Theoretical Studies and Rational Design of Organoborane Reactions

PISANO, P. L.; GRIMBLAT, N.; SAROTTI, A. M.; PELLEGRINET, S. C.

Columbus, Ohio, U.S.A.

Workshop; Gaussian Workshop "Introduction to Gaussian: Theory and Practice"; 2010

Gaussian, Inc.

We have performed several B3LYP/6-31G* studies of the Diels-Alder reactions of dihalovinylboranes, dialkylvinylboranes andvinylboronates with different dienes using Gaussian03. We carried out conformational searches for the reactants, the transition structures (TSs) and the products and calculated the reaction free energies and the activation free energies, in the gas phase and insolution. Our mail goal is to rationally design readily available chiral vinylboranes as highly reactive and enantioselective Diels-Alder dienophiles, which in turn could be used as precursors of versatile chiral building blocks for asymmetric synthesis. We first theoretically and experimentally studied the Diels-Alder reactions of chiral dialkylvinylboranes, such as those derived from theoptically pure terpenes (+)-a-pinene, (+)-2-carene and (+)-3-carene. Unfortunately, these compounds proved to be very hindered and showed no reactivity. We then investigated the Diels-Alder reactions of the corresponding alkylhalovinylboranes with computational tools. We assumed that the replacemen to fan alkyl group by an halogen atom would decrease the steric hindrance and enhance the electron deficiency of the boroactivated dienophile. Calculations predicted that the activation free energies for the alkylbromo vinylboranes would be 2Kcal/mol lower than those for the alkylchlorovinylboranes and 7Kcal/mol lower than the ones for the corresponding diallkylvinylboranes. Therefore, the reactivity would decrease in the order alkylbromo- > alkylchloro-> dialkylvinylborane. Moreover, alkylchlorovinilboranes would show higher endo:exo and facial Re:Si selectivities than alkylbromovinilboranes. This study also indicated that the alkylchlorovinilboranes derived from (-)-a-pinene and (+)-2-carene should exhibit the higher endo:exo and Re/Si selectivities with cyclopentadiene. In addition, the alkylchlorovinilborane derived from (+)-3-carene should give opposite facial selectivity. The experiments corroborated the high reactivity and selectivity of alkylhalovinylboranes and confirmed that the theoretical calculations correly predicted the endo:exo and Re/Si selectivity trends. To our knowledge, these are the most enantioselective Diels-Alder reactions of boron-activated alkenes known to date.