Asymmetric construction of acyclic quaternary stereocenters via direct enantioselective additions of α-alkynyl ketones to allenamides

Acyclic quaternary stereocenters are widely present in a series of biologically active natural products and pharmaceuticals. However, development of highly efficient asymmetric catalytic methods for the construction of these privileged motifs represents a longstanding challenge in organic synthesis. Herein, an efficient chiral phosphoric acid catalyzed direct asymmetric addition of α-alkynyl acyclic ketones with allenamides has been developed, furnishing the acyclic all-carbon quaternary stereocenters with excellent regioselectivities and high enantioselectivities. Extensive and detailed experimental mechanistic studies were performed to investigate the mechanism of this reaction. Despite a novel covalent allyl phosphate intermediate was found in these reactions, further studies indicated that a SN2-type mechanism with the ketone nucleophiles is not very possible. Instead, a more plausible mechanism involving the elimination of the allyl phosphate to give the α,β-unsaturated iminium intermediate, which underwent the asymmetric conjugate addition with the enol form of ketone nucleophiles under chiral anion catalysis, was proposed. In virtue of the fruitful functional groups bearing in the chiral products, the diverse derivatizations of the chiral products provided access to a wide array of chiral scaffolds with quaternary stereocenters.

Cobalt(III)-Catalyzed Diastereoselective Three-Component C–H Bond Addition to Butadiene and Activated Ketones

A highly diastereoselective three-component C–H bond addition across butadiene and activated ketones is described. This transformation provides homoallylic tertiary alcohols through the formation of two C–C σ-bonds and with complete selectivity for an E-alkene isomer. The reaction exhibits good scope with respect to activated ketone inputs, including highly strained cyclic and electron-deficient cyclic and acyclic ketones. Additionally, high diastereoselectivities were achieved for alcohols prepared from unsymmetrical ketones.

Application of spectral graph theory on the enthalpy change of formation of acyclic saturated ketones

The dependence of the enthalpy change of formation of saturated acyclic ketones on molecular structure (the number of carbon atoms, the position of the carbonyl group, and the branching of the molecules) was investigated. For this purpose, a simple computational model, the parameterization of which is based on spectral graph theory, was developed. It was found that the major part of the enthalpy change of formation is determined by molecular size, whereas the fine structure of the enthalpy change of formation is determined by the branching of the molecule and the position of the carbonyl group. The developed model proved itself very useful for such investigations. The model is simple and practical, and the agreement between the experimental and calculated enthalpy changes of formation is very good, with an average relative error of 0.7%.