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Intramolecular Carbolithiation Reactions of Chiral α ‐Amino‐organolithium Species
Author(s) -
Ashweek Neil J.,
Coldham Iain,
Snowden David J.,
Vennall Graham P.
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20020104)8:1<195::aid-chem195>3.0.co;2-h
Subject(s) - stereocenter , chemistry , enantioselective synthesis , alkene , enantiomeric excess , indolizidine , stereochemistry , racemization , ring (chemistry) , substituent , medicinal chemistry , organic chemistry , catalysis , alkaloid
Enantiomerically enriched α ‐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 ≈90 min at 23 °C. The epimerization of this organolithium species in hexane/Et 2 O 4:1 was calculated to have a half‐life, t 1/2 ≈30 min at 23 °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.