Formation of carbocycles by intramolecular conjugate displacement: scope and mechanistic insights.
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 S(N)2' 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 Cs(2)CO(3) in MeCN or THF. Acetate is a suitable leaving group and the electron-withdrawing substituent of the Michael acceptor unit can be CO(2)R, SO(2)Ph, 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.
Chemistry Department, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
Lihong
L
Wang
Bodhuri
B
Prabhudas
Derrick L J
DL
Clive
D000438:Alcohols / Q000737:chemistry; D000498:Allyl Compounds / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D002254:Carbonates / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis* / Q000737:chemistry; D012643:Selenium / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
D000438:Alcohols; D000498:Allyl Compounds; D002254:Carbonates; D006841:Hydrocarbons, Aromatic; D012997:Solvents; D002244:Carbon; D012643:Selenium