CCS Chemistry, Journal Year: 2020, Volume and Issue: 2(6), P. 642 - 651

Published: May 15, 2020

Open AccessCCS ChemistryRESEARCH ARTICLE1 Dec 2020Rhodium-Catalyzed Pyridine-Assisted C–H Arylation for the Synthesis of Planar Chiral Ferrocenes Chen-Xu Liu, Zhong-Jian Cai, Qiang Wang, Zhi-Jie Wu, Qing Gu and Shu-Li You Liu State Key Laboratory Organometallic Chemistry, Center Excellence in Molecular Synthesis, Shanghai Institute Organic University Chinese Academy Sciences, 200032 , Cai Wang Wu *Corresponding author: E-mail Address: [email protected] https://doi.org/10.31635/ccschem.020.202000157 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesTrack Citations ShareFacebookTwitterLinked InEmail chiral ferrocenes are widely applied organic synthesis, materials science, medicinal chemistry, but their synthesis is not trivial. Herein, a highly efficient planar ferrocene-based pyridine derivatives via Rh(I)-catalyzed direct coupling pyridylferrocenes with aryl halides was developed. Good yields excellent enantioselectivity (95–>99% ee) obtained wide range substrates. The compatibility gram-scale relatively low catalyst loading (down 1 mol% based on [Rh]) enhance practicality current method. generated products can be readily transformed into ligands. Mechanistic studies suggest that bond cleavage pyridylferrocene may reversible step rate-determining step. Significant nonlinear effects indicate existence multiple metals or ligands active catalyst. Download figure PowerPoint Introduction Ferrocene have been intensively studied areas chemistry because unique electronic structural properties.1,2 Particularly, utilized serving as versatile catalysts.3–6 With growing number pyridine-derived ligands/catalysts asymmetric catalysis,7 desirable. Transition metal-catalyzed functionalization reactions proved increasingly powerful methods construct C–C C–heteroatom bonds modern synthesis.8–10 progress transition introduce chirality ferrocene backbone has made during past decade.11–14 Nevertheless, majority them intramolecular designs construction ferrocenes.15–24 For intermolecular designs, dialkylamino groups25–29 used directing groups, others30–32 rarely reported. Pyridine known suitable group reported by Kasahara,33 Shibata,34 Butenschön,35 You.36 However, generally, challenges controlling mono-functionalization selectivity enantioselectivity. Of particular note, Shibata37 an Ir/chiral diene-catalyzed alkylation moderate good using isoquinolin-2-yl appropriately suppress secondary reactions. When group, poor mono-/di-selectivity obtained. Therefore, ferrocenyl pyridines high efficiency, mono-selectivity, remains challenging, likely result lack proper catalysts due strong coordination groups. Meanwhile, arylations also rapidly progressed.38–58 Breakthroughs achieved Glorius co-workers,55 who discovered rhodium(I) monodentate phosphonite complex enantioselective activation tetrahydroquinolines saturated aza-heterocycles. Inspired these pioneering results, we recently found arylation realized presence Rh(I)/chiral complex. This system delivers monoarylation Here, report results this study (Figure 1). Figure | Pyridine-assisted arylation. (a) Previous works ferrocenes. (b) group. (c) Our new strategy pyridine-assisted Experimental Methods General procedure arylation: A standard 10 mL Schlenk tube charged LiOtBu (48.0 mg, 0.6 mmol), L7 (25.3 0.04 [Rh(C2H4)2Cl]2 (3.9 0.01 (0.2 mmol, 1.0 equiv), bromide 2 (0.4 2.0 equiv). Then, flask evacuated backfilled argon three times, which followed addition tetrahydrofuran (THF) (2.0 mL). mixture stirred at 80 °C. After reaction complete (monitored thin layer chromatography [TLC]), cooled room temperature. diluted ethyl acetate (5.0 mL) filtered through pad celite. filtrate evaporated under reduced pressure. crude purified silica gel column (petroleum ether/ethyl = 20∶1) generate corresponding product 3. More experimental details characterization available Supporting Information. Results Discussion Reaction development Initially, began our investigation between 2-pyridylferrocene 1a 4-methoxybromobenzene 2a (Table desired 3aa 50% NMR yield >99% ee 5 [Rh(C2H4)2Cl]2, 20 L1,59,60 3.0 equiv (entry Screening variety bases disclosed optimal choice (see Information Table S1 details). solvent were examined, THF give better leading 76% 2). In addition, other solvents such toluene, p-xylene, mesitylene, 1,2-dichloroethane (DCE) gave comparable (25–48% yields, 99% ee, entries 3–6). Unfortunately, neither N,N-dimethylformamide (DMF) nor CH3OH (entries 7 8). Other aryl-substituted 4,5-Bis[hydroxy(diphenyl)methyl]-2,2-dimethyl-1,3-dioxolane (TADDOL)-derived 2-naphthyl, 3,5-(CF3)2-C6H3, 3,5-(tBu)2-C6H3 significantly 9–11). substituents attached phosphorus atom ligand investigated. Likely steric hindrance, tBu-substituted ( L5)-derived did promote 12). 3,5-(CF3)2-C6H3-substituted L6) similar those L1 (72% yield, entry 13). Interestingly, 3,5-(MeO)2-C6H3-substituted L7, 88% 14). utilization TADDOL-derived phosphoramidite L8 resulted slight decrease (68% 15). Using diastereoisomers Feringa L10 L11)61,62 led modest opposite absolute configuration, L11 (55% ee; 17 18). Spiro L1263,64 failed 19). Thus, choice. equivalents 2a, isolated 93% 22). Lowering temperature 60 °C afford (89% see S2 Finally, optimized conditions identified follows: (5 mol%), (20 (3.0 equiv) exclusive mono-selectivity bulkiness Optimization Conditions Entrya Ligand Solvent Yield (%)d (%)e Dioxane 50 >99 76 3 Toluene 48 99 4 p-Xylene 36 Mesitylene 28 6 DCE 25 DMF – 8 9 L2 23 98 L3 11 L4 42 86 12 L5 13 L6 72 14 88 15 68 16 L9 24 85 18 55 −99 19 L12 21b 92 22c 97 (93)f aReaction conditions: (0.1 (1.1 (0.02 (0.3 mmol) (1.0 b (1.5 c dNMR 1,3,5-trimethoxybenzene internal standard. eDetermined HPLC analysis. fIsolated 0.2 mmol scale. hand, next explored substrate scope First, slightly decreased 4-methoxyiodobenzene (73% 95% ee). substrate, 4-methoxychlorobenzene, compatible conditions, (84% that, series bromides bearing either electron-withdrawing electron-donating electron-rich (–OMe, –SMe, –NMe2) afforded arylated 3aa– 3ac, 86–93% contrast, containing groups (–Ph, CF3, –F, –Br, –COCH3) tended lower 3ae– 3ai, 52–90% Bromobenzene compatible, resulting isolation 3ad 87% ee. Cyano could tolerated, 3aj) 59% 97% meta-Substituted proceeded smoothly 3ak 3al) 85–95% ortho-substituted substrates 3am still acceptable (40% 2-Bromonaphthalene 3an 90% Substrates multisubstituted 3ao– 3ap, array hetero-aryl including benzothiophene, benzofuran, N-Ts indole, thiophene, furan motifs all tolerated 3aq– 3aw, 47–86% ee), well strongly coordinating partners 2-methyl-6-bromoquinoline 3ax, 2,6-dimethyl-4-bromopyridine 3ay, 80% Notably, configuration 3ax determined X-ray crystallographic diffraction Sp cyclic alkenyl giving 3az 40% dioxane. Scope Rh-Catalyzed C−H Atroposelective Aryl, Heteroaryl, Alkenyl Bromidesa aGeneral (0.04 (0.6 °C, h. product. Determined b4-Methoxyiodobenzene instead 2a. c4-Methoxychlorobenzene d[Rh(C2H4)2Cl]2 (10 mol%) (0.08 used. eDioxane solvent. Then examined 3). occurred 2-, 3-, 4-methyl 3ba– 3da, 91–96% 5-methyl sluggish, weak rhodium 3ea). 4-fluoro isoquinoline 3fa–3ga, 92–97% introducing substituent Cp ring tolerated. possessing methoxymethyl (MOM) iPr 3ha 3ia respectively. displays functional tolerance reflected fact sensitive 2-propenyl benzoyl, present 3ja 3ka, 82–91% Derivativesa Synthetic applications To further demonstrate potential utility reaction, carried out. Pleasingly, when [Rh], arylative 3ae 71% 98% 2h 3ah 63% Such unprecedented greatly improves its synthetic (Scheme 1a). Scheme Gram-scale reactions, transformations allylic reaction. Transformations 3ae. Application 4a Pd-catalyzed As demonstration method, various straightforward out prepare ligands, difficult access methods. illustrated 1b, converted ortho-lithiation subsequent electrophiles 4a–4d). bidentate P,N-ligand palladium-catalyzed (96% 1c). gain insights mechanism, preliminary experiments effect detected,65 suggesting more than one involved 2a). kinetic isotope only 1.23 (kH/kD) suggests 2b). Next, H/D exchange conditions. It deuterated 9% deuteration, 1a-[D] 21% deuteration after h 2c). occur absence Rh 37% observed recovered starting material performed CD3OD 2d). These competitive experiment 4-cyanobromobenzene 2j revealed electron-deficient reactive 2e). 31P analyses stoichiometric details) indicated preformed complexes do interact while signals appear 1a. studies. Nonlinear experiment. KIE parallel (d) (e) Competitive 2j. (f) Plausible pathways. On basis aforementioned precedent reports,57 plausible catalytic cycle proposed 2f, first coordinate N 1a, leads formation A. cyclometalation tbutoxide-assisted deprotonation intermediate B. oxidative B affords C species. reductive elimination 3aa. released Rh(I) coordinates another molecule generating species cycle. Another process involves ahead activation, then base-assisted metalation affording same cannot completely ruled stage. Additional necessary fully elucidate mechanism. Conclusions summary, developed mild processes take place levels efficiency. protocol provides concise enantiopure pyridines, offer platform designing catalysts. experiments, scrambling available. Conflict Interest authors declare no competing interest. Acknowledgments We thank National R&D Program China (2016YFA0202900), NSFC (21821002, 91856201), CAS (XDB20000000, QYZDY-SSW-SLH012) Science Technology Commission Municipality (18JC1411302) generous financial support. S.-L.Y. acknowledges support from Tencent Foundation XPLORER PRIZE. paper dedicated Professor Xue-Long Hou occasion his 65th birthday. References 1. Štěpnička P.Ferrocenes; Wiley-VCH: Weinheim, 2008. Google Scholar 2. Dai L.-X., X.-L.Chiral Asymmetric Catalysis; 2010. Schaarschmidt D.; Lang H.Selective Syntheses Planar-Chiral Ferrocenes.Organometallics2013, 32, 5668–5704. 4. L.-X.; Tu T.; S.-L.; Deng W.-P.; X.-L.Asymmetric Catalysis Ligands.Acc. Chem. Res.2003, 36, 659–667. 5. Arrayás R. G.; Adrio J.; Carretero J. C.Recent Applications Ligands Catalysis.Angew. Int. Ed.2006, 45, 7674–7715. 6. Fu G. C.Applications Heterocycles Catalysis.Acc. Res.2006, 39, 853–860. 7. Desimoni Faita Quadrelli P.Pyridine-2,6-bis(oxazolines), Helpful Catalysts.Chem. Rev.2003, 103, 3119–3154. 8. Yu J.-Q., Shi Z.C–H Activation. Topics Current Chemistry; Springer-Verlag: Heidelberg, 2010; Vol. 292. 9. Ding K., L.-X.Transition Metal-Catalyzed Functionalization: Synthetically Enabling Reactions Building Complexity. Chemistry-Breakthroughs Perspectives; 2012. 10. S.-L.Asymmetric Functionalization Bonds; RSC: Cambridge, 2015. 11. López L. A.; E.Recent Advances Bond Derivatives.Dalton Trans.2015, 44, 10128–10135. 12. Arae S.; Ogasawara M.Catalytic Transition-Metal Complexes.Tetrahedron Lett.2015, 56, 1751–1761. 13. Zhu D.-Y.; Chen P.; Xia J.-B.Synthesis Transition-Metal-Catalyzed Enantioselective Activation.ChemCatChem2016, 8, 68–73. 14. Gao D.-W.; Q.; Zheng C.; S.-L.Synthesis Direct Functionalization.Acc. Res.2017, 50, 351–365. 15. Yin S.-L.Enantioselective Pd(0)-Catalyzed Intramolecular Arylation.J. Am. Soc.2014, 136, 4841–4844. 16. R.; Huang Y.; Ma X.; Li B.; Kang Y.-B.; Z.Palladium-Catalyzed Functionalization/Cyclization Metallocenes: An Efficient Approach toward Metallocene Compounds.J. 4472–4475. 17. L.; Zhang A.-A.; Zhao R.-J.; F.; Meng T.-J.; Ishida N.; Murakami M.; W.-X.Asymmetric N-(2-Haloaryl)ferrocenecarboxamides.Org. Lett.2014, 16, 5336–5338. 18. Q.-W.; K.; L.-C.; Yue He W.Rhodium-Catalyzed Silylation Siloles.Angew. Ed.2015, 54, 6918–6921. 19. Shibata Shizuno Sasaki T.Enantioselective Benzosiloloferrocenes Silylation.Chem. Commun.2015, 51, 7802–7804. 20. Murai Matsumoto Takeuchi Takai K.Rhodium-Catalyzed Benzosilolometallocenes Dehydrogenative C(sp2)–H Bonds.Org. 17, 3102–3105. 21. Lu Ye Duan W.-L.Asymmetric Ferrocenes: Controlling Enantioselectivity Phosphoric Acids.Chin. Org. Chem.2016, 752–759. 22. Luo Xiong Z.; Q.Enantioselective Pyridoferrocenes Palladium-Catalyzed Imidoylative Cyclization Reactions.Org. Lett.2018, 20, 1837–1840. 23. W.-T.; Z.-Q.; H.; Xue X.-S.; D.Rhodium-Catalyzed 2-Arylphenol-Derived Six-Membered Silacyclization: Straightforward Access Dibenzooxasilines Silicon-Containing Metallocenes.ACS Catal.2018, 7997–8005. 24. Xu B.-B.; Yuan W.-L.Palladium-Catalyzed Benzothiophene-Fused Ferrocenes.ACS 11735–11740. 25. Y.-C.; Z.-L.; Coupling Arylboronic Acids.J. Soc.2013, 135, 86–89. 26. Pi Cui X.-L.; Han Y.-J.Redox Controlled Heck Dual Activation.Chem. Sci.2013, 4, 2675–2679. 27. X.-Y.; Guo M. H.-Y.; Y.-J.Synthesis Derivatives Chirality Activation.Org. 5164–5167. 28. S.-L.An Oxidative C–H/C–H Cross-Coupling Reaction: Highly Method Prepare Ferrocenes.J. Soc.2016, 138, 2544–2547. 29. Z.-J.; C.-X.; S.-L.Pd(II)-Catalyzed Regio- Azoles.Angew. Ed.2019, 58, 2149–2153. 30. Jin Ferrocenyl Ketones Enabled Transient Directing Group.Chem. Commun.2018, 689–692. 31. Kong W.-J.; Shao M.-H.; Zhou H.-X.; J.-Q.Copper-Mediated Diastereoselective Thiolation Ferrocenes.Organometallics2018, 37, 2832–2836. 32. S.-L.Thioketone-Directed Rhodium(I) Catalyzed Ferrocenes.Nature Commun.2019, 10, 4168. 33. Kasahara Izumi Maemura M.The σ-Bonded Palladium(II) Complex 2-Pyridylferrocene.Bull. Soc. Jpn.1977, 1878–1880. 34. Takebayashi T.[Ir(cod)2]BARF-Catalyzed Alkenylation Alkylation Ferrocenes.Organometallics.2012, 31, 4114–4117. 35. Schmiel Gathy Butenschön H.Cp*Co(CO)I2 Catalyst Ortho-C,H Activation Ferrocene: ODG-Dependent Preference 2-Mono- 2,5-Dialkenylation.Organometallics2018, 2095–2110. 36. S.-B.; S.-L.Rhodium(III)-Catalyzed Alkynylation Hypervalent Iodine Reagents.J. Chem.2017, 82, 11829–11835. 37. T.Iridium-Catalyzed Alkenes Diene Ligands.Angew. Ed.2014, 53, 5410–5413. 38. Ackermann Vicente Kapdi R.Transition-Metal-Catalyzed (Hetero)Arenes Cleavage.Angew. Ed.2009, 48, 9792–9826. 39. Oi Fukita Inoue Y.Rhodium-Catalysed ortho 2-Arylpyridines Arylstannanes Commun.1998, 2439–2440. 40. Bedford Coles S. Hursthouse Limmert E.The Catalytic Intermolecular Orthoarylation Phenols.Angew. Ed.2003, 42, 112–114. 41. Lewis Wiedemann Bergman Ellman A.Arylation Rhodium-Catalyzed Functionalization.Org. Lett.2004, 6, 35–38. 42. Yanagisawa Sudo Noyori Itami K.Direct Aryl Iodides Rhodium Catalysis.J. Soc.2006, 128, 11748–11749. 43. Berman A.Rh(I)-Catalyzed Activation: Expanded Insight.J. Soc.2008, 130, 2493–2500. 44. Z.Rhodium-Catalyzed Regioselective Decarbonylation Acid Chlorides Phosphine-Free Conditions.J. 8136–8137. 45. Vogler Studer A.Oxidative Acids Arenes Arylation.Org. Lett.2008, 129–131. 46. Miyamura Tsurugi Satoh Miura M.Rhodium-Catalyzed Phenylazoles Related Compounds Arylboron Reagents Cleavage.J. Organomet. Chem.2008, 693, 2438–2442. 47. Shuai Yang Baslé O.; C.-J.Rhodium-Catalyzed 2-Arylpyridine Aromatic Aldehydes.J. Soc.2010, 132, 12212–12213. 48. Pan Lei Sun Z.-J.Rhodium(I)-Catalyzed Redox-Economic Carboxylic Directed N-Containing Groups.Angew. Ed.2013, 52, 2063–2067. 49. J.-F.; R.-H.; Y.-X.; Yao W.-W.; Q.-S.; M.Ligand-Accelerated BINOL: Rapid One-Step Racemic 3,3′-Diaryl BINOLs.Angew. Ed.2016, 55, 14116–14120. 50. Kim Greßies Boultadakis-Arapinis Daniliuc F.Rh(I)/NHC*-Catalyzed Site- C(sp3)–H Bonds Toward Triarylmethanes.ACS Catal.2016, 7652–7656. 51. Tobisu Yasui Aihara Chatani N.C–O Bis(N-Heterocyclic Carbene) Catalyst: Carbamates Arylating Arylation.Angew. Ed.2017, 1877–1880. 52. Qiu Z.Rhodium(I)-Catalyzed Tertiary Phosphine Arylation: Construction Libraries.Angew. 7233–7237. 53. G.-R.; Szostak M.Site-Selective C–H/C–N Cooperative Catalysis: Primary Amides Arylation.ACS Catal.2017, 7, 7251–7256. 54. Z.Rhodium-Catalyzed, P-Directed Selective C7 Indoles.Sci. Adv.2018, eaau6468. 55. Gressies Klauck F. C. F.Ligand-Enabled Csp3–H Tetrahydroquinolines Saturated Aza-Heterocycles RhI.Angew. Ed.2018, 57, 9950–9954. 56. Z.PIII-Chelation-Assisted Indole C7-Arylation, Olefination, Methylation, Acylation Acids/Anhydrides 1504–1508. 57. C.-D.; Y.-Z.; G.-A.; Che C.-M.Synthesis peri-Substituted (Naphthalen-1-yl)Phosphine Rhodium(I)-Catalyzed Phosphine-Directed 1810–1814. 58. S.-L.Rhodium-Catalyzed Axially Heterobiaryls.J. Soc.2019, 141, 9504–9510. 59. Sakaki Schweizer W. Seebach D.Catalytic Hydrosilylation Complexes TADDOL-Derived Cyclic Phosphonites Phosphites.Helv. Chim. Acta1993, 76, 2654–2665. 60. Beck Heckel A.TADDOLs, Their Derivatives, TADDOL Analogues: Versatile Auxiliaries.Angew. Ed.2001, 40, 92–138. 61. L.Phosphoramidites: Marvellous Conjugate Addition.Acc. Res.2000, 33, 346–353. 62. Teichert Privileged Ed.2010, 49, 2486–2528. 63. G.-H.; Xie J.-H.; Xing Q.-L.Synthesis Monodentate Electronic Effect Hydrogenation.J. Chem.2004, 69, 8157–8160. 64. Q.-L.Chiral Diphosphine Phosphorus Scaffold Reactions.Acc. Res.2008, 41, 581–593. 65. Girard Kagan H. B.Nonlinear Effects Stereoselective Reactions: Ten Years Investigation.Angew. Ed. Engl.1998, 2922–2959. articleNext article FiguresReferencesRelatedDetails Issue AssignmentVolume 2Issue 6Page: 642-651Supporting Copyright & Permissions© 2020 Chemical SocietyKeywordsferroceneC–H arylationpyridineplanar chiralityasymmetric catalysisAcknowledgmentsWe Downloaded 1,974 times Loading ...

Language: Английский