Highly enantioselective syntheses of functionalized alpha-methylene-gamma-butyrolactones via Rh(I)-catalyzed intramolecular Alder ene reaction: application to formal synthesis of (+)-pilocarpine.
A highly enantioselective Rh(I)-catalyzed intramolecular Alder ene reaction has been developed. The desired products, 3-vinyl, vinyl acetate, and vinyl ether-substitued alpha-methylene-gamma-butyrolactones were formed in high yields. Aldehydes were produced with the formation of gamma-lactones when alcohols were substituted at allylic position in the substrates. All reactions with listed substrates proceeded in over 99% ee. A formal synthesis of (+)-pilocarpine is an excellent example to demonstrate the synthetic utility of this methodology.
Lei
Aiwen
A
Department of Chemistry, 152 Davey Laboratory, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
He
Minsheng
M
Zhang
Xumu
X
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D002384:Catalysis; D009281:Naphthalenes / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D010862:Pilocarpine / Q000138:chemical synthesis*; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
D000480:Alkynes; C406943:BINAP, 2-naphthol; D009281:Naphthalenes; D009942:Organometallic Compounds; D010862:Pilocarpine; C014096:alpha-methylene gamma-butyrolactone; D012238:Rhodium; D015107:4-Butyrolactone