Rhodium-Catalyzed [5 + 1 + 2] Cycloaddition of Yne-3-Acyloxy-1,4-Enynes (YACEs) and Carbon Monoxide: Reaction Development and Mechanism

Developing new reaction to synthesize challenging eight-membered carbocycles is a research frontier of organic synthesis. Reported here is the development of the first Rh-catalyzed [5 + 1 + 2] cycloaddition of yne-3-acyloxy-1,4-enyne (Yne-ACEs, short as YACEs) and CO, in which sequentially 5-carbon (generated from 3-acyloxy-1,4-enynes), 1-carbon (CO) and 2-carbon (alkynes) are embedded into the final 5/8 scaffold containing cyclooctatrienone structure. This reaction has broad scope and can be carried out under mild conditions. Keys to the success of the present [5 + 1 + 2] reaction, discovered and supported by experiments and ab initio calculations, include: using terminal alkyne in the 3-acyloxy-1,4-enyne moiety of the substrates so that 1,2-acyloxy migration (instead of 1,3-acyloxy migration, a step required for competing [4 + 2 + 1] reaction) can be realized; applying electron-rich aryl group (here is p-dimethylamino aryl) in the acyloxy group to make [5 + 1] pathway disfavored. Quantum chemical calculations have also been used to answer why this reaction is [5 + 1 + 2] but not [5 + 2 + 1] (where alkyne insertion is ahead of CO insertion), and the factors disfavoring the competitive [5 + 2], [5 + 1] and [4 + 2 + 1] reactions.