Stereoselective Reformatsky Reaction of Indium Enolates

Significance

There are very few highly selective Reformatsky reactions with ketones compared to the extensive results reported with aldehydes. The indium-mediated Reformatsky reactions tolerate moisture and thus allow nucleophilic additions to a carbonyl in the presence of a free hydroxyl moiety. This key feature is used to achieve high diastereoselectivity in the C-C bond formation and to control the three contiguous stereocenters in 3 and 6. The α-hydroxy ketone coordinates to the indium center and templates the reaction partners in a rigid cyclic transition state. The addition to α-hydroxy ketones has no equivalent with Zn or Sn (under the given conditions: Zn < 15%, Sn = 0%). Acyclic haloesters lead to the E-(O)-enolates with indium, so the diastereoselectivity indicated is relative to the R¹ and R³ substituents.