Iridium-Catalyzed Selective C-C Bond Cleavage of Nitriles and Ketones

Abstract

Selective and catalytic C-C bond cleavage of pentanedinitriles and 5-oxohexanenitriles can be performed in the presence of iridium hydride complex IrH₅(Pi-Pr₃)₂ (1). The key steps of this reaction are α-C-H activation of the cyano or carbonyl group and subsequent β-carbon elimination.

Key words

iridium hydride complex - C-H activation - β-carbon elimination - nitrile - ketone

References

• 1 Murakami M. Ito Y. Activation of Unreactive Bonds and Organic Synthesis, In Topics in Organometallic Chemistry   Vol 3:  Murai S. Springer; Berlin: 1999.  p.97 
• 2a Mitsudo T.-a. Kondo T. Synlett  2001,  309 
• 2b Nishimura T. Uemura S. Synlett  2004,  201 
• 3 Kaminsky W. Hartmann F. Angew. Chem. Int. Ed.  2000,  39:  331 
• 4a Butcher JA. inventors; US Pat. US  5315055. 
• 4b Dufaud V. Basset J.-M. Angew. Chem. Int. Ed.  1998,  37:  806 
• 4c Uemichi Y. Takuma K. Ayame A. Chem. Commun.  1998,  1975 
• 4d Pifer A. Sen A. Angew. Chem. Int. Ed.  1998,  37:  3306 
• For reviews, see:
• 5a Bishop KC. Chem. Rev.  1976,  76:  461 
• 5b Crabtree RH. Chem. Rev.  1985,  85:  245 
• 5c Rybtchinski B. Milstein D. Angew. Chem. Int. Ed.  1999,  38:  870 
• 5d Takahashi T. Kanno K.-i. Yuki Gosei Kagaku Kyokaishi  2003,  61:  938 
• 6a Murakami M. Amii H. Ito Y. Nature  1994,  370:  540 
• 6b Edelbach BL. Lachicotte RJ. Jones WD. J. Am. Chem. Soc.  1998,  120:  2843 
• 6c Suginome M. Matsuda T. Ito Y. J. Am. Chem. Soc.  2000,  122:  11015 
• 6d Kondo T. Kaneko Y. Taguchi Y. Nakamura A. Okada T. Shiotsuki M. Ura Y. Wada K. Mitsudo T.-a. J. Am. Chem. Soc.  2002,  124:  6824 
• 7a Suggs JW. Jun C.-H. J. Chem. Soc., Chem. Commun.  1985,  92 
• 7b Gozin M. Weisman A. Ben-David Y. Milstein D. Nature  1993,  364:  699 
• 7c Jun C.-H. Lee H. J. Am. Chem. Soc.  1999,  121:  880 
• 7d Chatani N. Ie Y. Kakiuchi F. Murai S. J. Am. Chem. Soc.  1999,  121:  8645 
• 7e Jun C.-H. Lee H. Lim S.-G. J. Am. Chem. Soc.  2001,  123:  751 
• 8a Watson PL. Roe DC. J. Am. Chem. Soc.  1982,  104:  6471 
• 8b Bunel E. Burger BJ. Bercaw JE. J. Am. Chem. Soc.  1988,  110:  976 
• 9a Harayama H. Kuroki T. Kimura M. Tanaka S. Tamaru Y. Angew. Chem., Int. Ed. Engl.  1997,  36:  2352 
• 9b Kondo T. Kodoi K. Nishinaga E. Okada T. Morisaki Y. Watanabe Y. Mitsudo T.-a. J. Am. Chem. Soc.  1998,  120:  5587 
• 9c Terao Y. Wakui H. Satoh T. Miura M. Nomura M. J. Am. Chem. Soc.  2001,  123:  10407 
• 9d Nishimura T. Araki H. Maeda Y. Uemura S. Org. Lett.  2003,  5:  2997 
• For stoichiometric reactions, see:
• 10a Flood TC. Statler JA. Organometallics  1984,  3:  1795 
• 10b McNeill K. Andersen RA. Bergman RG. J. Am. Chem. Soc.  1997,  119:  11244 
• For catalytic reactions, see:
• 11a Bessmertnykh AG. Blinov KA. Grishin YK. Donskaya NA. Tveritinova EV. Yur‘eva NM. Beletskaya IP. J. Org. Chem.  1997,  62:  6069 
• 11b Tsukada N. Shibuya A. Nakamura I. Yamamoto Y. J. Am. Chem. Soc.  1997,  119:  8123 
• 11c Nishimura T. Ohe K. Uemura S. J. Am. Chem. Soc.  1999,  121:  2645 
• 11d Park S.-B. Cha JK. Org. Lett.  2000,  2:  147 
• 11e Nishimura T. Uemura S. J. Am. Chem. Soc.  2000,  122:  12049 
• 11f Nishimura T. Matsumura S. Maeda Y. Uemura S. Chem. Commun.  2002,  50 
• 11g Itazaki M. Nishihara Y. Osakada K. J. Org. Chem.  2002,  67:  6889 
• 12a Murahashi S.-I. Takaya H. Acc. Chem. Res.  2000,  33:  225 
• 12b Murahashi S.-I. Takaya H. Naota T. Pure Appl. Chem.  2002,  74:  19 
• 13 Takaya H. Naota T. Murahashi S.-I. J. Am. Chem. Soc.  1998,  120:  4244 
• 14 Takaya H. Yoshida K. Isozaki K. Terai H. Murahashi S.-I. Angew. Chem. Int. Ed.  2003,  42:  3302 
• 16a Goldman AS. Halpern J. J. Am. Chem. Soc.  1987,  109:  7537 
• 16b Klabunde U. Parshall GW. J. Am. Chem. Soc.  1972,  94:  9081 
• 20a Nolan SP. Hoff CD. Stoutland PO. Newman LJ. Buchanan JM. Bergman RG. Yang GK. Peters KS. J. Am. Chem. Soc.  1987,  109:  3143 
• 20b Simoes JAM. Beauchamp JL. Chem. Rev.  1999,  90:  629 

15

General Procedure for the Iridium-Catalyzed C-C Bond Cleavage of 2-Methyl-2-phenyl-pentanedinitrile (5).
In a 25 mL sealed tube, iridium catalysts (0.1 mmol), 5
(1 mmol), and toluene (0.5 mL) were placed and stirred for 12 h at 150 °C under argon atmosphere. The yield of
2-phenylpropionitrile 6 was determined by NMR using dibenzyl as an internal standard.

17

General Procedure for the Iridium-Catalyzed C-C Bond Cleavage of Nitriles and Ketones.
In a 25mL of sealed tube, IrH₅ (Pi-Pr₃)₂ (1, 0.2 mmol), nitriles or ketones (1 mmol), and toluene (0.5 mL) were placed and stirred for 12 h at 150 °C under argon atmosphere. The yields of products were determined by NMR using dibenzyl as an internal standard. All the products were confirmed by ¹H NMR, ¹³C NMR, and HRMS.

18

In the case of the reaction of 2-methyl-2- phenylhexane-dinitrile (12), the formation of 2-amino-1-cyano-3-methyl-3-phenylcyclopentene (13) was observed.¹⁹ The cyclization would proceed via nucleophilic addition of alkyliridium intermediate to the CN triple bond of nitriles (Scheme [4] ). This cyclic product unequivocally supports the occurrence of α-C-H bond activation and the formation of intermediate 8 (Scheme [4] ).

Scheme 4

19

In a 25mL of sealed tube, 2-methyl-2- phenylhexanedinitrile (12, 200 mg, 1.0 mmol), IrH₅ (Pi-Pr₃)₂ (1, 52 mg, 0.1 mmol), and toluene (0.5 mL) were placed and stirred for 24 h at 150 °C under argon atmosphere. After removal of the solvent, the mixture was purified by silica gel column chromatography and by Kugelrohr distillation to give 2-amino-1-cyano-3-methyl-3-phenylcyclopentene (13, 1:0.8 diastereomer mixture) as a colorless oil (47 mg, 24%). ¹H NMR (270 MHz, CDCl₃): δ = 1.54 (s, 3 H, -CH ₃), 1.95-2.15 [m, 2 H, -CH ₂-C(Me)(Ph)-], 2.48-2.53 [m, 2 H, -CH ₂-C(CN)-], 4.25 (br, 2 H, -NH ₂), 7.22-7.40 (m, 5 H, -C₆ H ₅). ¹³C NMR (68 MHz, CDCl₃): δ = 167.2 (C-NH₂), 144.1
(-C ₆H₅), 128.4 (-C ₆H₅), 126.7 (-C ₆H₅), 126.2 (-C ₆H₅), 118.8 (-CN), 74.2 (C-CN), 53.0 (C-CH₃), 41.5 [-CH₂-C(Me)(Ph)-], 28.1 [-CH₂-C(CN)-], 22.9 (-CH₃). MS (EI, 70 eV):
m/z (%) = 198, 183, 168, 166, 140, 129, 115, 105, 91, 77.