title: Understanding the cooperative NHC/LA catalysis for stereoselective annulation reactions with homoenolates. A DFT study.
abstract: The role of Ti(Oi-Pr)(4) Lewis acid (LA) in the cooperative N-heterocyclic carbene (NHC)/LA catalyzed addition of enals to enones to yield cis-cyclopentenes has been investigated using DFT methods at the B3LYP/6-31G** computational level. Ti(IV) effectively catalyzes the reaction by formation of a complex with cinnamaldehyde 1, which favors the nucleophilic attack of NHC 5 on 1, and the subsequent proton abstraction to yield the extended Ti(IV)-Breslow intermediate 21. The nature of the metal involved in the LA catalyst plays a relevant role due to the more basic character of NHCs than aldehydes. Thus, strong LAs, such as Zn(OTf)(2), prevent the catalytic behavior of NHCs to form a very stable complex. The subsequent formation of a complex between chalcone 2 and the extended Ti(IV)-Breslow intermediate 21 favors the cis stereoselective C-C bond-formation. Analysis of the structures of Ti(IV)-complex precursors for the cis and trans C-C bond-formation steps allows for an explanation of the unexpected cis stereoselectivity.
authors.affiliation: Departamento de Química Orgánica, Universidad de Valencia, Dr Moliner 50, E-46100, Burjassot, Valencia, Spain. domingo@utopia.uv.es
authors.forename: Luis R
authors.initials: LR
authors.lastname: Domingo
authors.forename: Ramón J
authors.initials: RJ
authors.lastname: Zaragozá
authors.forename: Manuel
authors.initials: M
authors.lastname: Arnó