ADDITION CONJUGEE DANS LE THF-HMPT D'ARYLACETONITRILES LITHIES AUX CYCLOHEXEN-2 ONES SUBSTITUEES: INTERVENTION DES FACTEURS STERIQUES ET ELECTRONIQUES

Article abstract of DOI:10.1016/S0040-4020(01)97942-6

The reaction of lithiated arylacetonitriles 2a-c with 2-cyclohexenones 3-9 in THF-HMPA (80:20 v/v) at -70 deg C leads in all cases but one to δ-ketoalkylnitriles, resulting from 1,4-addition.The only case where some 1,2-addition takes place is the reaction of 2a with 4,4-dimethyl 2-cyclohexenone 7.The formation of allylic alcoholates, products of 1,2-addition, is shown to be reversible in this solvent mixture.However, in several cases, kinetic control of 1,4-addition is demonstrated.The rate of formation of 1,4-addition products depends upon the arylacetonitrile substituents: 2a<*>2b<*>2c (i.e. the higher lying the nucleophile HOMO the faster the reaction).It is also sensitive to the cyclohexenone substituents; although methyl on C-2 and gem-dimethyl on C-5 or t-butyl on C-4 have small influence on the reaction rate, methyl on C-3 or gem dimethyl on C-4 induce a noticeable rate decrease.The addition of 2b on 4-t-butyl 2-cyclohexenone 8 leads, at the early stage, to a predominating isomer 15b, to which the trans diaxial configuration of the substituents has been attributed by 250 MHz 1H NMR.A single transition state model, reagent-like, where the nucleophile approaches the C=C bond by the less hindered face of the 2-cyclohexenone in a 1,2-diplanar conformation, the CN substituent being directed towards the C=O group, accounts for all the substituent effectc and the stereoselectivity observed.