Polarity‐Directed One‐Pot Asymmetric Cascade Reactions Mediated by Two Catalysts in an Aqueous Buffer

Abstract

Modern organic synthesis predominately relies on functional group reactivity differences to achieve the chemoselective formation of desired products. Herein we report a one-pot multistep asymmetric catalytic reaction in which substrates with similar chemical reactivities are differentiated on the basis of polarity. The one-pot reaction involves two catalysts and three substrates in the presence of water. The reaction mixture consists of two phases: a polar aqueous phase and a hydrophobic organic phase. The biphasic nature of the reaction medium and the polarity properties of the substrates and catalysts enable the selective formation of a major product instead of a statistical mixture of four possible products. We chose a two-step reaction involving condensation and subsequent conjugate addition as a model to develop a polarity-directed cascade reaction. Both reaction steps can involve linear aliphatic aldehydes as substrates (Scheme 1). Our aim was to combine the two reaction