Iridium-Catalyzed Asymmetric Allylic Substitution Reactions

Chemical Reviews, Journal Year: 2018, Volume and Issue: 119(3), P. 1855 - 1969

Published: Dec. 24, 2018

In this review, we summarize the origin and advancements of iridium-catalyzed asymmetric allylic substitution reactions during past two decades. Since first report in 1997, Ir-catalyzed have attracted intense attention due to their exceptionally high regio- enantioselectivities. been significantly developed recent years many respects, including ligand development, mechanistic understanding, substrate scope, application synthesis complex functional molecules. an explicit outline ligands, mechanism, scope nucleophiles, applications is presented.

Language: Английский

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Iridium-Catalyzed Asymmetric Synthesis of Functionally Rich Molecules Enabled by (Phosphoramidite,Olefin) Ligands

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 52(9), P. 2657 - 2672

Published: June 19, 2019

ConspectusThe catalytic, asymmetric synthesis of complex molecules has been a core focus our research program for some time because developments in the area can have an immediate impact on identification novel strategies value-added molecules. In concert with this central interest, we emphasized design ligand scaffolds as tactic to discover and develop chemistry overcome well-recognized synthetic challenges. Based group's work chiral pool-derived diolefin ligands, designed implemented class hybrid (phosphoramidite,olefin) which combines properties both phosphoramidite olefin motifs impact, fine-tune, even override inherent reactivity metal center. Specifically, utilized these unique modifying ligands address several recognized limitations field iridium-catalyzed, allylic substitution. The methods documented typically employ branched, unprotected alcohols substrates obviate need rigorous exclusion air moisture.Following Takeuchi's seminal report demonstrating high aptitude Ir(I)-phosphite catalysts branch-selective substitution, concerted efforts from numerous laboratories led broadening utility reaction class. first section Account outlines process leading discovery unprecedented its validation iridium-catalyzed amination alcohols. This continues involving heteroatom-based nucleophiles within inter- intramolecular etherification, thioetherification spiroketalization processes. second highlights use readily available carbon possessing sp, sp2, sp3 hybridization series enantioselective carbon–carbon bond-forming reactions. We describe how alkylzinc, allylsilane, classes organotrifluoroborate be coupled enantioselectively enable construction key including 1,5-dienes, 1,4-dienes, 1,4-enynes. Since electronic steric renders (η3-allyl)-Ir(III) intermediate highly electrophilic, weak such alkyl olefins used. also show that more nucleophilic alkene enamines situ generated ketene acetals smoothly participate substitution reactions yield valuable piperidines γ,δ-unsaturated esters, respectively.The concept stereodivergent dual catalysis, synergistically amine catalysis iridium furnish α-allylated aldehydes containing two independently controllable stereocenters is then discussed. enabled independent, stereoselective all four possible product stereoisomers single set starting materials, was highlighted Δ9-tetrahydrocannabinol. concludes overview organometallic mechanistic studies regarding relevant intermediates catalytic cycle These allowed us better understand origin characteristics exhibited by catalyst comparison related systems.

Language: Английский

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Stereodivergent Allylation of Azaaryl Acetamides and Acetates by Synergistic Iridium and Copper Catalysis

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 140(4), P. 1239 - 1242

Published: Jan. 10, 2018

We report stereodivergent allylic substitution reactions of esters with prochiral enolates derived from azaaryl acetamides and acetates to form products addition the at most substituted carbon an allyl moiety two catalysts, a chiral metallacyclic iridium complex bisphosphine-ligated copper(I) complex, which individually control configuration electrophilic nucleophilic atoms, respectively. By simple permutations enantiomers all four stereoisomers containing stereogenic centers were synthesized high diastereoselectivity enantioselectivity. A variety bearing pyridyl, benzothiazolyl, benzoxazolyl, pyrazinyl, quinolinyl isoquinolinyl moieties found be suitable for this transformation.

Language: Английский

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Boron insertion into alkyl ether bonds via zinc/nickel tandem catalysis

Science, Journal Year: 2021, Volume and Issue: 372(6538), P. 175 - 182

Published: April 9, 2021

Slipping boron into alkyl ethers The carbon–oxygen bonds that hold together are relatively inert. Lyu et al. report zinc and nickel can team up to insert between the carbon oxygen using an unusual mechanism. First, a dibromoborane pries open bond with help from ion. Next, stitches boron, oxidation of metallic starts cycle over again. Versatile reactivity at inserted center then add carbons original ether or swap out for nitrogen. Science , this issue p. 175

Language: Английский

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Iridium‐Catalyzed Asymmetric Allylic Dearomatization by a Desymmetrization Strategy

Angewandte Chemie International Edition, Journal Year: 2017, Volume and Issue: 56(47), P. 15093 - 15097

Published: Oct. 5, 2017

Abstract A desymmetrization strategy was developed involving iridium‐catalyzed allylic dearomatization of indoles. The six‐membered‐ring spiroindolenines contain three contiguous stereogenic centers, including an all‐carbon quaternary center, and were obtained in up to 99 % yield with ee >95:5 d.r. When treated a catalytic amount tosylic acid, six‐membered spiroindolenine undergoes unprecedented six‐to‐seven‐membered ring expansion, affording the corresponding hexahydroazepino[4,5‐ b ]indole.

Language: Английский

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Generation and Application of (Diborylmethyl)zinc(II) Species: Access to Enantioenriched gem‐Diborylalkanes by an Asymmetric Allylic Substitution

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 57(39), P. 12930 - 12934

Published: July 2, 2018

We report the successful generation of (diborylmethyl)zinc(II) species by transmetallation beteween isolable (diborylmethyl)lithium and zinc(II) halide (X=Br, Cl) their application in synthesis enantioenriched gem-diborylalkanes bearing a stereogenic center at β-position diboryl groups an asymmetric allylic substitution reaction. The reaction has broad substrate scope, various can be obtained good yields with excellent enantioselectivity. Further elaboration provides access to diverse set valuable chiral building blocks.

Language: Английский

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Regio‐ and Enantioselective Iridium‐Catalyzed N‐Allylation of Indoles and Related Azoles with Racemic Branched Alkyl‐Substituted Allylic Acetates

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(23), P. 7762 - 7766

Published: April 9, 2019

Abstract Cyclometallated π‐allyliridium C,O‐benzoates modified with ( S )‐tol‐BINAP, which are stable to air, water, and SiO 2 , catalyze highly enantioselective N‐allylations of indoles related azoles. This reaction complements previously reported metal‐catalyzed indole allylations in that complete levels N versus C3 branched linear regioselectivity observed.

Language: Английский

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Sulfonate N‐Heterocyclic Carbene–Copper Complexes: Uniquely Effective Catalysts for Enantioselective Synthesis of C−C, C−B, C−H, and C−Si Bonds

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(48), P. 21304 - 21359

Published: May 4, 2020

A copper-based complex that contains a sulfonate N-heterocyclic carbene ligand was first reported 15 years ago. Since then, these organometallic entities have proven to be uniquely effective in catalyzing an assortment of enantioselective transformations, including allylic substitutions, conjugate additions, proto-boryl additions alkenes, boryl and silyl hydride-allyl alkenyl boronates, boron-containing allyl moieties N-H ketimines. In this review article, we detail the shortcomings state-of-the-art fueled development air stable class, members which can prepared on multigram scale. For each reaction type, when relevant, prior art at time advance involving NHC-Cu catalysts and/or subsequent key developments are briefly analyzed, relevance efficient total or formal synthesis biologically active molecules is underscored. Mechanistic analysis structural attributes responsible for their ability facilitate transformations with high efficiency as well regio- enantioselectivity detailed. This several formerly undisclosed methodological advances mechanistic analyses, latter constitute revision previously proposals.

Language: Английский

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Iridium‐Catalyzed Enantioselective Intermolecular Indole C2‐Allylation

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(19), P. 7598 - 7604

Published: Feb. 24, 2020

The enantioselective intermolecular C2-allylation of 3-substituted indoles is reported for the first time. This directing group-free approach relies on a chiral Ir-(P, olefin) complex and Mg(ClO4 )2 Lewis acid catalyst system to promote allylic substitution, providing C2-allylated products in typically high yields (40-99 %) enantioselectivities (83-99 % ee) with excellent regiocontrol. Experimental studies DFT calculations suggest that reaction proceeds via direct C2-allylation, rather than C3-allylation followed by situ migration. Steric congestion at indole-C3 position improved π-π stacking interactions have been identified as major contributors C2-selectivity.

Language: Английский

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Iridium‐Catalyzed Asymmetric Allylic Aromatization Reaction

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(31), P. 10493 - 10499

Published: May 13, 2019

Abstract Described herein is an asymmetric allylic aromatization (AAAr) strategy that employs readily accessible equivalents of benzylic nucleophiles in iridium‐catalyzed substitution reactions with the concomitant formation aromatic rings by aromatization. The optimized reaction conditions involving a catalyst derived from commercially available iridium precursor and Carreira ligand are compatible 4‐ or 5‐methyloxazoles, 5‐methylthiazoles, 5‐methylfurans, 2‐ 3‐methylbenzofurans, 3‐methylbenzothiophene, 3‐methylindole, 1‐methylnaphthalene, methylbenzene. This provides straightforward accesses to valuable heterocyclic compounds, bearing homobenzylic stereogenic center, enantiopure form would be difficult access otherwise. versatility was showcased further elaboration products into useful building blocks drug analogue.

Language: Английский

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