Kinetic Resolution of Unsaturated Amides in a Chlorocyclization Reaction: Concomitant Enantiomer Differentiation and Face Selective Alkene Chlorination by a Single Catalyst

The first example of a kinetic resolution
via chlorofunctionalization
of olefins is reported. The enantiomers of racemic unsaturated amides
were found to have different hydrogen-bonding affinities for chiral
Lewis bases in numerous solvents. This interaction was exploited in
developing a kinetic resolution of racemic unsaturated amides via
halocyclization. The same catalyst serves to both “sense chirality”
in the substrate as well as mediate a highly face-selective chlorine
delivery onto the olefin functionality, resulting in stereotriad products
in up to 99:1 dr and up to 98.5:1.5 er. The selectivity factors were typically greater than 50 to allow
for the simultaneous synthesis of both the products and unreacted
substrates in highly enantioenriched form at yields approaching 50%.
The reaction employs catalytic amounts (≤0.50 mol %) of a commercially
available and recyclable organocatalyst.