Estíbaliz Merino

Copper-catalyzed one-pot trifluoromethylation/aryl migration/desulfonylation and C(sp2)-N bond formation of conjugated tosyl amides.

A novel copper-catalyzed one-pot trifluoromethylation/aryl migration/desulfonylation and C(sp(2))-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.

Metal‐Free Aryltrifluoromethylation of Activated Alkenes

Metal-free: The first metal-free aryltrifluoromethylation of activated alkenes has been developed. With this method, trifluoromethylated isoquinolinediones, spirobicycles, oxindoles, and α-aryl-β-trifluoromethylamides were obtained with high control of the regioselectivity.

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

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 formal 1,4-aryl migration, and desulfonylation of the starting material explains the regioselective formation of densely functionalized heterocycles in a straightforward manner. Control experiments have unraveled the key intermediates as well as the sequence of individual steps involved in these transformations.

Arylphosphonylation and Arylazidation of Activated Alkenes

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.

Stereoselective Synthesis of Highly Functionalized Indanes and Dibenzocycloheptadienes through Complex Radical Cascade Reactions

Two highly stereoselective radical-mediated syntheses of densely functionalized indanes and dibenzocycloheptadienes from ortho-vinyl- and ortho-vinylaryl-substituted N-(arylsulfonyl)-acrylamides, respectively, are presented here. The chemoselective addition of in situ generated radicals (X(·)) onto the styrene moieties triggers an unprecedented reaction cascade, resulting in the formation of one new C-X bond and two new C-C bonds, a formal 1,4-aryl migration, and the extrusion of SO2 to generate an amidyl radical intermediate. This intermediate, upon H abstraction, leads to the observed 5- and 7-membered ring carbocyclic products, respectively, in a highly efficient manner.

Divergent reaction mechanisms in the aminofluorination of alkenes.

The aminofluorination of alkenes has become an attractive platform for the synthesis of β-amino-fluorinated compounds, valuable building blocks in medicinal and agricultural chemistry. The novel methodologies disclosed in recent years have unraveled a broad array of reaction mechanisms, so that the interest in these transformations transcends the mere synthetic aspects. This review aims to summarize the most relevant findings in this area attending at the nature of the fluorine source, and thus the specific mechanism operating in each of these transformations, namely electrophilic, nucleophilic, radical, and late transition metal-catalyzed reactions.

Stereoselective Carboperfluoroalkylation of Internal Alkynes: Mechanistic Insights

A Pd-catalyzed difunctionalization of internal alkynes combining boronic acids and perfluoroalkyl iodides under mild conditions is described here. Tetrasubstituted olefins containing perfluoroalkyl groups are synthesized in high yields in a regio- and stereoselective manner. Mechanistic studies have been carried out to shed light on the nature of the likely intermediates involved in these transformations.

Correction to "Cyclization Cascades via N-Amidyl Radicals toward Highly Functionalized Heterocyclic Scaffolds".

Highly Functionalized Heterocyclic Scaffolds” Noelia Fuentes, Wangqing Kong, Luis Fernańdez-Sańchez, Estíbaliz Merino, and Cristina Nevado* J. Am. Chem. Soc. 2015, 137, 964−973. DOI: 10.1021/ja5115858 Page 966. In Table 2, entries 27−31 were missing. Those entries are given below. Page 967. The text referring to those entries also needs to be corrected: “entries 27−32” should read “entries 27−31”.

Gold-catalyzed oxidative aminoesterification of unactivated alkenes

This paper describes an efficient aminoesterification of unactivated alkenes through Au(I)/Au(III) redox catalytic cycles using Selectfluor or hypervalent iodine(III) reagents.Graphical abstract