Synthesis of Diazaphospholenes for Improved Catalysis

Abstract

Diazaphospholene (DAP) synthesis and reactivity has been emerging over the last two decades. Recently, DAPs have been employed as catalysts for asymmetric reduction transformations. Specifically in the Speed group we use DAP catalysts for asymmetric reduction of imines. This thesis provides a comprehensive overview of the synthetic procedures employed to manipulate the substituents surrounding the DAP scaffold. The subsequent investigation involved testing each isolated DAP compound to assess its enhanced reactivity and selectivity in imine reduction.

Initially, the objective was to produce DAP variants with different substituents around the stereogenic centre, specifically larger aryl or alkyl groups that offer increased steric hindrance. We hypothesized that these bulkier substituents would establish a more restrictive stereochemical environment around the phosphorus centre, thereby improving enantioselectivity. However, this led to only one DAP variant that had comparable reactivity and selectivity to the current best DAP.

The synthesis of DAPs containing larger aryl or alkyl groups around the stereogenic centre led to more efficient syntheses of 1-dibenzothiophene derivatives and 3- bromonaphthothiophene as starting materials for additional DAP derivatives. However, neither DAPs were fruitful for improved reactivity or selectivity for imine reduction.

Considering the limited success achieved when modifying the substituents around the stereogenic centre, it became apparent that exploring alternative strategies was necessary. Consequently, attention was shifted towards alternating the backbone of the DAP scaffold. This led to a more rigid DAP that has shown improved enantioselectivity for imine reduction to make acyclic and exocyclic amines.