Chemistry Weekly Seminar - Steven Langdon

Title:

Harnessing organocatalysis for synthesis:

DFT and Experimental Examination of the N-Heterocyclic Carbene-Catalyzed Cross-Benzoin reaction

The benzoin reaction represents a well-known yet underutilized route to products containing α-hydroxy ketones. N-Heterocyclic Carbenes (NHCs) catalyze the coupling of two aldehydes in an umpolung process, forming a new carbon-carbon bond and a new stereocentre in the process. Although exquisite enantioselective approaches to homo-benzoin products are well established, until recently chemoselectivity issues have rendered high yielding aldehyde-aldehyde cross-benzoin reactions largely unfeasible. Several approaches are capable of generating cross-benzoin products in reasonable yields, however these typically rely on substrate control; couplings of aldehydes with ketones, sterically hindering one partner, or using pre-formed Breslow intermediates all furnish cross-benzoin products with high chemoselectivity. Work in our group has shown that chemoselective cross-benzoin couplings of aromatic and aliphatic aldehydes can be obtained using morpholinone- or piperidinone-based triazolium salts. A combination of computational and experimental work has been used to explore the origin of chemoselectivity in these systems. Ongoing work based on these computational models seeks to expand potential applications of the chemoselective cross-benzoin reaction through rational modification of the catalyst.