Remote γ-C(sp3)–H Alkylation of Aliphatic Carboxamides via an Unexpected Regiodetermining Pd Migration Process: Reaction Development and Mechanistic Study DOI
Ya Li, Pan Zhang, Yue‐Jin Liu

et al.

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(15), P. 8212 - 8222

Published: June 11, 2020

In the presence of accessible β-C–H bonds, γ-C–H activation saturated aliphatic carboxamides remains unresolved because is kinetically favored. This almost a dogma in development C–H reactions. Here we report strategy to change this dogma, as have found that Pd-catalyzed, ligand-enabled remote γ-alkylation can be realized more bonds by using strained bicyclic alkenes coupling partners. Density functional theory calculations and experiments suggested realization present reaction due regiodetermining step from commonly encountered irreversible activations, which are reversible here, an unexpected Pd migration process, regiodetermining. new achieve activation, compared with previous strategy, making both turnover- step.

Language: Английский

Transition-Metal-Catalyzed Functionalization of Alkynes with Organoboron Reagents: New Trends, Mechanistic Insights, and Applications DOI Creative Commons
Javier Corpas, Pablo Mauleón, Ramón Goméz Arrayás

et al.

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(12), P. 7513 - 7551

Published: June 9, 2021

Catalytic functionalization of alkynes with organoboron reagents provides a straightforward access to stereochemically defined multisubstituted alkenes, which are structural motifs commonly found in bioactive compounds and organic materials. Recent progress has substantially broadened the scope this field on several fronts. Strategies for regioselectivity control 1,2-migratory insertion across unsymmetrical internal alkynes, as well direct products anti-insertion stereochemistry, have been devised. The alkenyl-to-aryl 1,4-metal migration upon metal recently exploited powerful cascade sequences leading complex polycyclic scaffolds, including development enantioselective processes. Elegant enantiospecific dynamic kinetic resolution methods developed accessing chiral allenes from propargylic alcohol derivatives. Mechanistic manifolds emerged based single-electron transfer (SET) that provided fresh impetus alkyne 1,2-difunctionalization complementary stereoselectivity processes relying 1,2-insertion R–M species. Herein, we discuss most recent advances transition-metal-catalyzed using reagents, categorized according type mechanistic outcome. Emphasis is placed aspects, synthetic utility, limitations, challenges future research.

Language: Английский

Citations

148
Easy access to medium-sized lactones through metal carbene migratory insertion enabled 1,4-palladium shift DOI Creative Commons

Yinghua Yu,

Pushkin Chakraborty,

Jinshuai Song

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 23, 2020

Reactions that efficiently construct medium-sized lactones are significant, as they overcome the unfavorable entropic factor and transannular interactions for ring closure, produced common structural motifs recurring in many biologically active compounds. Herein, we describe a valuable strategy lactone synthesis by accomplishing site-selective C-H bond functionalization via palladium carbene migratory insertion enabled 1,4-palladium shift. The overall process achieves formal dimerization of two readily available benzaldehyde derivatives, providing value-added products lactones. Our method is amenable to late-stage modification approved drugs other complex molecules. Mechanistic studies including deuterium-labeling experiments DFT calculation shed light on reaction pathways.

Language: Английский

Citations

71
Remote sp2 C–H Carboxylation via Catalytic 1,4-Ni Migration with CO2 DOI
Marino Börjesson, Daniel Janssen‐Müller, Basudev Sahoo

et al.

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(38), P. 16234 - 16239

Published: Sept. 10, 2020

A remote catalytic reductive sp2 C-H carboxylation of arenes with CO2 (1 bar) via 1,4-Ni migration is disclosed. This protocol constitutes the first reported to date, thus offering new vistas in Ni-catalyzed coupling arena while providing an unconventional platform for incorporating electrophilic sites at linkages.

Language: Английский

Citations

71
Tandem Reactions involving 1,4‐Palladium Migrations DOI
Mengyao Li, Dong Wei, Chen‐Guo Feng

et al.

Chemistry - An Asian Journal, Journal Year: 2022, Volume and Issue: 17(15)

Published: June 6, 2022

Abstract Transition‐metal‐catalyzed tandem reactions have become a mainstay in organic chemistry owing to their high atom‐ and step‐economies. Metal‐migration‐based allow the engagement of simple starting materials for incorporating functional groups into certain positions constructing complex scaffolds, which provide novel means that are complementary traditional cross‐coupling or C−H activation processes. In light broad utility 1,4‐Pd migration reaction, this paper reviews its progress past two decades, summarizing process classifying it based on insertion, elimination, transmetalation, bond activation. Special emphasis is placed driving force Pd different mechanisms. Moreover, review also attempts summarize common strategies improving regio‐ site‐selectivities process.

Language: Английский

Citations

44
Inherently chiral calixarenes by a catalytic enantioselective desymmetrizing cross-dehydrogenative coupling DOI Creative Commons
Xin Zhang, Shuo Tong, Jieping Zhu

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 14(4), P. 827 - 832

Published: Dec. 6, 2022

Under the catalysis of PdBr2 and a chiral phosphoramidite ligand, upper-rim mono (2-bromoaroyl)-substituted calix[4]arene derivatives underwent facile enantioselective desymmetrization reaction to afford 9H-fluorene-embedded inherently calixarenes in good yields with excellent enantioselectivities. The transannular dehydrogenative arene-arene coupling proceeded most probably through an oxidative addition Caryl-Br bond ligated palladium catalyst followed by sequence 1,5-palladium migration intramolecular C-H arylation sequence. This new family possesses unique chiroptical properties thanks their highly rigid structure induced 9H-fluorene segment.

Language: Английский

Citations

44
Nickel-Catalyzed Migratory Cross-Coupling Reactions: New Opportunities for Selective C–H Functionalization DOI
You Wang, Yuli He, Shaolin Zhu

et al.

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(23), P. 3475 - 3491

Published: Nov. 16, 2023

ConspectusMigratory cross-coupling via metal migration is a process of significant academic and industrial interest. It provides an attractive alternative for the selective installation functional group at remote C-H positions from simple precursors, thus enabling direct synthesis challenging structures not accessible with traditional cross-coupling. In particular, merger 1,n-Ni/H shift nickel, Ni-catalyzed migratory functionalization precursors has undergone particularly intense development emerged as valuable field research in past few years. This Account will outline recent progress made this arena terms migration-functionalization modes, diverse functionalizations, strategies regio- stereocontrol. Mechanistic studies synthetic applications are also discussed.In detail, we systematically categorize our work into two parts based on modes. first part, platform created sp3 alkenes or alkyl halides iterative 1,2-Ni/H shift-selective The key reactive Ni(II)H species chain-walking could be generated situ either polarity-reversed fashion relying stoichiometric reductants (X-Ni(II)-H) redox-neutral participation nucleophilic coupling partners (FG-Ni(II)-H). One advantage associated NiH system use relatively stable, abundant, safe olefin surrogates instead sensitive organometallics required reactions. Another that including carbonation more amination thiolation smoothly achieved suitable electrophiles their precursors. Finally, to address multifaceted selectivity reactivity issues asymmetric reactions, have developed feasible ligand relay catalytic strategy. dynamic exchange process, one promotes rapid while other highly stereoselective coupling. innovative strategy overcomes formidable challenge stemming difficulty designing single efficiently promote both steps second new sp2 1,4-Ni/H been reported. Starting readily available aryl vinyl partners, situ-generated aryl- vinylnickel(II) undergo reversible along backbone, subsequent various would allow access 1,4-migratory products. success was discovery appropriate A vinyl-to-aryl successfully enables modular ipso/ortho difunctionalization aryl-to-vinyl functionalized trisubstituted alkenes.We hope inspire broad interest future We strongly believe continued efforts fascinating overcome many remaining challenges, cutting-edge ligand/catalyst design enhance selectivity, conceptually modes additional transformations, in-depth mechanistic rational reaction design.

Language: Английский

Citations

32
Cobalt-Catalyzed Diastereo- and Enantioselective Carbon–Carbon Bond Forming Reactions of Cyclobutenes DOI

Zhikun Liang,

Lei Wang, Yu Wang

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(6), P. 3588 - 3598

Published: Feb. 3, 2023

Catalytic enantioselective functionalization of cyclobutenes constitutes a general and modular strategy for construction enantioenriched complex cyclobutanes bearing multiple stereogenic centers, as chiral four-membered rings are common motifs in biologically active molecules versatile intermediates organic synthesis. However, synthesis through such remained significantly limited. Herein, we report series unprecedented cobalt-catalyzed carbon-carbon bond forming reactions that initiated carbometalation. The protocols feature diastereo- introduction allyl, alkynyl, functionalized alkyl groups. Mechanistic studies indicated an unusual 1,3-cobalt migration subsequent β-carbon elimination cascade process occurred the allyl addition. These new discoveries established elementary cobalt catalysis extension diversity nucleophiles transformations cyclobutenes.

Language: Английский

Citations

30
Facile Access to Quaternary Carbon Centers via Ni-Catalyzed Arylation of Alkenes with Organoborons DOI
Zi-Chao Wang, Lei Gao, Songyang Liu

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Quaternary carbon centers are widespread structural motifs, thus representing extensive interest in organic synthesis. We describe here an efficient nickel-catalyzed intermolecular, Markovnikov-selective arylation of minimally functionalized alkenes with stable organoborons, affording a broad range cyclic or acyclic quaternary under mild conditions. The utilization the diimine ligand is critical for high reactivity and chemoselectivity. Furthermore, using bulky chiral as Ni catalyst, stereocenters can be readily prepared levels enantiocontrol. Mechanism studies suggest that, before protonation, rare nickel shift from alkyl to aryl might occur.

Language: Английский

Citations

1
Direct Synthesis of Cyclopropanes from gem-Dialkyl Groups through Double C–H Activation DOI
Antonin Clemenceau, Pierre Thesmar,

Maxime Gicquel

et al.

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(36), P. 15355 - 15361

Published: Aug. 12, 2020

Cyclopropanes are important structural motifs found in numerous bioactive molecules, and a number of methods available for their synthesis. However, one the simplest cyclopropanation reactions involving intramolecular coupling two C–H bonds on gem-dialkyl groups has remained an elusive transformation. We demonstrate herein that this reaction is accessible using aryl bromide or triflate precursors 1,4-Pd shift mechanism. The use pivalate as base was to be crucial divert mechanistic pathway toward cyclopropane instead previously obtained benzocyclobutene product. Stoichiometric studies allowed identification aryl- alkylpalladium pivalates, which equilibrium via five-membered palladacycle. With pivalate, second C(sp3)–H activation leading four-membered palladacycle intermediate product favored. A catalytic developed showed broad scope generation diverse arylcyclopropanes, including valuable bicyclo[3.1.0] systems. This method applied concise synthesis lemborexant, recently approved anti-insomnia drug.

Language: Английский

Citations

65
Highly Regioselective C–H Alkylation of Alkenes Through an Aryl to Vinyl 1,4-Palladium Migration/C–C Cleavage Cascade DOI
Quannan Wang, Rongjun Chen, Jiang Lou

et al.

ACS Catalysis, Journal Year: 2019, Volume and Issue: 9(12), P. 11669 - 11675

Published: Nov. 13, 2019

Palladium-catalyzed C−H alkylation of gem-disubstituted ethylenes has been efficiently achieved with cyclobutanols as the coupling partners through an aryl to vinyl 1,4-palladium migration/ring-opening C–C cleavage cascade, giving trisubstituted alkenes in high yields. The protocol features good regioselectivity, yields, broad substrate scopes, and functional group tolerance. mechanistic studies implicate that cross-coupling reaction occurs via oxidative addition, migration, ring-opening cleavage, reductive elimination. DFT calculations have revealed efficiency is attributed thermodynamically favored migration assisted by 2-fluorophenol.

Language: Английский

Citations

61