Radical Deoxyfunctionalisation Strategies (original) (raw)
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Direct Aldehyde Csp(2) -H Functionalization through Visible-Light-Mediated Photoredox Catalysis
Chemistry (Weinheim an der Bergstrasse, Germany), 2017
The development of methods for carbon-carbon bond formation under benign conditions is an ongoing challenge for synthetic chemists. In recent years there has been considerable interest in using selective C-H activation as a direct route for generating reactive intermediates. Herein, the use of visible-light-mediated dual photoredox organocatalysis as a mild and effective method for Csp2 -H activation of aldehydes is reported, resulting in the generation of acyl radicals. These nucleophilic acyl radical species can undergo either addition to electrophilic alkenes or nickel-catalyzed cross-coupling reactions to provide a quick access to broad range of unsymmetrical ketones, which are abundantly found in many organic building blocks.
Dehydrogenative desaturation-relay via formation of multicenter-stabilized radical intermediates
Nature Communications
In organic molecules, the reactivity at the carbon atom next to the functional group is dramatically different from that at other carbon atoms. Herein, we report that a versatile copper-catalyzed method enables successive dehydrogenation or dehydrogenation of ketones, aldehydes, alcohols, α,β-unsaturated diesters, and N-heterocycles to furnish stereodefined conjugated dienecarbonyls, polyenecarbonyls, and nitrogen-containing heteroarenes. On the basis of mechanistic studies, the copper-catalyzed successive dehydrogenation process proceeds via the initial α,β-desaturation followed by further dehydrogenative desaturation of the resultant enone intermediate, demonstrating that the reactivity at α-carbon is transferred through carbon-carbon double bond or longer π-system to the carbon atoms at the positions γ, ε, and η to carbonyl groups. The dehydrogenative desaturation-relay is ascribed to the formation of an unusual radical intermediate stabilized by 5-or 7,-or 9-center π-systems. The discovery of successive dehydrogenation may open the door to functionalizations of the positions distant from functional groups in organic molecules.
European Journal of Inorganic Chemistry, 2011
Transition-metal-catalyzed atom transfer radical reactions of halogen compounds to olefins constitute a versatile tool in organic synthesis within the area of CC bond forming transformations. The inter-or intramolecular versions, respectively atom transfer radical addition (ATRA) or cyclization (ATRC), lead to the atom economic, valuable synthesis of compounds that can be further functionalized. This contribution summarizes the recent developments in this area in terms of catalyst design as well as the applicability of this methodology in sequential, domino or tandem reactions.
Photoenzymatic enantioselective intermolecular radical hydroalkylation
Nature, 2020
Enzymes are increasingly explored for use in asymmetric synthesis 1-3 , but their applications are generally limited by the reactions available to naturally occurring enzymes. Recently, interest in photocatalysis 4 has spurred the discovery of novel reactivity from known enzymes 5. However, so far photoinduced enzymatic catalysis 6 has not been used for the cross-coupling of two molecules. For example, the intermolecular coupling of alkenes with α-halo carbonyl compounds through a visible-light-induced radical hydroalkylation, which could provide access to important γ-chiral carbonyl compounds, has not yet been achieved by enzymes. The major challenges are the inherent poor photoreactivity of enzymes and the difficulty in achieving stereochemical control of the remote prochiral radical intermediate 7. Here we report a visible-light-induced intermolecular radical hydroalkylation of terminal alkenes that does not occur naturally, catalysed by an 'ene' reductase using readily available α-halo carbonyl compounds as reactants. This method provides an efficient approach to the synthesis of various carbonyl compounds bearing a γ-stereocentre with excellent yields and enantioselectivities (up to 99 per cent yield with 99 per cent enantiomeric excess), which otherwise are difficult to access using chemocatalysis. Mechanistic studies suggest that the formation of the complex of the substrates (α-halo carbonyl compounds) and the 'ene' reductase triggers the enantioselective photoinduced radical reaction. Our work further expands the reactivity repertoire of biocatalytic, synthetically useful asymmetric transformations by the merger of photocatalysis and enzyme catalysis.
Visible-Light Photoredox Enables Ketone Carbonyl Alkylation for Easy Access to Tertiary Alcohols
ACS Catalysis, 2019
Being a handle for synthesizing quaternary carbon centers and olefins, together with ubiquitous appearance in organic building blocks makes tertiary alcohols valuable targets in synthesis. However, traditional syntheses of these alcohols have faced several challenges including the employment of functionalized reactive reagents, undesirable side reactions and decomposition of the alcohol products under harsh conditions. The paucity of synthetic approach to bulky tertiary alcohols prompts our interest to develop a benign catalytic protocol to tackle the current issues. Here, we have successfully demonstrated the use of ketyl radicals in intermolecular cross radical-radical coupling, which has opened the new door for accessing complex tertiary alcohols. On the other hand, by starting from feedstock and naturally derived chemicals without any preactivation, it would be superior to traditional methodologies in industrial context.
Photoinduced Remote Functionalisations by Iminyl Radical Promoted C-C and C-H Bond Cleavage Cascades
Angewandte Chemie (International ed. in English), 2018
A photoinduced cascade strategy leading to a variety of differentially functionalised nitriles and ketones has been developed. These reactions rely on the oxidative generation of iminyl radicals from simple oximes. Radical transposition by C(sp)-(sp) and C(sp)-H bond cleavage gives access to distal carbon radicals that undergo S2 functionalisations. These mild, visible-light-mediated procedures can be used for remote fluorination, chlorination, and azidation, and were applied to the modification of bioactive and structurally complex molecules.
Recent Advances in Radical Dioxygenation of Olefins
European Journal of Organic Chemistry, 2017
Dioxygenation of olefins is a valuable synthetic tool for the construction of 1,2-diols and α-oxygenated ketones. The use of radical approaches to achieve this direct 1,2-difunctionalization has recently made considerable progress. The metalcatalyzed reactions employ molecular oxygen and air as the oxidants, whereas metal-free dioxygenation utilizes oxygen and
ACS Catalysis
A strategy for both cross-electrophile coupling and 1,2-dicarbofunctionalization of olefins has been developed. Carbon-centered radicals are generated from alkyl bromides by merging benzophenone hydrogen atom transfer (HAT) photocatalysis and silyl radical-induced halogen atom transfer (XAT) and are subsequently intercepted by a nickel catalyst to forge the targeted C(sp 3)−C(sp 2) and C(sp 3)−C(sp 3) bonds. The mild protocol is fast and scalable using flow technology, displays broad functional group tolerance, and is amenable to a wide variety of medicinally relevant moieties. Mechanistic investigations reveal that the ketone catalyst, upon photoexcitation, is responsible for the direct activation of the silicon-based XAT reagent (HAT-mediated XAT) that furnishes the targeted alkyl radical and is ultimately involved in the turnover of the nickel catalytic cycle.