Magnesium coordination-directed n-selective stereospecific alkylation of 2-pyridones, carbamates, and amides using α-halocarboxylic acids

J Am Chem Soc. 2010 Nov 10;132(44):15525-7. doi: 10.1021/ja107709w.

Abstract

A general inversion-stereospecific, N-selective alkylation of substituted 2-pyridones (and analogues), amides, and carbamates using chiral α-chloro- or bromocarboxylic acids in the presence of KOt-Bu (or KHMDS) and Mg(Ot-Bu)(2) is reported. The resulting α-chiral carboxylic acid products were isolated by crystallization in good chemical yields and in high ee (>90% ee). Mechanistic evidence suggests that the reaction proceeds through 2-pyridone O-coordinated Mg carboxylate intermediates, which afford the product through an intramolecular S(N)2 alkylation.

MeSH terms

  • Alkylation
  • Amides / chemistry*
  • Carbamates / chemistry*
  • Carboxylic Acids / chemistry*
  • Halogens / chemistry*
  • Hydrocarbons, Halogenated / chemistry
  • Magnesium / chemistry*
  • Molecular Structure
  • Pyridones / chemistry*
  • Stereoisomerism

Substances

  • Amides
  • Carbamates
  • Carboxylic Acids
  • Halogens
  • Hydrocarbons, Halogenated
  • Pyridones
  • Magnesium