A novel copper-catalyzed one-pot trifluoromethylation/aryl migration/desulfonylation and C(sp2)–N bond formation with conjugated tosyl amides as starting materials is presented here. The reaction affords α-aryl-β-trifluoromethyl amides bearing a quaternary stereocenter or trifluoromethylated oxindoles in a regioselective manner.

Copper-Catalyzed One-Pot Trifluoromethylation/Aryl Migration/Desulfonylation and C(sp2)–N Bond Formation of Conjugated Tosyl Amides

The addition of a variety of radicals to the double bond of N-(arylsulfonyl)acrylamides can trigger cyclization/aryl migration/desulfonylation cascades via amidyl radical intermediates 2. Herein, we demonstrate the synthetic utility of these intermediates in subsequent C–C and C–X bond-forming events to rapidly build up molecular complexity. First, we describe a regioselective one-pot synthesis of CF3-, SCF3-, Ph2(O)P-, and N3-containing indolo[2,1-a]isoquinolin-6(5H)-ones from N-[(2-ethynyl)arylsulfonyl]acrylamides through a multi-step radical reaction cascade. The process involves the one-pot formation of four new bonds (one C–X, two C–C, and one C–N), a formal 1,4-aryl migration, and desulfonylation of the starting material. Second, we present a one-pot synthesis of 3,3-disubstituted-2-dihydropyridinones from N-(arylsulfonyl)acrylamides and 1,3-dicarbonyl compounds. In this case, a silver-catalyzed radical cascade process involving the sequential formation of two new C–C bonds and one C–N bond, a forma...

Cyclization cascades via N-amidyl radicals toward highly functionalized heterocyclic scaffolds.

Radical aryl migration reactions are of particular interest to the chemical community due to their potential application in radical chemistry and organic synthesis. The neophyl rearrangements used as radical clocks for examining the radical–molecular reactions have been known for decades. The combinations of these migrations with other radical reactions have provided a wide range of novel synthetic methodologies that are complementary to nucleophilic rearrangements. This review will give an overview of various types of radical aryl migrations, with an emphasis on their mechanistic studies from a historical point of view, as well as their application in tandem radical reactions.

Radical aryl migration reactions and synthetic applications.

Two radical-mediated processes of activated alkenes, namely arylphosphonylation and arylazidation, are described. The difunctionalization of alkenes by a tandem process that involves radical addition, 1,4-aryl migration, and desulfonylation generates α-aryl-β-heterofunctionalized amides bearing a quaternary stereocenter when the substituent on the nitrogen atom is an aryl group. Alternatively, heterooxindoles or spirobicycles can be obtained with excellent regioselectivity in the presence of an alkyl substituent on the nitrogen atom.

Arylphosphonylation and Arylazidation of Activated Alkenes

The challenges of the modern society and the growing demand of high-technology sectors of industrial production bring about a new phase in the development of organic synthesis. A cutting edge of modern synthetic methods is introduction of functional groups and more complex structural units into organic molecules with unprecedented control over the course of chemical transformation. Analysis of the state-of-the-art achievements in selective organic synthesis indicates the appearance of a new trend — the synthesis of organic molecules, biologically active compounds, pharmaceutical substances and smart materials with absolute selectivity. Most advanced approaches to organic synthesis anticipated in the near future can be defined as 'atomic precision' in chemical reactions. The present review considers selective methods of organic synthesis suitable for transformation of complex functionalized molecules under mild conditions. Selected key trends in the modern organic synthesis are considered including the preparation of organofluorine compounds, catalytic cross-coupling and oxidative cross-coupling reactions, atom-economic addition reactions, methathesis processes, oxidation and reduction reactions, synthesis of heterocyclic compounds, design of new homogeneous and heterogeneous catalytic systems, application of photocatalysis, scaling up synthetic procedures to industrial level and development of new approaches to investigation of mechanisms of catalytic reactions. The bibliography includes 840 references.

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Development of new methods in modern selective organic synthesis: preparation of functionalized molecules with atomic precision

Synthesis of 3-Arylpiperidines by a Radical 1,4-Aryl Migration

Synthesis of substituted 3-arylpiperidines and 3-arylpyrrolidines by radical 1,4 and 1,2-aryl migrations

A route to 3-arylpiperidines and 3-arylpyrrolidines involving radical 1,4- and 1,2-aryl migrations has been explored For the piperidines, the first route requires a xanthate addition to an N-allylarylsulfonamide, followed by acetylation and treatment with lauroyl peroxide to give the corresponding 1,4-aryl transfer product This compound can be converted into the desired piperidine derivative following acidic hydrolysis For the second approach to piperidines, addition of an α-keto xanthate to olefins of type 14 causes 1,2-aryl migration leading to an α,β-unsaturated ester, which can be converted into a piperidine by the action of ammonia or a primary amine and sodium cyanoborohydride Substituted 3-arylpyrrolidines can be obtained by simply starting with an α-amido substituted xanthate

Alexandru Gheorghe

Papers

Synthesis of 3-Arylpiperidines by a Radical 1,4-Aryl Migration

Synthesis of substituted 3-arylpiperidines and 3-arylpyrrolidines by radical 1,4 and 1,2-aryl migrations

Synthesis of Substituted 3‐Arylpiperidines and 3‐Arylpyrrolidines by Radical 1,4 and 1,2‐Aryl Migrations.