Copper-Catalyzed Enantioselective Trifluoromethylthiolation of Secondary Propargyl Sulfonates

Open AccessCCS ChemistryCOMMUNICATION1 May 2021Copper-Catalyzed Enantioselective Trifluoromethylthiolation of Secondary Propargyl Sulfonates Xing Gao, Yu-Lan Xiao, Shu Zhang, Jian Wu and Xingang Zhang Gao Key Laboratory Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute Organic University Chinese Academy Sciences, 200032 Google Scholar More articles by this author , Xiao School Materials Energy, Electronic Science Technology China, Sichuan 611731 *Corresponding author: E-mail Address: [email protected] College Henan Advanced Technology, Zhengzhou University, 450001 https://doi.org/10.31635/ccschem.020.202000353 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesTrack Citations ShareFacebookTwitterLinked InEmail Although trifluoromethylthiolated compounds have privileged applications pharmaceuticals agrochemicals, efficient strategies the asymmetric construction Csp3–SCF3 bonds are limited. Specifically, catalytic nucleophilic trifluoromethylthiolation remains challenging. Here, we report a copper-catalyzed enantioselective secondary propargyl sulfonates with trifluoromethylthio silver. The reaction exhibits high efficiency, good enantioselectivity, functional group tolerance, broad substrate scope, paving new way synthesis compounds. Download figure PowerPoint Introduction (CF3S) has agrochemicals due its lipophilicity (CF3S, ? = 1.44; CF3, 0.88) metabolic stability. Its substitution biologically active molecules often leads profound changes physicochemical pharmacokinetic properties.1–5 Over past decade, various methods emerged site-selective introduction CF3S into organic molecules,6–10 most which focused on Csp2–SCF3 bonds.6–16 In contrast, at stereogenic center received less attention underdeveloped,17–23 although these chiral would substantial impacts research development drugs. To date, electrophilic trifluoromethylations been developed, organocatalysts17–21,24,25 or Lewis acids26 used enantioselectively catalyze formation bond (Schemes 1a 1b). Despite importance methods, their substrates restricted carbonyl compounds17–20,24–26 alkenes,21,27–29 limiting widespread discovering bioactive molecules. Thus, stereoselectively synthesize diversified is highly desirable. Scheme 1 | (a–c) Strategies trifluoromethylthiolation. *Optically pure context, envisioned that transition-metal-catalyzed provide opportunities difficult access through strategies. enables us employ variety readily available electrophiles, such as alkyl (Scheme 1c). however, strategy not reported challenging topic because lack system.30–33 We sought explore electrophiles via copper catalysis34–38 1c), lead structure after transformations alkynes. For process, hypothesized anion, soft nucleophile, may facilitate attack situ generated ?-electrophilic copper–allenylidene intermediate, thus rendering feasible. Herein, sulfonates, representing first example This method including bearing multichiral centers, represents route related chemistry. Experimental Methods 25 mL Schlenk tube were added L5 (15.3 mg, 0.036 mmol, 12 mol %), Cu(CH3CN)4PF6 (11.2 0.03 10 %) AgSCF3 2 (67 0.3 1.0 equiv) (Note: exact molecular formula 3CF3SAg·CH3CN. weight was calculated based CF3SAg·1/3(CH3CN)). After mixture evacuated backfilled argon three times, CH3CN (2 mL) CH3OH (0.5 added. stirred room temperature 20 min, then cooled –40 °C. sulfonate (0.6 2.0 DIPEA (0.36 1.2 stirring -40 °C 48 h, quenched saturated aqueous NH4Cl worked up ethyl acetate. resulting filtered pad celite. filtrate concentrated residue purified silica gel chromatography give product 3. Results Discussion Optimization studies test our hypothesis, chosen model substrate, stable silver (CF3SAg) fluorine source (Table 1). Good yield racemic 3a (70%) obtained when carried out presence CuOAc (10 iPr-PyBox L1 (12 (diisopropylethylamine, 15 (Entry Decreasing benefited enantioselectivity (Entries 3). At low ?30 °C, enantiomeric 67.5?32.5 er (enantiomeric ratio) obtained, expense (32%) A survey series PyBox ligands showed ligand flexible side chain had beneficial effect providing 82?18 value 7). Ligands L4 L3 one no methylene between phenyl oxzole ring could also improve value, but both activity 5 6). observed using iBu-PyBox L2 4). increasing rigidity failed ( Supporting Information Table S3). Further optimization conditions decreasing ?40 Cu(CH3CN)4PF6/ catalyst 87.5?12.5 8, details see Information). Encouraged results, chains examined 9–14). found L9 L10 longer length than still provided comparable enantioselectivities 9 10). But modification different aryl substituents did values 11–14). Other reagents, CsSCF3 Me4NSCF3, tested; lower poor (see S6), suggesting critical role CF3SAg reaction. Finally, optimized identified loading amount equiv 1f ligand, methanol39 cosolvent, 72% (upon isolation) 86?14 15). absence MeOH led decreased higher 16). Representative Copper-Catalyzed AgSCF3a Entry L Temperature (°C) (x) 3a, yieldb (%)/erc 70/50?50 ?20 45/61?39 3 32/67.5?32.5 4 34/75?25 32/65?35 6 29/70?30 7 36/82?18 8d 60 30/87.5?12.5 9d 33/87.5?12.5 10d 33/87?13 11d L11 31/26?74 12d L12 27/14?86 13d L13 24/16?84 14d L14 23/17.5?82.5 15d–f 120 73 (72)/86?14 16d,e 84/80?20 aReaction (unless otherwise specified): equiv), (0.3 (2.0 mL), 24–48 h. bDetermined 19F NMR fluorobenzene an internal standard; number given parentheses isolated yield. cDetermined HPLC analysis. dCu(CH3CN)4PF6 used. ePropargyl fMeOH Scope With viable hand, 2). Generally, yields obtained. Compared 1a, (95?5 97.5?2.5) spacer site shortened 3b– 3e). An attempt install aryl-substituted instability. However, following results more steric enantioselectivities. example, sterically hindered group, 1-naphthyl 3e) branched substituent 3f), applicable values. addition, long linear competent coupling partners 3g– 3p); even heptyl-substituted underwent smoothly 3p). High cyclic chain-substituted 3s, 3t, 3v), size ranging from six four members interfere stereoselectivity. Slightly six-membered rings (piperidine tetrahydropyran) position 3q 3r vs 3s; 3u enantioselectivity. Reaction scope AgSCF3.aaReaction mL). All yields. bGram-scale synthesis. exhibited tolerance. Versatile groups, ester, nitro, base-sensitive acetyl sulfonate, silyl ether, carbamate moiety, compatible 3i, 3j, 3l, 3n, 3o, 3q– 3t); pyridine- amino acid-containing furnished corresponding products 3k 3m). particular, proline derivative 3m dr (diastereomeric (94?6). (hetero)aryl halides 3b, 3c, 3j), chloride, bromide, iodide well ?-chloropyridine 3k), reaction, occur, be benefical downstream transformations. Furthermore, adjacent amenable producing 3w 3x). light versatility structural motifs, present potential interesting Most importantly, production can scalable, demonstrated gram-scale complex molecule 3x efficiency (69% yield) stereoselectivity (94?6 dr). absolute configuration enantioenriched assigned S-configured crystallographic characterization compound 4c, derived 3c [3 + 2] cyclization azide. case 3x, absolution R-configured. analysis 4c weak hydrogen fluoride benzylic hydride.40–42 unique property design molecules.43,44 further probe whether influence stereoselectivity, bulky moiety 1zd trifluoromethythiolation sensitive ligand. use (S,S)-phenethyl-PyBox protected aminoalcohol 5a 40% 60?40 value. finding contrast trifluoromethyltholation 1zb 1zc, 2, (65%) excellent (99?1) 5b opposite (R,R)-phenethyl-PyBox L5? 5b.45–47 similar 1zc These demonstrate affect key factor. proper matching existing deduction supported phenethyl-PyBox where 76?24 5. Synthetic utility protocol highlighted array acids. As depicted 4a, treatment 1ze, drived L-aspartic acid, acid diastereoselectivity dr) increased 99?1 purification chromatography. Compound serve versatile building block diversity-oriented instance, Sonogashira 2-iodothiophene cycloaddition nitrile oxide48 proceeded smoothly, heteroaryl-substituted acids 8a 8b 4b). relevant glycopeptide simple Deprotection trifluoroacetic (TFA), followed condensation dipeptide 9, tripeptide 4c). Subsequently, treament carbohydrate-derived azide 11 click chemistry efficiently 12.49 fluorinated peptide-based protein engineering,50–52 offer discover transformation shown 4d, TFA lactone 13 efficiently. compounds,17–21,24–29 it achieve developed demonstrating advantages current process. (a–d) Transformations origin explained Maarseveen’s model.53 On basis previous reports,33,53–58 cooperative catalysis involved Figure 1, binds trifluoromethythio, while other reacts produce intermediate. trifluoromethylthiocopper subsequently attacks Si-face configuration. Proposed mode sulfonates. Conclusion catalysis. allows flexibility factors Given synthetic carbon–carbon triple tolerance method, useful blocks compounds, glycopeptide, medicinal chemical biology. novel paves available. Conflict Interest There conflict interest report. Funding Financial support work National Natural Foundation China (nos. 21931013, 21702225, 21672238, 21421002) Strategic Priority Research Program Sciences (no. XDB20000000). Acknowledgments authors wish acknowledge Xiao-Long Wan conducting References 1. Hansch C.; Leo A.; Taft R. W.A Survey Hammett Substituent Constants Resonance Field Parameters.Chem. Rev.1991, 91, 165–195. 2. Haufe G.; Leroux F.Fluorine Life Sciences: Pharmaceuticals, Medicinal Diagnostics, Agrochemicals: Progress Fluorine Series; Amsterdam, Netherlands: Elsevier Science: 2018. Wang J.; Sánchez-Roselló M.; Aceña J. L.; del Pozo Sorochinsky A. E.; Fustero S.; Soloshonok V. Liu H.Fluorine Pharmaceutical Industry: Fluorine-Containing Drugs Introduced Market Last Decade (2001–2011).Chem. Rev.2014, 114, 2432–2506. 4. Hagmann W. K.The Many Roles Chemistry.J. Med. Chem.2008, 51, 4359–4369. Meanwell N. A.Fuorine Fluorinated Motifs Design Application Boisosteres Drug Design.J. Chem.2018, 61, 5822–5880. 6. Toulgoat F.; Alazet Billard T.Direct Reactions: “Renaissance” Old Concept.Eur. Org. Chem.2014, 2415–2428. 7. Shao X.; Xu Lu Shen Q.Shelf-Stable Electrophilic Reagents Trifluoromethylthiolation.Acc. Chem. Res.2015, 48, 1227–1236. 8. X.-H.; Matsuzaki K.; Shibata N.Synthetic Compounds Having CF3–S Units Carbon Trifluoromethylation, Trifluoromethylthiolation, Triflylation, Related Reactions.Chem. Rev.2015, 115, 731–764. 9. Qing F.Recent Advances Direct Trifluoromethylthiolation.Chin. Chem.2015, 35, 556–569. 10. Chachignon H.; Cahard D.State-of-the-Art Reagents.Chin. Chem.2016, 34, 445–454. 11. Teverovskiy Surry D. Buchwald S. L.Pd-Catalyzed Synthesis Ar-SCF3 Under Mild Conditions.Angew. Int. Ed.2011, 50, 7312–7314. 12. C.-P.; Vicic A.Nickel-Catalyzed Aryl Trifluoromethyl Sulfides Room Temperature.J. Am. Soc.2012, 134, 183–185. 13. Chen Xie Y.; Chu L.-L.; R.-W.; X.-G.; F.-L.Copper-Catalyzed Oxidative Boronic Acids TMSCF3 Elemental Sulfur.Angew. Ed.2012, 2492–2495. 14. Tran L. D.; Popov I.; Daugulis O.Copper-Promoted Sulfenylation sp2 C–H Bonds.J. 18237–18240. 15. Baert Colomb T.Electrophilic Trifluoromethanesulfanylation Organometallic Species Trifluoromethanesulfanamides.Angew. 10382–10385. 16. Yang Y.-D.; Azuma Tokunaga Yamasaki Shiro Trifluoromethanesulfonyl Hypervalent Iodonium Ylide Enamines, Indoles, ?-Keto Esters.J. Soc.2013, 135, 8782–8785. 17. Hardy M. D.Advances Asymmetric Di- Trifluoromethoxylation Reactions.Asian Chem.2019, 591–609. 18. T.; Phipps Toste F. Catalytic Fluorination, Mono-, Di-, 826–870. 19. Bootwicha Pluta R.; Atodiresei Rueping M.N-Trifluoromethylthiophthalimide: Stable SCF3-Reagent It’s Trifluoromethylsulfenylation.Angew. Ed.2013, 52, 12856–12859. 20. Cheng Q.Enantioselective ?-Ketoesters: Case Reactivity Selectivity Bias Organocatalysis.Angew. 12860–12864. 21. Luo Zhao X.Enantioselective Trifluoromethylthiolating Lactonization Catalyzed Indane-Based Chiral Sulfide.Angew. Ed.2016, 55, 5846–5850. 22. Z.; Sheng Yu W.; W.-D.; J.Catalytic [2, 3]-Sigmatropic Rearrangement Sulfonium Ylides.Nat. Chem.2017, 970–976. 23. Kondo Maeno Sasaki Guo Hashimoto N.Synthesis Nonracemic ?-Difluoromethylthio Tetrasubstituted Stereogenic Centers Palladium-Catalyzed Decarboxylative Allylic Alkylation.Org. Lett.2018, 20, 7044–7048. 24. Hu Sun S.Efficient ?-Trifluoromethylthiolation Aldehydes.New 40, 6550–6553. 25. Gelat Poisson Biju Pannecoucke Besset T.Trifluoromethylthiolation ?-Chloroaldehydes: Access Quaternary SCF3-Containing Centers.Eur. 3693–3696. 26. Deng Q.-H.; Rettenmeier Wadepohl Gade H.Copper–Boxmi Complexes Highly Catalysts Trifluoromethylthiolations.Chem. Eur. J.2014, 93–97. 27. Cao Q.; X.Selenide-Catalyzed Trifluoromethylthiolated Tetrahydronaphthalenes Merging Desymmetrization Trifluoromethylthiolation.Nat. Commun.2018, 527–535. 28. Liang Ji X.Chiral Selenide-Catalyzed Intermolecular Difunctionalization Alkenes: Efficient Construction C-SCF3 Molecules.J. Soc.2018, 140, 4782–4786. 29. Jin Li Huang Zhou Chung Carbonyl Diastereo Cu-Catalyzed Tandem Reaction.Chem. 54, 4581–4584. 30. Y.-L.; X.Copper-Catalyzed Stereoselective Trifluoromethylation Difluoroalkylation Sulfonates.Angew. Ed.2018, 57, 3187–3191. 31. Trost B. Gholami Zell D.Palladium-Catalyzed Fluoroalkylation/Trifluoromethylation.J. Soc.2019, 141, 11446–11451. 32. Gu Q.Ligand-Controlled Regioselective Difluoromethylation Chlorides/Bromides Bromides.Chin. 36, 55–58. 33. X.-L.; Difluoroenoxysilanes.Chem2019, 5, 2987–2999. 34. Geri Oilizzi Lardicci Caporusso M.Reactions Nitrogen Nucleophiles 1-Bromoallenes: Propargylamines.Gazz. Chim. Ital.1994, 124, 241. 35. Godfrey Mueller Sedergran T. Soundararajan N.; Colandrea J.Improved 1,1-Dimethylpropargyl Ethers.Tetrahedron Lett.1994, 6405–6408. 36. Miyake Uemura Nishibayashi Y.Catalytic Propargylic Substitution Reactions.ChemCatChem2009, 342–356. 37. Ding C. Hou X. L.Catalytic Propargylation.Chem. Rev.2011, 111, 1914–1937. 38. D.-Y.; X.-P.Recent Substitution.Tetrahedron Lett.2015, 56, 283–295. 39. Gómez Cristòfol À.; Kleij W.Copper-Catalyzed Tertiary Sulfones.Angew. Ed.2019, 58, 3903–3907. 40. Howard H. Hoy O’Lhagan Smith G. T.How Is Hydrogen Bond Acceptor.Tetrahedron1996, 12613–12622. 41. Dunitz Taylor R.Organic Hardly Ever Accepts Bonds.Chem. J.1997, 3, 89–98. 42. D.Organic Fluorine: Odd Man Out.ChemBioChem2004, 614–621. 43. A.Synopsis Some Recent Tactical Bioisosteres Chem.2011, 2529–2591. 44. Böhm H.-J.; Banner Bendels Kansy Kuhn B.; M?ller Obst-Sander U.; Stahl M.Fluorine Chemistry.ChemBioChem2004, 637–643. 45. Bifulco Dambruoso P.; Gomez-Paloma Riccio R.Determination Relative Configuration Spectroscopy Computational Methods.Chem. Rev.2007, 107, 3744–3779. 46. Ardá Nieto Blanco Jiménez Rodr?´guez J.Low-Temperature J-Based Configurational Analysis Flexible Acyclic Systems.J. Chem.2010, 75, 7227–7232. 47. Furihata Seto H.J-Resolved HMBC, New Technique Measuring Heteronuclear Long-Range Coupling Constants.Tetrahedron Lett.1999, 6271–6275. 48. Mukaiyama Hoshino T.The Reactions Primary Nitroparaffins Isocyanates.J. Soc.1960, 82, 5339–5342. 49. Thirumurugan Matosiuk Jozwiak K.Click Chemistry Development Diverse Chemical–Biology Applications.Chem. Rev.2013, 113, 4905–4979. 50. Smits Koksch B.How C?-Fluoroalkyl Amino Peptides Interact Enzymes: Studies Concerning Influence Proteolytic Stability, Enzymatic Resolution Peptide Coupling.Curr. Top. Chem.2006, 6, 1483–1498. 51. Salwiczek Nyakatura E. Gerling U. I. Ye B.Fluorinated Acids: Compatibility Native Protein Structures Effects Protein–Protein Interactions.Chem. Soc. Rev.2012, 41, 2135–2171. 52. Berger Völler J.-S.; Budisa O.Deciphering Code—the Hats Wears Environment.Acc. Res.2017, 2093–2103. 53. Detz J.Triazole-Based P, N Ligands: Discovery Copper Amination Reaction. PhD Thesis, 2009. 54. Nakajima Y.Copper-Catalyzed Etherification Esters Alcohols.J. Soc.2015, 137, 2472–2475. 55. Tsuchida Senda Y.Construction Tri- Tetra-Arylmethanes Bearing Centers: Propargylation Indoles Esters.Angew. 9728–9732. 56. T.-R.; L.-Q.; M.-M.; W.-J.Catalytic [4 1] Annulation Sulfur Ylides Copper–Allenylidene Intermediates.J. Soc.2016, 138, 8360–8363. 57. Díez Gamasa Panera M.Tetra-, Mononuclear Copper(I) Containing (S, S)-iPr-pybox (R, R)-Ph-pybox Ligands.Inorg. 45, 10043–10045. 58. Diez Merino Rubio P.Synthesis Enantiopure Pybox Ligands. First Assays Propargylamines Isolated Complexes.Inorg. Chem.2009, 11147–11160. Previous articleNext article FiguresReferencesRelatedDetails Issue AssignmentVolume 3Issue 5Page: 1463-1471Supporting Copyright & Permissions© 2020 Chemical SocietyKeywordscopper–allenylidenepropargyl sulfonatescopper catalysistrifluoromethylthiolationasymmetric synthesisAcknowledgmentsThe Downloaded 1,693 times Loading ...