Synthesis of Highly Hindered β-Hydroxy Ketones and E-Enones

Significance

The authors report on the scope of a carbonyl addition strategy initially developed in the context of total synthesis (J. Org. Chem. 2007, 72, 9736). Although the Reformatsky-type reaction has been extensively studied with SmI₂, its use had been mostly limited to intramolecular systems. The report shows that the side reactions that often occur with the two carbonyl components do not occur when α-halo ketones 1 or 4 bear an adacent quaternary center. Moreover, this feature brings an attractive solution to the synthetic challenge of obtaining typical aldol products of very hindered aldehydes, and especially ketones.