RESUMO
An operationally simple, open-air, and efficient light-mediated Minisci C-H alkylation method is described, based on the formation of an electron donor-acceptor (EDA) complex between nitrogen-containing heterocycles and redox-active esters. In contrast to previously reported protocols, this method does not require a photocatalyst, an external single electron transfer agent, or an oxidant additive. Achieved under mildly acidic and open-air conditions, the reaction incorporates primary-, secondary-, and tertiary radicals, including bicyclo[1.1.1]pentyl (BCP) radicals, along with various heterocycles to generate Minisci alkylation products in moderate to good yields. Additionally, the method is exploited to generate a stereo-enriched, hetereoaryl-substituted carbohydrate.
RESUMO
DNA-encoded library (DEL) technology has emerged as a time- and cost-efficient technique for the identification of therapeutic candidates in the pharmaceutical industry. Although several reaction classes have been successfully validated in DEL environments, there remains a paucity of DNA-compatible reactions that harness building blocks (BBs) from readily available substructures bearing multifunctional handles for further library diversification under mild, dilute, and aqueous conditions. In this study, the direct C-H carbofunctionalization of medicinally-relevant heteroarenes can be accomplished via the photoreduction of DNA-conjugated (hetero)aryl halides to deliver reactive aryl radical intermediates in a regulated fashion within minutes of blue light illumination. A broad array of electron-rich and electron-poor heteroarene scaffolds undergo transformation in the presence of sensitive functional groups.
RESUMO
A simple visible light photochemical, nickel-catalyzed synthesis of ketones from carboxylic acid-derived precursors is presented. Hantzsch ester (HE) functions as a cheap, green and strong photoreductant to facilitate radical generation and also engages in the Ni-catalytic cycle to restore the reactive species. With this dual role, HE allows for the coupling of a large variety of radicals (1°,2°, benzylic, α-oxy & α-amino) with aroyl and alkanoyl moieties, a new feature in reactions of this type. With both precursors deriving from abundant carboxylic acids, this protocol is a welcome addition to the organic chemistry toolbox. The reaction proceeds under mild conditions without the need for toxic metal reagents or bases and shows a wide scope, including pharmaceuticals and complex molecular architectures.
Assuntos
Cetonas , Níquel , Ácidos Carboxílicos , Catálise , OxirreduçãoRESUMO
DNA-encoded library (DEL) technology features a time- and cost-effective interrogation format for the discovery of therapeutic candidates in the pharmaceutical industry. To develop DEL platforms, the implementation of water-compatible transformations that facilitate the incorporation of multifunctional building blocks (BBs) with high C(sp3) carbon counts is integral for success. In this report, a decarboxylative-based hydroalkylation of DNA-conjugated trifluoromethyl-substituted alkenes enabled by single-electron transfer (SET) and subsequent hydrogen atom termination through electron donor-acceptor (EDA) complex activation is detailed. In a further photoredox-catalyzed hydroarylation protocol, the coupling of functionalized, electronically unbiased olefins is achieved under air and within minutes of blue light irradiation through the intermediacy of reactive (hetero)aryl radical species with full retention of the DNA tag integrity. Notably, these processes operate under mild reaction conditions, furnishing complex structural scaffolds with a high density of pendant functional groups.
RESUMO
A dual photochemical/nickel-mediated decarboxylative strategy for the assembly of C(sp3)-C(sp2) linkages is disclosed. Under light irradiation at 390 nm, commercially available and inexpensive Hantzsch ester (HE) functions as a potent organic photoreductant to deliver catalytically active Ni(0) species through single-electron transfer (SET) manifolds. As part of its dual role, the Hantzsch ester effects a decarboxylative-based radical generation through electron donor-acceptor (EDA) complex activation. This homogeneous, net-reductive platform bypasses the need for exogenous photocatalysts, stoichiometric metal reductants, and additives. Under this cross-electrophile paradigm, the coupling of diverse C(sp3)-centered radical architectures (including primary, secondary, stabilized benzylic, α-oxy, and α-amino systems) with (hetero)aryl bromides has been accomplished. The protocol proceeds under mild reaction conditions in the presence of sensitive functional groups and pharmaceutically relevant cores.
RESUMO
The one-pot sulfonylation/aminoalkylation of styrene derivatives furnishing substituted γ-sulfonylamines was accomplished through a photoredox-catalyzed four-component reaction. Besides one molecule of water and the sodium counterion of the sulfinate, all atoms of the starting materials are transferred to the final product, rendering this process highly atom-efficient. The operationally simple protocol allows for the simultaneous formation of three new single bonds (C-S, C-N, and C-C) and therefore grants rapid access to structurally diverse products.
RESUMO
Simultaneous sulfonylation/arylation of styrene derivatives is achieved in a photoredox-catalyzed three-component reaction using visible light. A broad variety of difunctionalized products is accessible in mostly excellent yields and high diastereoselectivity. The developed reaction is scalable and suitable for the modification of styrene-functionalized biomolecules. Mechanistic investigations suggest the transformation to be operating through a designed sequence of radical formation and radical combination.
RESUMO
Described is a cross-electrophilic, deaminative coupling strategy harnessing Katritzky salts as a new species of electrophile in Ni/photoredox dual catalytic reductive cross-coupling reactions. Distinguishing features of this arylation protocol include its mild reaction conditions, high chemoselectivity, and adaptability to a variety of complex substrates [i.e., pyridinium salts derived from amines and partners derived from (hetero)aryl bromides].
Assuntos
Aminas/química , Complexos de Coordenação/química , Níquel/química , Catálise , Corantes Fluorescentes/química , Radicais Livres/química , Oxirredução , Processos Fotoquímicos , Espectrometria de Fluorescência/métodosRESUMO
The synthesis of vinyl sulfones and (α,ß-unsaturated) nitriles from carboxylic acids was realized through oxidative decarboxylation with 1,4-dicyanoanthracene as an organic photoredox catalyst. Various types of C-radicals are generated and used to construct three different classes of potential covalent protease inhibitors. The procedure is functional group tolerant and applicable to natural products and druglike scaffolds. It may serve for the rapid construction of screening candidates as demonstrated by a three-step synthesis of the known protease inhibitor K11777.
Assuntos
Alcenos/química , Ácidos Carboxílicos/química , Inibidores Enzimáticos/síntese química , Peptídeos/química , Catálise , Dipeptídeos/síntese química , Nitrilas/síntese química , Oxirredução , Fenilalanina/análogos & derivados , Processos Fotoquímicos , Piperazinas , Inibidores de Proteases/síntese química , Sulfonas/síntese química , Compostos de Tosil , Compostos de Vinila/síntese químicaRESUMO
A visible light-promoted protocol for the redox-neutral coupling of N-hydroxyphthalimide esters with different N-heterocyclic compounds is described. The reaction proceeds through an alkyl radical intermediate generated by reductive decarboxylation of N-hydroxyphthalimide esters. In contrast to the original Minisci protocol, polyalkylation can largely be avoided. Mechanistic investigations revealed a radical chain mechanism which in some cases can proceed even if no photocatalyst is added. This valuable and functional group-tolerant reaction produces substituted heterocycles in moderate to excellent yield. The use of inexpensive starting materials and LEDs as the light source are key features of this C-C bond formation.
Assuntos
Ésteres/química , Ftalimidas/química , Catálise , Descarboxilação , Compostos Heterocíclicos/química , Luz , Estrutura Molecular , Processos FotoquímicosRESUMO
An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.