title: Intramolecular carbolithiation reactions of chiral alpha-amino-organolithium species.
abstract: Enantiomerically enriched alpha-amino-organolithium species, in which the lithium atom is attached to a stereogenic carbon centre, have been found to be chemically stable at room temperature in a solvent of very low polarity and undergo intramolecular carbolithiation onto an unactivated alkene. The configurational stability of the chiral organolithium species, bearing a variety of N-alkenyl substituents, was probed by studying the enantiomeric purity of the cyclization products. With N-but-3-enyl-2-lithiopyrrolidine, cyclization to the five-membered ring is more rapid than racemization and a high yield of the pyrrolizidine alkaloid (+)-pseudoheliotridane was obtained with no loss of optical purity. In contrast, with N-pent-4-enyl-2-lithiopyrrolidine, cyclization to the six-membered ring was found to occur with significant loss of optical purity. The cyclization to the six-membered ring was determined to occur with a half-life, t(1/2) approximately 90 min at 23 degrees C. The epimerization of this organolithium species in hexane/Et2O 4:1 was calculated to have a half-life, t(1/2) approximately 30 min at 23 degrees C. Enhanced levels of enantioselectivity for the formation of the indolizidine ring system were obtained using an alkene bearing a terminal phenylthio substituent. With N-[(3-phenylthio)-prop-2-enyl]-2-lithiopyrrolidine, cyclization to the four-membered ring occurs with poor enantioselectivity at low temperature in THF but is highly enantioselective at room temperature in a solvent of very low polarity.
authors.affiliation: School of Chemistry, University of Exeter, UK.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Ashweek
authors.forename: Iain
authors.initials: I
authors.lastname: Coldham
authors.forename: David J
authors.initials: DJ
authors.lastname: Snowden
authors.forename: Graham P
authors.initials: GP
authors.lastname: Vennall
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003500:Cyclization; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature; D013997:Time Factors; D014001:Tin / Q000737:chemistry*
chemical_list: D000475:Alkenes; D000588:Amines; D009942:Organometallic Compounds; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; D014001:Tin; D008094:Lithium