title: Doubly diastereoselective conjugate addition of homochiral lithium amides to homochiral alpha,beta-unsaturated esters containing cis- and trans-dioxolane units.
abstract: As part of a long-term goal directed towards the ab initio asymmetric synthesis of unnatural amino sugars, the doubly diastereoselective conjugate addition reactions of the antipodes of lithium N-benzyl-N-(alpha-methylbenzyl)amide to a range of homochiral alpha,beta-unsaturated esters containing cis- and trans-dioxolane units was investigated. These reactions resulted in "matching" and "mismatching" effects. In the "matched" cases a single diastereoisomer of the corresponding beta-amino ester (containing three contiguous stereocentres) is produced. Upon conjugate addition to a homochiral alpha,beta-unsaturated ester containing a cis-dioxolane unit, in the "mismatched" case it is the stereocontrol of the substrate which is dominant over that of the lithium amide, whilst upon addition to homochiral alpha,beta-unsaturated esters containing a trans-dioxolane unit the stereocontrol of the homochiral lithium amide is dominant. Hydrogenolytic N-deprotection of the beta-amino ester products of conjugate addition gives access to polyoxygenated beta-amino acid derivatives.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK. steve.davies@chem.ox.ac.uk
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Durbin
authors.forename: Euan C
authors.initials: EC
authors.lastname: Goddard
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kelly
authors.forename: Wataru
authors.initials: W
authors.lastname: Kurosawa
authors.forename: James A
authors.initials: JA
authors.lastname: Lee
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Nicholson
authors.forename: Paul D
authors.initials: PD
authors.lastname: Price
authors.forename: Paul M
authors.initials: PM
authors.lastname: Roberts
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Russell
authors.forename: Philip M
authors.initials: PM
authors.lastname: Scott
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
mesh_terms: D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis; D004148:Dioxolanes / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000577:Amides; D000596:Amino Acids; D004148:Dioxolanes; D004952:Esters; D008094:Lithium