Enantioselective Organocatalytic Singly Occupied Molecular Orbital Activation: The Enantioselective α-Enolation of Aldehydes
The first enantioselective organocatalytic α-enolation of aldehydes has been accomplished using singly occupied molecular orbital (SOMO) catalysis. Chiral secondary amines react with aldehydes to form transient enamines that undergo selective one-electron oxidation to generate electrophilic radical cations. These SOMO-activated radical cations are susceptible to attack by ketone-derived enol silanes, rendering α-substituted-γ-ketoaldehyde products with uniformly high levels of asymmetric induction. Wide latitude in both the aldehyde and enolsilane component is readily accommodated, allowing generic access to a diverse assortment of enantioenriched 1,4-dicarbonyl compounds. This report highlights the potential of SOMO catalysis to enable the development of entirely new classes of asymmetric reactions that have no traditional catalytic equivalents.
Additional Information© 2007 American Chemical Society. Received March 19, 2007. Publication Date (Web): May 12, 2007. Financial support was provided by the NIHGMS (Grant R01 GM078201-01-01) and kind gifts from Amgen and Merck. Robert A. Pascal is thanked for his assistance in carrying out DFT calculations.
Supplemental Material - ja0719428si20070430_050938.pdf