Non-Cryogenic CeCl3-Promoted Double Additions of Methyllithium and n-Butyllithium to Unsaturated Nitriles

John Limanto; Benjamin Dorner; Paul N. Devine

doi:10.1055/s-2006-950362

PAPER

Non-Cryogenic CeCl₃-Promoted Double Additions of Methyllithium and n-Butyllithium to Unsaturated Nitriles

John Limanto*, Benjamin Dorner, Paul N. Devine
Department of Process Research, Merck Research Laboratories, Merck & Co., Inc., P.O. Box 2000, Rahway, NJ 07065, USA
Fax: +1(732)5941499; e-Mail: john_limanto@merck.com;

Abstract

Alle Artikel dieser Rubrik

Abstract

Subjection of methyl or n-butyllithium to a mixture of nitriles and activated cerium chloride in THF at -10 to 0 °C afforded the corresponding carbinamines, which were isolated as either the hydrochloride salts or acetamide or benzamide derivatives in 30-91% yields.

Key words

carbinamines - carbinamides - organocerium reagents - non-cryogenic conditions - reaction optimization

Volltext

Referenzen

References

1 Layer RW. Chem. Rev. 1963, 63: 489

2a Steinig AG. Spero DM. Org. Prep. Proced. Int. 2000, 32: 205 ; and references cited therein

2b Charette AB. Mellon C . Tetrahedron 1998, 54: 10525

2c For a review on organocerium compounds in organic syntheses, see: Liu H.-J. Shia K.-S. Shang X. Zhu B.-Y. Tetrahedron 1999, 55: 3803

3a Amouroux R. Axiotis GP. Synthesis 1981, 270

3b Chastrette M. Axiotis GP. Synthesis 1980, 889

3c Henze HR. Thompson TR. J. Am. Chem. Soc. 1943, 65: 1422

3d Allen BB. Henze HR. J. Am. Chem. Soc. 1939, 61: 1790

4a Grassberger MA. Horvath A. Schulz G. Tetrahedron Lett. 1991, 32: 7393

4b Henze HR. Allen BB. Leslie WB. J. Am. Chem. Soc. 1943, 65: 87

For examples, see:

5a Fleming FF. Wang Q. Chem. Rev. 2003, 103: 2035

5b Fleming FF. Wang Q. Zhang Z. Steward OW. J. Org. Chem. 2002, 67: 5953

5c Fleming FF. Hussain Z. Weaver D. Norman RE. J. Org. Chem. 1997, 62: 1305

5d Basha FZ. DeBernardis JF. Spanton S. J. Org. Chem. 1985, 50: 4160

5e For organocerium reaction with benzamides, see: Calderwood DJ. Davies RV. Rafferty P. Twigger HL. Whelan HM. Tetrahedron Lett. 1997, 38: 1241

6a Ciganek E. J. Org. Chem. 1992, 57: 4521

6b Ciganek E. inventors; US Patent 5306821. ; Chem. Abstr. 1994, 121, 508195

6c For a subsequent example, see: Fadij V. Lenoir EA. Suto MJ. Zeller JR. Wemple J. Tetrahedron: Asymmetry 1994, 5: 1131

7 Imamoto T. Takiyama N. Nakamura K. Hatajima T. Kamiya Y. J. Am. Chem. Soc. 1989, 111: 4392

Typical temperature is 130-150 °C. For modified drying process, see:

8a Larkin JP. Wehrey C. Boffelli P. Lagraulet H. Lemaitre G. Nedelee A. Prat D. Org. Proc. Res. Dev. 2002, 6: 20

8b Dimitrov V. Kostova K. Genov M. Tetrahedron Lett. 1996, 37: 6787

8c For identification of the species obtained post drying, see: Evans WJ. Feldman JD. Ziller JW. J. Am. Chem. Soc. 1996, 118: 4581

CeCl₃-nTHF complex was proposed to be the required species for successful generation of the corresponding organocerium reagent (‘RCeCl₂’) (see ref. 7b). For activation of CeCl₃ via sonication, see:

9a Greeves N. Lyford L. Pease JE. Tetrahedron Lett. 1994, 35: 285

9b Greeves N. Lyford L. Tetrahedron Lett. 1992, 33: 4759

For representative examples, see:

10a Curtius rearrangement: Shiori Y. In Comprehensive Organic Synthesis Vol. 6: Trost BM. Fleming I. Pergamon; Oxford: 1991. p.795

10b Ritter reaction: Bishop R. In Comprehensive Organic Synthesis Vol. 6: Trost BM. Fleming I. Pergamon; Oxford: 1991. p.261

10c Addition to Ketimines, see ref. 2a and: Bloch R. Chem. Rev. 1998, 98: 1407

10d Nitro reduction: Weis CD. Newkome GR. Synthesis 1995, 1053 ; and references cited therein

11

For a previous report on reaction between ketone-CeCl₃ complexes and Grignard reagents at 0 °C, see ref. 3a.

12

Anhyd CeCl₃ for these studies was obtained from GFS Chemicals at $ 1.06/gram.

13 Conlon DA. Kumke D. Moeder C. Hardiman M. Hutson G. Sailer L. Adv. Synth. Catal. 2004, 346: 1307

14 For a review of the acidity strength of alkanenitrile, see: Hibbert F. In The Chemistry of Triple-Bonded Functional Groups, Part I Patai S. Rappoport Z. Wiley-Interscience; Chichester: 1983. p.699

For generation of ketones via additions of organolithium reagents to unsaturated nitriles at -78 °C, see for example:

15a Lashley MR. Dicus CW. Brown K. Nantz MH. Org. Prep. Proced. Int. 2003, 35: 231

15b Yoneda R. Harusawa S. Kurihara T. J. Chem. Soc., Perkin Trans. 1 1988, 3163

15c Fang JM. Chang HT. J. Chem. Soc., Perkin Trans. 1 1988, 1945