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Supporting Information (Amaike, Muto, Yamaguchi, Itami)Decarbonylative CH Coupling of Azoles and Aryl Esters

S1

Supporting Information

Decarbonylative CH Coupling of Azoles and Aryl Esters:

Unprecedented Nickel Catalysis and Application to the Synthesis

of Muscoride A

Kazuma Amaike, Kei Muto, Junichiro Yamaguchi,* and Kenichiro Itami*

Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464-8602, Japan

E-mail: [email protected], [email protected]

Table of Contents

1. General S2

2. Preparation of Phenyl Esters S3S6

3. Nickel-catalyzed Decarbonylative CH Coupling S6S104. 13C-labeling Experiment S11

5. Preparation of Ni(dcype)(CO)2 Complex (4) S11

6. X-ray Crystal Structure Analysis of4 S12S13

7. Effect of Parameters S14S15

8. Alternative Protocols for Decarbonylative CH Coupling S15S16

9. Formal Synthesis of Muscoride A S17S19

10. 1H and 13C NMR Spectra S20S65

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1. General

Unless otherwise noted, all materials including dry solvents were obtained from commercial

suppliers and used as received. Ni(cod)2 and K3PO4 were obtained from Wako Chemicals.

1,2-Bis(dicyclohexylphosphino)ethane (dcype) was obtained from Sigma-Aldrich. 1,4-Dioxane was

freshly distilled by calcium hydride before coupling reaction. 5-Phenyloxazole (1B)[ 1 ],

5-phenylthiazole (1C)[ 2 ] and 2-phenylthiazole-4-carboxylate[ 3 ] were synthesized according to

procedures reported in the literature. Unless otherwise noted, all reactions were performed with dry

solvents under an atmosphere of argon in flame-dried glassware using standard vacuum-line

techniques. All CH bond arylation reactions were performed in 20-mL glass vessel tubes equipped

with J. Young O-ring tap and heated in an 8-well reaction block (heater + magnetic stirrer) unless

otherwise noted. All work-up and purification procedures were carried out with reagent-grade solvents

in air.

Analytical thin-layer chromatography (TLC) was performed using E. Merck silica gel 60 F254

precoated plates (0.25 mm). The developed chromatogram was analyzed by UV lamp (254 nm). Flash

column chromatography was performed with E. Merck silica gel 60 (230400 mesh). Preparative

thin-layer chromatography (PTLC) was performed using Wakogel B5-F silica coated plates (0.75 mm)

prepared in our laboratory. High-resolution mass spectra (HRMS) were obtained from a JMS-T100TD

instrument (DART). Optical rotations were measured using a JASCO P-1010-GT digital polarimeter

with CHCl3 as the solvent. Nuclear magnetic resonance (NMR) spectra were recorded on a JEOL

JNM-ECA-600 (1H 600 MHz, 13C 150 MHz) spectrometer and a JEOL JNM-ECA-400 (1H 400 MHz,13C 100 MHz) spectrometer. Chemical shifts for1H NMR are expressed in parts per million (ppm)

relative to tetramethylsilane ( 0.00 ppm) or residual peak of benzene ( 7.16 ppm) or DMSO ( 2.50

ppm). Chemical shifts for13C NMR are expressed in ppm relative to CDCl3 ( 77.0 ppm), C6D6 (

128.06 ppm) or DMSO-d6 ( 39.52 ppm). Data are reported as follows: chemical shift, multiplicity (s

= singlet, d = doublet, dd = doublet of doublets, t = triplet, q = quartet, m = multiplet, br = broad

signal), coupling constant (Hz), and integration.

[1] Besselivre, F.; Mahuteau-Betzer, F.; Grierson, D. S.; Piguel, S.J. Org. Chem. 2008, 73, 3278.[2] Parisien, M.; Valette, D.; Fagnou, K.J. Org. Chem.2005, 70, 7578.[3] Chen, H.; O'Connor, S.; Cane, D. E.; Walsh, C. T. Chem. Biol.2001, 8, 899.

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2. Preparation of Phenyl Esters

Representative procedure: Phenyl nicotinate (2f)[4]

HO

O

N PhO

O

N

SOCl2, reflux 1h

;then NEt3, PhOH

DMAP, CH2Cl2RT, 1 h

[96%]

2f

Thionyl chloride (9 mL) was added to nicotinic acid (1.23 g, 10 mmol, 1.0 equiv) and the mixture was

stirred at reflux for 1 h. The solution was concentrated under vacuum. To a solution of the residue in

THF (10 mL) was added triethylamine (1.7 mL, 12 mmol, 1.2 equiv). After cooling the mixture to

0 C, phenol (941 mg, 10 mmol, 1.0 equiv) and a piece of 4,4-dimethylaminopyridine (DMAP) was

added and then the reaction mixture was warmed to room temperature. After stirring the mixture for 1

h, the resulting mixture was passed through a short silica gel pad with EtOAc. The filtrate was

concentrated under reduced pressure and the residue was purified by recrystallization from hexane to

afford 2fas a white solid (1.91 g, 96% yield). 1H NMR (400 MHz, CDCl3): 9.41 (d,J= 1.2 Hz, 1H),

8.86 (dd, J = 5.0, 1.8 Hz, 1H), 8.478.44 (m, 1H), 7.497.43 (m, 3H), 7.30 (t,J = 7.8 Hz, 1H),

7.267.22 (m, 2H); 13C NMR (100 MHz, CDCl3): 164.0, 154.2, 151.6, 150.7, 137.7, 129.8, 126.4,

125.8, 123.6, 121.7.

S

O

PhO

2b

Phenyl thiophene-2-carboxylate (2b)[5]

: Purification by recrystallization from hexane afforded 2b as

a white solid (96% yield). 1H NMR (400 MHz, CDCl3): 7.98 (dd,J= 4.0, 1.2 Hz, 1H), 7.66 (dd,J=

5.2, 1.2 Hz, 1H), 7.457.39 (m, 2H), 7.297.21 (m, 3H), 7.17 (dd,J= 5.2, 4.2 Hz, 1H); 13C NMR (100

MHz, CDCl3): 160.7, 150.7, 134.8, 133.6, 133.1, 129.6, 128.2, 126.1, 121.8.

S

O

PhO

2c

Phenyl thiophene-3-carboxylate (2c)[6]

: Purification by recrystallization from hexane afforded 2c as

a white solid (61% yield). 1H NMR (400 MHz, CDCl3): 8.31 (dd,J= 2.8, 1.2 Hz, 1H), 7.67 (dd,J=

[4] Yang, T.; Chan, N. Y.-K.; Sauve, A. A. J. Med. Chem.2007, 50, 6458.[5] Watson, D. A.; Fan, X.; Buchwald, S. L. J. Org. Chem.2008, 73, 7096.[6] Ren, W.; Emi, A.; Yamane, M. Synthesis2011, 2303.

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5.0, 1.4 Hz, 1H), 7.447.40 (m, 2H), 7.38 (dd,J= 5.0, 3.0 Hz, 1H), 7.297.25 (m, 1H), 7.217.19 (m,

2H); 13C NMR (100 MHz, CDCl3): 161.2, 150.8, 134.2, 133.1, 129.6, 128.4, 126.5, 126.0, 121.8.

O

O

PhO

2d

Phenyl furan-2-carboxylate (2d)[7]

: Purification by recrystallization from hexane afforded 2d as a

white solid (42% yield). 1H NMR (400 MHz, CDCl3): 7.68 (m, 1H), 7.457.38 (m, 3H), 7.297.21

(m, 3H), 6.60 (dd,J= 3.4, 1.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 157.1, 150.3, 147.3, 144.2,

129.7, 126.2, 121.7, 119.6, 112.3.

O

O

PhO

2e

Phenyl furan-3-carboxylate (2e): Purification by recrystallization from hexane afforded 2e as a

white solid (59% yield). 1H NMR (400 MHz, CDCl3): 8.19 (dd,J= 1.4, 0.6 Hz, 1H), 7.50 (t,J= 1.6

Hz, 1H), 7.447.39 (m, 2H), 7.287.24 (m, 1H), 7.197.16 (m, 2H), 6.87 (dd,J= 2.0, 0.8 Hz, 1H); 13C

NMR (100 MHz, CDCl3): 161.6, 150.6, 148.8, 144.2, 129.6, 126.1, 121.8, 119.0, 110.2; HRMS

(DART) m/zcalcd for C11H9O3 [MH]+: 189.05517, found 189.05517.

N

O

PhO

2g

Phenyl isonicotinate (2g): Purification by recrystallization from hexane afforded 2g as a white solid

(99% yield). 1H NMR (400 MHz, CDCl3): 8.87 (d,J= 6.0 Hz, 2H), 8.01 (d,J= 6.4 Hz, 2H), 7.46 (t,

J= 8.2 Hz, 2H), 7.337.22 (m, 3H); 13C NMR (100 MHz, CDCl3): 163.9, 151.0, 150.6, 137.0, 129.8,

126.5, 123.4, 121.5; HRMS (DART) m/zcalcd for C12H10NO2 [MH]+: 200.07115, found 200.07108.

N

O

PhO

2h

Phenyl picolinate (2h): Purification by recrystallization from hexane afforded 2h as a white solid

(99% yield). 1H NMR (400 MHz, CDCl3): 8.868.84 (m, 1H), 8.28 (d,J= 8.0 Hz, 1H), 7.92 (td,J=

8.0, 2.0 Hz, 1H), 7.577.54 (m, 1H), 7.487.41 (m, 2H), 7.317.25 (m, 3H);13C NMR (100 MHz,

[7] Zhang, L.; Zhang, G.; Zhang, M.; Cheng, J.J. Org. Chem.2010, 75, 7472.

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CDCl3): 164.0, 151.0, 150.3, 147.7, 137.4, 129.7, 127.5, 126.3, 126.0, 121.8; HRMS (DART)m/z

calcd for C12H10NO2 [MH]+: 200.07115, found 200.07113.

N

NO

PhO

2i

Phenyl pyrazine-2-carboxylate (2i): Purification by flash column chromatography (hexane/EtOAc =

3:1) afforded 2i as a white solid (51% yield). 1H NMR (400 MHz, CDCl3): 9.48 (s, 1H), 8.85 (d,J=

1.2 Hz, 1H), 8.82 (d,J= 1.2 Hz, 1H), 7.46 (t,J= 7.8 Hz, 2H), 7.397.21 (m, 3H); 13C NMR (100

MHz, CDCl3): 162.7, 150.6, 148.3, 146.9, 144.8, 143.1, 129.8, 126.6, 121.6; HRMS (DART)m/z

calcd for C11H9N2O2 [MH]+: 201.06640, found 201.06621

N

O

PhO

Ph

2j

Phenyl 2-phenylquinoline-4-carboxylate (2j): Purification by flash column chromatography

(hexane/EtOAc = 10:1) afforded 2j as a white solid (43% yield). 1H NMR (400 MHz, CDCl3): 8.86

(d,J= 8.8 Hz, 1H), 8.65 (s, 1H), 8.298.24 (m, 3H), 7.80 (dd,J= 8.4, 6.8 Hz, 1H), 7.65 (dd,J= 8.6,7.0 Hz, 1H), 7.56 (t,J= 7.8 Hz, 2H), 7.50 (t,J= 7.6 Hz, 3H), 7.367.32 (m, 3H); 13C NMR (100 MHz,

CDCl3): 164.9, 156.9, 150.7, 149.5, 138.8, 134.8, 130.6, 130.2, 130.0, 129.9, 129.1, 128.3, 127.6,

126.6, 125.4, 124.2, 121.8, 121.0; HRMS (DART) m/zcalcd for C22H16NO2 [MH]+: 326.11810, found

326.11815.

S

N

O

PhO

Ph2k

Phenyl 2-phenylthiazole-4-carboxylate (2k): Purification by flash column chromatography

(hexane/EtOAc = 5:1) afforded 2kas a white solid (73% yield). 1H NMR (400 MHz, CDCl3): 8.35 (s,

1H), 8.068.03 (m, 2H), 7.487.41 (m, 5H), 7.307.25 (m, 3H);13C NMR (100 MHz, CDCl3): 169.3,

159.9, 150.7, 147.2, 132.8, 131.0, 129.6, 129.2, 128.8, 127.1, 126.2, 121.8; HRMS (DART)m/zcalcd

for C16H12NO2S[MH]+: 282.05887, found 282.05868.

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PhO

O

2l

Phenyl naphthalene-2-carboxylate (2l)[8]

: Purification by recrystallization from hexane afforded 2l

as a white solid (99% yield). 1H NMR (400 MHz, CDCl3): 8.81 (d,J= 0.8 Hz, 1H), 8.21 (dd,J= 8.8,

1.6 Hz, 1H), 8.02 (dd,J= 8.0, 0.8 Hz, 1H), 7.987.91 (m, 2H), 7.677.56 (m, 2H), 7.507.44 (m, 2H),

7.337.27 (m, 3H); 13C NMR (100 MHz, CDCl3): 165.5, 151.2, 136.0, 132.7, 132.1, 129.7, 129.6,

128.8, 128.5, 128.0, 127.0, 126.9, 126.1, 125.6, 121.9.

O

13C

N

H

1A-13C

[2-13

C]Benzoxazole (1A-13C 99% purity): A mixture of triethyl orthoformate (formyl-13C, 99% purity,

500 mg, 3.4 mmol, 1.0 equiv) and 2-aminophenol (742 mg, 6.8 mmol, 2.0 equiv) was refluxed in

toluene (1.2 mL) for 2 h. After cooling the mixture to room temperature, the mixture was concentrated

and the residue was purified by flash column chromatography (hexane/EtOAc = 10:1) to afford

1A-13C(295.0 mg, 72%) as colorless oil. 1H NMR (400 MHz, CDCl3): 8.11 (d,1JCH = 232.4 Hz, 1H),

7.817.78 (m, 1H), 7.617.58 (m, 1H), 7.437.35 (m, 2H); 13C NMR (100 MHz, CDCl3): 152.6,

150.1 (JCC = 3.8 Hz), 140.2 (JCC = 2.9 Hz), 125.7, 124.7, 120.8 (JCC = 6.7 Hz), 111.1 (JCC = 3.8 Hz);

HRMS (DART) m/zcalcd for C613CH6NO[MH]

+: 121.04829, found 121.04836.

3. Nickel-catalyzed Decarbonylative CH Coupling

Ni(cod)2 (10 mol%)dcype (20 mol%)K3PO4 (2.0 equiv)

1,4-dioxane150 C, 24 h

Z

N

H PhO+

O

Z

N

Ar

Ar

1A1C (1.0 equiv) 2b2k (1.5 equiv) 3

Z = O, S

General Procedure:A 20-mL glass vessel equipped with J. Young O-ring tap containing a magnetic

stirring bar and K3PO4 (170.0 mg, 0.80 mmol, 2.0 equiv) was dried with a heatgun under reduced

pressure and filled with N2 after cooling to room temperature. To this vessel was added a phenyl ester

derivative 2 (0.60 mmol, 1.5 equiv), then introduced into an argon-atmosphere glovebox. To the

[8] Rosa, J. N.; Reddy, R. S.; Candeias, N, R.; Cal, P. M. S. D.; Gois, P. M. P. Org. Lett.2010, 12, 2686.

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reaction vessel were added Ni(cod)2 (11.2 mg, 0.04 mmol, 10 mol%) and

1,2-bis(dicyclohexylphosphino)ethane (dcype: 33.8 mg, 0.08 mmol, 20 mol%). The vessel was taken

out of the glovebox, then to it was added an azole1 (0.40 mmol) and dry 1,4-dioxane (1.5 mL) under a

stream of N2. The vessel was sealed with O-ring tap and then heated at 150 C for 24 h in an 8-well

reaction block with stirring. After cooling the reaction mixture to room temperature, the mixture was

passed through a short silica gel pad with EtOAc. The filtrate was concentrated and the residue was

subjected to preparative thin-layer chromatography to afford a decarbonylative coupling product

(2-arylated azole 3).

N

O S

3Ab: 96%

2-(Thiophen-2-yl)benzoxazole (3Ab)

[ 9 ]: Purification by preparative thin-layer chromatography

(hexane/EtOAc = 10:1) afforded 3Ab (77.3 mg, 96%) as a white solid. 1H NMR (400 MHz, CDCl3):

7.89 (dd,J= 3.8, 1.4 Hz, 1H), 7.767.70 (m, 1H), 7.567.50 (m, 2H), 7.367.29 (m, 2H), 7.16 (dd,J=

5.0, 3.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): 159.1, 150.5, 142.1, 130.3, 130.0, 129.7, 128.3,

125.2, 124.8, 119.9, 110.5; HRMS (DART) m/z calcd for C11H8NOS [MH]+: 202.03266, found

202.03279.

N

OS

3Ac: 96%

2-(Thiophen-3-yl)benzoxazole (3Ac)[9]

: Purification by preparative thin-layer chromatography

(hexane/EtOAc = 10:1) afforded 3Ac (77.2 mg, 96%) as a white solid. 1H NMR (400 MHz, CDCl3):

8.19 (dd,J= 2.6, 1.0 Hz, 1H), 7.79 (dd,J= 5.0, 1.0 Hz, 1H), 7.777.71 (m, 1H), 7.587.50 (m, 1H),

7.487.42 (m, 1H), 7.387.32 (m, 2H);13C NMR (100 MHz, CDCl3): 159.8, 150.4, 142.0, 129.4,

128.2, 127.1, 126.7, 125.1, 124.7, 120.0, 110.6; HRMS (DART) m/z calcd for C11H8NOS [MH]+:

202.03266, found 202.03249.

N

O O

3Ad: 86%

[9] Derridj, F.; Djebbar, S.; Benali-Baitich, O.; Doucet, H.J. Organomet. Chem.2008, 693, 135.

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2-(Furan-2-yl)benzoxazole (3Ad)[ 10 ]


(hexane/EtOAc = 10:1) afforded 3Ad (63.7 mg, 86%) as a white solid.1H NMR (400 MHz, CDCl3):

7.827.73 (m, 1H), 7.727.65 (m, 1H), 7.627.55 (m, 1H), 7.437.34 (m, 2H), 7.28 (d,J= 3.6 Hz,

1H), 6.62 (dd,J= 3.6, 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): 155.4, 150.2, 145.8, 142.7, 141.7,

125.4, 124.9, 120.2, 114.4, 112.4, 110.7; HRMS (DART) m/zcalcd for C11H8NO2 [MH]+: 186.05550,

found 186.05563.

N

OO

3Ae: 86%

2-(Furan-3-yl)benzoxazole (3Ae)[ 11 ]


(hexane/EtOAc = 10:1) afforded 3Ae (63.8 mg, 86%) as a white solid.1

H NMR (400 MHz, CDCl3): 8.22 (d,J= 0.8 Hz, 1H), 7.747.68 (m, 1H), 7.567.48 (m, 2H), 7.357.28 (m, 2H), 7.03 (d,J= 1.6

Hz, 1H); 13C NMR (100 MHz, CDCl3): 158.4, 150.3, 144.5, 144.4, 141.9, 125.0, 124.6, 119.8, 115.5,

110.5, 109.0; HRMS (DART) m/zcalcd for C11H8NO2 [MH]+: 186.05550, found 186.05544.

N

N

O

3Af: 70%

2-(Pyridin-3-yl)benzoxazole (3Af)[ 12 ]: Purification by preparative thin-layer chromatography

(hexane/EtOAc = 5:1) afforded 3Af(54.9 mg, 70%) as a white solid. 1H NMR (400 MHz, CDCl3):

9.45 (d, J = 1.6 Hz, 1H), 8.74 (dd, J = 5.0, 1.4 Hz 1H), 8.518.45 (m, 1H), 7.837.72 (m, 1H),

7.617.55 (m, 1H), 7.47 (dd,J= 8.2, 5.0 Hz, 1H), 7.407.34 (m, 2H);13C NMR (100 MHz, CDCl3):

160.8, 152.2, 150.9, 148.9, 141.9, 134.8, 125.8, 125.0, 123.8, 123.6, 120.4, 110.9; HRMS (DART)m/z

calcd for C12H9N2O[MH]+: 197.07149, found 197.07148.

N

N

O

3Ag: 92%

2-(Pyridin-4-yl)benzoxazole (3Ag)[9]


(hexane/EtOAc = 5:1) afforded 3Ag (72.6 mg, 92%) as a white solid.1H NMR (400 MHz, CDCl3):

8.81 (dd,J= 4.4, 1.6 Hz, 2H), 8.06 (dd,J= 4.6, 1.8 Hz, 2H), 7.877.78 (m, 1H), 7.657.58 (m, 1H),

[10] Guru, M. M.; Ali, M. A.; Punniyamurthy, T.J. Org. Chem.2011, 76, 5295.[11] Barbero, N.; Carril, M.; SanMartin, R.; Domnguez, E. Tetrahedron2007, 63, 10425.[12] Derridj, F.; Roger, J.; Geneste, F.; Djebbar, S.; Doucet, H.J. Organomet. Chem.2009, 694, 455.

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7.487.38 (m, 2H); 13C NMR (100 MHz, CDCl3): 160.6, 150.9, 150.8, 141.8, 134.3, 126.4, 125.2,

121.0, 120.7, 111.0; HRMS (DART) m/zcalcd for C12H9N2O[MH]+: 197.07149, found 197.07132.

N

N

O

3Ah: 57%

2-(Pyridin-2-yl)benzoxazole (3Ah)[12]


(hexane/EtOAc = 5:1) afforded 3Ah (44.5 mg, 57%) as a white solid.1H NMR (400 MHz, CDCl3):

8.82 (d, J = 4.4 Hz, 1H), 8.36 (d,J = 8.0 Hz, 1H), 7.957.80 (m, 2H), 7.67 (d,J = 7.2 Hz, 1H),

7.607.35 (m, 3H); 13C NMR (100 MHz, CDCl3): 161.5, 151.1, 150.4, 146.2, 141.9, 137.2, 126.1,

125.6, 125.0, 123.5, 120.7, 111.3; HRMS (DART) m/zcalcd for C12H9N2O[MH]+: 197.07149, found

197.07148.

N

NN

O

3Ai: 52%

2-(Pyrazin-2-yl)benzoxazole (3Ai): Purification by preparative thin-layer chromatography

(hexane/EtOAc = 5:1) afforded 3Ai (41.4 mg, 52%) as a white solid. 1H NMR (400 MHz, CDCl3):

9.58 (d,J= 1.2 Hz, 1H), 8.828.68 (m, 2H), 7.86 (dd,J= 6.6, 2.2 Hz, 1H), 7.68 (dd,J= 7.0, 1.8 Hz,

1H), 7.487.38 (m, 2H); 13C NMR (100 MHz, CDCl3): 159.4, 151.0, 146.2, 144.71, 144.65, 142.0,


198.06687.

N

N

O

Ph

3Aj: 85%

2-(2-Phenylquinolin-4-yl)benzoxazole (3Aj): Purification by preparative thin-layer chromatography

(hexane/EtOAc = 5:1) afforded 3Aj (109.8 mg, 85%) as a white solid. 1H NMR (400 MHz, CDCl3):

9.44 (d,J= 8.8 Hz, 1H), 8.73 (s, 1H), 8.28 (t,J= 7.2 Hz, 1H), 7.947.92 (m, 1H), 7.82 (t,J= 7.2 Hz,

1H), 7.747.70 (m, 2H), 7.58 (t,J= 7.6 Hz, 2H), 7.537.44 (m, 3H); 13C NMR (100 MHz, CDCl3):

161.0, 156.9, 150.4, 149.5, 142.2, 139.1, 131.9, 130.6, 130.2, 129.9, 129.1, 128.1, 127.7, 126.5, 126.3,


323.11834.

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SN

O

3Ak: 74%

NPh

2-(2-Phenylthiazol-4-yl)benzoxazole (3Ak): Purification by preparative thin-layer chromatography

(hexane/EtOAc = 5:1) afforded 3Ak(82.0 mg, 74%) as a white solid. 1H NMR (400 MHz, CDCl3):

8.228.21 (m, 1H), 8.118.09 (m, 2H), 7.847.82 (m, 1H), 7.647.62 (m, 1H), 7.487.47 (m, 3H),

7.407.37 (m, 2H); 13C NMR (100 MHz, CDCl3): 170.0, 158.4, 150.6, 144.5, 141.9, 132.8, 130.9,

129.1, 127.2, 125.7, 125.0, 122.3, 120.6, 111.0; HRMS (DART) m/z calcd for C16H11N2OS[MH]+:

279.05921, found 279.05907.

N

N

OPh

3Bf: 96%

5-Phenyl-2-(pyridin-3-yl)oxazole (3Bf)[13]


(hexane/EtOAc = 5:1) afforded 3Bf(85.0 mg, 96%) as a white solid. 1H NMR (400 MHz, CDCl3):

9.35 (d, J = 1.2 Hz, 1H), 8.70 (dd, J = 5.0, 1.4 Hz, 1H), 8.408.32 (m, 1H), 7.787.70 (m, 2H),

7.517.35 (m, 5H); 13C NMR (100 MHz, CDCl3): 158.9, 152.2, 151.1, 147.7, 133.5, 129.2, 129.0,


223.08715.

N

N

SPh

3Cf: 77%

5-Phenyl-2-(pyridin-3-yl)thiazole (3Cf): Purification by preparative thin-layer chromatography

(hexane/EtOAc = 5:1) afforded 3Cf(73.2 mg, 77%) as a white solid. 1H NMR (400 MHz, CDCl3):

9.18 (d, J = 1.6 Hz, 1H), 8.668.62 (m, 1H), 8.258.19 (m, 1H), 8.05 (s, 1H), 7.617.56 (m, 2H),

7.447.31 (m, 4H); 13C NMR (100 MHz, CDCl3): 163.5, 150.7, 147.6, 140.3, 139.5, 133.3, 130.9,

129.7, 129.2, 128.7, 126.8, 123.8; HRMS (DART) m/zcalcd for C14H11N2S[MH]+: 239.06429, found

239.06437.

[13] Santos, A.; Kam, L. E.; Grimaud, L.; Ronsseray, C. Chem. Commun. 2009, 3907.

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S11

4.13

C-labeling Experiment

O

13C

N

H +

PhO

O

N O

13C

N

N

standard

conditions

[72%]

1A-13C

(99% purity)2f

(1.5 equiv)3Af-13C

(99% purity)

3-(2-[2-13

C]Benzoxazolyl)pyridine (3Af-13C): Following the general procedure with 1A-13C (0.4

mmol) and 2f (0.6 mmol, 1.5 equiv), the crude product was purified by preparative thin-layer

chromatography (hexane/EtOAc = 5:1) to afford 3Af-13C (57.7 mg, 72%) as a white solid. 1H NMR

(400 MHz, CDCl3): 9.49 (t, J = 1.8 Hz, 1H), 8.78 (dd,J = 4.8, 0.8 Hz, 1H), 8.558.49 (m, 1H),

7.887.84 (m, 1H), 7.657.59 (m, 1H), 7.48 (dd,J= 8.2, 5.0 Hz, 1H), 7.447.37 (m, 2H); 13C NMR

(100 MHz, CDCl3): 160.7, 152.1, 150.8 (JCC = 3.8 Hz), 148.9 (JCC = 2.8 Hz), 141.9 (JCC = 1.9 Hz),

134.8, 125.8, 125.0, 123.7 (JCC = 4.8 Hz), 123.4 (JCC = 52.2 Hz), 120.4 (JCC = 7.7 Hz), 110.8 (JCC =

3.9 Hz); HRMS (DART) m/zcalcd for C1113CH9N2O[MH]

+: 198.07484, found 198.07500.

5. Preparation of Ni(dcype)(CO)2 Complex (4)

Ni

PP

OC CO

Ni(dcype)(CO)2 (4)

Ni(dcype)(CO)2 (4): In an argon-atmosphere glovebox,Ni(CO)2(PPh3)2 (1.92 g, 3.0 mmol, 1.0 equiv)

and 1,2-bis(dicyclohexylphosphino)ethane (dcype: 1.39 g, 3.3 mmol, 1.1 equiv) were added to the

reaction vessel. The vessel was taken out of the glovebox, then to it was added THF (9 mL). The

mixture was stirred at 40 C for 2 h. After cooling the mixture to room temperature, the mixture was

concentrated and the residue was purified by recrystallization from THF and hexane to afford 4 (1.55

g, 96%) as a white solid. 1H NMR (400 MHz, C6D6): 1.95 (br, 2H), 1.92 (br, 2H), 1.721.59 (m,

20H), 1.361.13 (m, 24H); 13C NMR (100 MHz, C6D6): 205.0, 35.8 (t,JPC = 8.2 Hz), 29.3, 28.5,

27.6, 27.53, 27.47, 27.41, 26.7, 23.2 (t,JPC = 19.7 Hz);31P NMR (160 MHz, C6D6): 64.0; IR (KBr):

1979, 1922, 1912 cm-1; anal calcd for C28H50O2P2Ni: C 62.35, H 9.34, found C 62.47, H 8.97.

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S12

6. X-ray Crystal Structure Analysis of 4

A suitable crystal of 4 was mounted with mineral oil on a glass fiber and transferred to the

goniometer of a Rigaku Saturn CCD diffractometer. Graphite-monochromated Mo K radiation (=

0.71070 ) was used. The structures were solved by direct methods with (SIR-97)[14] and refined by

full-matrix least-squares techniques against F2 (SHELXL-97).[15] The intensities were corrected for

Lorentz and polarization effects. The non-hydrogen atoms were refined anisotropically. Hydrogen

atoms were placed using AFIX instructions. Details of the crystal data and a summary of the intensity

data collection parameters for4 are listed in Table S1.

Table S1. Crystallographic data and structure refinement details for4.

4

formula C63H104Ni2O4P4

fw 1165.75

T(K) 123(2)

() 0.71070

cryst syst Monoclinic

space group P21/n

a, () 10.497(3)

b, () 18.260(4)

c, () 17.011(4)

,(deg) 90

, (deg) 107.278(3),(deg) 90

V, (3) 3113.7(13)

Z 2

Dcalc, (g / cm3) 1.243

m (mm-1) 0.751

F(000) 1258

cryst size (mm) 0.15 0.10 0.01

2 range, (deg) 3.0225.00

reflns collected 20681

indep reflns/Rint 5466/0.0574

params 352

GOF onF2 1.138

R1, wR2 [I>2(I)] 0.0672, 0.1448

R1, wR2 (all data) 0.0810, 0.1539

abs struct param -0.1(2)

[14] Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.; Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G.G.; Polidori, G.; Spagna, R.J. Appl. Crystallogr. 1999, 32, 115.

[15] Sheldrick, G. M. University of Gttingen: Gttingen, Germany, 1997.

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S13

Figure S1. ORTEP drawing of4 with 50% thermal ellipsoid. All hydrogen atoms are omitted for

clarity.

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S15

The reaction only worked when aryl esters were used (i.e. alkyl esters such as methyl esters, or

t-butyl esters did not work at all). The effect of the aryl-substituent of carboxylic acids is shown below

in Table S3. Although these results indicate that phenyl esters are not the best substrates for this

reaction (e.g., fluorophenyl esters give a higher yield), we used user-friendly phenyl esters in this

study.

Table S3. Effect of Parameters.

O

NH

O

ArO+

10 mol% Ni(cod)220 mol% dcype

2.0 equiv K3PO4

1,4-dioxane

150 C, 24 h1A (0.4 mmol) (1.5 equiv) 3Aa

O

N

MeMe

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

Me

o-

m-

p-

: 76%

: 76%

: 68%

82%[a] 46% 25%

57%

OMe

81%

OMe

MeO

F

91% 86%

96% 35%

MeO

F3C

6% 39% 41%

O

H

O

MeON

H

O

Aryl substituents(GC yield)

[a] Isolated yields.

8. Alternative Protocols for Decarbonylative CH Coupling

Ni(dcype)(CO)2 (10 mol%)K3PO4 (2.0 equiv)


O

NH +

O

N

1A (0.40 mmol) 2b (1.5 equiv) 3Ab

SPhO

O

S

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S16

A 20-mL glass vessel equipped with J. Young O-ring tap containing a magnetic stirring bar and

K3PO4 (170.0 mg, 0.80 mmol, 2.0 equiv) was dried with a heatgun under reduced pressure and filled

with nitrogen after cooling to room temperature. To this vessel were added 2b(122.6 mg, 0.60 mmol,

1.5 equiv) and Ni(dcype)(CO)2 (4: 21.6 mg, 0.04 mmol, 10 mol%). Then, this vessel was vacuumed

and backfilled with nitrogen for three times. To this vessel were added 1A (47.6 mg, 0.40 mmol) and

dry 1,4-dioxane (1.5 mL) under a stream of nitrogen. The vessel was sealed with O-ring tap and then

heated at 150 C for 24 h in an 8-well reaction block with stirring. After cooling the reaction mixture

to room temperature, the mixture was passed through a short silica gel pad with EtOAc. The filtrate

was concentrated and the residue was subjected to preparative thin-layer chromatography

(hexane/EtOAc = 10:1) to afford 3Ab (77.3 mg, 96%).

NiCl2 (10 mol%)dcype (20 mol%)

Zn (2.0 equiv)K3PO4 (2.0 equiv)


O

NH +

O

N

1A (0.40 mmol) 2b (1.5 equiv) 3Ab

SPhO

O

S

A 20-mL glass vessel equipped with J. Young O-ring tap containing a magnetic stirring bar and

K3PO4 (170.0 mg, 0.80 mmol, 2.0 equiv) was dried with a heatgun under reduced pressure and filled

with nitrogen after cooling to room temperature. To this vessel were added 2b(122.6 mg, 0.60 mmol,

1.5 equiv), NiCl2 (5.2 mg, 0.04 mmol, 10 mol%) and activated Zn (52.4 mg, 0.80 mmol, 2.0 equiv),

then introduced into an argon-atmosphere glovebox. To the reaction vessel was added

1,2-bis(dicyclohexylphosphino)ethane (dcype: 33.8 mg, 0.08 mmol, 20 mol%). The vessel was taken

out of the glovebox, then to it was added 1A (47.6 mg, 0.40 mmol) and dry 1,4-dioxane (1.5 mL)

under a stream of nitrogen. The vessel was sealed with O-ring tap and then heated at 150 C for 24 h

in an 8-well reaction block with stirring. After cooling the reaction mixture to room temperature, the

mixture was passed through a short silica gel pad with EtOAc. The filtrate was concentrated and the

residue was subjected to preparative thin-layer chromatography (hexane/EtOAc = 10:1) to afford 3Ab

(60.4 mg, 75%).

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S17

9. Formal Synthesis of Muscoride A

Methyl ester11 was prepared according to reported procedure by Wipf[16].

O

N

BocN

O

MeO

Me

LiOHH2O

THF/H2O (1 : 1)O

N

BocN

O

HO

Me

O

N

BocN

O

PhO

Me

PhOH

EDCHClcat. DMAP

CH2Cl2

phenyl ester 8methyl ester 11 carboxylic acid 12[84%, 2 steps]

H H H

Phenyl ester 8: To a 100-mL round bottom flask containing methyl ester11 (2.17 g, 7.0 mmol)

were added THF (20 mL), (20 mL), and LiOHH2O (590.0 mg, 2.0 equiv). After stirring the mixture

for 1 h at room temperature, THF was removed under the vacuo. Under 0 C, pH of this residue was

adjusted to 2 by addition of 1 M HCl. The reaction mixture was then extracted with CH2Cl2 (3 30

mL), and the combined organic layer was dried over Na2SO4 and then filtrated. After concentrating

this mixture, oxazole carboxylic acid 12 was obtained. This product was used without further

purification.

To a 100-mL round bottom flask containing 12 were added phenol (0.724 g, 1.1 equiv),

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCHCl: 1.48 g, 1.1 equiv),

N,N-dimethylaminopyridine (DMAP: 0.214 g, 0.25 equiv), and CH2Cl2 (60 mL). After stirring the

mixture for 9 h, this reaction mixture was quenched with saturated NaHCO3 aq. and extracted withCH2Cl2 (3 30 mL). The combined organic layer was dried over Na2SO4, and then filtrated.

Following evaporation of the solvent under reduced pressure, the residue was purified by flash column

chromatography (hexane/EtOAc = 3:1 to 2:1) to afford phenyl ester8 as colorless viscous oil (2.18 g,

84% over 2 steps). Rf 0.48 (hexane/EtOAc = 1:1);1H NMR (600 MHz, DMSO-d6, 373 K): 7.46 (t,J

= 7.6 Hz, 2H), 7.30 (t, J = 7.6 Hz, 1H), 7.23 (d,J = 7.6 Hz, 2H), 4.88 (dd,J = 7.6, 3.5 Hz, 1H),

3.523.41 (m, 2H), 2.64 (s, 3H), 2.372.26 (m, 1H), 2.101.97 (m, 2H), 1.961.88 (m, 1H), 1.35 (s,

9H); 13C NMR (150 MHz, DMSO-d6, 373 K): 162.6, 159.5, 156.3, 152.8, 149.8, 128.9, 126.0, 125.3,

121.1, 78.6, 53.7, 45.8, 30.9, 27.5, 22.8, 11.3; HRMS (DART) m/z calcd for C20H25N2O5 [MH]+:

373.17635, found 373.17613. []D20 = 62 (c = 1.0, CHCl3).

[16] Wipf, P.; Venkatraman, S.J. Org. Chem. 1996, 61, 6517.

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S18

Me O

O

CN

O

OMe+

DBU

THF, 0 C -> r.t.

[93%]

O

N

Me

OMe

OHO

Me

7

Methyl-5-methyloxazole carboxylate (7)[17]: To a solution of methyl 2-isocyanoacetate (2.41 g, 25

mmol) in 25 mL of THF was added DBU (1,8-diazabicyclo[5.4.0]undec-7-ene, 4.24 g, 1.1 equiv).

Cooling the reaction mixture to 0 C, the solution of acetic anhydride (2.81 g, 1.1 equiv) was added

slowly. Warming up to room temperature, the reaction mixture was stirred. The progress of the

reaction was monitored by TLC. On completion of reaction, the reaction mixture was concentrated in

vacuo. To this vessel was added 30 mL of EtOAc and 20 mL of water. The aqueous layer was

extracted with EtOAc (20 mL 3) and the combined organic layer was treated with Na2SO4 and thenfiltered. Following evaporation of the solvent under reduced pressure, the crude residue was purified

by flash column chromatography (hexane/EtOAc = 2:1) to afford 7 as a white solid (3.20 g, 93%

yield). Rf0.41 (hexane/EtOAc = 1:1);1H NMR (400 MHz, CDCl3): 7.75 (s, 1H), 3.92 (s 3H), 2.65 (s,

3H); 13C NMR (100 MHz, CDCl3): 162.5, 156.5, 148.8, 127.0, 51.9, 11.8.

Ni(cod)2 (20 mol%)

dcype (40 mol%)K3PO4 (2.0 equiv)


[39%]

O

N

Me

HO

N

Me

PhO

O

NO

t-BuO

O

OMe

+

7 (1.5 equiv) 8 (1.0 equiv)

H

N

OMe

O

OMe

O

N

Me

N

t-BuO

O

9

H

Methyl ester 9: A 20-mL glass vessel equipped with J. Young O-ring tap containing a magnetic

stirring bar was dried with a heatgun under reduced pressure and filled with nitrogen after cooling to

room temperature. To this vessel was added the solution of phenyl ester8 (111.7 mg, 0.30 mmol) in

CH2Cl2. After the concentration under the vacuo, to this was added oxazole 7 (63.5 mg, 1.5 equiv),

then introduced inside an argon atmosphere glovebox. In the glovebox, to the vessel were added

Ni(cod)2 (16.5 mg, 0.06 mmol, 20 mol%), 1.2-bis(dicyclohexylphosphino)ethane (dcype: 50.7 mg,

0.12 mmol, 40 mol%) and K3PO4 (127.3 mg, 2.0 equiv). The vessel was taken out of the glovebox,

then to it was added 1,4-dioxane (1.2 mL) under a stream of nitrogen. The vessel was sealed with

O-ring tap and then heated at 165 C for 2 h in an 8-well reaction block with stirring. After cooling the

reaction mixture to room temperature, the mixture was passed through a short silica gel pad with

EtOAc. The filtrate was concentrated and the residue was subjected to preparative thin-layer

[17] Muto, K.; Yamaguchi, J.; Itami, K.J. Am. Chem. Soc. 2012, 134, 169.

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S19

chromatography (hexane/EtOAc = 3:2) to afford coupling product 9 (45.7 mg, 39%) as a colorless

viscous oil. Rf = 0.31 (hexane/EtOAc = 1:1);1H NMR (600 MHz, DMSO-d6, 373 K): 4.86 (dd,J=

7.2, 3.0 Hz, 1H), 3.85 (s, 3H), 3.533.40 (m, 2H), 2.64 (s, 3H), 2.61 (s, 3H), 2.352.26 (m, 1H),

2.081.97 (m, 2H), 1.961.88 (m, 1H), 1.32 (s, 9H); 13C NMR (150 MHz, DMSO-d6, 373 K):

163.3, 161.4, 155.0, 153.0, 152.7, 149.2, 127.3, 123.5, 78.5, 53.7, 50.8, 45.8, 30.9, 27.5, 22.8, 11.0,

10.5; HRMS (DART) m/zcalcd for C19H25N3O6 [MH]+: 392.18216, found 392.18213. []D

21= 53 (c =

1.1, CHCl3)

10

O

N

Me

N

O

N

Me

O

O

O

t-BuO

HMeMe

Prenyl ester 10: Prenyl ester10 was synthesized from 9 according to the synthetic method developed

by Wipf[14]. 10 was obtained as colorless viscous oil. Rf = 0.42 (hexane/EtOAc = 1:1). 1H NMR (600

MHz, d6-DMSO, 373 K): 5.43 (t,J= 6.9 Hz, 1H), 4.894.84 (m, 1H), 4.78 (d,J= 6.9 Hz, 2H), 3.45

(m, 2H), 2.63 (s, 3H), 2.61 (s, 3H), 2.352.26 (m, 1H), 2.081.96 (m, 2H), 1.951.88 (m, 1H), 1.77 (s,

3H), 1.75 (s, 3H), 1.32 (s, 9H); 13C NMR (150 MHz, d6-DMSO, 373 K):

162.3, 160.9, 155.0, 153.0, 152.7, 149.2, 138.0, 127.5, 123.6, 118.2, 78.5, 60.5, 53.7, 45.8, 31.0, 27.

5, 24.7, 22.8, 17.3, 11.1, 10.6; 1H NMR (600 MHz, CDCl3, 333 K): 5.46 (t, J = 7.6 Hz,

1H), 5.004.86 (br, 1H), 4.82 (d,J= 6.9 Hz, 2H), 3.663.41 (br, 2H), 2.662 (s, 3H), 2.657 (s, 3H),

2.362.19 (br, 1H), 2.182.01 (m, 2H), 1.961.88 (m, 1H), 1.77 (s, 3H), 1.76 (s, 3H), 1.33 (s, 9H);13C

NMR (150 MHz, CDCl3, 333 K): 164.0, 162.3, 155.5, 154.2, 150.0, 138.9, 128.8, 124.8, 118.8, 80.0,

61.8, 54.8, 46.6, 32.4, 28.3, 25.6, 23.9, 19.0, 17.1, 12.1, 11.7; HRMS (DART) m/z calcd for

C23H31N3O6 [MH]+: 446.22911, found 446.22896. []D

21 = 49 (c = 0.95, CHCl3)

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S20

10.1H and

13C NMR Spectra

1H NMR (400 MHz, CDCl3) of 2e:

9.0

8.0

7

.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.197

8.196

8.194

8.192

7.497

7.414

7.412

7.3937.191

6.877

6.875

6.872

6.870

2.11

2.071.15

1.02

1.00

0.99

O

O

PhO

2e

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S21

13C NMR (100 MHz, CDCl3) of 2e:

:partsperMillion:13C

180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

1

00.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

161.553

150.555

148.811

144.184

129.631

126.068

121.833

119.026

110.222

O

O

PhO

2e

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S22

1H NMR (400 MHz, CDCl3) of 2g:

10.0

9.0

8.0

7.0

6.0

5.0

4.0

3

.0

2.0

1.0

0

8.876

8.861

8.020

8.004

7.458

7.437

7.312

7.264

7.261

7.239

7.236

7.222

7.219

7.217

3.49

2.02

2.00

1.98

N

O

PhO

2g

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S23

13C NMR (100 MHz, CDCl3) of 2g:

X:partsperMillion:13C

180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

163.922

150.999

150.637

136.979

129.807

126.526

123.350

121.547

N

O

PhO

2g

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S24

1H NMR (400 MHz, CDCl3) of 2h:

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.863

8.861

8.858

8.857

8.851

8.849

8.847

8.845

8.293

8.273

7.918

7.9147.443

7.441

7.422

7.289

7.277

7.274

7.270

7.256

7.253

3.17

2.07

1.02

1.02

1.01

1.00

N

O

PhO

2h

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S25

13C NMR (100 MHz, CDCl3) of 2h:


180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

1

00.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

164.018

151.047

150.255

147.651

137.351

129.654

127.546

126.287

125.992

121.805

N

O

PhO

2h

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S26

1H NMR (400 MHz, CDCl3) of 2i:

10.0

9.0

8.0

7.0

6.0

5.0

4.0

3

.0

2.0

1.0

0

9.475

8.852

8.849

8.824

8.821

7.4837.464

7.444

7.338

7.336

7.318

7.301

7.298

7.289

7.269

3.14

2.05

1.131.01

1.00

N

NO

PhO

2i

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S27

13C NMR (100 MHz, CDCl3) of 2i:

180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

10

0.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

62.674

50.574

48.265

46.924

44.778

43.140

29.794

26.623

21.565

N

NO

PhO

2i

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S28

1H NMR (400 MHz, CDCl3) of 2j:

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.875

8.853

8.647

8.285

8.260

8.239

7.804

7.800

7.651

7.565

7.544

7.520

7.501

7.482

7.341

7.338

7.316

3.04

3.00

2.982.03

1.01

1.00

1.00

0.98

N

O

PhO

Ph

2j

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S29

13C NMR (100 MHz, CDCl3) of 2j:

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100

.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

164.916

156.926

150.708

149.539

138.819

134.757

130.609

130.235

129.995

129.871

129.143

128.300

127.648

126.556

125.445

124.247

121.814

121.028

N

O

PhO

Ph

2j

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S30

1H NMR (400 MHz, CDCl3) of 2k:

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.350

8.055

8.051

8.041

8.033

8.031

7.476

7.469

7.460

7.433

7.413

7.277

7.274

7.271

7.252

7.250

5.03

3.08

2.04

1.00

S

N

O

PhO Ph

2k

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S31

13C NMR (100 MHz, CDCl3) of 2k:


180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

1

00.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

169.323

159.867

150.727

147.240

132.764

130.982

129.622

129.152

128.779

127.141

126.182

121.785

S

N

O

PhO Ph

2k

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S32

1H NMR (400 MHz, CDCl3) of 1A-

13C:

abundance

01.02.03.04.05.0X:partsperMillion:1H

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.393

7.812

7.799

7.793

7.609

7.607

7.6027.593

7.587

7.585

7.424

7.420

7.406

7.401

7.397

7.389

7.382

7.378

7.374

7.359

2.08

2.01

1.00

O

13C

N

H

1A-13C

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S33

13C NMR (100 MHz, CDCl3) of 1A-

13C:

abundance

01.02.03.0X:arts

erMillion:13C

180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

152.605

150.066

150.037

140.131

140.093

125.694

124.678

120.731

120.664

111.074

111.036

O

13C

N

H

1A-13C

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S34

1H NMR (400 MHz, CDCl3) of 3Ab:

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

7.899

7.896

7.890

7.886

7.540

7.537

7.527

7.524

7.335

7.333

7.323

7.321

7.311

7.309

7.174

7.165

7.162

7.152

2.03

2.031.00

1.00

1.00

N

O S

3Ab

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S35

13C NMR (100 MHz, CDCl3) of 3Ab:


180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

159.115

150.503

142.081

130.331

130.017

129.730

128.338

125.162

124.800

119.888

110.512

N

O S

3Ab

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S36

1H NMR (400 MHz, CDCl3) of 3Ac:

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.196

8.194

8.189

8.187

7.802

7.799

7.789

7.787

7.7367.349

7.343

7.340

7.335

7.332

7.326

2.12

1.08

1.05

1.04

1.04

1.00

N

OS

3Ac

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S37

13C NMR (100 MHz, CDCl3) of 3Ac:


180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

159.800

150.440

142.038

129.354

128.166

127.102

126.709

125.100

124.678

119.994

110.567

N

OS

3Ac

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S38

1H NMR (400 MHz, CDCl3) of 3Ad:

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

7.774

7.678

7.676

7.673

7.371

7.364

7.361

7.357

7.353

7.347

7.2877.278

6.630

6.625

6.621

6.616

2.13

1.04

1.03

1.000.96

1.04

N

O O

3Ad

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S39

13C NMR (100 MHz, CDCl3) of 3Ad:

X


180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

155.377

150.226

145.830

142.701141.729

125.372

124.943

120.231

114.366

112.353

110.656

N

O O

3Ad

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S40

1H NMR (400 MHz, CDCl3) of 3Ae:

9.0

8.0

7.

0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.217

8.215

7.724

7.712

7.543

7.539

7.535

7.531

7.339

7.329

7.327

7.319

7.317

7.028

7.024

2.09

2.06

1.03

1.02

1.00

N

OO

3Ae

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S41

13C NMR (100 MHz, CDCl3) of 3Ae:

1

80.0

170.0

160.0

150.0

140

.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

158.411

150.296

144.462

144.404141.856

125.042

124.630

119.764

115.520

110.461

109.043

N

OO

3Ae

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S42

1H NMR (400 MHz, CDCl3) of 3Af:

10.0

9.0

8

.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

9.492

9.488

9.483

8.782

8.780

8.770

8.768

8.526

8.522

7.820

7.808

7.797

7.627

7.615

7.415

7.412

7.409

7.402

7.395

7.391

2.121.06

1.06

1.05

1.03

1.01

1.00

N

N

O

3Af

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S43

13C NMR (100 MHz, CDCl3) of 3Af:


180.0

170.0

160.0

150.0

1

40.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

160.748

152.136

150.823

150.785

148.878148.850

141.856

141.837

134.757

125.780

124.995

123.969

123.768

123.720

123.174

120.396

120.319

110.864

110.825

N

N

O

3Af

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S44

1H NMR (400 MHz, CDCl3) of 3Ag:

9.0

8.0

7

.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.815

8.811

8.804

8.800

8.069

8.064

8.057

8.053

7.803

7.798

7.612

7.595

7.420

7.415

7.409

7.403

7.396

7.390

2.00

1.94

1.93

0.97

0.92

N

N

O

3Ag

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S45

13C NMR (100 MHz, CDCl3) of 3Ag:


180.0

170.0

160.0

150.0

14

0.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

160.622

150.875

150.780

141.776

134.328

126.354

125.172

121.013

120.727

110.989

N

N

O

3Ag

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S46

1H NMR (400 MHz, CDCl3) of 3Ah:

9.0

8.0

7

.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.825

8.814

8.367

8.347

7.900

7.880

7.861

7.843

7.826

7.821

7.678

7.660

7.457

7.444

7.437

7.426

7.4137.409

7.401

7.399

7.389

3.08

2.26

1.01

1.00

0.97

N

N

O

3Ah

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S47

13C NMR (100 MHz, CDCl3) of 3Ah:

X

:arts

erMillion:13C

180.0

170.0

160.0

150.0

14

0.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

161.538

151.142

150.389

146.163

141.872

137.170

126.135

125.648

125.019

123.531

120.727

111.323

N

N

O

3Ah

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S48

1H NMR (400 MHz, CDCl3) of 3Ai:

10.0

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

9.582

9.579

8.775

8.769

8.766

8.739

8.733

7.873

7.856

7.6917.687

7.669

7.455

7.451

7.441

7.436

7.431

7.422

7.419

2.06

2.01

1.10

1.00

0.99

N

NN

O

3Ai

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S49

13C NMR (100 MHz, CDCl3) of 3Ai:


180.0

170.0

160.0

150.0

1

40.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

159.369

151.043

146.167

144.711144.653

142.019

141.588

126.700

125.339

121.028

111.323

N

NN

O

3Ai

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S50

1H NMR (400 MHz, CDCl3) of 3Aj:

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

9.455

9.433

8.725

8.295

8.277

7.926

7.716

7.713

7.698

7.696

7.577

7.557

7.526

7.507

7.462

7.446

3.09

3.01

2.07 2.02

1.01

1.00

0.990.98

N

N

O

Ph3Aj

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S51

13C NMR (100 MHz, CDCl3) of 3Aj:


180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

1

00.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

161.017

156.926

150.373

149.511

142.210

139.097131.940

130.599

130.216

129.852

129.095

128.079

127.677

126.499

126.278

125.157

123.692

121.019

119.630

110.998

N

N

O

Ph3Aj

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S52

1H NMR (400 MHz, CDCl3) of 3Ak:

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

8.218

8.213

8.108

8.102

8.098

8.094

8.091

7.483

7.478

7.474

7.470

7.467

7.395

7.393

7.386

7.3837.379

7.376

3.172.11

2.09

1.05

1.04

1.00

SN

O

3Ak

NPh

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S53

13C NMR (100 MHz, CDCl3) of 3Ak:

:arts

erMillion:13C

180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

169.965

158.363

150.641

144.538

141.875

132.822

130.925

129.124

127.160

125.684

124.966

122.322

120.597

110.988

SN

O

3Ak

NPh

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S54

1H NMR (400 MHz, CDCl3) of 2Cf:

9.0

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

9.181

9.177

8.649

8.641

8.637

8.237

8.221

8.217

8.047

7.414

7.404

7.399

7.394

7.385

7.372

7.364

7.353

7.352

4.19

2.09

1.02

1.01

1.01

1.00

N

N

SPh

3Cf

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S55

13C NMR (100 MHz, CDCl3) of 3Cf:


180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

163.450

150.737

147.575

140.285

139.509

133.310

130.934

129.679

129.219

128.664

126.767

123.759

N

N

SPh

3Cf

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S56

1H NMR (400 MHz, C6D6) of 4:

8.0

7.0

6.0

5.0

4.0

3.0

2.0

1.0

0

1.9501.918

1.719

1.696

1.678

1.645

1.591

1.359

1.316

1.293

1.259

1.228

1.197

1.171

1.150

1.127

24.00

20.14

2.182.00

Ni

PP

OC CO

Ni(dcype)(CO)2 (4)

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S57

13C NMR (100 MHz, C6D6) of 4:

X:partsperMillion:13C

210.0

200.0

190.0

180.0

170.0

160.0

150.0

140.0

130.0

120.0

110.0

100.0

90.0

80.0

70.0

60.0

50.0

40.0

30.0

20.0

10.0

0

205.038

35.840

35.754

35.677

29.344

28.520

27.591

27.534

27.467

27.409

26.68123.376

23.175

22.983

NiPP

OC CO

Ni(dcype)(CO)2 (4)

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S58

1H NMR (600 MHz, DMSO-d

6, 373 K) of phenyl ester 8

O

N

BocN

O

PhO Me

phenyl ester 8

H

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S59

13C NMR (150 MHz, DMSO-d

6, 373 K) of phenyl ester 8

O

N

BocN

O

PhO

Me

phenyl ester 8

H

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S60


6, 373 K) of methyl ester 9

N

OMe

O

OMe

O

N

Me

N

t-BuO

O

9

H

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S61


6, 373 K) of methyl ester 9

N

OMe

O

OMe

O

N

Me

N

t-BuO

O

9

H

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S62


6, 373 K) of prenyl ester 10

10

O

N

Me

N

O

N

Me

O

O

O

t-BuO

HMeMe

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S63


6, 373 K) of prenyl ester 10

10

O

N

Me

N

O

N

Me

O

O

O

t-BuO

HMeMe

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S64

1H NMR (600 MHz, CDCl3, 333 K) of prenyl ester 10

10

O

N

Me

N

O

N

Me

O

O

O

t-BuO

HMeMe

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13C NMR (150 MHz, CDCl3, 333 K) of prenyl ester 10

10

O

N

Me

N

O

N

Me

O

O

O

t-BuO

HMeMe

Ja306062c Si 002-Bzoxozale

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