DFT study of the mechanism and stereochemistry of the Rh(I)-catalyzed Diels-Alder reactions between electronically neutral dienes and dienophiles.

Diels-Alder reaction between electronically neutral dienes and dienophiles is usually sluggish under thermal conditions and has to be catalyzed by transition metal catalysts. We report here our DFT study of the mechanism and stereochemistry of the Rh-catalyzed Diels-Alder reaction between electronically neutral dienes and dienophiles (alkenes and alkynes), finding that this reaction includes a reaction sequence of oxidative cyclization between diene and alkene/alkyne and a reductive elimination step. The alkyne's oxidative cyclization is much faster than alkene's due to the additional coordination of alkyne to the Rh center in the oxidative cyclization transition state. For both intermolecular and intramolecular reactions, the reductive elimination step in the catalytic cycle is rate-determining. The different reactivity of ene-diene and yne-diene substrates can be rationalized by the model that reductive elimination to form a C(sp(2))-C(sp(3)) bond is easier than that for the formation of a C(sp(3))-C(sp(3)) bond, due to the additional coordination of the double bond to the Rh center in the transition state in the former. We also uncovered the reasons for the high para-selectivity of the intermolecular Diels-Alder reaction of dienes and alkynes. In addition, DFT calculations aiming to understand the high diastereoselectivity of an intramolecular [4 + 2] reaction of ene-dienes with substituents adjacent to the diene and ene moieties of the substrates found that the substituents in the substrates favor staying away from the Rh center in the oxidative cyclization transition states. This preference leads to the generation of the final [4 + 2] products with the substituents and the bridgehead hydrogen atoms in a cis-configuration.