Enantioselective Organocatalytic Singly Occupied Molecular Orbital Activation:  The Enantioselective α-Enolation of Aldehydes

• Published in: Journal of the American Chemical Society 2007-06, Vol.129 (22), p.7004-7005
• Main Authors: Jang, Hye-Young, Hong, Jun-Bae, MacMillan, David W. C
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Allyl Compounds - chemistry; Catalysis; Cyclization; Ketones - chemical synthesis; Ketones - chemistry; Models, Molecular; Silanes - chemistry; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0719428

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.