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6925740 
Journal Article 
Structure-directed reversion in the pi-facial stereoselective alkylation of chiral bicyclic lactams 
Soteras, I; Lozano, O; Escolano, C; Orozco, M; Amat, M; Bosch, J; Luque, FJ; , 
2008 
Yes 
Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904 
AMER CHEMICAL SOC 
WASHINGTON 
7756-7763 
English 
18763825 
WOS:000259574700042 
The reversal of the pi-facial diastereoselectivity observed in the benzyl bromide alkylation of the enolate of phenylglycinol-derived oxazolopiperidone is examined by means of theoretical calculations and experimental assays. When the angular carbon adopts an R configuration, the endo addition is intrinsically favored due to the lower torsional strain induced in the TS, but for the reaction with benzyl bromide, which affords the exo product. This reversal is attributed to the formation of a C-H center dot center dot center dot pi hydrogen bond between the C-H unit of the C8a angular position and the benzene ring of the alkylating reagent. A similar secondary interaction explains the stereochemical reversion observed in the benzyl alkylation of the enolate of oxazolopyrrolidinone. These findings point out that the delicate balance between factors that dictate the diastereoselectivity in the alkylation of chiral byciclic lactams can be unexpectedly altered by weak secondary interactions. The results presented here provide valuable guidelines to tune the selective preparation of enantiopure bioorganic and pharmaceutical compounds.