Computational investigation of mechanistic aspects of the alkylation of chiral enamines

We studied the Michael reaction between the imines derived from the (5R)-dihydrocarvone and the homochiral 1-phenylethylamine (PEA), using semi-empirical AM1 method for conformational analysis and ab initio RHF/6-31G* for transition state calculations. Experimental results for this reaction show that the proportion of products depend strongly on the chirality of the amine moiety. With the conformational analysis, we found a pyramidal geometry of the nitrogen and could rationalize the significant role played by the sterical hindrance. We were able to explain the formation of the only product in the S amine diastereoisomer (matched case), but the analysis was not conclusive regarding the R one, where two products are formed (mismatched case). The results of our transition state calculations, however, helped us to understand the proportion of the products. In the matched case, the axial attack in the most favored conformer has a energy barrier significantly lower than the equatorial attack and we can explain the formation of only one product. On the other side, in the mismatched case, there is only a small difference between the most favorable attacks leading to either products, making plausible the formation of a mixture of products.