%0 Journal Article
%A Wang, Lihong
%A Prabhudas, Bodhuri
%A L. J. Clive, Derrick
%D 2009
%T Formation of Carbocycles by Intramolecular Conjugate Displacement: Scope and Mechanistic Insights
%U https://acs.figshare.com/articles/journal_contribution/Formation_of_Carbocycles_by_Intramolecular_Conjugate_Displacement_Scope_and_Mechanistic_Insights/2860978
%R 10.1021/ja900857h.s001
%2 https://ndownloader.figshare.com/files/4558804
%K allylic position
%K intramolecular addition
%K material
%K substituent
%K proton source
%K THF
%K Cs 2CO
%K DBU
%K displacement
%K Intramolecular Conjugate Displacement
%K Michael acceptor unit
%K ring closure
%K formation
%K Michael acceptor subunit
%K Michael acceptors
%K carbanion
%K Michael addition
%K transition metal
%K CN
%K CP
%K SN
%K ICD reactions
%K Michael acceptor
%K reaction conditions
%K mechanism
%K Mechanistic InsightsA
%K CO 2R
%X A detailed study has been made of a method of ring closure categorized as an all-carbon intramolecular conjugate displacement (ICD). This reaction involves intramolecular addition of a carbanion, which is stabilized by at least one electron-withdrawing group, to a Michael acceptor which has a leaving group in an allylic position. The process formally resembles a combination of Michael addition and SN2′ displacement. The overall result is formation of a ring with loss of the allylic leaving group and shift of the original double bond to a new location spanning the positions of the electron-withdrawing substituent of the Michael acceptor subunit and the original allylic leaving group. The starting materials are easily prepared by a selenium-based version of the Morita−Baylis−Hillman reaction. The cyclizations are transition metal free and occur under mild conditions, using DBU or Cs2CO3 in MeCN or THF. Acetate is a suitable leaving group and the electron-withdrawing substituent of the Michael acceptor unit can be CO2R, SO2Ph, or CN. Six- and seven-membered rings are formed efficiently, and complex structures, such as those resembling the core of CP-225,917, are easily assembled. The products of these ICD reactions are themselves classical Michael acceptors. A range of mechanisms probably operates, depending on the structure of the starting material and the reaction conditions, but conclusive evidence for a stepwise mechanism was obtained in a suitably biased case, while other observations are compatible with a concerted process or a stepwise path involving a short-lived carbanion that evades capture by a proton source.
%I ACS Publications