Asymmetric Synthesis of Axially Chiral Isoquinolones: Nickel-Catalyzed Denitrogenative Transannulation.

The first Ni(0)/bis(oxazoline)-catalyzed asymmetric denitrogenative transannulation of 1,2,3-benzotriazin-4(3H)-ones with bulky internal alkynes to form novel axially chiral isoquinolones in an atroposelective manner has been developed. This method provides direct asymmetric access to axially chiral isoquinolones with excellent functional-group tolerance in excellent yields and stereoselectivities from readily available starting materials under mild reaction conditions. These axially chiral isoquinolones exhibit high cytotoxicity against a number of human cancer cell lines. DFT calculations reveal the nature of the transition state in the key annulation step.

Palladium-catalyzed enantioselective alkenylation of alkenylbenzene derivatives.

A regioselective and enantioselective palladium-catalyzed relay Heck alkenylation of alkenylbenzene derivatives to construct remote stereocenters is disclosed. Various ß-substituted styrenes were readily obtained in moderate yields with good to excellent levels of enantioselectivity. This strategy provides rapid access to enantioenriched δ, ε, ζ, and η-alkenyl aryl compounds from simple starting materials. Mechanistic studies suggest that termination of the relay reaction is controlled by affinity of the arene for the Pd complex during migration.

Predictive and mechanistic multivariate linear regression models for reaction development.

Multivariate Linear Regression (MLR) models utilizing computationally-derived and empirically-derived physical organic molecular descriptors are described in this review. Several reports demonstrating the effectiveness of this methodological approach towards reaction optimization and mechanistic interrogation are discussed. A detailed protocol to access quantitative and predictive MLR models is provided as a guide for model development and parameter analysis.

Amide groups switch selectivity: C-H trifluoromethylation of α,ß-unsaturated amides and subsequent asymmetric transformation.

The first direct C-H ß-trifluoromethylation of unsubstituted or α-alkyl-substituted α,ß-unsaturated carbonyl compounds under metal-free conditions was realized with excellent regio- and stereoselectivity as well as a very broad substrate scope. Both olefinic and allylic trifluoromethylation products are accessible with high selectivities by altering the substrate substitutions. The resultant olefinic products, namely (E)-ß-trifluoromethyl (CF3) α,ß-unsaturated hydroxamic acid derivatives, served as acceptors in organocatalytic asymmetric Michael addition reactions to give hydroxamic acid derivatives bearing a chiral CF3-substituted stereocenter with high enantioselectivities.