Recent Advances in C–H Functionalisation through Indirect Hydrogen Atom Transfer

Molecules, Journal Year: 2023, Volume and Issue: 28(16), P. 6127 - 6127

Published: Aug. 18, 2023

The functionalisation of C–H bonds has been an enormous achievement in synthetic methodology, enabling new retrosynthetic disconnections and affording simple equivalents for synthons. Hydrogen atom transfer (HAT) is a key method forming alkyl radicals from substrates. Classic reactions, including the Barton nitrite ester reaction Hofmann–Löffler–Freytag reaction, among others, provided early examples HAT. However, recent developments photoredox catalysis electrochemistry have made HAT powerful tool capable introducing wide range functional groups into bonds. Moreover, greater mechanistic insights stimulated development increasingly site-selective protocols. Site-selectivity can be achieved through tuning electron density at certain using additives, judicious choice reagent, solvent system. Herein, we describe latest methods functionalizing C–H/Si–H/Ge–H indirect between 2018–2023, as well critical discussion reagents, aspects, substrate scopes, background contexts

Language: Английский

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Radical reactions enabled by polyfluoroaryl fragments: photocatalysis and beyond

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(9), P. 4741 - 4785

Published: Jan. 1, 2024

The review summarizes advances in the radical chemistry of polyfluorinated arenes under photocatalytic conditions. fluoroaryl fragment serves as enabling motif for reaction design and efficient generation reactive intermediates.

Language: Английский

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Nickel-Catalyzed Radical Migratory Coupling Enables C-2 Arylation of Carbohydrates

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(23), P. 8590 - 8596

Published: June 4, 2021

Nickel catalysis offers exciting opportunities to address unmet challenges in organic synthesis. Herein we report the first nickel-catalyzed radical migratory cross-coupling reaction for direct preparation of 2-aryl-2-deoxyglycosides from readily available 1-bromosugars and arylboronic acids. The features a broad substrate scope tolerates wide range functional groups complex molecular architectures. Preliminary experimental computational studies suggest concerted 1,2-acyloxy rearrangement via cyclic five-membered-ring transition state followed by carbon–carbon bond formation. novel reactivity provides an efficient route valuable C-2-arylated carbohydrate mimics building blocks, allows new strategic disconnections, expands profile nickel catalysis.

Language: Английский

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Selective Transformations of Carbohydrates Inspired by Radical-Based Enzymatic Mechanisms

ACS Chemical Biology, Journal Year: 2021, Volume and Issue: 16(10), P. 1814 - 1828

Published: May 14, 2021

Enzymes are a longstanding source of inspiration for synthetic reaction development. However, enzymatic reactivity and selectivity frequently untenable in context, as the principles that govern control an setting often do not translate to small molecule catalysis. Recent methods have revealed viability using catalysts promote highly selective radical-mediated transformations minimally protected sugar substrates. These share conceptual similarities with radical SAM enzymes found microbial carbohydrate biosynthesis present opportunities chemists access unnatural building blocks without need protecting groups or lengthy sequences. Here, we highlight strategies through which pathways can enable site-, regio-, diastereoselective transformation carbohydrates both systems.

Language: Английский

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A Unified Strategy to Access 2- and 4-Deoxygenated Sugars Enabled by Manganese-Promoted 1,2-Radical Migration

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(34), P. 13798 - 13805

Published: Aug. 18, 2021

The selective manipulation of carbohydrate scaffolds is challenging due to the presence multiple, nearly chemically indistinguishable O-H and C-H bonds. As a result, protecting-group-based synthetic strategies are typically necessary for modification. Here we report concise semisynthetic strategy access diverse 2- 4-deoxygenated carbohydrates without relying on exhaustive use protecting groups achieve site-selective reaction outcomes. Our approach leverages Mn2+-promoted redox isomerization step, which proceeds via sugar radical intermediates accessed by neutral hydrogen atom abstraction under visible light-mediated photoredox conditions. resulting deoxyketopyranosides feature distinguishable functional readily transformed into structures. To showcase versatility this method, expedient syntheses rare sugars l-ristosamine, l-olivose, l-mycarose, l-digitoxose from commercial l-rhamnose. findings presented here validate potential facilitate transformation step efficiency advantages attendant that minimize reliance upon groups.

Language: Английский

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Diverse Catalytic Reactions for the Stereoselective Synthesis of Cyclic Dinucleotide MK-1454

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(13), P. 5855 - 5863

Published: March 25, 2022

As practitioners of organic chemistry strive to deliver efficient syntheses the most complex natural products and drug candidates, further innovations in synthetic strategies are required facilitate their construction. These aspirational breakthroughs often go hand-in-hand with considerable reductions cost environmental impact. Enzyme-catalyzed reactions have become an impressive necessary tool that offers benefits such as increased selectivity waste limitation. amplified when enzymatic processes conducted a cascade combination novel bond-forming strategies. In this article, we report highly diastereoselective synthesis MK-1454, potent agonist stimulator interferon gene (STING) signaling pathway. The begins asymmetric construction two fluoride-bearing deoxynucleotides. routes were designed for maximum convergency selectivity, relying on same benign electrophilic fluorinating reagent. From these subunits, four enzymes used construct bridging thiophosphates selective, high yielding process. Critical success reaction was thorough understanding role transition metals play bond formation.

Language: Английский

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C2-ketonylation of carbohydrates via excited-state palladium-catalyzed 1,2-spin-center shift

Chemical Science, Journal Year: 2022, Volume and Issue: 13(21), P. 6276 - 6282

Published: Jan. 1, 2022

C2-ketonyl-2-deoxysugars, sugars with the C2-hydroxyl group replaced by a ketone side chain, are important carbohydrate mimetics in glycobiology and drug discovery studies; however, their preparation remains vital challenge organic synthesis. Here we report first direct strategy to synthesize this class of glycomimetics from readily available 1-bromosugars silyl enol ethers via an excited-state palladium-catalyzed 1,2-spin-center shift (SCS) process. This step-economic reaction features broad substrate scope, has high functional tolerance, can be used late-stage functionalization natural product- drug-glycoconjugates. Preliminary experimental computational mechanistic studies suggested non-chain radical mechanism involving photoexcited palladium species, 1,2-SCS process, Mizoroki-Heck reaction.

Language: Английский

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Synthesis of a C₂-Symmetric Chiral Borinic Acid and Its Application in Catalytic Desymmetrization of 2,2-Disubstituted-1,3-Propanediols

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(15), P. 8338 - 8343

Published: April 10, 2023

Notwithstanding the common use of boronic acids in catalysis, design and synthesis efficient chiral remains a formidable challenge. Herein we disclose rational concise series novel C2-symmetric disubstituted acids, or borinic acids. Chiral have been found to be excellent agents that can achieve highly enantioselective desymmetrization 2,2-disubstituted-1,3-propanediols, providing diols with quaternary stereocenter, which has regarded recent years as challenging. A wide range substrates are tolerated this reaction, high enantioselectivity. The presence tetracoordinate borinate catalytic cycle proven by 11B NMR studies, stereocontrol model proposed.

Language: Английский

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Synthesis of Ketodeoxysugars from Acylated Pyranosides Using Photoredox Catalysis and Hydrogen Atom Transfer

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(17), P. 11171 - 11179

Published: Aug. 23, 2021

The combined action of a photoredox catalyst, hydrogen atom transfer mediator, and bond acceptor cocatalyst has been used to achieve the transformation pyranoside-derived esters into ketodeoxysugars. position acyl group dictates site deoxygenation, enabling preparation 2-deoxy- 4-deoxyketosugar derivatives. products are useful precursors rare sugar components bioactive secondary metabolites. Computational studies consistent with radical lyaselike mechanism wherein key elimination step proceeds via 1,2-acyloxy migration in intermediate.

Language: Английский

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Site- and Stereoselective C–H Alkylations of Carbohydrates Enabled by Cooperative Photoredox, Hydrogen Atom Transfer, and Organotin Catalysis

Organic Letters, Journal Year: 2021, Volume and Issue: 23(13), P. 5180 - 5185

Published: June 16, 2021

Diorganotin dihalides act as cocatalysts for site-selective and stereoselective couplings of diol-containing carbohydrates with electron-deficient alkenes in the presence an Ir(III) photoredox catalyst quinuclidine, a hydrogen atom transfer mediator. Quantum-chemical calculations support proposed mechanism involving formation cyclic stannylene acetal intermediate that shows enhanced reactivity toward abstraction by quinuclidinium radical cation. Addition carbon-centered to alkene partner results C-alkylation carbohydrate substrate.

Language: Английский

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