Cross-Coupling Reactions between C(sp^²)-H and C(sp^³)-H Bonds via Sequential Dehydrogenation and C-H Insertion

Abstract

Formal C(sp^²)-H and C(sp^³)-H cross-coupling reactions were carried out by iridium-catalyzed transfer dehydrogenation of primary alcohols and sequential manganese-catalyzed insertion of the formed aldehydes into a carbon-hydrogen bond of aromatic or olefinic compounds.

manganese - iridium - C-H activation - dehydrogenation - cross-coupling

References and Notes

1 Metal-Catalyzed Cross Coupling Reactions   2nd ed., Vol. 1 and 2:  de Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004. 

For recent examples of carbon-metal and carbon-hydrogen bond coupling, see:

2a Giri R. Maugel N. Li J.-J. Wang D.-H. Breazzano SP. Saunders LB. Yu J.-Q. J. Am. Chem. Soc.  2007,  129:  3510 

For reviews, see:

2b Li B.-J. Yang S.-D. Shi Z.-J. Synlett  2008,  949 

2c Chen X. Engle KM. Wang D.-H. Yu J.-Q. Angew. Chem. Int. Ed.  2009,  48:  5094 

For recent examples of carbon-hydrogen and carbon-halogen bond coupling, see:

3a Wang X. Lane BS. Sames D. J. Am. Chem. Soc.  2005,  127:  4996 

3b Oi S. Sakai K. Inoue Y. Org. Lett.  2005,  7:  4009 

3c Kobayashi K. Sugie A. Takahashi M. Masui K. Mori A. Org. Lett.  2005,  7:  5083 

3d Ackermann L. Althammer A. Born R. Angew. Chem. Int. Ed.  2006,  45:  2619 

3e Yanagisawa S. Sudo T. Noyori R. Itami K. J. Am. Chem. Soc.  2006,  128:  11748 

3f Berman AM. Lewis JC. Bergman RG. Ellman JA. J. Am. Chem. Soc.  2008,  130:  14926 

3g Do H.-Q. Daugulis O. J. Am. Chem. Soc.  2007,  129:  12404 

For reviews, see:

3h Bellina F. Rossi R. Tetrahedron  2009,  65:  10269 

3i Daugulis O. Top. Curr. Chem.  2010,  292:  57 

3j Beck EM. Gaunt MJ. Top. Curr. Chem.  2010,  292:  85 

3k Bouffard J. Itami K. Top. Curr. Chem.  2010,  292:  231 

For recent examples of carbon-hydrogen and carbon-hydrogen bond coupling, see:

4a Stuart DR. Fagnou K. Science  2007,  316:  1172 

4b Hull KL. Sanford MS.
J. Am. Chem. Soc.  2007,  129:  11904 

4c Zhao X. Yeung CS. Dong VM. J. Am. Chem. Soc.  2010,  132:  5837 

For representative examples, see:

5a Sezen B. Sames D. J. Am. Chem. Soc.  2005,  127:  5284 

5b Li Z. Li C.-J.
J. Am. Chem. Soc.  2005,  127:  6968 

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5d Li C.-J. Acc. Chem. Res.  2009,  42:  335 

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6 Fujita K.-i. Furukawa S. Yamaguchi R. J. Organomet. Chem.  2002,  649:  289 

7a Kuninobu Y. Nishina Y. Takeuchi T. Takai K. Angew. Chem. Int. Ed.  2007,  46:  6518 

In addition, we have also reported on rhenium-catalyzed insertion of aldehydes into a C-H bond of aromatic and olefinic compounds. See also:

7b Kuninobu Y. Nishina Y. Nakagawa C. Takai K. J. Am. Chem. Soc.  2006,  128:  12376 

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9

When (E)-3-methyl-3-penten-2-one (2) was used as a hydrogen acceptor, 3-methylpentan-2-one was formed. This result shows that the olefinic moiety of 2 was reduced.

10

Investigation of hydrogen acceptors in dehydrogenation of alcohol 1a {hydrogen acceptor: 1.5 equiv; [Cp*IrCl₂]₂: 0.50 mol%; K₂CO₃: 5.0 mol%; toluene, 150 ˚C; 18 h}: (E)-3-methyl-3-penten-2-one >99%; (1E,4E)-1,5-diphenyl-1,4-pentadien-3-one >99%; 3-methyl-2-cyclohexenone 92%; (E)-4-phenyl-3-buten-2-one 92%; 1-penten-3-one 82%; p-benzoquinone 78%; 2-cyclohexenone 57%; 2-cyclo-pentenone 52%; 3-ethoxy-2-cyclohexenone 8%.

11

First, we conducted the reactions between benzyl alcohol (1a), (E)-3-methyl-3-penten-2-one (2), 1-methyl-2-phenyl-1H-imidazole (3a), and HSiEt₃ in the presence of catalytic amounts of an iridium complex, [Cp*IrCl₂]₂, K₂CO₃, and a manganese complex, MnBr(CO)₅, in toluene. However, the desired reaction did not proceed at all. Therefore, we carried out the coupling reactions in two steps.

12

3-Methyl-2-pentanone, which is formed by hydrogenation of (E)-3-methyl-3-penten-2-one (2), was observed by ^¹H NMR and GCMS.

13

General Procedure of Formal Cross-Coupling Reaction
A mixture of alcohol (1, 0.500 mmol), (E)-3-methyl-3-penten-2-one (2, 73.6 mg 0.750 mmol), [Cp*IrCl₂]₂ (2.0 mg, 0.0025 mmol), K₂CO₃ (3.5 mg, 0.025 mmol), and toluene (1.0 mL) was heated at 150 ˚C for 18 h. Then, imidazole
(3, 0.250 mmol), HSiEt₃ (58.1 mg, 0.500 mmol), and MnBr(CO)₅ (3.4 mg, 0.013 mmol) were added, and the mixture was stirred at 115 ˚C for 24 h. The product was isolated by column chromatography on silica gel [hexane-EtOAc = 5:1. Before column chromatography, the silica
gel was treated with Et₃N {5% solution in hexane-EtOAc
(5/1)}.] to give 4.

14

1-Methyl-2-[2-( p -tolyltriethylsilanyloxymethyl)phenyl]-1 H -imidazole (4c)
^¹H NMR (400 MHz, CDCl₃): δ = 0.54 (q, J = 8.0 Hz, 6 H), 0.86 (t, J = 8.0 Hz, 9 H), 2.23 (s, 3 H), 2.69 (s, 3 H), 6.15 (s, 1 H), 6.74 (d, J = 8.8 Hz, 2 H), 6.81 (s, 1 H), 6.93 (d, J = 6.8 Hz, 2 H), 7.11 (d, J = 7.2 Hz, 1 H), 7.18 (s, 1 H), 7.28 (t, J = 7.2 Hz, 1 H), 7.50 (t, J = 7.2 Hz, 1 H), 8.03 (d, J = 7.6 Hz, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 4.7, 6.7, 32.4, 72.5, 120.2, 125.7, 126.1, 126.8, 127.8, 128.1, 128.3, 129.3, 129.8, 136.2, 141.7, 146.4, 146.6; IR (nujol): ν = 1178 (m), 1117 (m), 1072 (m), 1011 (m), 851 (m) cm^-¹. HRMS (EI⁺): m/z calcd for C₂₃H₃₄N₂OSi [M⁺]: 392.2284; found: 392.2291.