An NBO-TS predictive approach for torquoselectivity of ring opening in 3-substituted cyclobutenes

The torquoselectivity, the inward or outward ring opening of 3-substituted cyclobutenes, is conventionally guided by the donor and/or acceptor ability of the substituent (S). It is typically predicted by estimating the respective ring opening transition state (TS) barriers. While there is no known dissent in regard to the outward rotation of electron-rich substituents from the approaches of TS calculations, the inward rotation was predicted for some electron-accepting substituents and outward for others. To address this divergence in predicting the torquoselectivity, we have used reliable orbital descriptors through natural bond orbital theoretical calculations and demonstrated that (a) interactions nS→s*C3C4 for a lone pair containing substituent, sS→s*C3C4 for a s-donor substituent, sC3C4→p*S for a resonance-accepting substituent and sC3C4→s*S for a s-acceptor substituent constitute the true electronic controls of torquoselectivity, and (b) reversibility of the ring opening event is an additional important contributor to the observed product distribution.