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

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.

SUBMITTER: Fowler BS

PROVIDER: S-EPMC2832744 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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

Fowler Brandon S BS Mikochik Peter J PJ Miller Scott J SJ

Journal of the American Chemical Society 20100301 9

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 ...[more]

PMID: 20158213

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