Chemo- and diastereoselective four-component reactions with Rh carbynoids

Abstract

Multi-component reactions (MCRs) provide an efficient method for constructing multiple chemical bonds by combining three or more starting materials in a single operational step, enabling rapid and cost-effective synthesis of structurally diverse compounds. Although carbynoids (R-C:+) have shown potential for the development of selective MCRs due to their unique carbene and carbocation characteristics, their application in four-component reactions (4CRs) has been constrained by challenges in chemoselectivity. Herein, we provide a general solution to the challenges of chemoselective 4CR, using halo diazo reagents as carbynoid precursors, followed by reacting with pyrazoles, alcohols and imines sequentially. This approach allows the simultaneous construction of three different C (sp³)-N, C (sp³)-O, and C (sp³)-C (sp³) bonds on the same carbon. The success of this protocol mainly depends on precise control of chemical kinetics. Detailed experimental studies elucidate that the generation rate of aza-Rh(II)-carbene is faster than oxy-Rh(II)-carbene.