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Highly Diastereo- and Enantioselective Additions of Homoenolates to Nitrones Catalyzed by N-Heterocyclic Carbenes

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posted on 27.02.2008, 00:00 by Eric M. Phillips, Troy E. Reynolds, Karl A. Scheidt
The diastereo- and enantioselective addition of N-heterocyclic carbene-generated homoenolates to nitrones is reported. This formal [3 + 3] addition of α,β-unsaturated aldehydes and nitrones generates unusual morpholinone heterocycles which are converted into γ-hydroxy amino esters by addition of methanol to the reaction. The use of a chiral N-heterocyclic carbene (NHC) as the catalyst provides the amino esters in high diastereoselectivity (up to 20:1 dr) and enantioselectivity (up to 94%). The process accommodates α,β-unsaturated aldehydes with β-alkyl and β-aryl substituents. The γ-hydroxy amino esters can be converted to optically enriched γ-lactams by a two-step procedure involving mild reduction of the N−O bond and acid-catalyzed amide formation.