Peptide-catalyzed kinetic resolution of formamides and thioformamides as an entry to nonracemic amines.
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.
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, USA.
Brandon S
BS
Fowler
Peter J
PJ
Mikochik
Scott J
SJ
Miller
D000588:Amines / Q000737:chemistry*; D002254:Carbonates / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D007700:Kinetics; D010455:Peptides / Q000737:chemistry*
D000588:Amines; D002254:Carbonates; D010455:Peptides; C027600:bis(tert-butoxycarbonyl)oxide