Enantioselective iridium-catalyzed carbonyl allylation from the alcohol or aldehyde oxidation level using allyl acetate as an allyl metal surrogate

The allylation of carbonyl functionalities is a primary synthetic method that offers access to polyketide natural products. A widely used strategy to carbonyl allylation requires the generation of preformed allyl metal species as well as stoichiometric amounts of metal-based reductants. A recent study employed allenes and dienes as allyl donors in carbonyl allylation of alcohol and aldehyde under transfer hydrogenation conditions using iridium and ruthenium catalysts. However, the cost and tractability of allyl acetate make it an attractive donor for carbonyl allylation. This study unveils the iridium-catalyzed allyl acetate-alcohol and acetate-aldehyde transfer hydrogenative coupling that resulted in the formation of C-allylation products in good yield and excellent enantioselectivity. Under optimal conditions, which employ a catalyst generated from [Ir(cod)Cl]₂ and BIPHEP, and Cs ₂CO₃ and m-NO₂BzOH additives in THF at 100°C, benzylic alcohol 1a was smoothly converted to racemic 2a in 80% isolated yield. Alternatively, the use of (R)-BINAP as ligand under identical conditions furnished 2a in 72% isolated yield and 91% ee. Subsequently, the coupling of allyl acetate with various benzylic alcohols 1a-i under the same set of conditions afforded C-allylation products 2a-i in good yield and exceptional enantioselectivity (Table 1). Banking on expansive applications of this carbonyl allylation protocol, allylation of aldehydes 3a-i was explored. Under standard reaction conditions using isopropanol as terminal reductant and (-)-TMBTP as ligand, identical allylation products 2a-i were also obtained in excellent yield and enantioselectivity (Table 2). (Table Presented) Interestingly, crotyl acetate failed to couple under standard conditions, but the isomeric 3-acetoxy-1-butene efficiently coupled with alcohols 1a-c to yield the crotylation products 4a-c (Table 3).