Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation

The applications of axially chiral benzonitriles and their derivatives remain mostly unexplored due to their synthetic difficulties. Here we disclose an unusual strategy for atroposelective access to benzonitriles via formation of the nitrile unit on biaryl scaffolds pre-installed with stereogenic axes in racemic forms. Our method starts with racemic 2-arylbenzaldehydes and sulfonamides as the substrates and N-heterocyclic carbenes as the organocatalysts to afford axially chiral benzonitriles in good to excellent yields and enantioselectivities. DFT calculations suggest that the loss of p-toluenesulfinate group is both the rate-determining and stereo-determining step. The axial chirality is controlled during the bond dissociation and CN group formation. The reaction features a dynamic kinetic resolution process modulated by both covalent and non-covalent catalytic interactions. The axially chiral benzonitriles from our method can be easily converted to a large set of functional molecules that show promising catalytic activities for chemical syntheses and anti-bacterial activities for plant protections.

Kinetic Resolution in Transannular Morita-Baylis-Hillman Reaction: An Approximation to the Synthesis of Sesquiterpenes from Guaiane Family

An approximation to the synthesis of several sesquiterpenes from the Guaiane family is described in which the core structure was obtained through a transannular Morita-Baylis-Hillman reaction performed under kinetic resolution. Several manipulations of the obtained MBH adduct have been carried out directed towards the total synthesis of γ-Gurjunene, to the formal synthesis of Clavukerin A, to the synthesis of a non-natural isomer of isoguaiane and to the synthesis of an advanced intermediate in the total synthesis of Palustrol.

Acylative kinetic resolution of racemic methyl-substituted cyclic alkylamines with 2,5-dioxopyrrolidin-1-yl (R)-2-phenoxypropanoate

Diastereoselective acylation of a number of racemic methyl-substituted cyclic alkylamines with active esters of 2-phenoxypropanoic acid was studied in detail. Ester of (R)-2-phenoxypropanoic acid and N-hydroxysuccinimide was found to be...

Access to Enantioenriched Molecules with Diverse Fluorinated Tetrasubstituted Stereocenters Using Hydroxy as Kinetic Resolution Auxiliary Group

Developing a general method affording optically pure fully-substituted carbon molecules bearing various fluorinated groups is highly important but very challenging. Here we show that using secondary OH as the kinetic...

Correction: The kinetic resolution of oxazinones by alcoholysis: access to orthogonally protected β-amino acids

Correction for ‘The kinetic resolution of oxazinones by alcoholysis: access to orthogonally protected β-amino acids’ by Sarah A. Cronin et al., Org. Biomol. Chem., 2021, 19, 7348–7352, DOI: 10.1039/D1OB01306H.