From allylic alcohols to aldols through a new nickel-mediated tandem reaction: synthetic and mechanistic studies.
Nickel hydride type complexes have been successfully developed as catalysts for the tandem isomerization-aldolization reaction of allylic alcohols with aldehydes. Optimization of the reaction conditions has shown that a cocatalyst, such as MgBr2, 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 nonracemic 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 deuterated catalyst. They gave strong support to a mechanism involving first a transition-metal-mediated isomerization 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.
Cuperly
David
D
ENSCR, Laboratoire de Synthèses et Activations de Biomolécules, CNRS UMR 6052, Avenue du Général Leclerc, 35700 Rennes Beaulieu, France.
Petrignet
Julien
J
Crévisy
Christophe
C
Grée
René
R
D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D009532:Nickel / Q000737:chemistry; D020005:Propanols / Q000737:chemistry
D000447:Aldehydes; D020005:Propanols; C006463:allyl alcohol; D009532:Nickel; C116609:3-hydroxybutanal