Cumyl: A Better N-Protecting Group of α-Diazo Acetamides for Intra­molecular C-H Insertion Reaction and its Application in the Synthesis of ­Pregabalin and 3-Benzyloxy Pyrrolidine

Abstract

Via intramolecular C-H insertion of N-cumyl α-diazo ­acetamides, γ-lactams were efficiently synthesized with excellent regioselectivity. A concise route for the preparation of pregabalin (79% overall yield) and 3-benzyloxy pyrrolidine (21% overall yield) were reported.

cumyl - C-H insertion - pregabalin - pyrrolidine

References

1a Ye T. Mckervey MA. Chem. Rev.  1994,  94:  1091 

1b Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds   Wiley; New York: 1998.  p.129 

1c Doyle MP. Forbes DC. Chem. Rev.  1998,  98:  911 

1d Merlic CA. Zechman AL. Synthesis  2003,  1137 

1e Davies HML. Beckwith REJ. Chem. Rev.  2003,  103:  2861 

2 Zhenliang C. Zhiyong C. Yaozhong J. Wenhao H. Synlett  2003,  1965 

3a Padwa A. Austin DJ. Hornbuckle SF. Semenes MA. J. Am. Chem. Soc.  1992,  114:  1874 

3b Padwa A. Austin DJ. Price AT. Semones MA. Doyle MP. Protopopova MN. Winchester WR. Tran A. J. Am. Chem. Soc.  1993,  115:  8669 

3c Watanabe N. Anada M. Hashimoto S. Ikegami S. Synlett  1994,  1031 

3d Yoon CH. Zaworotho MJ. Moulton B. Jung KW. Org. Lett.  2001,  3:  3539 

3e Yoon CH. Nagle A. Chen C. Gandhi D. Jung KW. Org. Lett.  2003,  5:  2259 

4 Anada M. Mita O. Watanabe H. Kitagaki S. Hashimoto S. Synlett  1999,  1775 

5 Wee AGH. Liu B. Zhang L. J. Org. Chem.  1992,  57:  4404 

6 Doyle MP. Hu W. Wee AGH. Wang Z. Duncan C. Org. Lett.  2003,  5:  407 

7 Yuen P. Kanter GD. Taylor CP. Vartanian MG. Bioorg. Med. Chem. Lett.  1994,  4:  823 

8 Wee AGH. Duncan SC. Tetrahedron Lett.  2002,  43:  6173 

9 Clayden J. Menet CJ. Tchabanenko K. Tetrahedron  2002,  58:  4727