“Water” accelerated B(C6F5)3-catalyzed Mukaiyama-aldol reaction: outer-sphere activation model

Abstract

A “water” accelerated metal-free catalytic system has been discovered for the Mukaiyama-aldol reaction. The system involves the use of B(C6F5)3 as a catalyst, which is water-tolerant and able to activate the carbonyl group through a hydrogen bonding network generated by the catalyst. This activation method allows the reactions to be performed with very low catalyst loading, as low as 0.5 mol%. The scope of substrates is broad and a wide variety of functional groups are well tolerated. Diverse aliphatic aldehydes, aromatic aldehydes, unsaturated aldehydes and aromatic ketones coupled with silyl enol ethers/silyl ketone acetals to generate their corresponding β-hydroxy carbonyl compounds in moderate to good yields. This discovery represents a significant advancement in the field of organic synthesis, as it provides a new, practical and sustainable solution for carbon-carbon bond formation in water.