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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Gaussian Process Regression for Transition State Search

Journal of Chemical Theory and Computation, Journal Year: 2018, Volume and Issue: 14(11), P. 5777 - 5786

Published: Oct. 23, 2018

We implemented a gradient-based algorithm for transition state search which uses Gaussian process regression. Besides description of the algorithm, we provide method to find starting point optimization if only reactant and product minima are known. perform benchmarks on 27 test systems against dimer partitioned rational function as in DL-FIND library. found new optimizer significantly decrease number required energy gradient evaluations.

Language: Английский

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Recent advances in metal-catalysed asymmetric sigmatropic rearrangements

Chemical Science, Journal Year: 2022, Volume and Issue: 13(42), P. 12290 - 12308

Published: Jan. 1, 2022

Catalytic asymmetric sigmatropic rearrangements induced by chiral metal catalysis have been intensively explored. This review summarizes recent significant advances, mainly involving [3,3], [2,3] and [1,3]-rearrangements.

Language: Английский

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Synergistic catalysis for cascade allylation and 2-aza-cope rearrangement of azomethine ylides

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

Published: April 8, 2019

The efficient construction of enantiomerically enriched molecules from simple starting materials via catalytic asymmetric synthesis strategies is a key challenge in synthetic chemistry. Metallated azomethine ylides are commonly-used synthons for the preparation N-heterocycles and α-amino acids. Remarkably, to date, utilization facile access chiral amines has proven elusive. Here, we report that synergistic Cu/Ir-catalytic system combined with careful tuning steric congestion can be used convert aldimine esters variety homoallylic cascade allylation/2-aza-Cope rearrangement. elucidation distinct effects each stereogenic center allylation intermediates on stereochemical outcome chirality transfer rearrangement further guided selection catalysts combination.

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. S.-Y.; Chong K.-W.; Nge C.-E.; Low Y.-Y.; K.-S.; Kam T.-S.Cytotoxic Vobasine, Tacaman, Corynanthe-Tryptamine Bisindole Tabernaemontana Structure Revision Tronoharine.J. Prod.2014, 77, 2504–2512. 4. Shi M.; Xu Y.-M.Catalytic, Baylis–Hillman Imines Methyl Vinyl Ketone Acrylate.Angew. Chem. Int. Ed.2002, 41, 4507–4510. 5. Jacobsen E. N.; Markó I.; Mungall W. Schröeder K. B.Asymmetric Dihydroxylation Ligand-Accelerated Catalysis.J. Am. Soc.1988, 110, 1968–1970. 6. O'Donnell J.; Wu Huffman C.A Active Species Alkylation Phase-Transfer Catalysis.Tetrahedron1994, 50, 4507–4518. 7. Trampuz A.; Jereb Muzlovic Prabhu R. M.Clinical Review: Severe Malaria.Crit. Care2003, 7, 315–323. 8. Dorman S. E.; Cannon Telford Frank Churchill H.Fulminant Babesiosis Treated Clindamycin, Quinine, Whole-Blood Exchange Transfusion.Transfusion2000, 40, 375–380. 9. Hamama El-Magid O. Zoorob H. H.Chemistry Quinuclidines Nitrogen Bicyclic Bridged-Ring Structures.J. Heterocyclic. Chem.2006, 43, 1397–1420. 10. 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Language: Английский

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Organocatalytic regio-, diastereo- and enantioselective γ-additions of isoxazol-5(4H)-ones to β,γ-alkynyl-α-imino esters for the synthesis of axially chiral tetrasubstituted α-amino allenoates

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(6), P. 1243 - 1248

Published: Jan. 1, 2021

The chiral phosphoric acid catalyzed regio-, diastereo- and enantioselective reaction of isoxazol-5(4H)-ones with β,γ-alkynyl-α-imino esters has been developed.

Language: Английский

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Catalytic Asymmetric Synthesis of α-Trifluoromethyl Homoallylic Amines via Umpolung Allylation/2-Aza-Cope Rearrangement: Stereoselectivity and Mechanistic Insight

Organic Letters, Journal Year: 2019, Volume and Issue: 21(12), P. 4842 - 4848

Published: May 30, 2019

An unprecedented Ir-catalyzed asymmetric cascade umpolung allylation/2-aza-Cope rearrangement of trifluoroethylisatin ketimines has been realized. The current method provides a facile access to biologically important α-trifluoromethyl-containing homoallylic amines in high yields with excellent enantioselectivity. Notably, reactivity ketimine was discovered for the first time. Mechanism studies revealed key intermediates initial allylation and stereospecific chirality transfer subsequent 2-aza-Cope rearrangement.

Language: Английский

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Catalytic Asymmetric Synthesis of α-Tetrasubstituted α-Trifluoromethyl Homoallylic Amines by Ir-Catalyzed Umpolung Allylation of Imines

Organic Letters, Journal Year: 2019, Volume and Issue: 21(17), P. 6951 - 6956

Published: Aug. 16, 2019

A general and mild method to prepare enantioenriched α-trifluoromethyl, α-stereogenic homoallylic amines is established. This reaction, which involves an Ir-catalyzed umpolung allylation of imines a 2-aza-Cope rearrangement cascade, could yield both tetrasubstituted trisubstituted stereocenters. transformation employs readily available starting materials displays broad substrate scope. The isolation structural determination reaction intermediates revealed factors critical for the efficiency stereoselectivity this transformation.

Language: Английский

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Catalytic Asymmetric Umpolung Allylation/2-Aza-Cope Rearrangement for the Construction of α-Tetrasubstituted α-Trifluoromethyl Homoallylic Amines

Organic Letters, Journal Year: 2019, Volume and Issue: 21(17), P. 6940 - 6945

Published: Aug. 19, 2019

A general protocol for the preparation of enantioenriched α-tetrasubstituted α-trifluoromethyl homoallylic amines is disclosed. Despite significant challenge in stereoselectivity control, Ir-catalyzed asymmetric cascade umpolung allylation/2-aza-Cope rearrangement trifluoromethylated fluorenone imines with allylic carbonates was realized excellent efficiency and remarkable stereoselectivity. These were enabled by suitable protective imino moiety an unexpectedly exclusive E-geometrical imine allylation intermediate. This methodology also applicable to facile access chiral α-trisubstituted similarly high yield

Language: Английский

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Calyciphylline B-type Alkaloids: Evolution of a Synthetic Strategy to (−)-Daphlongamine H

The Journal of Organic Chemistry, Journal Year: 2019, Volume and Issue: 84(21), P. 14069 - 14091

Published: Sept. 19, 2019

We provide a full account of our synthetic studies targeting the hexacyclic calyciphylline B-type alkaloids, subfamily Daphniphyllum natural products. Following an initial set strategies focused on constructing piperidine core framework via 6π-azaelectrocyclization, as well exploiting reactivity underexplored oxazaborinine heterocycles, we ultimately designed highly functionalized acyclic precursor which underwent carefully orchestrated and efficient cyclizations to forge architecturally complex product scaffold. Our efforts have culminated in development first total synthesis (−)-daphlongamine H, provided access its C5-epimer, (−)-isodaphlongamine led structural revision deoxyisocalyciphylline B.

Language: Английский

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