Doubly diastereoselective conjugate addition of homochiral lithium amides to homochiral alpha,beta-unsaturated esters containing cis- and trans-dioxolane units.
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.
Davies
Stephen G
SG
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK. steve.davies@chem.ox.ac.uk
Durbin
Matthew J
MJ
Goddard
Euan C
EC
Kelly
Peter M
PM
Kurosawa
Wataru
W
Lee
James A
JA
Nicholson
Rebecca L
RL
Price
Paul D
PD
Roberts
Paul M
PM
Russell
Angela J
AJ
Scott
Philip M
PM
Smith
Andrew D
AD
D000577:Amides / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis; D004148:Dioxolanes / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry; D013237:Stereoisomerism
D000577:Amides; D000596:Amino Acids; D004148:Dioxolanes; D004952:Esters; D008094:Lithium