Transition-Metal-Catalyzed Asymmetric Allylic Dearomatization Reactions

Accounts of Chemical Research, Journal Year: 2014, Volume and Issue: 47(8), P. 2558 - 2573

Published: June 18, 2014

ConspectusDearomatization reactions serve as powerful methods for the synthesis of highly functionalized, three-dimensional structures starting with simple planar aromatic compounds. Among processes this type, catalytic asymmetric dearomatization (CADA) are attractive owing to large number compounds that readily available and fact they enable direct access enantiopure polycycles spirocycles, which frequently key structural motifs in biologically active natural products pharmaceuticals. However, a consequence their high stabilities, arenes only difficultly participate take place levels enantioselectivity.Transition-metal-catalyzed allylic substitution have been demonstrated be enantioselective formation C–C C–X (X = O, N, S, etc.) bonds. scope these has explored mainly using soft carbon nucleophiles, some hard nucleophiles such enolates preformed organometallic reagents, heteroatom nucleophiles. Readily accessible rarely used directly reactions.In Account, we present results studies conducted aimed at development transition-metal-catalyzed reactions. By utilizing general process, devised indoles, pyrroles, phenols, naphthols, pyridines, pyrazines, produce various functionalized bearing all-carbon quaternary stereogenic centers straightforward manner. In mechanistic investigations found five-membered spiroindolenines intermediates, undergo stereospecific migration form corresponding tetrahydro-1H-carbazoles upon treatment amount TsOH. It is worth noting no notable loss enantiomeric excess spiroindolenine derivatives takes during rearrangement process intervention "three-center–two-electron"-type transition state, proposal gained support from DFT calculations. Equally intriguing, tuning electronic nature tethers, pyrroles or indoles unprecedented Ir Ru catalyzed intramolecular alkylation promoted dearomatization/migration The operation novel reaction pathway provides additional information leading greater understanding functionalizations indoles. combined effort provide not efficient enantioenriched fused spiro but also strategies field catalysis.

Language: Английский

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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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Combinations of Aminocatalysts and Metal Catalysts: A Powerful Cooperative Approach in Selective Organic Synthesis

Chemical Reviews, Journal Year: 2016, Volume and Issue: 116(22), P. 13512 - 13570

Published: Oct. 10, 2016

The cooperation and interplay between organic metal catalyst systems is of utmost importance in nature chemical synthesis. Here innovative selective cooperative can be designed by combining two catalysts that complement rather than inhibit one another. This refined strategy permit transformations unmanageable either the alone. review summarizes innovations developments synthesis have used dual catalysis simple aminocatalysts with catalysts. Considerable efforts been devoted to this fruitful field. emerging area employs different activation modes amine as a platform address challenging reactions. Here, aminocatalysis (e.g., enamine catalysis, iminium single occupied molecular orbital (SOMO) photoredox catalysis) employed activate unreactive carbonyl substrates. transition complements activating variety substrates through range interactions electrophilic π-allyl complex formation, Lewis acid activation, allenylidene C-H etc.), thereby novel concepts within are created. inclusion heterogeneous strategies allows for "green" chemistry development, recyclability, more eco-friendly valuable compounds.

Language: Английский

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Stereodivergence in Asymmetric Catalysis

Journal of the American Chemical Society, Journal Year: 2017, Volume and Issue: 139(16), P. 5627 - 5639

Published: April 6, 2017

This Perspective presents an overview of catalytic enantioselective transformations that allow convenient access to all stereoisomers a given product with multiple stereogenic centers. Particular focus is placed on discussion the concept stereodivergent dual catalysis and its application in target-oriented synthesis. The potential this development new as well implications for achieving stereochemical diversity library design diversity-oriented synthesis are also discussed.

Language: Английский

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Stereodivergent Catalysis

Chemical Reviews, Journal Year: 2018, Volume and Issue: 118(10), P. 5080 - 5200

Published: April 20, 2018

This review covers diastereo- and enantiodivergent catalyzed reactions in acyclic cyclic systems using metal complexes or organocatalysts. Among them, nucleophilic addition to carbon–carbon carbon–nitrogen double bonds, α-functionalization of carbonyl compounds, allylic substitutions, ring opening oxiranes aziridines are considered. The diastereodivergent synthesis alkenes from alkynes is also included. Finally, stereodivergent intramolecular intermolecular cycloadditions other cyclizations reported.

Language: Английский

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An Ir/Zn Dual Catalysis for Enantio- and Diastereodivergent α-Allylation of α-Hydroxyketones

Journal of the American Chemical Society, Journal Year: 2016, Volume and Issue: 138(35), P. 11093 - 11096

Published: Aug. 22, 2016

An Ir/Zn dual catalysis has been developed for the enantio- and diastereodivergent α-allylation of unprotected α-hydroxyketones under mild conditions, in absence any additional base. The cooperative action a chiral iridium complex derived from phosphoramidites Zn-ProPhenol is most likely responsible its high reactivity, excellent enantioselectivity (up to >99% ee), good diastereoselectivity >20:1 dr). All four product stereoisomers could be prepared same set starting materials identical conditions by simple selection appropriate catalyst combinations.

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 Synthesis of α,α-Disubstituted α-Amino Acids via Synergistic Cu/Ir Catalysis

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 140(4), P. 1508 - 1513

Published: Jan. 5, 2018

Cu/Ir dual catalysis has been developed for the stereodivergent α-allylation of aldimine esters. The method enables preparation a series nonproteinogenic α-amino acids (α-AAs) bearing two contiguous stereogenic centers in high yield with excellent stereoselectivity. All four product stereoisomers could be obtained from same set starting materials via pairwise combination chiral catalysts. Notably, one-pot protocol successfully applied bimetallic complexes to simplify manipulation catalysis. This further utilized construction key intermediate bioactive pyrrolidine derivative and concise synthesis plant growth regulator (2S,3S)-2-amino-3-cyclopropylbutanoic acid.

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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Applications of Iridium-Catalyzed Asymmetric Allylic Substitution Reactions in Target-Oriented Synthesis

Accounts of Chemical Research, Journal Year: 2017, Volume and Issue: 50(10), P. 2539 - 2555

Published: Sept. 22, 2017

ConspectusMetal catalyzed allylic substitution is a cornerstone of organometallic and synthetic chemistry. Enantioselective versions have been developed with catalysts derived from transition metals, most notably molybdenum, nickel, ruthenium, rhodium, iridium, palladium, copper. The palladium- the iridium-catalyzed turned out to be particularly versatile in organic synthesis because very broad scope nucleophile great functional group compatibility. Assets reaction are formation branched, chiral products simple monosubstituted substrates, high degrees regio- enantioselectivity, use modular, readily available ligands. possibility carbon, nitrogen, oxygen, sulfur compounds as well fluoride nucleophiles allows wide range building blocks prepared.Our Account begins presentation fundamental schemes We will focus our discussion on reactions promoted by phosphoramidite ligands, though numerous ligands employed. subsequent section presents brief overview mechanism experimental conditions. Two emerged. In type 1 (introduced 1997), linear esters commonly used substrates under basic 2 2007), environmentally friendly branched alcohols can reacted acidic conditions; occasionally, derivatives also applied. A unique feature that highly electrophilic intermediates brought weakly activated alkenes.The text ordered according strategies followed transform desired targets, which natural or drugs. Syntheses starting an intermolecular discussed first. Some fairly complex for example, potent nitric oxide inhibitor (−)-nyasol drug (−)-protrifenbute, synthesized via less than five steps materials.Most targets cyclic compounds. Intermolecular ring closing metathesis powerful strategy their synthesis. Highlights stereodivergent syntheses Δ9-tetrahydrocannabinols (THC), wherein iridium- organocatalysis combined (dual catalysis). combination alkylation Diels–Alder was utilized synthesize ketide apiosporic acid fesoterodine (Toviaz). Sequential amination, hydroboration Suzuki–Miyaura coupling generates enones suitable conjugate addition reactions; this employed variety alkaloids, poison frog alkaloid (+)-cis-195A (pumiliotoxin C).Intramolecular substitutions offer interesting possibilities build up stereochemical complexity short routes. For diastereoselective cyclizations compounds, substrate control overruled catalyst order generate cis- trans-isomers selectively given precursor. This approach prepare piperidine pyrrolidine alkaloids. Finally, polycyclic structures, including structurally unusual indolosesquiterpenoid mycoleptodiscin A, generated diastereo- enantioselectively olefins polyene electron-rich arenes, such indoles, dearomatization reactions.

Language: Английский

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