From Allylic Alcohols to Aldols through a New Nickel-Mediated Tandem Reaction:Synthetic and Mechanistic Studies

摘要

Nickel hydride type complexes have been successfully developed as catalysts for the tandem isom-erization-aldolization reaction of allylic alcohols with aldehydes.Optimization of the reaction conditions has shown that a cocatalyst,such as MgBr_2,has a very positive effect on the kinetics of the reaction and in the yields of aldols.Under such optimized conditions ([NiHCl(dppe)]+MgBr_2 at 3-5 mol%)},this reaction affords the aldols in good to excellent yields.It is a full-atom-economy-type reaction that occurs under mild conditions.Furthermore,it has a broad scope for the allylic alcohols and it is compatible with a wide range of aldehydes,including very bulky derivatives.The reaction is completely regioselective,but it exhibits a low stereoselectivity,except for allylic alcohols with a bulky substituent at the carbinol center.The use of chiral non-racemic catalysts was not successful,affording only racemic compounds.However,it was possible to use asymmetric synthesis for the preparation of optically active aldols.Various mechanistic studies have been performed using,for instance,a deuterated alcohol or a deu-terated catalyst.They gave strong support to a mechanism involving first a transition-metal-mediated isomeriza-tion of the allylic alcohol into the free enol,followed by the addition of the latter intermediate onto the aldehyde in an "hydroxyl-carbonyl-ene" type reaction.These results confirm that allylic alcohols can be considered as new and useful partners in the development of the aldol reaction.