ABSTRACT
The mechanism of nickel-catalyzed reductive alkyne-aldehyde coupling reactions has been investigated using density functional theory. The preferred mechanism involves oxidative cyclization to form the nickeladihydrofuran intermediate followed by transmetalation and reductive elimination. The rate- and selectivity-determining oxidative cyclization transition state is analyzed in detail. The d --> pi*(perpendicular) back-donation stabilizes the transition state and leads to higher reactivity for alkynes than alkenes. Strong Lewis acids accelerate the couplings with both alkynes and alkenes by coordinating with the aldehyde oxygen in the transition state.
ABSTRACT
A computational method for probing furanose conformation has been developed using a methylated monosaccharide derivative 1. First, a large library of conformers was generated by a systematic pseudo Monte Carlo search followed by optimization with the AMBER molecular mechanics force field. A subset of these conformers was then subjected to ab initio and density functional theory calculations in both the gas and aqueous phases. These calculations indicate that entropic contributions to the Gibbs free energy are important determinants of the Boltzmann distribution for the conformational preferences of 1 in the gas phase. The results obtained at each level of theory are discussed and compared with the experimentally determined conformer distribution from NMR studies in aqueous solution. In addition, the ability of each level of theory to reproduce the experimentally measured 1H-1H coupling constants in 1 is discussed. Empirical Karplus equations and density functional theory methods were used to determine average 3J(H1,H2), 3J(H2,H3), and 3J(H3,H4) for each level of theory. On the basis of this comparison, consideration of solvation with the MN-GSM model provided good agreement with the experimental data.
