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A significant improvement of the available organocatalytic methods (in terms of product substrate scope and product enantiomeric excess) for the generation of enantioenriched α-amino acid thioesters via the dynamic kinetic resolution of azlactones is reported. C-9 arylated cinchona alkaloid catalysts have been found to be considerably superior to other bifunctional alkaloid catalysts as the promoters of this asymmetric process.

Bifunctional urea-based cinchona alkaloid derivatives have been shown to promote highly efficient DKR reactions of azalactones using an alcohol nucleophile. The optimum catalyst is remarkably insensitive to the steric bulk of the amino acid residue, allowing alanine-, methionine-, and phenylalanine-derived azalactones to undergo DKR with unprecedented levels of enantioselectivity using a synthetic catalyst. The first DKR of these substrates by thiols and the highly enantioselective desymmetrization of a meso-glutaric anhydride by thiolysis are also reported.

An in silico study examined the stabilities of hydrogen-bonded complexes between simple thiourea catalysts and three different electrophiles and identified a novel, highly active N-tosyl urea catalyst for the promotion of addition reactions to epoxide electrophiles. Synthesis and evaluation of 6 revealed it to be a powerful catalyst for the addition of 1,2-dimethylindole to styrene oxide under conditions in which simple N,N-bis-aryl ureas and thioureas (including 1) are inactive. Subsequent studies determined 6 to be compatible with a range of indole and epoxide substrates (including (E)-stilbene oxide) and found that relatively poor nucleophiles such as sterically and electronically deactivated anilines, thiophenol, and benzyl alcohol could be efficiently and regioselectively added to oxiranes under mild conditions.