How an early or late transition state impacts the stereoselectivity of tetrahydropyran formation by intramolecular oxa-Michael addition

• Main Authors: Csókás, Dániel, Ho, Annabel Xuan Ying, Ramabhadran, Raghunath O., Bates, Roderick Wayland
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Chemistry; Oxa-Michael Addition; Stereoselectivity
• Online Access: https://hdl.handle.net/10356/141244
• Institution: Nanyang Technological University

The intramolecular oxa-Michael addition giving tetrahydropyrans has been examined experimentally using both acidic and basic catalysis. With acidic catalysis, the diequatorial product is exclusively obtained in a kinetically controlled reaction in all cases. Under basic conditions at low temperature, the reaction is again under kinetic control, but formation of the axial-equatorial isomer is generally favoured with an (E)-Michael acceptor, although isomerisation to the diequatorial isomer is observed at higher temperatures. Computationally, it is found that the acid catalysed reaction has a late transition state and the kinetic favouring of the diequatorial isomer has a steric explanation. In contrast, under strongly basic conditions, an early transition state is found. Electrostatic effects are likely to be the main contributor to the stereoselectivity for the (E)-isomer and steric interactions for the (Z)-isomer.