Zinc-mediated α-regioselective Barbier-type cinnamylation reactions of aldehydes, ketones and esters

Abstract

We report a simple, efficient, and general method for the zinc-mediated regioselective cinnamylation of aldehydes and ketones under Barbier-type conditions in a one-pot synthesis affording the corresponding α-cinnamylated alcohols in moderate to excellent yields. Compared to the literature procedures, this approach is operationally simple, uses simple reactants, and provides direct access to linear α-cinnamylated alcohols with excellent regioselectivity. Experimental results suggest that the reactions proceed through the radical pathway. In addition, the reaction was found to be scalable to the gram-scale and the one-pot protocol is also applicable to less reactive esters leading to bishomoallylic alcohols which were valuable intermediates for desymmetrizing intramolecular Heck cyclization, allowing for the elaboration to functionalized building blocks.

Enantioselective Desymmetrization Triggered by Iminium‐Enamine Activation: Access to Complex Cyclohepta[b]indoles

“…Treatment of 4 a with excess NaBH 4 at room temperature provided diol 7 in 89 % yield with exclusive diastereoselectivity. However, the zinc‐mediated Barbier‐type allylation on aldehyde 4 a furnished desired product 8 with poor diastereoselectivity [17] . Chemoselective Wittig olefination of 4 a followed by hydrogenation resulted in saturated ester 9 with a high yield.…”

“…However, the zinc-mediated Barbier-type allylation on aldehyde 4 a furnished desired product 8 with poor diastereoselectivity. [17] Chemoselective Wittig olefination of 4 a followed by hydrogenation resulted in saturated ester 9 with a high yield.…”

Zinc/Bismuth-Mediated Allylation Reaction of Biomass Feedstocks: Synthesis of Furanic Diols

“…Similar Bi-mediated Barbier-type reaction undergoes a-substitution as opposed to −substitution (reported here for 32 and 33). 18,19 To our knowledge, such mono-allylation of dialdehydes are not known. This interesting result motivated us to apply the protocol to aryl dicarboxaldehydes to synthesize corresponding mono-allylated derivatives.…”

“…1,1'-(furan-2,5-diyl)bis(but-3-en-1-ol), 19; light yellow oil; yield 82%; following procedure 2; 1 H (400 MHz, CDCl3) δ 6. 19…”

“…Similar Bi-mediated Barbier-type reactions undergo -substitution as opposed to -substitution (reported here for 32 and 33). 18,19 To our knowledge, such monoallylations of dialdehydes are not known.…”