Unveiling the Reaction Mechanism of the Das/Chechik/Marek Synthesis of Stereodefined Quaternary Carbon Centers

The reaction mechanism of the Cu+-catalyzed introduction two all-carbon-substituted stereocenters in an ynamide system using a Grignard reagent, zinc carbenoid, and aldehyde, was investigated density-functional theory. In contrast to formation organocopper(I) compound subsequent carbocupration reaction, previously postulated as initial step, proved instead proceed through complexation substrate alkyne bond by Cu+-catalyst, which primes this for with reagent. Subsequent addition carbenoid then enables nucleophilic attack on incoming is revealed rate-limiting step. Our computations have also identified factors governing regio- setereoselectivity interesting suggest possible paths its further development.