Enantioselective conjugate addition of stabilized arylzinc halides to enones

The enantioselective addition of organometallic compounds is particularly important in the field of the total synthesis of natural products. Several organometallics have been used for this purpose but, except for some seminal works, the enantioselective addition of organozinc halides to enones remains undeveloped with respect to the reaction of other organometallics like, for example, organoboron. A few examples of this chemistry with organozinc halides have been reported and, in all cases, the organometallics used in the addition have been made by transmetalation from highly reactive organolithium species. This latter aspect limits the application of the reaction from the point of view of functional group tolerance, environmental friendliness, and general usability. We developed an enantioselective conjugate addition protocol of organozinc halides to enones, both cyclic and linear. The organozinc reagents employed in our protocol have been made by direct insertion of zinc metal into organic halides and have been stabilized with TMEDA to improve the functional group tolerance. Yields and enantiomeric excess are good to excellent and the protocol has general applicability.