Mechanisms, regio- and stereoselectivities involved in NHC-catalyzed dearomatizing annulation of ester with ylide: A computational study

The catalytic mechanism for dearomatizing annulation of ester with ylide by a chiral NHC catalyst is investigated by density functional theory (M06-2X) computations. After precatalyst activation giving active NHC, the transformation proceeds via five steps: (1) nucleophilic addition of the NHC to ester, (2) alpha- C-H deprotonation to generate acylazolium intermediate, (3) coupling acylazolium intermediate with ylide to form a new C - C bond, (4) ring closure and (5) elimination of the NHC with formation of the annulation product tricyclic dihydroisoquinoline. The regio- and stereoselectivity controlling step is C - C bond formation. For regioselectivity, local reactivity index analysis indicates that the C1-addition is more favorable than either C3 or C4 addition. The stereoselectivity for the formation of SS-configurational product is ascribed to a number of noncovalent interactions (C-H & sdot;O, C-H & sdot;N and C-H & sdot;pi). Electron localization function (ELF) analyses reveal the important role of the NHC in Ccarbonyl-Ocarbonyl bond breaking. These results enable both in-depth understanding of NHC catalysis and rational design of catalytic reactions.