title: An experimental and theoretical study of the asymmetric lithiation of 1,2,3,5,6,7-hexahydro-3a,4a-diazacyclopenta[def]phenanthren-4-one.
abstract: The inability of bis-N-Boc-protected octahydrophenanthroline to undergo asymmetric lithiation with (-)-sparteine is circumvented by use of a urea functionality as the directing group. Asymmetric lithiation followed by electrophile quench gives products substituted alpha to nitrogen in better yield (17-30%) but slightly lower enantiomeric ratio (er 84:16) than analogous lithiation of N-Boc-piperidine (er 87:13). Computational studies at the MP2/6-316(d)//B3LYP/6-316(d) level indicate that the prochiral equatorial S-hydrogen is removed preferentially over the pro-R hydrogen, with a difference in transition state activation energies of 1.26 kcal/mol, corresponding to a predicted er of 89:11. The predicted stereochemistry of the reaction was confirmed by single-crystal X-ray analysis of an aryl dibromide prepared from the enantiomerically enriched alpha-methyl-substituted product.
authors.affiliation: Department of Chemistry, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada. metallic@brocku.ca
authors.forename: Costa
authors.initials: C
authors.lastname: Metallinos
authors.forename: Travis
authors.initials: T
authors.lastname: Dudding
authors.forename: Josh
authors.initials: J
authors.lastname: Zaifman
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Chaytor
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Taylor