Coupling Reactions. Supporting Information

A β-Keto Ester as a Novel, Efficient and Versatile Ligand for Copper(I) Catalyzed C-N, C-O and C-S

Coupling Reactions

Xin Lv and Weiliang Bao*

Department of Chemistry, Xixi Campus, Zhejiang University, Hangzhou 310028, P. R. China

[email protected]

Supporting Information

List of Contents

(A)Typical Experimental Procedure S2-S3 (B) Analytical data for 1a-1j, 2a-2e, 3a-3d, 4a-4g S3-S8 (C) References S8-S9 (D) Spectra S10-S36

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(A) Typical Experimental Procedure

Typical Procedure A: Coupling of Aryl Iodides with Amides at Room Temperature.

(Table 2, entry 1): An oven-dried Schlenk tube equipped with a Teflon valve was charged with a magnetic stir bar, Cs2CO3 (684 mg, 2.1 mmol), CuBr (15 mg, 0.10 mmol, 10 mol%), and ethyl 2- oxocyclohexanecarboxylate (34 mg, 0.20 mmol, 20 mol%) The tube was evacuated and backfilled with N2 (this procedure was repeated three times). Under a counter flow of N2, DMSO (0.5 mL) was added by syringe at room temperature (25-30 °C) and pre-stirred for 0.5 h. Then a solution of iodobenzene (204 mg, 1.0 mmol), 2-pyrrolidinone (102 mg, 1.2 mmol) in DMSO (0.5 mL) was added via syringe under a counter flow of N2. The tube was sealed and the mixture was allowed to stir for 22 h at room temperature. The reaction mixture was directly passed through celite. After rinsed with further 60 mL of ethyl acetate, the combined filtrate was washed by saturated brine (10 ml × 2). After the organic layer was dried by Na2SO4, it was concentrated by rotatory evaporation. The residue was purified by column chromatography on silica gel using hexane/ethyl acetate (1:1) as eluent to give a white solid of 1- phenylpyrrolidin-2-one (155 mg, 96 %).

Typical Procedure B: Coupling of Aryl halides with Amides, Imidazoles, Phenols or Thiols.

(Table 2, entry 4): An oven-dried Schlenk tube equipped with a Teflon valve was charged with a magnetic stir bar, Cs2CO3 (684 mg, 2.1 mmol), CuBr (15 mg, 0.10 mmol, 10 mol%), and ethyl 2- oxocyclohexanecarboxylate (34 mg, 0.20 mmol, 20 mol%) The tube was evacuated and backfilled with N2 (this procedure was repeated three times). Under a counter flow of N2, DMSO (0.5 mL) was added by syringe at room temperature (25-30 °C) and pre-stirred for 0.5 h. Then a solution of 1-iodo-4- methylbenzene (218 mg, 1.0 mmol), 2-pyrrolidinone (102 mg, 1.2 mmol) in DMSO (0.5 mL) was added via syringe under a counter flow of N2. The tube was sealed and the mixture was allowed to stir for 24 h at 60 ºC. The reaction mixture was directly passed through celite. After rinsed with further 60 mL of ethyl acetate, the combined filtrate was washed by saturated brine (10 ml × 2). After the organic layer was dried by Na2SO4, it was concentrated by rotatory evaporation. The residue was purified by

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column chromatography on silica gel using hexane/ethyl acetate (1:1) as eluent to give a white solid of 1-p-tolylpyrrolidin-2-one (151 mg, 86 %).

(B) Analytical data for 1a-1j, 2a-2e, 3a-3d, 4a-4g

1a, 1-phenylpyrrolidin-2-one¹ (Table 2, entry 1) ^N

O

Procedure A was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.60 (2 H, d, J = 8.0 Hz), 7.36 (2 H, t, J = 7.8 Hz), 7.13 (1 H, t, J = 7.4 Hz), 3.82-3.86 (2 H, m), 2.57-2.61 (2 H, m), 2.10-2.17 (2 H, m);

13C NMR (50 MHz, CDCl3) δ 174.4, 139.6, 129.0, 124.7, 120.2, 49.0, 33.0, 18.3 (CDCl3 δ 77.3).

1b, 1-(4-chlorophenyl)pyrrolidin-2-one² (Table 2, entry 2) ^N

O Cl

Procedure A was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.57 (2H, d, J = 8.8 Hz), 7.31 (2H, d, J = 8.0 Hz), 3.83 (2H, t, J = 7.0 Hz), 2.60 (2H, t, J = 8.0 Hz), 2.12-2.20 (2H, m); ¹³C NMR (50 MHz, CDCl3) δ 174.5, 138.2, 129.7, 129.0, 121.1, 48.9, 32.9, 18.1 (CDCl3 δ 77.3).

1c, 1-(4-bromophenyl)pyrrolidin-2-one³ (Table 2, entry 3) ^N

O Br

Procedure A was followed. Pale yellow solid; ¹H NMR (400 MHz, CDCl3) δ7.30-7.58 (4H, m), 3.83 (2H, t, J = 7.0 Hz), 2.58-2.62 (2H, t, J = 8.0 Hz), 2.12-2.20 (2H, m); ¹³C NMR (50 MHz, CDCl3) δ 174.5, 138.7, 132.0, 121.5, 117.4, 48.8, 32.9, 18.1 (CDCl3 δ 77.3).

1d, 1-p-tolylpyrrolidin-2-one⁴ (Table 2, entry 4, 10) ^N

O

Procedure B was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.46-7.48 (2 H, d, J = 8.0 Hz), 7.16 (2 H, d, J = 8.0 Hz), 3.82 (2 H, t, J = 7.2 Hz), 2.58 (2 H, t, J = 8.0 Hz), 2.32 (3H, s), 2.10-2.17 (2 H, m); ¹³C NMR (50 MHz, CDCl3) δ 174.3, 137.1, 134.4, 139.6, 120.3, 49.1, 32.9, 21.1, 18.3 (CDCl3 δ 77.3).

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1e, 1-(4-methoxyphenyl)pyrrolidin-2-one⁵ (Table 2, entry 5, 11) ^N

O ^OMe

Procedure B was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.46-7.50 (2H, m), 6.88-6.91 (2H, m), 3.79-3.83 (5H, m), 2.58 (2H, t, J = 8.0 Hz), 2.10-2.18 (2H, m); ¹³C NMR (50 MHz, CDCl3) δ 174.2, 156.8, 132.9, 122.1, 114.3, 55.7, 49.4, 32.7, 18.3 (CDCl3 δ 77.3).

1f, 1-phenylpyridin-2(1H)-one¹ (Table 2, entry 6) ^N

O

Procedure B was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.52-7.57 (2H, m), 7.43-7.50 (4H, m), 7.38-7.40 (1H, m), 6.72 (1H, d, J = 8.8 Hz), 6.27-6.31 (1H, m) (TMS δ 0.06); ¹³C NMR (50 MHz, CDCl3) δ 162.6, 141.2, 140.1, 138.2, 129.6, 128.7, 126.8, 122.2, 106.1 (CDCl3 δ 77.3).

1g, 1-p-tolylpyridin-2(1H)-one⁶ (Table 2, entry 7) ^N

O

Procedure B was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.37-7.42 (1H, m), 7.31-7.34 (1H, m), 7.26-7.29 (4H, m), 6.66 (1H, d, J = 8.4 Hz), 6.23 (1H, t, J = 6.6 Hz), 2.41 (3H, s); ¹³C NMR (50 MHz, CDCl3) δ 162.8, 140.0, 138.7, 138.4, 130.2, 126.5, 122.0, 106.0, 21.4 (CDCl3 δ 77.4).

1h, N-phenylnicotinamide⁷ (Table 2, entry 8) ^N

O Ph NH

Procedure B was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 9.05 (1H, s), 8.70 (1 H, d, J = 4.0 Hz), 8.52 (1H, s), 8.16 (1 H, d, J = 8.0 Hz), 7.62 (2 H, d, J = 8.0 Hz), 7.32-7.38 (3 H, m), 7.14-7.18 (1 H, m); ¹³C NMR (50 MHz, CDCl3) δ 164.6, 152.4, 148.3, 137.9, 135.8, 131.2, 129.3, 125.3, 123.9, 121.0 (CDCl3 δ 77.3).

1i, N-phenylacetamide⁸ (Table 2, entry 9) ^NH

O

Procedure B was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.71 (1H, br), 7.50 (2H, d, J = 8.0 Hz), 7.26-7.31 (2H, m), 7.07-7.11 (1 H, m), 2.15 (3 H, s); ¹³C NMR (50 MHz, CDCl3) δ 169.4, 138.3, 129.1, 124.5, 120.5, 24.6 (CDCl3 δ 77.3).

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1j, 1-(pyridin-2-yl)pyrrolidin-2-one⁹ (Table 2, entry 12) ^{N N}

O

Procedure B was followed. Pale yellow solid; ¹H NMR (400 MHz, CDCl3) δ 8.40 (1 H, d, J = 8.4 Hz), 8.36 (1H, dd, J1 = 0.8 Hz, J2 = 4.8 Hz), 7.67-7.72 (1 H, m), 7.02-7.05 (1 H, m), 4.12 (2 H, t, J = 7.2 Hz), 2.67 (2 H, t, J = 8.2 Hz), 2.10-2.18 (2 H, m) (TMS δ 0.01); ¹³C NMR (50 MHz, CDCl3) δ 175.1, 152.1, 149.6, 137.7, 119.6, 114.8, 47.5, 33.9, 17.9 (CDCl3 δ 77.4).

Characterization data for products shown in Table 3.

2a, 1-phenyl-1H-imidazole¹ (Table 3, entries 1 and 5) ^N

N

Procedure B was followed. Slightly yellow oil; ¹H NMR (400 MHz, CDCl3) δ 7.79 (1 H, s), 7.38-7.42 (2 H, m), 7.27-7.32 (3 H, m), 7.21 (1 H, s), 7.15 (1 H, s) (TMS δ –0.05); ¹³C NMR(100 MHz, CDCl3) δ 137.2, 135.4, 130.3, 129.7, 127.3, 121.3, 118.1 (CDCl3 δ 77.0).

2b, 1-(4-chlorophenyl)-1H-imidazole¹⁰ (Table 3, entries 2 and 6) ^N

N

Cl

Procedure B was followed. Yellow solid; ¹H NMR (400 MHz, CDCl3) δ 7.82 (1 H, s), 7.43-7.46 (2H, m), 7.32-7.35 (2H, m), 7.25 (1H, s), 7.21 (1 H, s); ¹³C NMR (100 MHz, CDCl3) δ 135.7, 135.4, 133.0, 130.6, 129.9, 122.6, 118.0 (CDCl3 δ 77.0).

2c, N-(Phenyl)benzimidazole¹¹ (Table 3, entries 3 and 7) ^N

N

Procedure B was followed. Slightly yellow oil. ¹H NMR (400 MHz, CDCl3) δ 8.09 (1H, s), 7.88-7.90 (1H, m), 7.50-7.55 (3H, m), 7.41-7.47 (3H, m), 7.28-7.35 (2H, m); ¹³C NMR (100 MHz, CDCl3) δ 143.7, 142.0, 136.0, 133.3, 129.7, 127.7, 123.6, 123.4, 122.5, 120.3, 110.2 (CDCl3 δ 77.0).

2d, 1-p-tolyl-1H-imidazole¹⁰ (Table 3, entry 4) ^N

N

Me

Procedure B was followed. Yellow solid. ¹H NMR (400 MHz, CDCl3) δ 7.81 (1H, s), 7.25-7.28 (4H, m), 7.24 (1H, m), 7.19 (1H, s), 2.40 (3H, s); ¹³C NMR(100 MHz, CDCl3) δ 137.3, 135.5, 134.9, 130.2, 130.1, 121.3, 118.2, 20.8 (CDCl3 δ 77.0).

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2e, 1-(4-methoxyphenyl)-1H-imidazole¹ (Table 3, entry 8)^{N N}

OMe

Procedure B was followed. Yellow solid. ¹H NMR (400 MHz, CDCl3) δ 7.72 (1H, s), 7.25-7.27 (2H, m), 7.15-7.17 (2H, m), 6.94-6.96 (2H, m), 3.81 (3H, s); ¹³C NMR (100 MHz, CDCl3) δ 158.8, 135.8, 130.6, 130.0, 123.1, 118.7, 114.8, 55.5 (CDCl3 δ 77.0).

Characterization data for products shown in Table 4.

3a, diphenyl ether¹² (Table 4, entries 1 and 5)

O

Procedure B was followed. Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.39-7.40 (1H, m), 7.37-7.38 (2H, m), 7.35-7.37 (1H, m), 7.13-7.17 (2H, m), 7.07-7.08 (2H, m), 7.06-7.07 (2H, m); ¹³C NMR (100 MHz, CDCl3) δ 157.2, 129.7, 123.2, 118.8 (CDCl3 δ 77.0).

3b, Phenyl-p-tolyl ether¹³ (Table 4, entries 2 and 6)

O

Me

Procedure B was followed. Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.34-7.38 (2H, m), 7.18-7.20 (2H, m), 7.08-7.15 (1H, m), 7.03-7.05 (2H, m), 6.97-6.99 (2H, m), 2.38 (3H, s); ¹³C NMR(100 MHz, CDCl3) δ 157.6, 154.5, 132.7, 130.0, 129.5, 122.6, 118.9, 118.1, 20.51 (CDCl3 δ 77.0).

3c, 1-methoxy-4-phenoxybenzene¹² (Table 4, entries 3 and 7)

O

OMe

Procedure B was followed. Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.38 (2H, t, J = 7.6 Hz), 7.12 (1H, t, J = 7.6 Hz), 7.02-7.08 (4H, m), 6.97 (2H, d, J = 8.4 Hz), 3.88 (3H, s) (TMS δ 0.10); ¹³C NMR (100 MHz, CDCl3) δ 158.2, 155.7, 149.8, 129.3, 122.1, 120.6, 117.3, 114.5, 55.3 (CDCl3 δ 77.0).

3d, 2-phenoxynaphthalene¹⁴ (Table 4, entry 8)

O Ph

Procedure B was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.86-7.90 (2H, m), 7.74-7.76 (1H, m), 7.29-7.52 (6H, m), 7.13-7.21 (3H, m); ¹³C NMR (100 MHz, CDCl3) 157.1, 155.0, 134.3, 130.1, 129.8 (2 peaks), 127.7, 127.1, 126.5, 124.6, 123.4, 119.9, 119.1, 114.0 (CDCl3 δ 77.0).

Characterization data for products shown in Table 5.

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4a, diphenyl sulfide¹⁵ (Table 5, entry 1)

S

Procedure B was followed. Colorless oil; ¹H NMR (400 MHz, CDCl3) 7.24-7.36 (10H, m); ¹³C NMR (100 MHz, CDCl3) 135.7, 131.0, 129.1, 127.0 (CDCl3 δ 77.0).

4b, phenyl(p-tolyl)sulfane¹⁶ (Table 5, entry 2)

S

Me

Procedure B was followed. Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.37 (2H, d, J = 8.0 Hz), 7.24- 7.33 (4H, m), 7.16-7.20 (3H, m), 2.40 (3H, s); ¹³C NMR (100 MHz, CDCl3) δ 137.5, 137.0, 132.1, 131.2, 130.1, 129.7, 128.9, 126.3, 21.0 (CDCl3 δ 77.0).

4c, (4-methoxyphenyl)(phenyl)sulfane¹⁶ (Table 5, entry 3)

S MeO

Procedure B was followed. Slightly yellow oil; ¹H NMR (400 MHz, CDCl3) δ 7.44-7.47 (2H, m), 7.16- 7.28 (5H, m), 6.92-6.94 (2H, m), 3.84 (3H, s); ¹³C NMR (100 MHz, CDCl3) δ 159.7, 138.5, 135.3, 128.8, 128.1, 125.6, 124.1, 114.9, 55.3 (CDCl3 δ 77.0).

4d, (4-methoxyphenyl)(p-tolyl)sulfane¹⁷ (Table 5, entry 4)

S

MeO Me

Procedure B was followed. Colorless oil; ¹H NMR (400 MHz, CDCl3) δ 7.36 (2H, d, J = 8.8 Hz), 7.13 (2H, d, J = 8.2 Hz), 7.06 (2H, J = 8.2 Hz), 6.86 (2H, d, J = 8.8 Hz), 3.80 (3H, s), 2.30 (3H, s); ¹³C NMR (100 MHz, CDCl3) δ 159.4, 136.1, 134.3 (2 peaks), 129.7, 129.3, 125.5, 114.8, 55.3, 21.0 (CDCl3 δ 77.0).

4e, 4,6-dimethyl-2-(phenylthio)pyrimidine (Table 5, entry 5 )

S N

N Ph

Procedure B was followed. Yellow solid; Mp 61-62 °C; ¹H NMR (400 MHz, CDCl3) δ 7.62-7.64 (2H, m), 7.39-7.41 (3H, m), 6.70 (1H, s), 2.34 (6H, s); ¹³C NMR (100 MHz, CDCl3) δ 171.1, 167.3, 134.8, 130.2, 128.7, 128.6, 116.3, 23.8 (CDCl3 δ 77.0). IR (KBr, cm^-1): 3073, 3011, 2920, 2854, 1579, 1530, 1437, 1256, 1176, 749. Anal. Calcd. for C12H12N2S requires C: 66.63, H: 5.59, N: 12.95, found C: 66.78, H: 5.60, N: 12.93.

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4f, benzyl(phenyl)sulfane¹⁶ (Table 5, entry 6)

S

Procedure B was followed. White solid; ¹H NMR (400 MHz, CDCl3) δ 7.19-7.26 (10H, m), 4.15 (2H, s);

13C NMR (100 MHz, CDCl3) δ 137.4, 136.3, 129.7. 128.8, 128.5, 127.1, 126.3, 39.0 (CDCl3 δ 77.0).

4g, naphthalen-2-yl(phenyl)sulfane¹⁸ (Table 5, entry 7)

S Ph

Procedure B was followed. Slightly yellow solid; ¹H NMR (400 MHz, CDCl3) δ 7.86 (1H, s), 7.74-7.83 (3 H, m), 7.46-7.52 (2H, m), 7.41-7.44 (3H, m), 7.31-7.35 (2H, m), 7.26-7.30 (1H, m); ¹³C NMR (100 MHz, CDCl3) δ 135.8, 133.7, 132.9, 132.2, 130.9, 129.9, 129.2, 128.8, 128.7, 127.7, 127.4, 127.0, 126.6, 126.2 (CDCl3 δ 77.0).

(C) References

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(2) Heine, H. W.; Love, P.; Bove, J. L. J. Am. Chem. Soc. 1955, 77, 5420.

(3) Lucas-Lopez, C.; Patterson, S.; Blum, T.; Straight, A. F.; Toth, J.; Slawin, A. M. Z.; Mitchison, T. J.;

Seller, J. R.; Westwood, N. J. Euro. J. Org. Chem. 2005, 1736.

(4) Michael, J. P.; Koning, C. B.; Hosken, G. D.; Stanbury, T. V. Tetrahedron 2001, 57, 9635.

(5) Reference: Easton, C. J.; Pitt, M. J.; Ward, C. M. Tetrahedron 1995, 51, 12781.

(6) Sugahara, M.; Ukita, T. Chem. Pharm. Bull. 1997, 45, 719.

(7) Chen, J.; Ling, G.; Yu, Z.; Wu, S.; Zhao, X.; Wu, X.; Lu, S. Adv. Syn. Cat. 2004, 346, 1615.

(8) Rao, H.; Jin, Y.; Fu, H.; Jiang, Y.; Zhao, Y. Chem. Eur. J. 2006, 12, 3636.

(9) Renger, B.; Hoechst, A. –G.; Frankfurt, F. Synthesis 1985, 856.

(10) Lv, X.; Wang, Z.; Bao, W. Tetrohedron 2006, 62, 4756.

(11) Liu, L. B.; Frohn, M.; Xi, N.; Dominguez, C.; Hungate, R.; Reider, P. J. J. Org. Chem. 2005, 70, 10135.

(12) Ma, D.; Cai, Q. Org. Lett. 2003, 5, 3799.

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(13) Quach, T. D.; Batey, R. A. Org. Lett. 2003, 5, 1381.

(14) Liu, Z. J.; Larock, R. C. J. Org. Chem. 2006, 71, 3198.

(15) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org. Lett. 2002, 4, 2803.

(16) Itoh, T.; Mase, T. Org. Lett. 2004, 6, 4587.

(17) Schopfer, U.; Schlapbach, A. Tetrahedron 2001, 57, 3069.

(18) Mispelaere-Canivet, C.; Spindler, J. –F.; Perrio, S.; Beslin, P. Tetrahedron 2005, 61, 5253.

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(D) Spectra

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