Benjamin I. Andrews

Asymmetric alkylation of glycine imines using in situ generated phase-transfer catalysts

In this paper we report an investigation into the possibility of effecting the asymmetric alkylation of glycine imines using chiral quaternary ammonium salt catalysts that are generated in situ. It is demonstrated that O-alkyl N-alkyldihydrocinchonidinium salts can be assembled from the parent alkaloid under the reaction conditions required for the liquid–liquid phase-transfer alkylation of glycine imines, and that reactions performed in this way give enantioselectivities comparable to those obtained using pre-prepared catalysts. Utilization of this methodolgy in the generation and screening of catalyst libraries is also demonstrated.

Enantioselective synthesis of aroylalanine derivatives

Abstract In this paper we report the development of a highly enantioselective method for the synthesis of aroylalanines. The approach described employs a protected 2-amino-4-bromopent-4-enoic acid, generated via the asymmetric phase-transfer catalyzed alkylation of a glycine imine, as a key intermediate. Suzuki coupling with an aryl boronic acid followed by ozonolysis of the resulting styrene provides efficient access to the aroylalanine derivatives. The utility of this methodology is illustrated by the synthesis of l -kynurenine along with several aroylalanine inhibitors of the kynurenine pathway.

First asymmetric desymmetrisation of a centrosymmetric molecule: CBS reduction of a 2-pyridone [4 + 4]-photodimer derivative

The B-Me-(S)-CBS catalysed borane reduction of centrosymmetric bis-N-Boc tetrahydro photodimer 3 has been achieved with virtually complete enantiotopic group selectivity (>97% ee) and in good yield (76%).

Computational screening of combinatorial catalyst libraries.

A catalyst design methodology, utilizing combinatorial synthesis in parallel with chemometric analysis, is presented, which considers the 3D steric and electrostatic properties of substituents about a constant core structure.