Cooperative Tertiary Amine/Chiral Iridium Complex Catalyzed Asymmetric [4+3] and [3+3] Annulation Reactions

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(42), P. 15021 - 15025

Published: Aug. 15, 2019

Abstract Asymmetric reactions merging organocatalysis and metal catalysis significantly broaden the scope of organic synthesis. Nevertheless, accomplishment stereoselective annulations combining two types dipole species, independently generated from activations organocatalysts complexes, still remains as a challenging task. Now, Morita–Baylis–Hillman carbonates isatins carbamate‐functionalized allyl could be chemoselectively activated by achiral Lewis basic tertiary amines chiral iridium complexes. The zwitterionic allylic ylides 1,4‐π‐allyliridium dipoles formed in situ are assembled highly [4+3] annulation pattern. Similar cooperative catalytic strategy applied for vinyl aziridines, furnishing an asymmetric [3+3] reaction also with excellent stereocontrol.

Language: Английский

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Recent advances of Pd-π-allyl zwitterions in cycloaddition reactions

Chinese Chemical Letters, Journal Year: 2023, Volume and Issue: 34(11), P. 108401 - 108401

Published: March 30, 2023

Language: Английский

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Enantioselective Total Synthesis of (−)-Daphenylline

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(2), P. 1262 - 1268

Published: Jan. 5, 2024

A concise enantioselective total synthesis of (−)-daphenylline, a hexacyclic Daphniphyllum alkaloid with unique benzene ring, was achieved in 14 steps. The commences two chiral stereocenters, C2 and C18, readily installed via Carreira's Ir/amine dual-catalyzed allylation. allylic bridgehead amine 6 rapidly prepared through Wickens' photoredox-catalyzed hydrocarboxylation olefin CuBr2-catalyzed α-amination ketone. tetracycle 4 formed Pd-catalyzed reductive Heck reaction or, more concisely, by Krische's Rh-catalyzed 1,6-enyne cyclization. In this synthesis, newly reported used twice, Friedel–Crafts acylation thrice.

Language: Английский

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Highly Diastereo‐ and Enantioselective Synthesis of Tetrahydro‐5H‐Indolo[2,3‐b]quinolines through Copper‐Catalyzed Propargylic Dearomatization of Indoles

Chemistry - A European Journal, Journal Year: 2017, Volume and Issue: 23(51), P. 12489 - 12493

Published: July 27, 2017

The first copper-catalyzed intermolecular asymmetric propargylic dearomatization/annulation cascade sequence of indoles via a copper-allenylidene amphiphilic intermediate has been achieved. This protocol provides direct synthetic method for the preparation tetrahydro-5H-indolo[2,3-b]quinolines, core structure indole alkaloids communesins A-H and perophoramidine. features excellent yields, high diastereoselectivity (up to >19:1 d.r.) enantioselectivity 94 % ee), mild conditions wide substrate scope.

Language: Английский

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Total Synthesis and Anti-Cancer Activity of All Known Communesin Alkaloids and Related Derivatives

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(36), P. 14411 - 14420

Published: Aug. 17, 2019

A unified enantioselective total synthesis and anticancer evaluation of all known epoxide-containing communesin alkaloids related derivatives is described. Our predicated on the convergent modular diazene-directed assembly two complex fragments to secure critical C3a-C3a' linkage followed by a guided biomimetic aminal reorganization deliver heptacyclic core these alkaloids. Concise syntheses were devised, with highlights including application rationally designed sulfinamide chiral auxiliary, an efficient calcium trifluoromethanesulfonate promoted intramolecular amination, diastereoselective epoxidation that simultaneously converts new auxiliary versatile amine protective group. The modularity our approach enabled rapid members family from single heterodimeric intermediate, first communesins C-E, G-I, facilitated stereochemical revision (-)-communesin I, most recently isolated alkaloid. Furthermore, generality biogenetically inspired heterodimer rearrangement was demonstrated in derivative unnatural topology. Finally, we report comparative analysis activities naturally occurring A-I eight against five human cancer cell lines. From data, have identified B as potent natural discovered

Language: Английский

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Divergent Synthesis of Polycyclic Indolines: Copper-Catalyzed Cascade Reactions of Propargylic Carbamates and Indoles

Organic Letters, Journal Year: 2017, Volume and Issue: 19(15), P. 4098 - 4101

Published: July 25, 2017

Polycyclic indolines are the common and core structural motif of many indole alkaloids that usually exhibit biological activities. Here, we describe two copper-catalyzed cascade reactions between propargylic carbamates indoles. By doing so, one-step divergent synthesis structurally distinct polycyclic indolines, quinoline-fused C(3a)-indolyl furoindolines, pyrroloindolines was achieved in high synthetic efficiency selectivity.

Language: Английский

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Tryptophol and derivatives: natural occurrence and applications to the synthesis of bioactive compounds

Natural Product Reports, Journal Year: 2018, Volume and Issue: 36(3), P. 490 - 530

Published: Sept. 19, 2018

This report presents some fundamental aspects related to the natural occurrence and bioactivity of tryptophol as well synthesis tryptophols their utilization for preparation naturally occurring alkaloid metabolites embedding indole system.

Language: Английский

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Catalytic Asymmetric Dearomatization of Indolyl Dihydropyridines through an Enamine Isomerization/Spirocyclization/Transfer Hydrogenation Sequence

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 57(10), P. 2653 - 2656

Published: Jan. 12, 2018

Abstract A highly efficient synthesis of enantioenriched spiroindolines by catalytic asymmetric dearomatization indolyl dihydropyridines through a chiral phosphoric acid catalyzed enamine isomerization/spirocyclization/transfer hydrogenation sequence has been developed. This reaction proceeds under mild conditions, affording novel in good yields (up to 88 %) with excellent enantioselectivity 97 % ee ). DFT calculations provide insights into the mechanism as well origin stereochemistry.

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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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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