• 10.1021/jo972350i
  • The Journal of Organic Chemistry
  • Volume 63
  • May 1998
  • pp 3677-3679

Not reproducible. Experimental produced mixture


This paper by Verkade and co-workers describes a superbase P(MeNCH2CH2)3N mediated selective monoalkylation of active-methylene compounds. Although malonate alkylation has been known for many years, it is very difficult to obtain really good yields for mono-alkylation of malonate due to the competitive di-alkylation and O-alkylation side reactions. In this regard, this methodology represents an efficient method to obtain the remarkable selectivity for mono-alkylation over di-alkylation and O-alkylation. However, when I tried to reproduce the preparation of 5a (diethyl malonate, methyl iodide, and superbase in CH3CN) following this literature reported procedure, I got a mixture of mono-alkylated and di-alkylated product in 2:3 ratio. I thought perhaps there were something wrong with my synthesized superbase P(MeNCH2CH2)3N (following a literature procedure: Tetrahedron Lett. 1993, 34, 2903). Therefore, we purchased this superbase from Sigma-Aldrich and used it to try this protocol again and got similar result (a mixture mono-alkylated and di-alkylated product in 2:3 ratio). Finally, I pre-purified the diethyl malonate and pre-dried the acetonitrile. Subsequential attempt to reproduce this methodology again failed.      

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