Density functional theory studies of hetero-Diels-Alder reactions

Transition structures for hetero-Diels-Alder reactions involving the heteroatoms O, S and N in dienes as well as in dienophiles have been determined at the MP2 (MP2/6-31G*//MP2/6-31G*) and hybrid DFT (B3LYP/6-31G*//B3LYP/6-31G*) levels of theory. The transition structures are predicted to be relatively early, concerted and asynchronous in all cases, with the DFT transition structures being more asynchronous than the MP2 ones. The reactions of butadiene with formaldehyde, thioformaldehyde and formaldimine proceed by diene HOMO-dienophile LUMO interactions whereas those of ethylene with acrolein, 1-thiabutadiene and 1-azabutadiene proceed by reverse electron demand interactions. In all the hetero-Diels-Alder reactions, the C-C bond is more fully formed than the heteroatom-carbon bond in the transition structure with the exception of the reaction between formaldimine and butadiene for which C-N bond formation is ahead of C-C bond making. All the reactions are highly exothermic. The reactions are facilitated by heteroatoms in both the diene and dienophile, and bond formation between two heteroatoms is disfavored. The reaction of formaldimine shows an endo preference whereas that of 1-azabutadiene leads to an exo preference of the imino hydrogen; these preferences of ca. 4 kcal mol(-1) are caused mostly by inter-hydrogen steric effects in the transition structures. We conclude that the DFT calculations provide an economical way of accounting for electron correlation effects at nearly the same level as the MP2 ones in the investigations of hetero-Diels-Alder reactions.