Nonenzymatic dynamic kinetic resolution of secondary alcohols via enantioselective acylation: Synthetic and mechanistic studies

Sarah Yunmi Lee, Jaclyn M. Murphy, Atsushi Ukai, Gregory C. Fu

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Because of the ubiquity of the secondary carbinol subunit, the development of new methods for its enantioselective synthesis remains an important ongoing challenge. In this report, we describe the first nonenzymatic method for the dynamic kinetic resolution (DKR) of secondary alcohols (specifically, aryl alkyl carbinols) through enantioselective acylation, and we substantially expand the scope of this approach, vis-à-vis enzymatic reactions. Simply combining an effective process for the kinetic resolution of alcohols with an active catalyst for the racemization of alcohols did not lead to DKR, due to the incompatibility of the ruthenium-based racemization catalyst with the acylating agent (Ac2O) used in the kinetic resolution. A mechanistic investigation revealed that the ruthenium catalyst is deactivated through the formation of a stable ruthenium-acetate complex; this deleterious pathway was circumvented through the appropriate choice of acylating agent (an acyl carbonate). Mechanistic studies of this new process point to reversible N-acylation of the nucleophilic catalyst, acyl transfer from the catalyst to the alcohol as the rate-determining step, and carbonate anion serving as the Brønsted base in that acyl-transfer step.

Original languageEnglish
Pages (from-to)15149-15153
Number of pages5
JournalJournal of the American Chemical Society
Volume134
Issue number36
DOIs
Publication statusPublished - 2012 Sep 12

Fingerprint

Acylation
Ruthenium
Alcohols
Catalysts
Kinetics
Carbonates
Methanol
Anions
Acetates
Negative ions

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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Nonenzymatic dynamic kinetic resolution of secondary alcohols via enantioselective acylation : Synthetic and mechanistic studies. / Lee, Sarah Yunmi; Murphy, Jaclyn M.; Ukai, Atsushi; Fu, Gregory C.

In: Journal of the American Chemical Society, Vol. 134, No. 36, 12.09.2012, p. 15149-15153.

Research output: Contribution to journalArticle

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