Sterically Controlled Stereoregulation in Aldol Reactions of 3-Aryl-1-alkyl Dihydrothiouracils

Abstract

Aldol reactions of 3-aryl-1-alkyl dihydrothiouracils were investigated with respect to the orientation of the exocyclic group at N1, electronic effects of the aryl substituent at N3 and the steric demands of the electrophile. The reactions highlight the preference for formation of the anti aldol diastereomer with increasing steric constraints of the reactants.

aldol reaction - cyclization - aldehyde - dihydrothio­uracils - stereoselectivity

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11a Energy calculations were performed using the Gaussian 03 program. Computational calibrations were done on a model compound {(6S)-methyl-3-(4-cyano-3-chlorophenyl)--1-[(S)-1-phenylethyl]-2-thioxotetrahydropyrimidin-4(1H)-one} by energy minimizations using the semi-empirical method MM2, and ab initio calculations by Gaussian B3LYP with basis set 6-31G* (d,p). The outcomes of these independent calculations were perfectly in agreement with the structure of the molecule, as confirmed by single crystal X-ray diffraction analysis, see reference 9b

11b

The present studies involve another molecule of the same template, and the structure was optimized by ab initio calculation using Gaussian B3LYP.