Conjugate addition of homochiral lithium amides to methyl 4-(N-benzyl-N-allylamino)but-2-enoate, chemoselective N-deprotection and concomitant cyclisation, followed by enolate functionalisation and deprotection allows access to syn- and anti-3,4-disubstituted aminopyrrolidines in > 98% d.e. and > 98% e.e.

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.

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Dedicated to Peter Vollhardt on the occasion of his 69 th birthday enantiopure w-arylb-benzamido ester (n = 0, 1, or 2) 3-amino-substituted 1-indanones, 1-tetralones, and 1-benzosuberones Friedel-Crafts cyclisation OMe OMeAbstract Conjugate addition of enantiopure lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to a range of ω-aryl-α,β-unsaturated esters gives the corresponding ω-aryl-β-amino esters as single diastereoisomers in high yields. Friedel-Crafts cyclisation of the pendant carbonyl group onto the ω-aryl ring then gives a range of 3-amino-substituted 1-indanones, 1-tetralones, and 1-benzosuberones, representing an efficient and short protocol for the preparation of these benzo-fused carbocycles in enantiopure form.

Pyrrole derivatives R 0120Lithium Amide Conjugate Addition for the Asymmetric Synthesis of 3-Aminopyrrolidines. -Conjugate addition of enantiopure lithium amides to enoate (I) is used as the key step for a simple and efficient approach to polysubstituted aminopyrrolidines, such as (VIII), (X) and (XIII). -(DAVIES*, S. G.; GARNER, A. C.; GODDARD, E. C.; KRUCHININ, D.; ROBERTS, P. M.; RODRIGUEZ-SOLLA, H.; SMITH, A. D.; Chem. Commun. (Cambridge) 2006, 25, 2664-2666; Chem. Res. Lab., Dep. Org. Chem., Univ. Oxford, Oxford OX1 3TA, UK; Eng.) -M. Paetzel 45-105