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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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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Nine-Membered Benzofuran-Fused Heterocycles: Enantioselective Synthesis by Pd-Catalysis and Rearrangement via Transannular Bond Formation

Journal of the American Chemical Society, Journal Year: 2017, Volume and Issue: 139(43), P. 15304 - 15307

Published: Oct. 17, 2017

The first enantioselective formal [5+4] cycloaddition is realized under palladium catalysis to deliver benzofuran-fused nine-membered rings. These medium-sized heterocycles and derivatives undergo unique rearrangements induced by transannular bond formation, resulting in the production of two classes densely substituted polycyclic excellent efficiency stereoselectivity.

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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Pd‐Catalyzed Enantioselective [6+4] Cycloaddition of Vinyl Oxetanes with Azadienes to Access Ten‐Membered Heterocycles

Angewandte Chemie International Edition, Journal Year: 2017, Volume and Issue: 57(6), P. 1596 - 1600

Published: Dec. 19, 2017

Abstract We report herein the first enantioselective cycloaddition of vinyl oxetanes, reaction which with azadienes provided unprecedented access to ten‐membered heterocycles through a [6+4] cycloaddition. By using commercially available chiral Pd‐SIPHOX catalyst, wide range benzofuran‐ as well indole‐fused could be accessed in excellent yield and enantioselectivity. A unique Lewis acid induced fragmentation these was also discovered.

Language: Английский

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Enantioselective Synthesis of Chiral Medium-Sized Cyclic Compounds via Tandem Cycloaddition/Cope Rearrangement Strategy

ACS Catalysis, Journal Year: 2019, Volume and Issue: 9(3), P. 1645 - 1654

Published: Jan. 11, 2019

The nine-membered ring-bearing bicyclo[5.2.2]tetrahydrooxonines frameworks have enantioselectively been constructed via a tandem [3 + 2] cycloaddition/Cope rearrangement reaction of vinylethylene carbonates (VECs) with coumalates or pyrones. Under mild conditions, palladium-catalyzed asymmetric various substituted VECs and pyrones proceeds smoothly to produce the corresponding medium-sized heterocyclic compounds in high yields very enantioselectivities. Moreover, on gram scale further diverse transformations products were workable. mechanism was investigated through control experiments DFT calculations, which show pathway rather than [5 4] cycloaddition pathway.

Language: Английский

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Stereoselective Access to Polyfunctionalized Nine‐Membered Heterocycles by Sequential Gold and Palladium Catalysis

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(23), P. 12775 - 12780

Published: March 30, 2021

Abstract We report herein a gold and palladium sequential catalysis system to access furan‐fused nine‐membered heterocycles in high efficiency enantioselectivity. In this one‐pot procedure, easily accessible enynamides undergo cyclization generate azadienes situ that participate enantioselective formal [5+4] cycloaddition with vinyl ethylene carbonates. Conformation‐controlled highly diastereoselective derivatizations of these medium‐sized rings, coupled oxidative furan cleavage, have enabled the diverse densely‐functionalized lactams.

Language: Английский

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Iridium-Catalyzed Intramolecular Asymmetric Allylic Alkylation of Hydroxyquinolines: Simultaneous Weakening of the Aromaticity of Two Consecutive Aromatic Rings

Journal of the American Chemical Society, Journal Year: 2018, Volume and Issue: 140(8), P. 3114 - 3119

Published: Feb. 12, 2018

Intramolecular asymmetric allylic alkylation reactions of 5- and 7-hydroxyquinoline derivatives were realized by a chiral Ir/NHC catalyst. A series functionalized cyclic enones afforded in excellent yields (up to 99%) high enantioselectivity 97% ee). Theoretical computations revealed that the aromaticity two consecutive rings hydroxyquinoline substrates is significantly weakened. highly efficient formal synthesis (-)-gephyrotoxin was accomplished based on this method.

Language: Английский

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Highly Diastereo- and Enantioselective Synthesis of Quinuclidine Derivatives by an Iridium-Catalyzed Intramolecular Allylic Dearomatization Reaction

CCS Chemistry, Journal Year: 2019, Volume and Issue: 1(1), P. 106 - 116

Published: April 1, 2019

Open AccessCCS ChemistryRESEARCH ARTICLE1 Apr 2019Highly Diastereo- and Enantioselective Synthesis of Quinuclidine Derivatives by an Iridium-Catalyzed Intramolecular Allylic Dearomatization Reaction Lin Huang, Yue Cai, Hui-Jun Zhang, Chao Zheng, Li-Xin Dai Shu-Li You Huang State Key Laboratory Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute Organic University Chinese Academy Sciences, 200032 (China) , Cai Zhang Zheng *Corresponding author: E-mail Address: [email protected] Collaborative Innovation Chemical Science Engineering, Tianjin https://doi.org/10.31635/ccschem.019.20180006 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Asymmetric construction quinuclidine derivatives has been realized iridium-catalyzed allylic dearomatization reaction. The catalytic system, derived from [Ir(cod)Cl]2 the Feringa ligand, tolerates a broad range substrates. A large array can be obtained under mild conditions good excellent yields (68%–96%), diastereoselectivity (up >20/1 dr), enantioselectivity >99% ee). These products feature versatile functional group diversity undergo diverse transformations. model that accounts origin stereoselectivity proposed based on density theory (DFT) calculations. Download figure PowerPoint Introduction Quinuclidine, also named 1-azabicyclo[2.2.2]octane, exists number naturally occurring compounds, biologically active agents, privileged catalysts ligands asymmetric catalysis (Figure 1).1–6 In particular, quinine, kind cinchona alkaloid, recognized as medication treatment malaria babesiosis.7,8 are widely utilized homogeneous or heterogeneous various processes such Morita–Baylis–Hillman reactions,4 Sharpless dihydroxylation reactions,5 phase-transfer reactions.6 Therefore, development synthetic approaches efficient novel is great significance. Figure 1 | Selected natural molecules containing scaffolds. this regard, efforts have devoted new methods toward preparation derivatives.9 Traditionally, scaffolds constructed second-order nucleophilic substitution (SN2) reaction condensation piperidine derivatives.10–12 However, most these reactions racemic chiral auxiliary-assisted processes. formed conveniently introducing substituents into ring,13 but scope method rather limited available source starting materials. Catalytic emerged powerful tool transformation planar aromatic compounds highly enantio-enriched three-dimensional molecules.14–49 our ongoing investigate transition-metal-catalyzed reactions, several straightforward protocols access spiroindolenine spiroindoline were revealed.50–53 Recently, we reported unprecedented synthesis indole-annulated, medium-sized ring tetrahydro-γ-carboline- hexahydroazepino[4,3-b]indole-derived carbonates via cascade Ir-catalyzed dearomatization/retro-Mannich/hydrolysis (Scheme 1a).54 Notably, intermediate I was reactive could not isolated. We envisaged if tetrahydro-β-carboline-derived employed protocol, retro-Mannich should avoided due existence two methylene groups between indole nitrogen atom. As consequence, interesting indolenine-fused 2 might afforded major 1b). Herein, report derivatives. Scheme design plan study. Results Our study commenced with evaluation using tetrahydro-β-carboline derivative 1a substrate system consisting iridium precursor [2 mole percent (mol %)] phosphoramidite ligand (4 mol %) tetrahydrofuran (THF) at 50 °C (Table 1).55–85 First, influence ( L1–L8) considered Cs2CO3 (100 base (entries 1–8). L1)86 occurred smoothly (entry 1), delivering product 2a yield (74%) moderate dr value (5.2/1). both diasteroisomers enantiopurity (95% generated L2 Alexakis L3),87 respectively, lead comparable diasteroisomers. dropped slightly 3). addition, Me-THQphos L4) BHPphos L5) developed less terms 4 5). Further more L6–L8) only gave poor 6–8). order improve reaction, bases including DBU, K3PO4, K2CO3, KOAc, NaOAc tested 9–13). found best choice concerning (74%), (7.9/1 ee isomer 96% minor isomer) 13). When no used, completed even after 48 h 14). Inspired work Hartwig co-workers,88 effect counteranion complex examined adding silver salts AgOAc, AgSO3Me, AgOTf, AgBF4 15–18). To delight, all cases, single diastereoisomer. Of particular note, absence base, AgOAc give almost same results 19), while AgSO3Me just 20). Finally, optimal determined described entry 19, where desired isolated 86% ee. Table Optimization Conditionsa Entry L Base Time (h) Yield (%)b drc (major) (%)d (minor) L1 3 74 5.2/1 95 82 4.4/1 94 L3 76 2.9/1 97 4e L4 14 24 8.8/1 / 5e L5 18 5.0/1 6 L6 1.4/1 96 99 7 L7 19 >99 8 L8 42 28 3.0/1 89 85 9 DBU 73 93 10 K3PO4 80 5.4/1 11 K2CO3 6.0/1 12 KOAc 4.5/1 13 7.9/1 23 4.0/1 15f 16g 17h 68 71 18i 83 19/1 91 19f (86j) 20g 6.7/1 Notes: aReaction conditions: (0.2 mmol), (2 %), (2.0 mL) °C. Catalyst prepared nPrNH2 activation.60bCombined diastereoisomers proton nuclear magnetic resonance (1H NMR) analysis CH2Br2 (0.1 mmol) internal standard. cDetermined 1H NMR crude mixtures. dDetermined high-performance liquid chromatography (HPLC) stationary phase. eIn refluxing dioxane. fWith (8 %). gWith hWith AgOTf iWith jIsolated yield. Under optimized conditions, tethered explored examine generality 2). Substrates bearing varied 4-, 5-, 6-position moiety proceed their corresponding yields, diastereo- 2a–2l, 68%–92% 14/1 dr, 88%–96% values lower when seven-substituted indole-derived substrates used 2m, 72% yield, 6/1 95% ee; 2n, 16/1 88% electronic property does show notable influence. either electron-withdrawing (F Cl) electron-donating (Me, MeO, BnO) well tolerated. Moreover, tryptophan-derived substrates, which contain one center ring, underwent smoothly, affording 2o–2q, 91%–96% 8/1 dr). relatively 2q probably caused mismatch R configuration 1q (S,S,Sa)- transition state. gem-dimethyl carboline 2r combined (94%) (>99% [major isomer] 99% [minor isomer]), (1.8/1 carbonate skipped (m = 2), target proceeded well. diastereomeric ratios despite high enantiomeric purity 2s, 71% 94% isomer], 1.1/1 dr; 2t, 69% 1.5/1 stereochemistry 2p (4R,4aR,11S) (4R,4aR,11R) established Overhauser enhancement spectroscopy X-ray crystallographic analysis, respectively.89 absolute other (major isomers) assigned analogy. Substrate scope. activation.60 Combined reported. analysis. Enantiomeric excess (ee) generally exhibit 20/1 It known catalyst Feringa-type control position. utilized, Si-face position allowed attacked. it facial selectivity prochiral nucleophile determines obtained. At stage, calculations90 (M06-2X/SDD/6-31G**) shed some light selectivity. formation selected Two states, TS-2a-( Si ) Re ), leading (4R,4aR) (4R,4aS) 2a, located calculated Gibbs free energy than 1.2 kcal/mol, agreement experimental results. structure relative positively charged allyl electron-rich –synclinal [defined dihedral angle D (Ca–Cb–Cc–Cd), below]. favorable interaction overlapped parts exist help stabilize On hand, antiperiplanar conformation, thus, stabilization expected structure. believe inherent preference 2a.91 noted, strength weak nonbonding sensitive external perturbations. reasonable different solvents counter anions Ir-catalyst employed. Optimized structures Si, Si) Re) (in kcal/mol). (a) (b) side views; (c) (d) Newman projection along forming Cb–Cc bond. associated Ir omitted clarity. green pink, respectively. additional introduced certain positions significantly 2r, 1.8/1 Similar computational investigations applied models. shown 4, difference competitive states TS-2r-( isomers reduced 0.8 kcal/mol. geometric similar ). (–synclinal) (antiperiplanar). causes stronger steric repulsion formal case, exemplified closer hydrogen atom pairs (B[H1⋯H4] 2.15 Å, B(H3⋯H4) 2.09 B[H5⋯H6] 2.10 Å) compared (B[H2⋯H4] 2.37 B[H3⋯H4] 2.16 2.06 Å). brought about overlap diminished energetic gap reduces. situation elongated tether very For state TS-2s'-( keep (–synclinal), strain must suffered bridged cyclic conformation require strong strain.92 minimized 0.3 5 short, qualitatively reproduced trend observed three kinds largely originates beneficial states. will lowered stabilizing neutralized operating Synthetic applications demonstrate utility newly gram-scale carried out. standard 1p 3.76 mmol scale 76% (0.85 g) Gram-scale herein readily transformations Subjecting Pd/C-catalyzed hydrogenation 87% dr. Reduction sodium cyanoborohydride furnished 77% meantime, imine easily converted enamine reacting methyl chloroformate. Transformations products. Conclusion summary, enantioselective Ir-catalyzed, intramolecular, general, diastereoselectivity, spectrum conditions. DFT calculations propose working accounting stereoselectivity. Conflicts Interest authors declare competing interests. Acknowledgments thank National Research Development Program China (2016YFA0202900), Basic (2015CB856600), Natural Foundation (21332009, 21572252, 21772219), Technology Commission Municipality (16XD1404300, 18QA1404900, 16490712200), Strategic Priority (XDB20000000), Frontier Sciences (QYZDYSSWSLH012), Youth Promotion Association (2017302) generous financial support. References 1. Maehara S.; Simanjuntak P.; Kitamura C.; Ohashi K.; Shibuya H.Bioproduction Cinchona Alkaloids Endophytic Fungus Diaporthe sp. Associated Ledgeriana.Chem. Pharm. Bull.2012, 60, 1301–1304. Google Scholar 2. Díaz J. G.; Sazatornil Rodríguez M. L.; Mesía L. R.; Arana G. V.Five New Leaves Remijia p eruviana.J. Nat. Prod.2004, 67, 1667–1671. 3. Sim D. 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Language: Английский

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Highly Regioselective Synthesis of Multisubstituted Pyrroles via Ag-Catalyzed [4+1C]^insert Cascade

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(6), P. 3733 - 3740

Published: Feb. 6, 2020

An efficient [4+1C]insert approach to the coupling of enaminones with donor/acceptor or donor/donor carbenes by AgOTf-catalyzed C–C bond carbenoid formal insertion/cyclization/[1,5]-shift cascade reaction was successfully developed, providing distinct chemo- and regioselective multisubstituted pyrroles. The plausible mechanism involves two catalytic cycles: in first one, silver ions regioselectively catalyze insertion reaction; second control cyclization [1,5]-shift reactions. This method not only provides convenience applies atom economy synthesis pyrroles but also presents an entry point for further pyrrole diversification via facile modification resulting 4H-pyrrole products, as displayed a short natural product lamellarin L.

Language: Английский

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