Stereoselective Homoallylation of Aldehydes and Ketones

Key words

homoallylation - nickel - aldehydes - ketones

Significance

In the presence of catalytic Ni(acac)₂ and stoichiometric Et₃B or Et₂Zn, 1,3-dienes are added to aldehydes and ketones to stereoselectively afford homoallylation products. Aromatic aldehydes react in the presence of Et₃B with 1,3-anti selectivity whereas aliphatic aldehydes react in the presence of Et₂Zn to give exclusively 1,3-anti products. Terminally substituted dienes generally afford 1,2-anti products, except hydroxyterminal dienes which afford 1,2-syn products. Less reactive moieties such as ketones and cyclohexadiene required Et₂Zn, and afforded the product in moderate yields, with cyclohexadiene affording allylation, not homallylation products. Catalyst loadings as low as 1 mol% were used on a 50-mmol scale and the diene loading was decreased to 1.1 equivalents. The method was applied to a 10-g scale reaction of isoprene and dehydrocinnamaldehyde, affording product in 80% yield.

Comment

This report is a thorough examination of the Ni-catalyzed homoallylation of aldehydes and ketones, which explored nearly all of the factors affecting the reaction. Mechanistically, it is proposed that Ni(0) coordinates to the diene and aldehyde, promoting aldehyde addition and Ni(II)-π-allyl formation. Ethyl transfer from Et₃B or Et₂Zn forms an ethylnickel(II) species which undergoes β-hydride elimination followed by reductive elimination to generate Ni(0) and the product.