A practical aryl unit for azlactone dynamic kinetic resolution: orthogonally protected products and a ligation-inspired coupling process.

The first strategy for bringing about enantioselective azlactone dynamic kinetic resolution to generate orthogonally protected amino acids has been developed. In the presence of a C2-symmetric squaramide-based catalyst, benzyl alcohol reacts with novel yet readily prepared tetrachloroisopropoxycarbonyl-substituted azlactones to generate trapped phthalimide products of significant synthetic interest with excellent enantiocontrol. These materials are masked amino acids which are demonstrably orthogonally protected: cleavage of the phthalimide can be achieved in the presence of the ester and vice versa. This process could be utilized to bring about a highly stereoselective ligation-type coupling of protected serines (at stoichiometric loadings) with racemic azlactones derived from both natural and abiotic amino acids. After deprotection, a subsequent base-mediated O→N acyl transfer occurs to form a dipeptide.

Catalytic, enantio- and diastereoselective synthesis of γ-butyrolactones incorporating quaternary stereocentres.

A new, highly enantio- and diastereoselective catalytic asymmetric formal cycloaddition of aryl succinic anhydrides and aldehydes which generates paraconic acid (γ-butyrolactone) derivatives is reported.

A catalytic asymmetric reaction involving enolizable anhydrides.

In the presence of a highly efficient novel bifunctional organocatalyst at low loadings under mild conditions, enolizable homophthalic anhydrides can be added to a range of aromatic and aliphatic aldehydes to give dihydroisocoumarins, with excellent yields and diastereo- and enantiocontrol (up to 99% ee).

The dynamic kinetic resolution of azlactones with thiol nucleophiles catalyzed by arylated, deoxygenated cinchona alkaloids.

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.

Organocatalytic asymmetric addition of alcohols and thiols to activated electrophiles: efficient dynamic kinetic resolution and desymmetrization protocols.

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.