No abstract

The palladium-catalyzed alpha-arylation of ketones has become a useful and general synthetic method. In this process, an enolate is generated from a ketone and base in the presence of an aryl halide, and a palladium catalyst couples this enolate with the aryl halide. With the advent of new catalysts composed of sterically hindered, electron-rich alkylphosphine and N-heterocyclic carbene ligands, this process now encompasses a broad range of enolates and related anions, including those derived from amides, esters, aldehydes, nitriles, malonates, cyanoesters, nitroalkanes, sulfones, and lactones. In the proposed mechanism for this reaction, the carbon-carbon bond of the product is formed by reductive elimination from an arylpalladium enolate intermediate. The structures and reactions of arylpalladium complexes of enolate, cyanoalkyl, and malonate ions have been studied to determine how the binding mode and electronic and steric parameters influence the rate and mechanism of reductive elimination.

A series of arylpalladium alkyl complexes of the formula [(DPPBz)Pd(Ar)(R)] (DPPBz ) 1,2-bis(diphenylphosphino)benzene; R ) methyl, benzyl, enolate, cyanoalkyl, trifluoroalkyl, or malonate) has been prepared to reveal the influence of steric and electronic parameters on structure, stability, and reactivity. Arylpalladium enolate and cyanoalkyl complexes ligated by EtPh 2 P, 1,1′-bis(diisopropylphosphino)ferrocene (D i PrPF), and BINAP were prepared to evaluate the effect of the ancillary ligand. The coordination modes of the enolate and cyanoalkyl complexes were determined by spectroscopic methods, in combination with X-ray crystallography. In the absence of steric effects, the C-bound isomer was favored electronically if the enolate or cyanoalkyl group was located trans to a phosphine, and the O-bound isomer was favored if the enolate was located trans to an aryl group. The thermodynamic stability of the enolate and cyanoalkyl complexes was controlled by the steric properties of the enolate or cyanoalkyl group, and complexes with more substitution at the R-carbon were less stable. Arylpalladium methyl, benzyl, enolate, cyanoalkyl, and trifluoroethyl complexes underwent carbon-carbon bond-forming reductive elimination upon heating. Reductive elimination was faster from complexes with electron-withdrawing substituents on the palladium-bound aryl group and with sterically hindered alkyl groups. The electronic properties of the alkyl group had the largest impact on the rate of reductive elimination: electron-withdrawing groups on the R-carbon retarded the rate of reductive elimination. The rates of reductive elimination correlated with the Taft polar substituent constants of the groups on the carbon alpha to the metal.

The zwitterionic ring-opening polymerization of lactide initiated by N-heterocyclic carbenes generates cyclic polylactides with well-defined molecular weights between M(n) = 5000 and 30,000 g/mol with narrow polydispersities (M(w)/M(n) < or = 1.31). These zwitterionic polymerizations are extremely rapid (k(p) = 48.7 M(-1) s(-1)), but also exhibit exceptional control of molecular weight and molecular weight distribution. The unusual kinetic features of these zwitterionic polymerizations are illuminated with kinetic and mechanistic investigations, which implicate a mechanism that involves a slow initiation step (second order in [M]), a propagation step (first order in [M]) that is much faster than initiation (k(i) = 0.274 M(-2) s(-1)), cyclization (k(c) = 0.0575 s(-1)), and depropagation (k(d) = 0.208 s(-1)). Numerical and stochastic simulations of the kinetic data provide a kinetic rationale for the evolution of molecular weight with monomer conversion: the molecular weights increase with increasing monomer conversion, exhibit a nonzero intercept near 0% monomer conversion, and are relatively insensitive to the initial monomer-to-initiator ratio. The observed narrow molecular weight distributions are due to a high rate of propagation relative to cyclization and chain transfer. Kinetic simulations define the kinetic criteria under which the active zwitterions remain in solution; these simulations were substantiated by chain-extension experiments, which provide experimental evidence for chain extension of the zwitterions and reinitiation by the N-heterocyclic carbenes liberated upon macrocyclization. The kinetic model rationalizes some of the unique features of zwitterionic ring-opening polymerization and provides a useful mechanistic framework to optimize these polymerizations as a strategy to generate well-defined cyclic polyesters.