a

S82


0102030405060708090100110120130140150160170180190f1 (ppm)

37.5

2

52.3

7

76.7

577

.00

77.2

5

128.

6312

9.43

129.

8213

0.17

131.

7913

4.70

136.

2613

9.93

166.

50

171.

21

NH

O

OMeO4a

S83


125130135140145150155160165170f1 (ppm)

128.

6312

9.43

129.

8213

0.17

131.

79

134.

70

136.

26

139.

93

166.

50

171.

21

NH

O

OMeO4a

S84


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

2.00

2.04

2.23

2.11

1.08

3.24

2.18

2.17

62.

192

2.20

72.

223

2.23

8

3.41

33.

429

3.44

53.

535

3.55

13.

567

4.35

04.

365

4.37

9

7.26

07.

363

7.38

17.

399

7.47

57.

494

7.50

87.

523

7.94

97.

968

8.09

9

NH

O

OOBr

3

4b

S85


-100102030405060708090100110120130140150160170180190f1 (ppm)

29.3

331

.33

37.4

7

62.9

9

76.6

877

.00

77.3

2

128.

6912

9.33

129.

8013

0.11

131.

7313

4.71

136.

1714

0.15

165.

83

171.

35

NH

O

OOBr

3

4b

S86


126128130132134136138140142144146148150152154156158160162164166168170172f1 (ppm)

128.

6912

9.33

129.

8013

0.11

131.

73

134.

71

136.

17

140.

15

165.

83

171.

35

NH

O

OOBr

3

4b

S87


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

1.93

1.94

2.07

2.00

4.12

2.05

2.04

0.99

1.01

2.19

32.

209

2.22

42.

240

2.25

5

3.39

93.

415

3.43

13.

603

3.62

03.

637

4.38

24.

397

4.41

2

7.26

07.

376

7.39

47.

412

7.42

27.

440

7.45

17.

459

7.47

07.

488

7.61

97.

637

7.64

07.

701

7.70

67.

722

7.72

67.

748

7.75

27.

783

7.79

77.

812

8.04

18.

061

NH

O

OOBr

3

Ph

4c

S88


6.56.66.76.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.38.4f1 (ppm)

4.12

2.05

2.04

0.99

1.01

7.26

0

7.37

67.

394

7.41

27.

422

7.44

07.

451

7.45

97.

470

7.48

8

7.61

97.

637

7.64

07.

701

7.70

67.

722

7.72

67.

748

7.75

27.

783

7.79

77.

812

8.04

18.

061

NH

O

OOBr

3

Ph

4c

S89


-100102030405060708090100110120130140150160170180190f1 (ppm)

29.2

531

.45

37.5

7

63.1

1

76.6

877

.00

77.3

2

127.

2812

7.39

128.

1112

8.93

130.

5013

2.11

133.

4013

6.19

139.

6314

0.29

143.

01

165.

81

171.

15

NH

O

OOBr

3

Ph

4c

S90


122124126128130132134136138140142144146148150152154156158160162164166168170172174f1 (ppm)

127.

2812

7.39

128.

1112

8.93

130.

50

132.

11

133.

40

136.

19

139.

6314

0.29

143.

01

165.

81

171.

15

NH

O

OOBr

3

Ph

4c

S91


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

1.68

2.78

1.12

2.00

1.93

2.16

3.19

0.98

2.16

22.

183

2.19

92.

215

2.23

02.

245

3.42

23.

427

3.43

93.

442

3.45

53.

472

3.49

13.

508

3.59

23.

609

3.62

6

4.35

04.

364

4.37

84.

392

4.40

14.

407

4.41

74.

432

4.44

5

7.26

07.

489

7.50

57.

514

7.52

67.

550

7.55

37.

567

7.57

07.

586

7.59

07.

608

7.61

27.

625

7.62

97.

863

7.86

67.

885

7.90

37.

924

8.49

38.

513

NH

O

OO4d

Br

3

S92


6.66.76.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.38.48.58.68.78.8f1 (ppm)

1.93

2.16

3.19

0.98

7.26

0

7.48

97.

505

7.51

47.

526

7.55

07.

553

7.56

77.

570

7.58

67.

590

7.60

87.

612

7.62

57.

629

7.86

37.

866

7.88

57.

903

7.92

4

8.49

38.

513

NH

O

OO4d

Br

3

S93


0102030405060708090100110120130140150160170180190f1 (ppm)

29.4

431

.27

37.8

2

63.0

4

76.6

877

.00

77.3

2

125.

4812

7.08

127.

1112

7.46

127.

9712

9.51

130.

1313

0.52

131.

8413

3.14

136.

6214

1.66

165.

77

170.

26

NH

O

OO4d

Br

3

S94


122124126128130132134136138140142144146148150152154156158160162164166168170172f1 (ppm)

125.

48

127.

0812

7.11

127.

4612

7.97

129.

5113

0.13

130.

52

131.

84

133.

14

136.

62

141.

66

165.

77

170.

26

NH

O

OO4d

Br

3

S95


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.21

3.00

1.95

1.92

1.17

1.98

1.89

1.24

41.

255

1.26

11.

279

2.21

0

3.47

93.

494

4.23

24.

250

4.26

84.

286

7.27

17.

290

7.29

37.

396

7.39

97.

415

7.41

87.

433

7.43

77.

444

7.44

87.

463

7.46

77.

482

7.48

67.

953

7.95

77.

972

7.97

57.

986

NH

O

OEt

MeO

4e

S96


6.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.3f1 (ppm)

1.17

1.98

1.89

7.27

17.

290

7.29

3

7.39

67.

399

7.41

57.

418

7.43

37.

437

7.44

47.

448

7.46

37.

467

7.48

27.

486

7.95

37.

957

7.97

27.

975

7.98

6

NH

O

OEt

MeO

4e

S97


-100102030405060708090100110120130140150160170180f1 (ppm)

14.0

6

21.0

8

44.8

4

61.1

1

76.6

877

.00

77.3

2

127.

7212

7.93

129.

9013

0.43

132.

0113

3.79

134.

04

144.

66

168.

1517

1.05

NH

O

OEt

MeO

4e

S98


110114118122126130134138142146150154158162166170174f1 (ppm)

127.

7212

7.93

129.

9013

0.43

132.

01

133.

7913

4.04

144.

66

168.

15

171.

05

NH

O

OEt

MeO

4e

S99


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

3.55

3.00

1.96

1.87

0.96

0.98

0.97

0.95

1.23

81.

255

1.27

3

2.26

6

3.49

13.

506

4.24

44.

262

4.28

04.

298

7.26

0

7.57

07.

637

7.65

7

8.05

28.

072

8.21

18.

225

8.23

9

NH

O

OEt

MeO

F3C

4f

S100


3.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

1.96

1.87

0.96

0.98

0.97

0.95

3.49

13.

506

4.24

44.

262

4.28

04.

298

7.26

0

7.57

07.

637

7.65

7

8.05

28.

072

8.21

18.

225

8.23

9

NH

O

OEt

MeO

F3C

4f

S101


0102030405060708090100110120130140150160170180190f1 (ppm)

13.9

5

21.3

4

45.0

5

61.3

6

76.6

877

.00

77.3

2

122.

0812

4.32

124.

3612

4.39

124.

4312

4.79

125.

1812

5.22

125.

2612

5.30

130.

5813

0.79

132.

0613

2.39

132.

7113

4.77

136.

82

147.

68

167.

2016

9.94

NH

O

OEt

MeO

F3C

4f

S102


110114118122126130134138142146150154158162166170174f1 (ppm)

122.

0812

4.32

124.

3612

4.39

124.

4312

4.79

125.

2212

5.26

130.

5813

0.79

131.

7313

2.06

132.

3913

2.71

134.

77

136.

82

147.

68

167.

20

169.

94

NH

O

OEt

MeO

F3C

4f

S103


5101520253035404550556065707580859095100105110115120125130135140145150f1 (ppm)

13.9

5

21.3

3

45.0

6

61.3

6

124.

3612

4.39

125.

2312

5.26

130.

59

NH

O

OEt

MeO

F3C

4f

S104


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.01

3.08

1.95

3.00

1.98

0.94

0.98

0.93

0.97

1.24

81.

266

1.28

4

2.17

2

3.46

73.

483

3.81

9

4.22

74.

245

4.26

34.

281

6.77

36.

779

6.93

26.

938

6.95

46.

960

7.26

0

7.62

17.

635

7.65

07.

910

7.93

2

NH

O

OEt

MeO

MeO

4g

S105


0102030405060708090100110120130140150160170180f1 (ppm)

14.1

1

21.0

7

44.7

9

55.3

5

61.1

3

76.6

877

.00

77.3

2

112.

2411

4.17

126.

53

131.

9813

2.04

135.

65

144.

06

160.

89

168.

2017

0.80

NH

O

OEt

MeO

MeO

4g

S106


129.0129.5130.0130.5131.0131.5132.0132.5133.0133.5134.0134.5135.0135.5136.0136.5137.0137.5f1 (ppm)

131.

9813

2.04

135.

65

NH

O

OEt

MeO

MeO

4g

S107


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.06

3.00

1.97

1.94

1.93

0.97

0.94

1.25

51.

273

1.29

1

2.20

1

3.45

43.

470

4.23

94.

257

4.27

44.

292

7.26

07.

630

7.65

17.

720

7.72

47.

740

7.74

48.

138

8.15

28.

166

NH

O

OEt

MeO

I

4h

S108


-100102030405060708090100110120130140150160170f1 (ppm)

14.0

7

21.2

4

44.8

4

61.2

9

76.6

877

.00

77.3

2

97.2

1

130.

6413

1.30

133.

1913

5.64

136.

7513

6.92

146.

49

167.

45

170.

48

NH

O

OEt

MeO

I

4h

S109


95100105110115120125130135140145150155160165170f1 (ppm)

97.2

1

130.

6413

1.30

133.

19

135.

6413

6.75

136.

92

146.

49

167.

45

170.

48

NH

O

OEt

MeO

I

4h

S110


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.89

2.96

3.00

1.99

1.86

0.99

0.91

0.86

1.27

11.

289

1.30

6

2.27

7

2.63

9

3.50

73.

523

4.26

44.

282

4.29

94.

317

7.26

0

7.77

07.

925

7.93

8

4i

NH

O

OEt

MeO

O2N

Me

S111


-100102030405060708090100110120130140150160170180f1 (ppm)

14.0

7

19.9

221

.44

45.1

9

61.5

6

76.6

877

.00

77.3

2

124.

52

130.

2813

2.76

133.

1113

4.35

137.

26

147.

6814

9.79

166.

8916

9.09

4i

NH

O

OEt

MeO

O2N

Me

S112


110114118122126130134138142146150154158162166170f1 (ppm)

124.

52

130.

28

132.

7613

3.11

134.

35

137.

26

147.

68

149.

79

166.

89

169.

09

4i

NH

O

OEt

MeO

O2N

Me

S113


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (ppm)

3.00

3.00

0.99

0.99

1.96

0.91

0.92

0.94

1.14

61.

164

1.18

2

2.37

3

3.34

63.

362

3.38

13.

398

3.54

73.

562

3.58

33.

598

4.09

84.

107

4.11

54.

125

4.13

14.

143

4.14

94.

160

4.16

74.

176

4.18

54.

194

7.26

0

7.50

97.

514

7.79

67.

801

8.50

8

NH

O

Me

4j

Cl

ClOEtO

S114


6.66.76.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.38.48.58.68.7f1 (ppm)

0.91

0.92

0.94

7.26

0

7.50

97.

514

7.79

67.

801

8.50

8

NH

O

Me

4j

Cl

ClOEtO

S115


-100102030405060708090100110120130140150160170180f1 (ppm)

13.8

4

20.5

2

46.0

8

61.1

8

76.6

877

.00

77.3

2

127.

7712

7.87

131.

5513

2.43

134.

3713

4.83

137.

25

151.

80

165.

87

169.

13

NH

O

Me

4j

Cl

ClOEtO

S116


124126128130132134136138140142144146148150152154156158160162164166168170f1 (ppm)

127.

7712

7.87

131.

55

132.

43

134.

3713

4.83

137.

25

151.

80

165.

87

169.

13

NH

O

Me

4j

Cl

ClOEtO

S117


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)

2.69

2.00

1.78

4.95

3.01

0.96

0.95

0.92

70.

944

0.96

2

3.85

73.

873

3.99

14.

009

4.02

74.

044

7.26

07.

332

7.33

87.

349

7.36

17.

369

7.37

57.

390

7.39

57.

451

7.46

07.

466

7.47

97.

486

7.50

17.

504

7.51

67.

520

7.64

28.

012

8.03

1

NH

O

OEt

PhO

4k

S118


3.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.28.48.68.8f1 (ppm)

2.00

1.78

4.95

3.01

0.96

0.95

3.85

73.

873

3.99

14.

009

4.02

74.

044

7.26

07.

332

7.33

87.

349

7.36

17.

369

7.37

57.

390

7.39

57.

451

7.46

07.

466

7.47

97.

486

7.50

17.

504

7.51

67.

520

7.64

28.

012

8.03

1

NH

O

OEt

PhO

4k

S119


0102030405060708090100110120130140150160170180f1 (ppm)

13.5

6

44.9

5

61.2

4

76.6

877

.00

77.3

2

127.

3312

7.71

128.

3912

8.54

128.

6113

0.44

130.

8213

3.47

133.

9013

3.99

139.

42

144.

79

168.

4517

0.45

NH

O

OEt

PhO

4k

S120


126127128129130131132133134135136137138139140141142143144145146147148149f1 (ppm)

127.

33

127.

71

128.

3912

8.54

128.

61

130.

44

130.

82

133.

4713

3.90

133.

99

139.

42

144.

79

NH

O

OEt

PhO

4k

S121


-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.61

3.00

2.01

1.77

8.20

0.97

0.92

40.

942

0.95

9

2.40

5

3.84

43.

860

3.99

74.

015

4.03

34.

051

7.26

07.

272

7.29

07.

322

7.33

87.

348

7.35

17.

359

7.37

07.

373

7.37

77.

382

7.91

47.

935

NH

O

OEt

PhO

Me

4l

S122


4.04.55.05.56.06.57.07.58.0f1 (ppm)

2.01

1.77

8.20

0.97

3.84

43.

860

3.99

74.

015

4.03

34.

051

7.26

07.

272

7.29

07.

322

7.33

87.

348

7.35

17.

359

7.37

07.

373

7.37

77.

382

7.91

47.

935

NH

O

OEt

PhO

Me

4l

S123


0102030405060708090100110120130140150160170f1 (ppm)

13.5

5

21.4

6

44.9

7

61.2

0

76.6

877

.00

77.3

2

127.

3212

8.04

128.

3212

8.53

129.

6013

0.53

131.

2813

3.36

134.

0013

9.51

141.

2114

4.40

168.

5717

0.50

NH

O

OEt

PhO

Me

4l

S124


116120124128132136140144148152156160164168172f1 (ppm)

127.

3212

8.04

128.

3212

8.53

129.

6013

0.53

131.

28

133.

3613

4.00

139.

51

141.

21

144.

40

168.

57

170.

50

NH

O

OEt

PhO

Me

4l

S125


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.56

2.00

1.69

1.87

2.92

0.98

0.91

0.88

0.99

0.90

60.

924

0.94

1

3.87

03.

886

4.00

24.

019

4.03

74.

055

7.26

07.

316

7.32

17.

325

7.32

87.

334

7.34

07.

388

7.40

67.

702

7.70

67.

722

7.72

67.

792

7.89

37.

897

8.09

38.

114

NH

O

OEt

PhO

NC

4m

S126


3.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.2f1 (ppm)

2.00

1.69

1.87

2.92

0.98

0.91

0.88

0.99

3.87

03.

886

4.00

24.

019

4.03

74.

055

7.26

07.

316

7.32

17.

325

7.32

87.

334

7.34

07.

388

7.40

6

7.70

27.

706

7.72

27.

726

7.79

27.

893

7.89

7

8.09

38.

114

NH

O

OEt

PhO

NC

4m

S127


0102030405060708090100110120130140150160170180f1 (ppm)

13.4

5

44.8

5

61.7

3

76.6

877

.00

77.3

2

114.

77

117.

66

127.

1912

8.69

128.

8913

1.25

131.

3213

1.83

134.

3913

7.63

138.

85

147.

44

167.

5816

8.93

NH

O

OEt

PhO

NC

4m

S128


105110115120125130135140145150155160165170f1 (ppm)

114.

77

117.

66

127.

1912

8.69

128.

89

131.

2513

1.32

131.

83

134.

39

137.

63

138.

85

147.

44

167.

58

168.

93

NH

O

OEt

PhO

NC

4m

S129


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.57

5.00

1.71

1.97

5.94

0.97

0.92

80.

946

0.96

4

3.85

03.

869

3.98

44.

002

4.01

94.

037

6.98

96.

995

7.01

77.

022

7.26

07.

329

7.33

67.

347

7.36

07.

373

7.42

7

7.98

28.

003

NH

O

OEt

PhO

MeO

4n

S130


3.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.2f1 (ppm)

5.00

1.71

1.97

5.94

0.97

3.85

03.

869

3.98

44.

002

4.01

94.

037

6.98

96.

995

7.01

77.

022

7.26

07.

329

7.33

67.

347

7.36

07.

373

7.39

07.

394

7.41

17.

427

7.98

28.

003

NH

O

OEt

PhO

MeO

4n

S131


0102030405060708090100110120130140150160170180f1 (ppm)

13.5

7

44.9

6

55.4

0

61.2

4

76.6

877

.00

77.3

2

112.

2611

4.78

126.

6512

7.32

128.

3712

8.53

132.

4813

3.67

135.

1113

9.41

144.

66

161.

14

168.

4417

0.37

NH

O

OEt

PhO

MeO

4n

S132


105110115120125130135140145150155160165170175f1 (ppm)

112.

26

114.

78

126.

6512

7.32

128.

3712

8.53

132.

4813

3.67

135.

11

139.

41

144.

66

161.

14

168.

44

170.

37

NH

O

OEt

PhO

MeO

4n

S133


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.59

2.00

1.73

4.92

1.00

0.90

0.91

0.99

0.92

00.

938

0.95

5

3.85

63.

872

3.99

84.

016

4.03

44.

052

7.26

07.

318

7.33

37.

338

7.35

57.

371

7.38

27.

390

7.42

07.

425

7.44

27.

447

7.53

77.

541

7.59

37.

951

7.97

2

NH

O

OEt

PhO

Cl

4o

S134


4.04.55.05.56.06.57.07.58.0f1 (ppm)

2.00

1.73

4.92

1.00

0.90

0.91

0.99

3.85

63.

872

3.99

84.

016

4.03

44.

052

7.26

07.

318

7.33

37.

338

7.35

57.

371

7.38

27.

390

7.42

07.

425

7.44

27.

447

7.53

77.

541

7.59

3

7.95

17.

972

NH

O

OEt

PhO

Cl

4o

S135


-100102030405060708090100110120130140150160170180f1 (ppm)

13.5

1

44.9

3

61.4

8

76.6

877

.00

77.3

2

127.

2712

7.64

128.

6212

8.84

132.

0113

2.38

132.

7313

4.95

137.

1213

9.14

146.

08

167.

9116

9.67

NH

O

OEt

PhO

Cl

4o

S136


124126128130132134136138140142144146148150152154156158160162164166168170172f1 (ppm)

127.

2712

7.64

128.

6212

8.84

132.

0113

2.38

132.

73

134.

95

137.

12

139.

14

146.

08

167.

91

169.

67

NH

O

OEt

PhO

Cl

4o

S137


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.63

3.00

2.06

1.85

1.13

7.13

1.01

0.93

20.

950

0.96

8

2.43

5

3.85

13.

867

3.99

24.

010

4.02

84.

045

7.10

67.

260

7.31

17.

315

7.33

17.

335

7.34

97.

360

7.37

07.

378

7.84

3

4p

NH

O

OEt

PhO

Me

S138


3.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.0f1 (ppm)

2.06

1.85

1.13

7.13

1.01

3.85

13.

867

3.99

24.

010

4.02

84.

045

7.10

67.

260

7.31

17.

315

7.33

17.

335

7.34

97.

360

7.37

07.

378

7.84

3

4p

NH

O

OEt

PhO

Me

S139


-100102030405060708090100110120130140150160170180f1 (ppm)

13.5

8

21.1

7

45.0

4

61.2

1

76.6

877

.00

77.3

2

127.

3412

7.77

128.

3212

8.55

130.

7913

1.84

133.

7113

4.04

138.

9113

9.48

143.

75

168.

5917

0.40

4p

NH

O

OEt

PhO

Me

S140


122124126128130132134136138140142144146148150152154156158160162164166168170172174176178f1 (ppm)

127.

3412

7.77

128.

3212

8.55

130.

79

131.

84

133.

7113

4.04

138.

9113

9.48

143.

75

168.

59

170.

40

4p

NH

O

OEt

PhO

Me

S141


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.80

2.00

1.82

1.97

0.96

4.89

0.96

0.99

61.

013

1.03

1

3.82

13.

837

4.02

54.

042

4.06

04.

078

7.20

67.

227

7.26

07.

317

7.45

57.

458

7.46

07.

468

7.47

37.

477

7.48

67.

491

7.50

67.

513

7.52

37.

527

7.53

28.

010

8.01

58.

030

8.03

3

NH

O

OEtO

Br4q

S142


6.856.957.057.157.257.357.457.557.657.757.857.958.058.15f1 (ppm)

1.97

0.96

4.89

0.96

7.20

67.

227

7.26

0

7.31

7

7.45

57.

458

7.46

07.

468

7.47

37.

477

7.48

67.

491

7.50

67.

513

7.52

37.

527

7.53

2

8.01

08.

015

8.03

08.

033

NH

O

OEtO

Br4q

S143


0102030405060708090100110120130140150160170180f1 (ppm)

13.6

7

44.8

2

61.4

5

76.6

877

.00

77.3

2

122.

6512

7.73

128.

8812

9.02

130.

5313

0.95

131.

7713

3.18

138.

24

143.

40

168.

1317

0.27

NH

O

OEtO

Br4q

S144


122124126128130132134136138140142144146148150152154156158160162164166168170172f1 (ppm)

122.

65

127.

7312

8.88

129.

02

130.

5313

0.95

131.

77

133.

1813

3.92

134.

50

138.

24

143.

40

168.

13

170.

27

NH

O

OEtO

Br4q

S145


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.80

2.00

1.79

1.92

0.89

1.03

2.81

0.97

0.99

21.

010

1.02

8

3.81

83.

834

4.03

44.

051

4.06

94.

087

7.19

47.

215

7.26

07.

415

7.44

17.

446

7.46

37.

467

7.50

57.

509

7.51

67.

537

7.94

97.

970

NH

O

OEtO

Br4r

Cl

S146


4.04.55.05.56.06.57.07.58.0f1 (ppm)

2.00

1.79

1.92

0.89

1.03

2.81

0.97

3.81

83.

834

4.03

44.

051

4.06

94.

087

7.19

47.

215

7.26

07.

415

7.44

17.

446

7.46

37.

467

7.50

57.

509

7.51

67.

537

7.94

97.

970

NH

O

OEtO

Br4r

Cl

S147


0102030405060708090100110120130140150160170f1 (ppm)

13.6

3

44.7

8

61.6

9

76.6

877

.00

77.3

2

122.

9212

7.66

128.

9412

9.11

131.

8513

2.08

132.

3013

7.27

137.

94

144.

69

167.

5916

9.51

NH

O

OEtO

Br4r

Cl

S148


116118120122124126128130132134136138140142144146148150152154156158160162164166168170172f1 (ppm)

122.

92

127.

6612

8.94

129.

11

131.

8513

2.08

132.

3013

3.30

134.

65

137.

2713

7.94

144.

69

167.

59

169.

51

NH

O

OEtO

Br4r

Cl

S149


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

2.76

2.00

1.64

0.85

0.86

3.56

0.89

0.92

1.25

61.

273

1.29

1

3.83

33.

894

3.90

3

4.29

34.

311

4.32

94.

346

6.45

26.

457

6.46

16.

465

6.64

26.

650

7.44

97.

453

7.46

67.

496

7.49

97.

505

7.51

1

7.77

6

8.00

28.

020

NH

O

OEtO

O

4s

S150


3.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.2f1 (ppm)

2.00

1.64

0.85

0.86

3.56

0.89

0.92

3.83

33.

894

3.90

3

4.29

34.

311

4.32

94.

346

6.45

26.

457

6.46

16.

465

6.64

26.

650

7.26

07.

449

7.45

37.

466

7.49

67.

499

7.50

57.

511

7.77

6

8.00

28.

020

NH

O

OEtO

O

4s

S151


0102030405060708090100110120130140150160170180f1 (ppm)

14.0

1

40.8

3

61.6

6

76.6

877

.00

77.3

2

111.

4411

2.02

127.

1012

8.57

129.

6712

9.87

130.

6913

0.99

133.

2813

3.75

143.

96

150.

21

168.

7017

0.65

NH

O

OEtO

O

4s

S152


110114118122126130134138142146150154158162166170174f1 (ppm)

111.

4411

2.02

127.

1012

8.57

129.

6712

9.87

130.

6913

0.99

133.

2813

3.75

143.

96

150.

21

168.

70

170.

65

NH

O

OEtO

O

4s

S153


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.03

3.00

2.17

1.76

0.95

0.96

2.08

0.92

0.97

0.97

1.25

81.

276

1.29

3

2.39

2

3.83

73.

876

3.88

9

4.29

74.

315

4.33

34.

351

6.44

86.

452

6.45

66.

461

6.62

46.

633

7.24

67.

260

7.26

57.

294

7.44

57.

448

7.66

67.

898

7.91

8

NH

O

OEtO

O

Me

4t

S154


3.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.0f1 (ppm)

2.17

1.76

0.95

0.96

2.08

0.92

0.97

0.97

3.83

73.

876

3.88

9

4.29

74.

315

4.33

34.

351

6.44

86.

452

6.45

66.

461

6.62

46.

633

7.24

67.

260

7.26

57.

294

7.44

57.

448

7.66

6

7.89

87.

918

NH

O

OEtO

O

Me

4t

S155


0102030405060708090100110120130140150160170180f1 (ppm)

14.0

0

21.4

7

40.8

6

61.6

1

76.6

877

.00

77.3

2

111.

2811

1.98

127.

4412

9.56

129.

6312

9.79

130.

7713

1.10

133.

17

141.

3714

3.86

150.

31

168.

8017

0.71

NH

O

OEtO

O

Me

4t

S156


126127128129130131132133134135136137138139140141142143144145146147148149150151f1 (ppm)

127.

44

129.

5612

9.63

129.

79

130.

7713

1.10

133.

17

141.

37

143.

86

150.

31

NH

O

OEtO

O

Me

4t

S157


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

2.67

2.00

1.59

0.85

0.86

0.82

0.61

1.08

0.89

0.70

1.27

41.

291

1.30

9

3.85

33.

883

4.31

34.

330

4.34

84.

366

6.46

96.

474

6.47

86.

482

6.65

86.

666

7.26

07.

467

7.47

17.

632

7.68

67.

707

7.76

37.

767

7.78

47.

788

7.86

97.

873

NH

O

OEtO

O

I

4u

S158


4.04.55.05.56.06.57.07.58.0f1 (ppm)

2.00

1.59

0.85

0.86

0.82

0.61

1.08

0.89

0.70

3.85

33.

883

4.31

34.

330

4.34

84.

366

6.46

96.

474

6.47

86.

482

6.65

86.

666

7.26

0

7.46

77.

471

7.63

27.

686

7.70

77.

763

7.76

77.

784

7.78

87.

869

7.87

3

NH

O

OEtO

O

I

4u

S159


0102030405060708090100110120130140150160170f1 (ppm)

14.0

2

40.7

5

61.8

8

76.6

877

.00

77.3

2

97.9

8

112.

0311

2.16

128.

2113

0.86

132.

0813

3.11

134.

9113

5.85

137.

60

144.

33

149.

89

168.

1617

0.02

NH

O

OEtO

O

I

4u

S160


95100105110115120125130135140145150155160165170f1 (ppm)

97.9

8

112.

0311

2.16

128.

21

130.

8613

2.08

133.

1113

4.91

135.

8513

7.60

144.

33

149.

89

168.

16

170.

02

NH

O

OEtO

O

I

4u

S161


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.00

2.25

1.99

2.37

1.09

1.16

1.12

1.13

1.06

1.08

1.10

21.

120

1.13

8

3.94

73.

963

4.11

44.

132

4.15

04.

167

6.03

6

6.80

96.

925

6.94

67.

030

7.04

07.

043

7.05

27.

147

7.15

07.

157

7.15

97.

264

7.40

07.

402

7.41

27.

415

7.61

17.

632

4v

NH

O

OO

O OEt S

S162


4.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.6f1 (ppm)

2.25

1.99

2.37

1.09

1.16

1.12

1.13

1.06

1.08

3.94

73.

963

4.11

44.

132

4.15

04.

167

6.03

6

6.80

96.

925

6.94

67.

040

7.04

37.

052

7.14

77.

150

7.15

9

7.26

4

7.40

07.

402

7.41

27.

415

7.61

17.

632

4v

NH

O

OO

O OEt S

S163


0102030405060708090100110120130140150160170f1 (ppm)

13.6

6

46.6

6

61.3

9

76.6

877

.00

77.3

2

101.

99

109.

14

116.

85

125.

7212

7.43

127.

5912

7.81

128.

1812

8.50

138.

7813

9.89

144.

99

149.

30

167.

3116

9.36

4v

NH

O

OO

O OEt S

S164


126128130132134136138140142144146148150152154156158160162164166168170f1 (ppm)

125.

72

127.

4312

7.59

127.

8112

8.18

128.

50

138.

78

139.

89

144.

99

149.

30

167.

31

169.

36

4v

NH

O

OO

O OEt S

S165


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

3.00

2.07

2.29

1.92

1.91

0.95

1.68

1.87

0.97

0.90

00.

918

0.93

61.

300

1.31

81.

337

1.35

61.

375

1.38

71.

393

1.59

21.

611

1.63

01.

643

1.64

71.

667

2.69

02.

709

2.72

7

3.55

83.

574

3.59

1

7.10

87.

126

7.14

47.

260

7.66

27.

683

7.68

97.

693

7.80

17.

805

7.82

27.

826

NH

O

BuO

I

4w

S166


6.36.46.56.66.76.86.97.07.17.27.37.47.57.67.77.87.98.08.1f1 (ppm)

0.95

1.68

1.87

0.97

7.10

87.

126

7.14

4

7.26

0

7.66

27.

683

7.68

97.

693

7.80

17.

805

7.82

27.

826

NH

O

BuO

I

4w

S167


-100102030405060708090100110120130140150160170180190200210f1 (ppm)

13.8

5

22.3

0

26.4

4

37.6

039

.40

76.6

877

.00

77.3

2

97.1

4

131.

5313

3.50

134.

1413

7.78

138.

11

143.

69

170.

33

200.

69

NH

O

BuO

I

4w

S168


95100105110115120125130135140145150155160165170175180185190195200205f1 (ppm)

97.1

4

131.

5313

3.50

134.

14

137.

7813

8.11

143.

69

170.

33

200.

69

NH

O

BuO

I

4w

S169


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.513.5f1 (ppm)

3.00

0.92

1.00

1.91

1.90

0.79

3.86

9

7.07

57.

260

7.33

97.

354

7.36

87.

401

7.41

77.

431

7.72

47.

739

12.0

24

5

HN N

PhCO2CH3

S170


-100102030405060708090100110120130140150160170f1 (ppm)

52.1

5

76.6

877

.00

77.3

2

105.

59

125.

6912

8.64

128.

9313

0.64

149.

39

161.

08

5

HN N

PhCO2CH3

S171


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

9.00

1.04

1.96

0.97

0.96

0.90

0.89

0.88

1.33

1

1.94

51.

955

1.96

51.

977

1.98

51.

997

2.90

72.

919

2.93

82.

950

2.96

42.

970

2.98

12.

994

3.01

23.

026

3.20

13.

218

3.23

23.

239

3.25

13.

269

3.27

8

4.51

34.

532

6.53

7

7.26

0

7.53

77.

543

7.64

87.

653

NH

OCl

ClO OtBu

6

S172


2.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.8f1 (ppm)

1.04

1.96

0.97

0.96

0.90

0.89

0.88

1.94

51.

955

1.96

51.

977

1.98

51.

997

2.90

72.

919

2.93

82.

950

2.96

42.

970

2.98

12.

994

3.01

23.

026

3.20

13.

218

3.23

23.

239

3.25

13.

269

3.27

8

4.51

34.

532

6.53

7

7.26

0

7.53

77.

543

7.64

87.

653

NH

OCl

ClO OtBu

6

S173


0102030405060708090100110120130140150160170f1 (ppm)

27.5

0

31.7

9

38.9

2

43.7

6

76.6

877

.00

77.3

2

82.4

0

128.

2213

1.40

132.

4813

3.89

134.

5513

7.97

170.

3717

0.97

NH

OCl

ClO OtBu

6

S174


124126128130132134136138140142144146148150152154156158160162164166168170172174f1 (ppm)

128.

22

131.

40

132.

48

133.

8913

4.55

137.

97

170.

3717

0.97

NH

OCl

ClO OtBu

6

S175


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)

9.00

0.98

0.95

0.94

0.89

0.86

0.88

1.38

3

2.87

52.

889

2.89

72.

912

2.92

62.

934

2.94

83.

801

3.81

43.

817

3.83

13.

837

3.85

13.

854

3.86

83.

924

3.93

73.

945

3.95

8

7.26

07.

454

7.46

97.

485

7.59

17.

596

7.73

17.

736

NH

OCl

ClO OtBu

O

7

S176


2.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.8f1 (ppm)

0.98

0.95

0.94

0.89

0.86

0.88

2.87

52.

889

2.89

72.

912

2.92

62.

934

2.94

8

3.80

13.

814

3.81

73.

831

3.83

73.

851

3.85

43.

868

3.92

43.

937

3.94

53.

958

7.26

0

7.45

47.

469

7.48

57.

591

7.59

67.

731

7.73

6

NH

OCl

ClO OtBu

O

7

S177


0102030405060708090100110120130140150160170f1 (ppm)

27.6

2

43.4

3

57.6

4

61.4

1

76.6

877

.00

77.3

2

83.9

4

128.

6712

8.89

132.

1313

5.45

136.

2713

7.57

166.

20

169.

04

NH

OCl

ClO OtBu

O

7

S178


130135140145150155160165170f1 (ppm)

128.

6712

8.89

132.

13

135.

45

136.

27

137.

57

166.

20

169.

04

NH

OCl

ClO OtBu

O

7

S179


-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)

9.00

1.99

1.03

1.18

1.51

4

3.51

63.

532

3.53

43.

549

6.96

0

7.26

07.

265

7.28

37.

302

NH

O

OtBuO[D4]-3a

D4

S180


3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.6f1 (ppm)

1.99

1.03

1.18

3.51

63.

532

3.53

43.

549

6.96

0

7.26

07.

265

7.28

37.

302

NH

O

OtBuO[D4]-3a

D4

S181


0102030405060708090100110120130140150160170f1 (ppm)

28.0

4

37.6

1

76.7

577

.00

77.2

581

.88

132.

1413

4.53

138.

0813

8.41

165.

21

171.

08

NH

O

OtBuO[D4]-3a

D4

S182


0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0

f1 (ppm)

9.00

1.98

0.74

1.01

1.74

1.82

1.50

5

3.50

33.

520

3.53

6

7.26

07.

280

7.29

87.

439

7.44

77.

454

7.45

87.

467

7.49

57.

499

7.50

87.

511

7.92

37.

933

7.95

2

NH

O

OtBuO

[D4]-3a/3a

D4/H4

S183


3.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.28.4f1 (ppm)

1.98

0.74

1.01

1.74

1.82

3.50

33.

520

3.53

6

7.26

07.

280

7.29

87.

447

7.45

87.

467

7.49

57.

499

7.50

87.

511

7.92

37.

933

7.95

2

NH

O

OtBuO

[D4]-3a/3a

D4/H4

S184


Documents

Institute of Materia Medica and College of Pharmaceutical ...Institute of Materia Medica and College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P.R.China E-mail: