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. Stork Niu D.; Fujimoto Koft Balkovec Tata Dake R.The First Stereoselective Total Quinine.J. Soc.2001, 123, 3239–3242. 11. Raheem I. T.; Goodman N.Catalytic Syntheses Quinine Quinidine.J. Soc.2004, 126, 706–707. 12. Johns Mori Williams M.Synthetic Studies Quinine: Construction Enolate Regio- Diastereoselective Pd-Mediated Alkylation.Org. Lett.2006, 8, 4051–4054. 13. Brown Clarke Foubister A. Freeman Harrison P. Johnson Mallion B.; McCormick McTaggart F.; Reid Smith Taylor J.Synthesis Activity Novel Series 3-Biarylquinuclidine Squalene Synthase Inhibitors.J. Med. Chem.1996, 39, 2971–2979. 14. Roche Porco A.Dearomatization Strategies Complex Products.Angew. Ed.2011, 4068–4093. 15. Zhuo C.-X.; W.; S.-L.Catalytic Reactions.Angew. Ed.2012, 51, 12662–12686. 16. Ding Q.; Zhou X.; Fan R.Recent Advances Heteroaromatic Compounds.Org. Biomol. Chem.2014, 12, 4807–4815. 17. Transition-Metal Catalysis: Method Aromatic Compounds.Chem2016, 1, 830–857. 18. Manoni De Nisi Bandini M.New Opportunities Indoles.Pure Appl. Chem.2016, 88, 207–214. 19. W.-T.; (CADA) Reactions Phenol Aniline Derivatives.Chem. Soc. Rev.2016, 45, 1570–1580. 20. Sun Li Hong Wang R.Asymmetric Phenols.Org. 14, 2164–2176. 21. Wen-Ting Liming Z.; Y.Recent Progress Gold-Catalyzed Reactions.Acta Chim. Sinica2017, 75, 419–438. 22. Chen J.-B.; Jia Y.-X.Recent Transition-Metal-Catalyzed Indole Functionalizations.Org. Chem.2017, 15, 3550–3567. 23. S.-L., Ed. Reactions; Wiley-VCH: Weinheim, 2016. 24. Romano Monari M.Metal-Free Electrophilic Activation Allenamides: Indoles.Angew. Ed.2014, 53, 13854–13857. 25. Zi H.; Toste F. D.Gold(I)-Catalyzed Dearomative Rautenstrauch Rearrangement: Access Cyclopenta[b]indoles.J. Soc.2015, 137, 3225–3228. 26. Zhao Liu Mei Guo Feng X.Asymmetric Indoles through Michael/Friedel–Crafts-Type Cascade Construct Polycyclic Spiroindolines.Angew. Ed.2015, 54, 4032–4035. 27. Shen R.-R.; R.-J.; Y.-L.; T.-F.; Gao J.-R.; Y.-X.Enantioselective Arylative Pd-Catalyzed Reductive Heck Reactions.J. 4936–4939. 28. Shao C.-J.; S.-L.Copper-Catalyzed Intermolecular Propargylic 7684–7687. 29. Kubota Hayama Iwamoto Ito H.Enantioselective Borylative Copper(I) Catalysis.Angew. 8809–8813. 30. Xing Y.-K.; Qiu Tao H.-Y.; C.-J.Catalytic Vinylogous Mukaiyama 1,6-Michael/Michael Addition 2-Silyloxyfurans Azoalkenes: Direct Approach Fused Butyrolactones.J. 10124–10127. 31. Lian X.Chiral N,N′-Dioxide–Scandium(III)-Catalyzed 2-Naphthols Amination Reaction.Chem. Eur. J.2015, 21, 17453–17458. 32. Ocello Yang Q.-Q.; Giacinto Bottoni Miscione M.Gold(I)-Catalyzed [2+2]-Cycloaddition Activated Allenes: Experimental–Computational Study.Chem. 18445–18453. 33. Yi J.-C.; Z.-B.; Tang Y.; L.-X.; S.-L.Enantioselective 3a-Amino-Pyrroloindolines Copper-Catalyzed Tryptamines.Angew. Ed.2016, 55, 751–754. 34. Chang C.-J.Cu(I)-Catalyzed Multicomponent Inverse Electron-Demand Aza-Diels–Alder/Nucleophilic Addition/Ring-Opening Involving 2-Methoxyfurans Efficient Dienophiles.J. Soc.2016, 138, 3998–4001. 35. Liddon T. James O'Brien Unsworth P.Catalyst-Driven Scaffold Diversity: Selective Spirocycles, Carbazoles Quinolines Indolyl Ynones.Chem. J.2016, 22, 8777–8780. 36. Xia Z.-L.; Gu S.-L.Chiral Phosphoric Acid Catalyzed Michael Enones.Org. Lett.2017, 762–765. 37. Liang T.-Y.; Zeng X.-Y.; Wei Y.-R.Ir-Catalyzed (–)-Communesin F.J. Soc.2017, 139, 3364–3367. 38. L.-P.; Y.Access Hexahydrocarbazoles: Thorpe–Ingold Effects Ligand Enantioselectivity.Angew. Ed.2017, 56, 6942–6945. 39. Bera Daniliuc C. Studer A.Oxidative N-Heterocyclic Carbene Spirocyclic Indolenines Quaternary Carbon Stereocenter.Angew. 7402–7406. 40. Y.-G.; B.-B.; R.-X.; Difunctionalization Palladium-Catalyzed Heck/Sonogashira Sequence.Angew. 7475–7478. 41. Y.-P.; G.-P.; Zhu S.-F.; Q.-L.Highly Copper- Iron-Catalyzed Cyclopropanation Indoles.J. 7697–7700. 42. Ma J.-Y.; G.-J.; F.Catalytic Chemodivergent Tryptophols.Chem. Commun.2017, 12124–12127. 43. He Pitsch X.Enantioselective Tandem Cyclization Alkyne-Tethered Using Cooperative Silver(I)/Chiral 12206–12209. 44. L.Highly Tetrahydro-5H-Indolo[2,3-b]quinolines

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