Jean-Nicolas Desrosiers

Enantioselective Acylation of Silyl Ketene Acetals through Fluoride Anion-Binding Catalysis

A highly enantioselective acylation of silyl ketene acetals with acyl fluorides has been developed to generate useful α,α-disubstituted butyrolactone products. This transformation is promoted by a new thiourea catalyst and 4-pyrrolidinopyridine and represents the first example of enantioselective thiourea anion-binding catalysis with fluoride.

Efficient asymmetric synthesis of P-chiral phosphine oxides via properly designed and activated benzoxazaphosphinine-2-oxide agents.

A general, efficient, and highly diastereoselective method for the synthesis of structurally and sterically diverse P-chiral phosphine oxides was developed. The method relies on sequential nucleophilic substitution on the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced and differentiated P-N and P-O bond reactivity toward nucleophiles. The reactivities of both bonds are fine-tuned to allow cleavage to occur even with sterically hindered nucleophiles under mild conditions.

Nickel-Catalyzed Esterification of Aliphatic Amides

Recent studies have demonstrated that amides can be used in nickel-catalyzed reactions that lead to cleavage of the amide C-N bond, with formation of a C-C or C-heteroatom bond. However, the general scope of these methodologies has been restricted to amides where the carbonyl is directly attached to an arene or heteroarene. We now report the nickel-catalyzed esterification of amides derived from aliphatic carboxylic acids. The transformation requires only a slight excess of the alcohol nucleophile and is tolerant of heterocycles, substrates with epimerizable stereocenters, and sterically congested coupling partners. Moreover, a series of amide competition experiments establish selectivity principles that will aid future synthetic design. These studies overcome a critical limitation of current Ni-catalyzed amide couplings and are expected to further stimulate the use of amides as synthetic building blocks in C-N bond cleavage processes.

Catalytic enantioselective addition of diorganozinc reagents to vinyl sulfones.

An efficient method for the catalytic asymmetric conjugate addition of diorganozinc reagents to vinyl sulfones is reported. Using a Binap*Cu complex, enantioselectivities up to 98% ee and high yields can be attained for a variety of substrates. Several dialkylzinc reagents are also compatible with this procedure.

Asymmetric catalytic addition of diorganozinc reagents to imines: Scope and application

The copper-catalyzed diorganozinc addition to N-diphenylphosphinoylimines was shown to proceed with a very high degree of enantiocontrol if the reaction was run in the presence of Me-DuPHOS monoxide ligand (BozPHOS). The scope of the reaction is described as well as our efforts to identify the nature of the enantioactive metal complex responsible for the high asymmetric induction.

Efficient Asymmetric Synthesis of Structurally Diverse P-Stereogenic Phosphinamides for Catalyst Design†

The use of chiral phosphinamides is relatively unexplored because of the lack of a general method for the synthesis. Reported herein is the development of a general, efficient, and highly enantioselective method for the synthesis of structurally diverse P-stereogenic phosphinamides. The method relies on nucleophilic substitution of a chiral phosphinate derived from the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide. These chiral phosphinamides were utilized for the first synthesis of readily tunable P-stereogenic Lewis base organocatalysts, which were used successfully for highly enantioselective catalysis.

A Mild Dihydrobenzooxaphosphole Oxazoline/Iridium Catalytic System for Asymmetric Hydrogenation of Unfunctionalized Dialins

Air-stable P-chiral dihydrobenzooxaphosphole oxazoline ligands were designed and synthesized. When they were used in the iridium-catalyzed asymmetric hydrogenation of unfunctionalized 1-aryl-3,4-dihydronaphthalenes under one atmosphere pressure of H2 , up to 99:1 e.r. was obtained. High enantioselectivities were also observed in the reduction of the exocyclic imine derivatives of 1-tetralones.

Diastereoselective Synthesis of α-Quaternary Aziridine-2-carboxylates via Aza-Corey–Chaykovsky Aziridination of N-tert-Butanesulfinyl Ketimino Esters

A general, scalable, and highly diastereoselective aziridination of N-tert-butanesulfinyl ketimino esters is described. The methodology has been utilized to provide straightforward access to previously unobtainable, biologically relevant α-quaternary amino esters and derivatives starting from readily available precursors.

New methods in asymmetric catalysis based on new hemi-labile bidentate ligands

Chiral bidentate hemi-labile bis(phosphine) monoxide ligands were shown to be quite effective in various copper-catalyzed transformations. Among them, the nucleophilic addition to imines, the conjugate addition to α,β-unsaturated nitro derivatives, and the conjugate reduction of α,β-unsaturated sulfones generally gave good to excellent yields and high enantiomeric excesses.

Construction of Quaternary Stereocenters by Nickel‐Catalyzed Heck Cyclization Reactions

A nickel-catalyzed Heck cyclization for the construction of quaternary stereocenters is reported. This transformation is demonstrated in the synthesis of 3,3-disubstituted oxindoles, which are prevalent motifs seen in numerous biologically active molecules. The method shows broad scope, proceeds in synthetically useful yields, and provides a rare means to construct stereochemically complex frameworks by nonprecious-metal catalysis.