From C4 to C7: Innovative Strategies for Site-Selective Functionalization of Indole C–H Bonds

Accounts of Chemical Research, Journal Year: 2021, Volume and Issue: 54(7), P. 1723 - 1736

Published: March 12, 2021

The widespread presence of hydrocarbons makes C-H functionalization an attractive alternative to traditional cross-coupling methods. As indole is important heteroarene in a plethora natural products and pharmaceuticals, moieties has emerged as one the most topics this field. Due multiple bonds indoles, site selectivity long-standing challenge. Much effort been devoted indoles at C3 or C2 position, while accessing benzene core (from C4 C7) considerably more challenging.This Account summarizes our recent efforts toward site-selective based on innovative strategies. A common method solve issue involves development directing groups (DGs). Our early studies establish that installation N-P(O)tBu2 group N position can produce C7 C6 arylation using palladium copper catalysts, respectively. developed system also be extended direct C5 positions by installing pivaloyl position. Further investigation bearing N-PtBu2 shows diverse reactivity for functionalizations including arylation, olefination, acylation, alkylation, silylation, carbonylation with different coupling partners. Compared P(V) DG, P(III) easily attached substrates detached from products. However, these reactions rely mostly precious metal catalysts ligands; requirement significant limitation, particularly large-scale syntheses necessity removal toxic trace metals pharmaceutical We have uncovered general strategy chelation-assisted aromatic borylation just simple BBr3 under mild conditions, which N1 selectively deliver boron species unfavorable allow subsequent without any metal. This transition-metal-free synthesize hydroxylated boron-mediated directed hydroxylation reaction conditions broad functional compatibility.In Account, we describe contributions topic since 2015. These provide efficient methods divergent synthesis valuable substituted insights into exploration new strategies directives other heteroarenes.

Language: Английский

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Recent Advances in Metal‐Catalyzed Functionalization of Indoles

Advanced Synthesis & Catalysis, Journal Year: 2021, Volume and Issue: 363(11), P. 2723 - 2739

Published: April 7, 2021

Abstract Indole is one of the most important heterocycles in organic synthesis, natural products, and drug discovery. Recently, tremendous advances selective functionalization indoles have been reported. Although powered by transition metal catalysis, exceedingly useful methods absence metals also In this review, we provide an overview reactions that published last years with a focus on recent advances, aims, future trends. The review organized positional selectivity type used for functionalization. particular, discuss major transition‐metal‐catalyzed C−H at classical C2/C3 positions, remote C4/C7 cross‐coupling, transition‐metal‐free magnified image

Language: Английский

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Interfacial Ti−S Bond Modulated S‐Scheme MOF/Covalent Triazine Framework Nanosheet Heterojunctions for Photocatalytic C−H Functionalization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(27)

Published: May 3, 2023

Constructing photocatalyst systems to functionalize the inert C-H bonds has attracted extensive research interest. However, purposeful modulation of interfacial charge transfer in heterostructures remains a challenge, as it usually suffers from sluggish kinetics. Reported herein is an easy strategy construct heteroatom-induced interface for developing titanium-organic frameworks (MOF-902) @ thiophene-based covalent triazine (CTF-Th) nanosheets S-scheme heterojunctions with controllable oxygen vacancies (OVs). Specifically, Ti atoms were first anchored onto heteroatom site CTF-Th nanosheets, and then grown into MOF-902 via Ti-S linkage, generating OVs. Using situ X-ray photoelectron spectroscopy (XPS), extended absorption fine structure (EXAFS) density functional theory (DFT) calculations, enhanced separation induced by moderate OVs pre-designed was validated. The exhibited improved efficiency photocatalytic C3-acylation indoles under mild conditions yield 8.2 times larger than pristine or enabled scope substrates (15 examples). This performance superior state-of-the-art can be retained, without significant loss, after 12 consecutive cycles.

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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Recent advances in iridium-catalyzed enantioselective allylic substitution using phosphoramidite-alkene ligands

Catalysis Science & Technology, Journal Year: 2022, Volume and Issue: 12(13), P. 4100 - 4112

Published: Jan. 1, 2022

This minireview describes the recent progress of iridium-catalyzed enantioselective allylic substitution using phosphoramidite-alkene ligands realizing highly carbon–carbon and carbon–heteroatom bond formation.

Language: Английский

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Cooperative Catalyst‐Enabled Regio‐ and Stereodivergent Synthesis of α‐Quaternary α‐Amino Acids via Asymmetric Allylic Alkylation of Aldimine Esters with Racemic Allylic Alcohols

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(46)

Published: Sept. 26, 2022

We describe cooperative bimetallic catalysis that enables regio-/stereodivergent asymmetric α-allylations of aldimine esters. By employing Et3 B as the key activator, racemic allylic alcohols can be directly ionized to form Pd or Ir-π-allyl species in presence achiral chiral Ir complexes, respectively. The less more substituted termini metal-π-allyl are amenable nucleophilic attack by Cu-azomethine ylide, formation which is simultaneously facilitated B, affording α-quaternary α-amino acids with high regioselectivity and excellent stereoselectivity. use readily available electrophilic precursors represents an improvement from environmental atom/step economy perspective. Computational mechanistic studies reveal crucial role additive origins stereo- regioselectivities analyzing steric effects, dispersion interactions, frontier orbital population.

Language: Английский

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Au(I)/Au(III) Catalytic Allylation Involving π-Allyl Au(III) Complexes

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(2), P. 993 - 1003

Published: Jan. 3, 2022

A (MeDalphos)AuCl complex was found to efficiently catalyze the cross-coupling of indoles and allyl acetates/alcohols. The reaction tolerates many functional groups selectively affords branched C3-allylated products from both α- γ-substituted substrates. It takes advantage hemilabile character P∧N ligand. C(sp2)–C(sp3) coupling operates via a Au(I)/Au(III) redox cycle involves dicationic π-allyl Au(III) as key intermediate. In this case, moiety adopts an asymmetric σ + π-coordination mode, substantiated by NMR spectroscopy density theory (DFT) calculations.

Language: Английский

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Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(10)

Published: Jan. 4, 2023

Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition dialkylzinc reagents to cyclic enones with iridium-catalyzed allylic substitution reaction. Good excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction adjacent (1,2-position) reported in literature, current reaction achieve nonadjacent (1,3-position) proper combination two chiral catalysts different enantiomers.

Language: Английский

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Ir‐Catalyzed Enantioselective Synthesis of gem‐Diborylalkenes Enabled by 1,2‐Boron Shift

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(32)

Published: June 15, 2023

Abstract Asymmetric cross‐couplings based on 1,2‐carbon migration from B‐ate complexes have been developed efficiently to access valuable organoboronates. However, enantioselective reactions triggered by 1,2‐boron shift remained be unaddressed synthetic challenge. Here, Ir‐catalyzed asymmetric allylic alkylation enabled was developed. In this reaction, we disclosed that excellent enantioselectivities were achieved through an interesting dynamic kinetic resolution (DKR) process of carbonates at the elevated temperature. Notably, highly (bis‐boryl)alkenes array diversifications versatile molecules. Extensive experimental and computational studies conducted elucidate reaction mechanism DKR clarify origin enantioselectivities.

Language: Английский

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Rhodium‐Catalyzed Enantio‐ and Regioselective Allylation of Indoles with gem‐Difluorinated Cyclopropanes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(22)

Published: March 22, 2024

Abstract The use of gem ‐difluorinated cyclopropanes ( ‐DFCPs) as fluoroallyl surrogates under transition‐metal catalysis has drawn considerable attention recently but such reactions are restricted to producing achiral or racemic mono‐fluoroalkenes. Herein, we report the first enantioselective allylation indoles rhodium with ‐DFCPs. This reaction shows exceptional branched regioselectivity towards ‐DFCPs, which provides an efficient route enantioenriched fluoroallylated wide substrate scope and good functional group tolerance.

Language: Английский

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