Synthesis of Ketonylated Carbocycles via Excited-State Copper-Catalyzed Radical Carbo-Aroylation of Unactivated Alkenes.

Carbocycles are core skeletons in natural and synthetic organic compounds possessing a wide diversity of important biological activities. Herein, we report the development of an excited-state copper-catalyzed radical carbo-aroylation of unactivated alkenes to synthesize ketonylated tetralins, di- and tetrahydrophenanthrenes, and cyclopentane derivatives. The reaction is operationally simple and features mild reaction conditions that tolerate a broad range of functional groups. Preliminary mechanistic studies suggest a reaction pathway beginning with photoexcitation of [CuI-BINAP]2 and followed by a single electron transfer (SET), radical aroylation of unactivated alkenes, radical cyclization, and re-aromatization, affording the desired ketonylated carbocycles.

Excited-State Copper-Catalyzed [4 + 1] Annulation Reaction Enables Modular Synthesis of α,ß-Unsaturated-γ-Lactams.

Synthesis of α,ß-unsaturated-γ-lactams continue to attract attention due to the importance of this structural motif in organic chemistry. Herein, we report the development of a visible-light-induced excited-state copper-catalyzed [4 + 1] annulation reaction for the preparation of a wide range of γ-H, -OH, and -OR-substituted α,ß-unsaturated-γ-lactams using acrylamides as the 4-atom unit and aroyl chlorides as the 1-atom unit. This modular synthetic protocol features mild reaction conditions, broad substrate scope, and high functional group tolerance. The reaction is amenable to late-stage diversification of complex molecular architectures, including derivatives of marketed drugs. The products of the reaction can serve as versatile building blocks for further derivatization. Preliminary mechanistic studies suggest an inner-sphere catalytic cycle involving photoexcitation of the Cu(BINAP) catalyst, single-electron transfer, and capture of radical intermediates by copper species, followed by reductive elimination or protonation to give the desired γ-functionalized α,ß-unsaturated-γ-lactams.

Synthetic utility of biomimicking vanadium bromoperoxidase and n-tetrabutylammonium tribromide (TBATB) in organic synthesis.

Nature has established a broad spectrum of methods to introduce halogen atoms in organic compounds. Recent developments have revealed that haloperoxidases are one of the major sources responsible for incorporating bromines to produce bromoorganics in nature. Pioneering studies of numerous researchers have unravelled the details of haloperoxidases, mainly vanadium dependent enzyme bromo- and iodo-peroxidases, including reaction mechanism, kinetics and especially biomimicking studies. In this review, we initially have described the scope of biomimicking vanadium bromoperoxidase in producing the bromonium ion and its further utilisation in conducting oxidative bromination or cleavage of various organic molecules. Moreover, by biomicmicking, the synthesis of OATB and the synthetic utility of various organic ammonium tribromides (OATBs) have been discussed. Among such OATBs, n-tetrabutylammonium tribromide (TBATB) has been explored for bromination of organic molecules as well as in the facile removal of several protecting groups and as a potential catalyst in various synthetic transformations. This review attempts to compile a myriad of reactions concerning the catalytic activity of vanadium bromoperoxidases and the usefulness of various OATBs, particularly with special emphasis on TBATB in various organic transformations.

Excited-State Copper Catalysis for the Synthesis of Heterocycles.

Heterocycles are one of the largest groups of organic moieties with significant medicinal, chemical, and industrial applications. Herein, we report the discovery and development of visible-light-induced, synergistic excited-state copper catalysis using a combination of Cu(IPr)I as a catalyst and rac-BINAP as a ligand, which produces more than 10 distinct classes of heterocycles. The reaction tolerates a broad array of functional groups and complex molecular scaffolds, including derivatives of peptides, natural products, and marketed drugs. Preliminary mechanistic investigation suggests in situ generations of [Cu(BINAP)2 ]+ and [Cu(IPr)2 ]+ catalysts that work cooperatively under visible-light irradiation to facilitate catalytic carbo-aroylation of unactivated alkenes, affording a wide range of useful heterocycles.

Photocatalytic Radical Aroylation of Unactivated Alkenes: Pathway to ß-Functionalized 1,4-, 1,6-, and 1,7-Diketones.

We report the development of a photocatalytic strategy for the synthesis of ß-functionalized unsymmetrical 1,4-, 1-6 and 1,7-diketones from aroyl chlorides and unactivated alkenes at room temperature. The mild reaction conditions not only tolerate a wide range of functional groups and structural moieties, but also enable migration of a variety of distal groups including (hetero)arenes, nitrile, aldehyde, oxime-derivative, and alkene. The efficiency of chirality transfer, factors that control the distal-group migration, and synthesis of carbo- and heterocycles from the diketones are also described. Mechanistic studies suggest a reaction pathway involving a photocatalytic radical aroylation of unactivated alkenes followed by a distal-group migration, oxidation, and deprotonation to afford the desired diketones.

C-H functionalisation of cycloalkanes.

Among organic compounds hydrocarbons are inexpensive and possibly the most abundant among natural resources. Developing strategies for selective functionalisation of inert hydrocarbon C-H bonds is one of the most ideal synthetic paths that a synthetic chemist could think of. This critical review focuses on the recent development of various directed and non-directed cycloalkylations leading to the formation of carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds. Apart from various transition metal catalysed cycloalkylations, this review also covers various metal-free cycloalkylation processes.

Beyond conventional routes, an unprecedented metal-free chemoselective synthesis of anthranilate esters via a multicomponent reaction (MCR) strategy.

A hitherto unreported route for the synthesis of anthranilate esters is demonstrated using 2-nitrobenzaldehyde, malonitrile and an alcohol or amine via a metal and oxidant free multicomponent reaction (MCR) strategy. This process simultaneously installs an ester and urea or urethane functionality via CO and CN bond formations via concurrent oxidation of the aldehyde group and reduction of the nitro group involving an intramolecular redox process.