Tetracoordinate Boron Intermediates Enable Unconventional Transformations

Accounts of Chemical Research, Journal Year: 2021, Volume and Issue: 54(9), P. 2298 - 2312

Published: April 14, 2021

ConspectusOrganoboron compounds are a class of multifunctional reagents for the construction carbon–carbon and carbon–heteroatom bonds in modern synthetic chemistry. The transformations organoboron usually carried out through tetracoordinate boron intermediates mainly include additions to unsaturated bonds, rearrangement reactions, transmetalation so on. Although great progress has been achieved improving intermediates, there still shortcomings, such as sparse activation modes, paucity reaction strategies difficulties stereoselective control. In this Account, we discuss our recent advances development unconventional based on design including following three topics: (1) C–B bonds; (2) C–C (3) application chiral boron.The new build is interest chemists. We have developed tandem reactions involving multiple selective borylations alkynes synthesis stable boron, domino-borylation-protodeboronation (DBP) strategy alkynes, highly regio-, stereo-, chemoselective Cu-catalyzed diborylation β-CF3-1,3-enynes cascade B–Cl/C–B cross-metathesis C–H bond borylation triarylboranes. also novel form because formation an enduring theme organic disclosed long distance or migration coupling partners 1,4-migrations nitrile oxide nitrilium migrations isocyanide intermediate, palladium-catalyzed Suzuki–Miyaura thioureas thioamides, copper-catalyzed atroposelective Michael-type addition, Catellani reaction. Moreover, terms control found that tricoordinate complex could activate water with Brønsted acidity, which successfully applied high enantioselectivity asymmetric catalytic reduction challenging indoles.This Account summarizes efforts using not only precise wide range diverse but acid indoles.

Language: Английский

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The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(5), P. 2441 - 2511

Published: Feb. 21, 2024

Boron-containing compounds (BCC) have emerged as important pharmacophores. To date, five BCC drugs (including boronic acids and boroles) been approved by the FDA for treatment of cancer, infections, atopic dermatitis, while some natural are included in dietary supplements. Boron's Lewis acidity facilitates a mechanism action via formation reversible covalent bonds within active site target proteins. Boron has also employed development fluorophores, such BODIPY imaging, carboranes that potential neutron capture therapy agents well novel diagnostics therapy. The utility synthetic become multifaceted, breadth their applications continues to expand. This review covers many uses targets boron medicinal chemistry.

Language: Английский

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Iridium-Catalyzed Asymmetric Difunctionalization of C–C σ-Bonds Enabled by Ring-Strained Boronate Complexes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16508 - 16516

Published: July 20, 2023

Enantioenriched organoboron intermediates are important building blocks in organic synthesis and drug discovery. Recently, transition metal-catalyzed enantioselective 1,2-metalate rearrangements of alkenylboronates have emerged as an attractive protocol to access these valuable reagents by installing two different carbon fragments across C═C π-bonds. Herein, we report the development iridium-catalyzed asymmetric allylation-induced rearrangement bicyclo[1.1.0]butyl (BCB) boronate complexes enabled strain release, which allows difunctionalization C-C σ-bonds, including dicarbonation carboboration. This provides a variety enantioenriched three-dimensional 1,1,3-trisubstituted cyclobutane products bearing boronic ester that can be readily derivatized. Notably, reaction gives trans diastereoisomers result from anti-addition σ-bond, is contrast syn-additions observed for reactions promoted PdII-aryl other electrophiles our previous works. The diastereoselectivity has been rationalized based on combination experimental data density functional theory calculations, suggest BCB highly nucleophilic react via early states with low activation barriers.

Language: Английский

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Synthesis of Borylated Carbocycles by [2 + 2]-Cycloadditions and Photo-Ene Reactions

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(14), P. 10142 - 10149

Published: March 27, 2024

Saturated bicyclic compounds make up a valuable class of building blocks in the development agrochemicals and pharmaceuticals. Here, we present synthesis borylated bicyclo[2.1.1]hexanes via crossed [2 + 2]-cycloaddition. Due to presence C–B bond, variety structures can be easily prepared that are not accessible by other methods. Moreover, rare photo-ene reaction is also disclosed, allowing for diastereoselective trisubstituted cyclopentanes.

Language: Английский

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Asymmetric Radical Cyclopropanation of α,β-Unsaturated Amides with α-Boryl and α-Silyl Dibromomethanes via Cr(II)-Based Metalloradical Catalysis

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7282 - 7292

Published: Feb. 20, 2025

Transition-metal-catalyzed asymmetric carbene-transfer reactions represent a powerful strategy for synthesizing chiral cyclopropanes. However, current methods predominantly rely on stabilized carbene-bearing α-π-conjugated groups, restricting access to less carbenes, such as α-silyl and α-boryl carbenes. Herein, we present an unprecedented Cr(II)-based metalloradical system the cyclopropanation of α,β-unsaturated amides with dibromomethanes in presence Mn reducing agent. Employing chromium complex, reaction proceeds under mild conditions, yielding cyclopropanes three contiguous stereocenters high diastereo- enantioselectivities. This method features Cr-catalyzed radical-based stepwise mechanism. The broad substrate scope, encompassing various amides, demonstrates protocol's versatility robustness. Mechanistic insights, supported by experimental computational studies, suggest formation α-Cr(III)-alkyl radical intermediates, delineating pathway distinct from that classical concerted cyclopropanations. approach provides tool highly functionalized cyclopropanes, offering potential applications drug discovery development.

Language: Английский

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Stereospecific 1,2‐Migrations of Boronate Complexes Induced by Electrophiles

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(39), P. 16859 - 16872

Published: June 27, 2020

The stereospecific 1,2-migration of boronate complexes is one the most representative reactions in boron chemistry. This process has been used extensively to develop powerful methods for asymmetric synthesis, with applications spanning from pharmaceuticals natural products. Typically, driven by displacement an α-leaving group, oxidation α-boryl radical, or electrophilic activation alkenyl complex. aim this article summarize recent advances rapidly expanding field electrophile-induced groups sp

Language: Английский

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Advances in transition metal-free deborylative transformations of gem-diborylalkanes

Chemical Communications, Journal Year: 2021, Volume and Issue: 57(36), P. 4346 - 4353

Published: Jan. 1, 2021

This article highlights recent advances on the base-promoted deborylative carbon–carbon and carbon–boron bond-forming reactions using gem-diborylalkanes as sources of α-borylcabanions.

Language: Английский

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Intermolecular Crossed [2 + 2] Cycloaddition Promoted by Visible-Light Triplet Photosensitization: Expedient Access to Polysubstituted 2-Oxaspiro[3.3]heptanes

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(10), P. 4055 - 4063

Published: March 5, 2021

This paper describes an intermolecular cross-selective [2 + 2] photocycloaddition reaction of exocyclic arylidene oxetanes, azetidines, and cyclobutanes with simple electron-deficient alkenes. The takes place under mild conditions using a commercially available Ir(III) photosensitizer upon blue light irradiation. transformation provides access to range polysubstituted 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, spiro[3.3]heptane motifs, which are prime interest in medicinal chemistry as gem-dimethyl carbonyl bioisosteres. A variety further transformations the initial cycloadducts demonstrated highlight versatility products enable selective either syn- or anti-diastereoisomer through kinetic thermodynamic epimerization, respectively. Mechanistic experiments DFT calculations suggest that this proceeds sensitized energy transfer pathway.

Language: Английский

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Construction of Axially Chiral Arylborons via Atroposelective Miyaura Borylation

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(27), P. 10048 - 10053

Published: June 28, 2021

Compared with the well-developed centrally chiral boron chemistry, C–B axially chemistry remains elusive and challenging. Herein we report first atroposelective Miyaura borylation of bromoarenes unsymmetrical diboron reagents for direct catalytic synthesis optically active atropisomeric arylborons. This reaction features broad substrate scope produces arylborons high yields good enantioselectivities.

Language: Английский

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Selective Coupling of 1,2‐Bis‐Boronic Esters at the more Substituted Site through Visible‐Light Activation of Electron Donor–Acceptor Complexes

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(18)

Published: Feb. 25, 2022

1,2-Bis-boronic esters are useful synthetic intermediates particularly as the two boronic can be selectively functionalized. Usually, less hindered primary ester reacts, but herein, we report a coupling reaction that enables reversal of this selectivity. This is achieved through formation boronate complex with an electron-rich aryllithium which, in presence electron-deficient aryl nitrile, leads to electron donor-acceptor complex. Following visible-light photoinduced transfer, radical generated which isomerizes more stable secondary before radical-radical arene radical-anion, giving β-aryl products. The reactions proceed under catalyst-free conditions. method also allows stereodivergent cyclic cis-1,2-bis-boronic provide trans-substituted products, complementing selectivity observed Suzuki-Miyaura reaction.

Language: Английский

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