Peptide-catalyzed kinetic resolution of formamides and thioformamides as an entry to nonracemic amines

J Am Chem Soc. 2010 Mar 10;132(9):2870-1. doi: 10.1021/ja9107897.

Abstract

We report a fundamentally unique approach to the catalytic kinetic resolution of amine derivatives based on formamide and thioformamide substrates. Readily accessible histidine-containing peptides mediate the kinetic resolutions with as little as 5 mol % catalyst. Selectivity factors (k(rel)) as high as 43.7 were observed under simple reaction conditions utilizing Boc(2)O as the reagent at room temperature. Mechanistic experiments were conducted that established a higher level of reactivity for thioformamide substrates than for their formamide analogues. The products of these asymmetric reactions were shown to be readily converted to desirable building blocks such as N-Boc-amines and the parent chiral formamide compounds.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amines / chemistry*
  • Carbonates / chemical synthesis
  • Carbonates / chemistry*
  • Catalysis
  • Kinetics
  • Peptides / chemistry*

Substances

  • Amines
  • Carbonates
  • Peptides
  • bis(tert-butoxycarbonyl)oxide