A peptide-embedded trifluoromethyl ketone catalyst for enantioselective epoxidation

Abstract

The development of peptide-based oxidation catalysts that use a transiently generated dioxirane as the chemically active species is reported. The active catalyst is a chiral trifluoromethyl ketone (Tfk) with a pendant carboxylic acid that can be readily incorporated into a peptide. These peptides were capable of epoxidizing alkenes in high yield (up to 89%) and enantiomeric ratios (er) ranging from 69.0:31.0 to 91.0:9.0, depending on the alkene substitution pattern.

Figure 1

Venerable reactions of dioxiranes. (a) Asymmetric epoxidation with the catalyst of Shi. (b) Regioselective C-H oxidation of a Bryostatin analogue reported by Wender.

Figure 2

Peptide-based catalysts for asymmetric epoxidation. (a) Nucleophilic epoxidation through the Juliá-Colonna process. (b) Catalytic asymmetric epoxidation with aspartyl peptides. (c) Proposed peptide-embedded ketone catalysts for oxidation.

Figure 3

Structures of representative catalysts.

Figure 4

(a) Spiro transition state that gives the observed stereochemistry. (b) X-ray crystal structure of 18•H₂O.

Scheme 1

Synthesis of Tfk precursor.

Scheme 2

Incorporation of 9 into a peptide.

Scheme 3

Optimized conditions for epoxidation.