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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Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to α,α-Disubstituted α-Amino Acids Bearing Vicinal Stereocenters

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 140(6), P. 2080 - 2084

Published: Jan. 30, 2018

We describe a fully stereodivergent synthesis of range α,α-disubstituted α-amino acids via an Ir/Cu-catalyzed α-allylation readily available imine esters. The introduction Cu-Phox complex-activated ester into the chiral iridium-catalyzed allylic allylation process is crucial for its high reactivity and excellent enantio- diastereoselectivity (up to >99% ee >20:1 dr). Importantly, two catalysts allow full control over configuration stereocenters, affording all stereoisomers desired products. utility this methodology was demonstrated by synthesizing dipeptides analogues bioactive molecules in manner.

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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Synergetic iridium and amine catalysis enables asymmetric [4+2] cycloadditions of vinyl aminoalcohols with carbonyls

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: June 20, 2019

Abstract Catalytic asymmetric cycloadditions via transition-metal-containing dipolar intermediates are a powerful tool for synthesizing chiral heterocycles. However, within the field of palladium catalysis, compared with well-developed normal electron-demand electrophilic dipolarophiles, general strategy inverse ones nucleophilic dipolarophiles remains elusive, due to inherent linear selectivity in key palladium-catalyzed intermolecular allylations. Herein, based on switched regioselectivity iridium-catalyzed allylations, we achieved two [4+2] vinyl aminoalcohols aldehydes and β,γ-unsaturated ketones through synergetic iridium amine catalysis. The activation by catalysts carbonyls provide foundation subsequent resulting iridium-containing 1,4-dipoles (di)enamine dipolarophiles. former provides straightforward route diverse set enantio-enriched hydroquinolines bearing quaternary stereocenters, later represent an enantio- diastereodivergent synthesis hydroquinolines.

Language: Английский

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Sequence‐Dependent Stereodivergent Allylic Alkylation/Fluorination of Acyclic Ketones

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 59(5), P. 2039 - 2043

Published: Nov. 6, 2019

Abstract The stereodivergent iridium‐catalyzed allylic alkylation and fluorination of acyclic ketones is described. α‐Pyridyl‐α‐fluoroketones with vicinal tertiary quaternary stereocenters were obtained in moderate to excellent yields stereoselectivities. Distinct from known synthesis, for which two different chiral catalysts are required general, herein we report a sequence‐dependent synthesis. With only single Ir catalyst, all four possible stereoisomers the products prepared same starting materials by simply adjusting sequence asymmetric varying absolute configuration catalyst.

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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Ir/Zn Dual Catalysis: Enantioselective and Diastereodivergent α-Allylation of Unprotected α-Hydroxy Indanones

Organic Letters, Journal Year: 2017, Volume and Issue: 19(20), P. 5513 - 5516

Published: Oct. 6, 2017

A one-step enantioselective and diastereodivergent α-allylation of unprotected α-hydroxy indanones has been developed using an Ir/Zn dual catalyst system; no additional base is required. The cyclic tertiary α-hydroxyketones containing vicinal stereocenters can be synthesized with excellent enantioselectivity (up to >99% ee) good diastereoselectivity 12:1 dr). By a simple choice the appropriate chiral metal combination, all four product stereoisomers could obtained from same starting materials under identical conditions.

Language: Английский

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Coordination-Induced Stereocontrol over Carbocations: Asymmetric Reductive Deoxygenation of Racemic Tertiary Alcohols

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(11), P. 4738 - 4748

Published: Feb. 20, 2019

The inherent difficulty in eliciting facial control over carbocations has limited their utility as intermediates asymmetric catalysis. We have now shown that a docking strategy involving the reversible coordination of substrate to chiral transition-metal catalyst can be used enable highly stereoselective nucleophilic attack on intermediate tertiary carbocations. This approach been implemented achieve first example enantioselective reductive deoxygenation alcohols. reduction occurs with high enantio- (up 96% ee) and regioselectivity >50:1 rr) by applying novel Hantzsch ester analogue convenient hydride source. In-depth mechanistic studies support involvement carbocation is coordinated iridium metal center via key allene moiety.

Language: Английский

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Ketones and Aldehydes asO-Nucleophiles in Iridium-Catalyzed Intramolecular Asymmetric Allylic Substitution Reaction

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(6), P. 2228 - 2232

Published: Jan. 28, 2019

Ketones and aldehydes are employed as enol O-nucleophiles in an iridium-catalyzed asymmetric allylic substitution reaction. The reaction proceeds well the presence of a well-defined chiral iridium complex under mild conditions. A series 2H-1,4-oxazine skeletons can be obtained up to 94% yield with 99% ee. utility this novel method has been demonstrated by its implementation first enantioselective synthesis (+)-chelonin A.

Language: Английский

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