Regioselective γ-Alkylation of tert-Butyl 2,4-Dioxopiperidine-1-carboxylate

Abstract

A method for the regioselective γ-alkylation of N-Boc protected piperidine-2,4-dione is reported. The use of a wide variety of electrophiles demonstrates the robustness of the procedure. The reaction offers facile access to synthetically useful derivatives. A mechanistic hypothesis is given, explaining the essential role played by the lithium counter-ion.

Key words

γ-alkylation - regioselectivity - carbanions - β-keto­amides - piperidine-2,4-dione

References

• 1 Thompson CM. Green DLC. Tetrahedron  1991,  47:  4223 
• 2 Thompson CM. Dianion Chemistry in Organic Synthesis   CRC Press Inc.; Boca Raton: 1994. 
• 3 D’Alessio R, Tibolla M, Varasi M, Vanotti E, Montagnoli A, Santocanale C, Martina K, and Menichincheri M. inventors; WO  2005/013986. 
• 4 D’Alessio R, Tibolla M, Varasi M, Vanotti E, Montagnoli A, Santocanale C, Orsini P, and Pillan A. inventors; WO  2005/014572. 
• 5 Weiler L. J. Am. Chem. Soc.  1970,  92:  6702 
• 6 Huckin SN. Weiler L. J. Am. Chem. Soc.  1974,  96:  1082 
• 7 Szczecinski P. Gryff-Keller A. Molchanov S. J. Org. Chem.  2006,  71:  4636 
• 8 Ibenmoussa S. Chavignon O. Teulade J. Viols H. Debouzy J. Chapat J. Gueiffier A. Heterocycl. Commun.  1998,  4:  317 
• 9 Colombo M. Riccardi-Sirtori F. Rizzo V. Rapid Commun. Mass Spectrom.  2004,  18:  511