Radical Perfluoroalkylation of Arenes via Carbanion Intermediates.

The use of sodium dithionite with perfluoroalkyl iodides under basic conditions facilitates the direct perfluoroalkylation of arenes with pendant benzylic electron-withdrawing groups. This occurs via attack of the arene on the electrophilic perfluoroalkyl radical, through the donation of electron density from a benzylic anion. The substrate scope was expanded beyond benzylic nitriles with cyclic substrates bearing electron-withdrawing groups at the benzylic position-enforcing donation of electron density to the aromatic ring and enabling attack on the perfluoroalkyl radical.

Discovery of Annulating Reagents Enabling the One-Step and Highly Stereoselective Synthesis of Cyclopentyl and Cyclohexyl Cores.

The use of the unprecedented annulating reagents methyl N-(tert-butylsulfinyl)-4-chlorobutanimidate and methyl N-(tert-butylsulfinyl)-5-bromopentanimidate enables the diastereoselective preparation of 5- and 6-membered carbocycles bearing three contiguous stereocenters. These synthons undergo cycloaddition with a variety of Michael acceptors to form cyclopentane/cyclohexane rings with excellent stereochemical control, generating only one of the eight possible diastereomers. This novel methodology has enabled the highly enantioselective and high yielding synthesis of novel chemotypes of pharmacological relevance.

One-Step Diastereoselective Pyrrolidine Synthesis Using a Sulfinamide Annulating Reagent.

This communication highlights the use of chiral sulfinamides as nitrogen nucleophiles in intermolecular aza-Michael reactions. When chiral sulfinamides are coupled to a chloroethyl group, the corresponding novel annulating reagents can be used to streamline the stereoselective synthesis of complex pyrrolidine-containing molecules. As a result, it has enabled a medicinal chemistry campaign for the synthesis of biologically active RORγt inverse agonists.

Palladium(0)-Catalyzed Directed syn-1,2-Carboboration and -Silylation: Alkene Scope, Applications in Dearomatization, and Stereocontrol by a Chiral Auxiliary.

We report the development of palladium(0)-catalyzed syn-selective 1,2-carboboration and -silylation reactions of alkenes containing cleavable directing groups. With B2 pin2 or PhMe2 Si-Bpin as nucleophiles and aryl/alkenyl triflates as electrophiles, a broad range of mono-, di-, tri- and tetrasubstituted alkenes are compatible in these transformations. We further describe a directed dearomative 1,2-carboboration of electron-rich heteroarenes by employing this approach. Through use of a removable chiral directing group, we demonstrate the viability of achieving stereoinduction in Heck-type alkene 1,2-difunctionalization. This work introduces new avenues to access highly functionalized boronates and silanes with precise regio- and stereocontrol.

Enantioselective Synthesis of Nonracemic Geminal Silylboronates by Pt-Catalyzed Hydrosilylation.

A Pt-catalyzed enantioselective hydrosilylation of alkenylboronates is described. This reaction occurs with high regio- and enantioselectivity, providing a convenient route to chiral non-racemic geminal silylboronates. These compounds are useful reagents in stereoselective synthesis.

Improving Robustness: In Situ Generation of a Pd(0) Catalyst for the Cyanation of Aryl Bromides.

Conditions have been developed for the palladium-catalyzed cyanation of aryl bromides utilizing the air-stable XantPhos-PdCl2 precatalyst. By employing a trialkylamine as a reducing agent, the active Pd(0) species is generated in situ, alleviating the need to employ the air-sensitive Pd2(dba)3. Twenty-two substituted benzonitriles have been synthesized using this method.

Catalytic Enantioselective Functionalization of Unactivated Terminal Alkenes.

Terminal alkenes are readily available functional groups which appear in α-olefins produced by the chemical industry, and they appear in the products of many contemporary synthetic reactions. While the organic transformations that apply to alkenes are amongst the most studied reactions in all of chemical synthesis, the number of reactions that apply to nonactivated terminal alkenes in a catalytic enantioselective fashion is small in number. This Minireview highlights the cases where stereocontrol in catalytic reactions of 1-alkenes is high enough to be useful for asymmetric synthesis.

Synthesis of vinyl boronates from aldehydes by a practical boron-Wittig reaction.

A highly stereoselective boron-Wittig reaction between stable and readily accessible 1,1-bis(pinacolboronates) and aldehydes furnishes a variety of synthetically useful di- and trisubstituted vinyl boronate esters.

Enantiomerically enriched tris(boronates): readily accessible conjunctive reagents for asymmetric synthesis.

The catalytic enantioselective diboration of vinyl boronate esters furnishes chiral tris(boronates) in a selective fashion. Subsequent deborylative alkylation occurs in a diastereoselective fashion, both for intermolecular and intramolecular processes.

Enantioselective carbocycle formation through intramolecular Pd-catalyzed allyl-aryl cross-coupling.

Aryl electrophiles containing tethered allylboronate units undergo efficient intramolecular coupling in the presence of a chiral palladium catalyst to give enantioenriched carbocyclic products. The reaction is found to be quite general, affording 5, 6, and 7-membered carbocyclic products as single regioisomers and with moderate enantioselectivities. Examination of differential coupling partners points to rapid allyl-equilibration as a key stereodefining feature.

Scope and mechanism of the Pt-catalyzed enantioselective diboration of monosubstituted alkenes.

The Pt-catalyzed enantioselective diboration of terminal alkenes can be accomplished in an enantioselective fashion in the presence of chiral phosphonite ligands. Optimal procedures and the substrate scope of this transformation are fully investigated. Reaction progress kinetic analysis and kinetic isotope effects suggest that the stereodefining step in the catalytic cycle is olefin migratory insertion into a Pt-B bond. Density functional theory analysis, combined with other experimental data, suggests that the insertion reaction positions platinum at the internal carbon of the substrate. A stereochemical model for this reaction is advanced that is in line both with these features and with the crystal structure of a Pt-ligand complex.