Mechanism and Regioselectivity of Intramolecular [2+2] Cycloaddition of Ene–Ketenes: A DFT Study

Intramolecular [2+2] cycloaddition of ene–ketenes gives either fused‐ring (via normal [2+2] cycloaddition) or bridged‐ring (via cross‐[2+2] cycloaddition) cyclobutanones. For example, terminal ene–ketenes give the fused‐ring cycloadducts, whereas dimethyl‐substituted ene–ketenes furnish bridged‐ring cycloadducts. For monomethyl‐substituted ene–ketenes, both [2+2] cycloadducts are generated. However, there are no systematic theoretical studies on such regiochemistry in the literature. Herein, we report our DFT study on the mechanism and regioselectivity of these intramolecular [2+2] cycloadditions. DFT calculations reveal that both normal and cross‐[2+2] cycloadditions are concerted processes. The normal [2+2] cycloaddition transition state is forming an internal carbocation while the cross‐[2+2] cycloaddition transition state is generating an external carbocation (see Scheme 1 of the paper). On the basis of the relative stability of these carbocations, which is affected by both the tether and the substituent(s) on the alkene, a regiochemistry prediction model is proposed to understand and predict the reaction outcome.