Palladium‐Catalyzed Site‐Selective C−H Functionalization of Weakly Coordinating Sulfonamides: Synthesis of Biaryl Sulfonamides

A novel and site selective C?H functionalization of unsubstituted sulfonamides has been developed for the synthesis of ortho aryl sulfonamides. The reaction involves highly regioselective ortho mono arylation of weakly coordinating SO₂NH₂ directing group by means of aryl iodides. Palladium acetate in the presence of silver(I) oxide is found to be the most effective catalytic system.     

Desulfinative palladium‐catalyzed cross‐coupling of arylsulfonyl hydrazides with aryl bromides under air

A highly efficient and mild palladium‐catalyzed cross‐coupling of arylsulfonyl hydrazides and aryl bromides for the selective synthesis of unsymmetrical biaryls has been developed. This methodology has the advantages of easily accessible starting materials, functional group tolerance and a wide range of substrates, which provide rapid access to biaryls derivatives. In this protocol, abundant and stable aryl bromides serve as the aryl sources by coupling reaction of the aryl group generated from arylsulfonyl hydrazides via in situ release of nitrogen and sulfur dioxide. No external oxidants or acids are needed for this kind of transformation.     

Nickel‐Catalyzed Cross‐Coupling of Sulfonamides With (Hetero)aryl Chlorides

The development of Ni‐catalyzed C?N cross‐couplings of sulfonamides with (hetero)aryl chlorides is reported. These transformations, which were previously achievable only with Pd catalysis, are enabled by use of air‐stable ( L )NiCl(o‐tol) pre‐catalysts (L= PhPAd‐DalPhos and PAd2‐DalPhos ), without photocatalysis. The collective scope of (pseudo)halide electrophiles (X=Cl, Br, I, OTs, and OC(O)NEt₂) demonstrated herein is unprecedented for any reported catalyst system for sulfonamide C?N cross‐coupling (Pd, Cu, Ni, or other). Preliminary competition experiments and relevant coordination chemistry studies are also presented.     

Alkaline‐Earth‐Catalyzed Dehydrocoupling of Amines and Boranes

Dehydrocoupling reactions between the boranes HBpin and 9‐borabicyclo[3.3.1]nonane and a range of amines and anilines ensue under very mild reaction conditions in the presence of a simple β‐diketiminato magnesium n‐butyl precatalyst. The facility of the reactions is suggested to be a function of the Lewis acidity of the borane substrate, and is dictated by resultant pre‐equilibria between, and the relative stability of, magnesium hydride and borohydride intermediates during the course of the catalysis.     

Combining Organometallic Reagents,the Sulfur Dioxide Surrogate DABSO,and Amines: A One‐Pot Preparation of Sulfonamides,Amenable to Array Synthesis

We describe a method for the synthesis of sulfonamides through the combination of an organometallic reagent, a sulfur dioxide equivalent, and an aqueous solution of an amine under oxidative conditions (bleach). This simple reaction protocol avoids the need to employ sulfonyl chloride substrates, thus removing the limitation imposed by the commercial availability of these reagents. The resultant method allows access to new chemical space, and is also tolerant of the polar functional groups needed to impart favorable physiochemical properties required for medicinal chemistry and agrochemistry. The developed chemistry is employed in the synthesis of a targeted 70 compound array, prepared using automated methods. The array achieved a 93 % success rate for compounds prepared. Calculated molecular weights, lipophilicities, and polar surface areas are presented, demonstrating the utility of the method for delivering sulfonamides with drug‐like properties.     

Nickel‐catalyzed oxidative esterification of formamides with 1,3‐dicarbonyl compounds under mild reaction conditions

Synthesis of enol carbamates was achieved via nickel‐catalyzed oxidative coupling of formamides with 1,3‐dicarbonyl compounds in the presence of tert ‐butyl hydroperoxide at 40 °C. Various derivatives of enol carbamates were synthesized by this method in good to excellent yields.     

Ruthenium‐Catalyzed Modular Synthesis of Cyclic Tertiary Amines from Lactams

Reported is the development of a novel catalytic cascade reaction facilitating the modular synthesis of cyclic tertiary amines from simple lactam substrates and secondary alcohols. Using a single molecular ruthenium‐triphos catalyst in the presence of molecular hydrogen enabled the versatile formation of various amines in high yield with excellent selectivity. Extending the reaction system to using an alcohol as the hydrogen transfer reagent allowed the reduction of lactams without the need for molecular hydrogen.     

Copper‐Catalyzed Aerobic Oxidative Reaction of Sulfonyl Hydrazides with Alcohols: An Easy Access to Sulfinates

A Cu‐catalyzed aerobic oxidative reaction between sulfonyl hydrazides and alcohols has been developed. In this reaction, sulfonyl hydrazides act as the sulfinic acid precursors to react with alcohols, resulting in sulfinic esters with up to 72 % yield. This catalytic system tolerates a wide range of sulfonyl hydrazide substrates, and represents a new strategy for the transformation of readily available sulfonyl hydrazides.     

An Efficient Method for the Preparation of Sulfonamides from Sodium Sulfinates and Amines

Sulfonamides have a special role on medicine due to their broad biological activities, as bacterial infections, diabetes mellitus, oedema, hypertension prevention and treatment. In addition, sulfonamides are also useful in herbicides and pesticides. Herein, we communicate an efficient strategy for the preparation of sulfonamides via NH₄I‐mediated amination of sodium sulfinates. This new method provides a general and environmentally friendly access to sulfonamide compounds and tolerates a wide range of functional groups.     

TBAI/TBHP‐Promoted Generation of Malonyl Radicals: Oxidative Coupling with Styrenes Leads to γ‐Keto Diesters

A metal‐free protocol for oxidative coupling of malonic esters with styrenes to form γ‐keto diesters has been developed. Key to the success of this process is the generation of malonyl radicals from unfunctionalized malonic esters under organo‐catalysis conditions with TBAI and TBHP. This process tolerates both terminal and internal olefins with diverse malonic esters. It provides a new green metal‐free alternative to traditional metal mediated process for generation of malonyl radicals and there by γ‐keto diesters.     

Palladium‐Catalyzed Synthesis of Ammonium Sulfinates from Aryl Halides and a Sulfur Dioxide Surrogate: A Gas‐ and Reductant‐Free Process

Sulfonyl‐derived functional groups populate a broad range of useful molecules and materials, and despite a variety of preparative methods being available, processes which introduce the most basic sulfonyl building block, sulfur dioxide, using catalytic methods, are rare. Described herein is a simple reaction system consisting of the sulfur dioxide surrogate DABSO, triethylamine, and a palladium(0) catalyst for effective convertion of a broad range of aryl and heteroaryl halides into the corresponding ammonium sulfinates. Key features of this gas‐ and reductant‐free reaction include the low loadings of palladium (1 mol %) and ligand (1.5 mol %) which can be employed, and the use of isopropyl alcohol as both a solvent and formal reductant. The ammonium sulfinate products are converted in situ into a variety of sulfonyl‐containing functional groups, including sulfones, sulfonyl chlorides, and sulfonamides.     

Copper‐Catalyzed Aerobic Decarboxylation/Ketooxygenation of Electron‐Deficient Alkenes

A copper‐catalyzed ketooxygenation of electron‐deficient alkenes was developed. This approach combines O?H alkylation, aerobic decarboxylation, and oxygenation in one transformation. Mechanistic investigation of this reaction showed that the copper salt is responsible for both generating the amidoxyl radical and promoting aerobic decarboxylation.