Construction of Planar Chiral Ferrocenes by Cobalt-Catalyzed Enantioselective C–H Acyloxylation Enabled by Dual Ligands

Open AccessCCS ChemistryRESEARCH ARTICLES22 Mar 2024Construction of Planar Chiral Ferrocenes by Cobalt-Catalyzed Enantioselective C–H Acyloxylation Enabled by Dual Ligands Fan-Rui Huang, Peng Zhang, Qi-Jun Yao and Bing-Feng Shi Fan-Rui Huang Center of Chemistry for Frontier Technologies, Department of Chemistry, Zhejiang University, Hangzhou 310027 , Peng Zhang Center of Chemistry for Frontier Technologies, Department of Chemistry, Zhejiang University, Hangzhou 310027 , Qi-Jun Yao *Corresponding authors: E-mail Address: email protected E-mail Address: email protected Center of Chemistry for Frontier Technologies, Department of Chemistry, Zhejiang University, Hangzhou 310027 and Bing-Feng Shi *Corresponding authors: E-mail Address: email protected E-mail Address: email protected Center of Chemistry for Frontier Technologies, Department of Chemistry, Zhejiang University, Hangzhou 310027 College of Material, Chemistry and Chemical Engineering, Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Hangzhou Normal University, Hangzhou 311121 https://doi.org/10.31635/ccschem.024.202303709 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Oxy-substituted planar chiral ferrocenes are of great importance in asymmetric synthesis and pharmaceuticals. However, enantioselective C–H activation of ferrocenes that form C–O bonds remains a huge challenge and has not yet been reported. Herein, the asymmetric synthesis of oxy-substituted planar chiral ferrocenes is achieved by cobalt-catalyzed enantioselective dehydrogenative C–H acyloxylation. The use of a dual-ligand system consisting of a chiral salicyloxazoline (Salox) ligand and a neutral phosphine oxide ligand, which is oxidized in situ from the corresponding phosphine, resulted in good yield (up to 83%) and excellent enantioselectivity (90–99% ee). The utility of this unprecedented protocol is highlighted by its versatile synthetic transformations. Download figure Download PowerPoint Introduction Planar chiral ferrocenes are privileged skeletons for chiral ligands and catalysts in asymmetric synthesis,1–9 and they are widely applied in materials science,10,11 pharmaceuticals,12–14 and industrial production.15,16 Therefore, extensive efforts have been devoted to the efficient synthesis of planar chiral ferrocenes.1,4 Among many existing strategies, transition-metal-catalyzed enantioselective C–H activation17–26 has emerged as an efficient strategy for the generation of planar chiral ferrocenes.27–31 In a seminal study in 1997, Siegel and Schmalz32 demonstrated a copper-catalyzed intramolecular enantioselective carbene insertion into C–H bonds of ferrocene with up to 78% ee. The major breakthroughs were made in 2013 by the groups of You33 and Wu.34 They independently realized the Pd(II)-catalyzed enantioselective C–H functionalization of dialkylaminomethylferrocenes using N-monoprotected amino acids (MPAA) as chiral ligands, affording the desired chiral ferrocenes with up to 99% ee. Inspired by these pioneering works, significant advances have been achieved in the design and synthesis of planar chiral ferrocenes through asymmetric C–H activation strategy.27–31,35–51 Despite these significant advances and applications, these methodologies generally rely on the use of precious 4d and 5d transition metal catalysts (such as Pd,35–41 Ir,42,43 Rh,44–47 Pt,48 and Au49,50) and half-sandwich chiral rare-earth catalysts,51 while sustainable synthetic approaches based on inexpensive and less toxic earth-abundant 3d metals remain underdeveloped.52–58 As a result, the development of new catalysts based on more sustainable and earth-abundant 3d metals for the asymmetric synthesis of chiral ferrocenes is highly desirable. Recently, oxy-substituted chiral ferrocenes have been found to possess unique properties and application in asymmetric catalysis and biomedical research (Scheme 1a).59–62 Traditionally, the preparation of such compounds has involved multistep sequences, including installation of chiral auxiliaries, diastereoselective ortho-C–H lithiation/iodination, Ullman coupling, or SNAr substitution, followed by removal of chiral auxiliaries (Scheme 1b).60–62 We envisioned that the enantioselective dehydrogenative C-H acyloxylation reaction of prochiral ferrocenes with simple carboxylic acids would be a more straightforward and atom-economic approach to the preparation of oxygen-substituted chiral ferrocenes. However, this process would be extremely challenging due to the competitive coordination of the large excess of carboxylate anions63 and the oxidative lability of the resulting electron-rich ferrocenes.64 Our longstanding interest in cobalt-catalyzed enantioselective C–H activation reactions motivated us to address this challenge.65–86 We speculated that the cobalt/salicyloxazoline (Salox) catalysis65–76 might fulfill the goal, because: (1) Salox coordinates permanently with cobalt catalyst which outcompetes the interference of carboxylate anions;65 and (2) the coordination of Salox reduces the oxidation potential for the oxidation of Co(II) to Co(III).70 Herein, we report the successful establishment of planar chirality in oxy-substituted ferrocenes through cobalt-catalyzed enantioselective C–H acyloxylation enabled by a dual-ligand system. The target chiral ferrocenes were prepared in moderate to good yields with excellent enantioselectivities (Scheme 1c). Scheme 1 | The importance and synthesis of oxy-substituted chiral ferrocenes. Download figure Download PowerPoint Experimental Methods General procedure for enantioseletive cobalt/Salox-catalyzed C–H acyloxylation with aromatic carboxylic acids (Conditions A) To an oven-dried vial equipped with stirring bar, ferrocenecarboxamide 1 (0.1 mmol), aromatic carboxylic acid 2 (0.1 mmol), Co(SCN)2 (10 mol %), (R)- L5 (15 mol %), Ag2CO3 (0.2 mmol), Na2CO3 (0.2 mmol), PCy3•HBF4 (10 mol %), and dichloromethane (DCM; 1.0 M, 1.0 mL) were added. The vial was instantly placed in a heating block set at 70 °C for 24 h. The reaction mixture was then cooled to room temperature. The resulting mixture was filtered through a celite pad and concentrated in vacuo. The residue was purified by preparative thin-layer chromatography (TLC) using petroleum ether (PE)/DCM/EtOAc as the eluent to afford the product 3 ( 3aa–3az, 3bh–3fh). General procedure for enantioseletive cobalt/Salox-catalyzed C–H acyloxylation with sodium carboxylates (Conditions B) To an oven-dried vial equipped with stirring bar, N-(quinolin-8-yl)ferrocene-1-carboxamide 1a (0.1 mmol), sodium carboxylates 2 (0.1 mmol), Co(SCN)2 (10 mol %), (S)- L6 (15 mol %), Ag2CO3 (0.2 mmol), PCy3•HBF4 (10 mol %), and DCM (1.0 M, 1.0 mL) were added. The vial was instantly placed in a heating block set at 90 °C for 12 h. The reaction mixture was then cooled to room temperature. The resulting mixture was filtered through a celite pad and concentrated in vacuo. The residue was purified by preparative TLC using PE/DCM/EtOAc as the eluent to afford the product 3 ( 3aaa–3aee). More experimental details and characterization are available in the Supporting Information. Results and Discussion Reaction optimization We began our investigation by using N-(quinolin-8-yl)ferrocene-1-carboxamide ( 1a) as the model substrate,87–89 and enantioselective C–H acyloxylation with 1.0 equiv of benzoic acid ( 2a) was selected as the model reaction since the ester group of product can be easily converted into other important functional groups. Initially, Salox L1 was chosen as the chiral ligand, and the reaction of 1a was performed in the presence of 2.0 equiv of Ag2CO3 and 2.0 equiv of Na2CO3. Various reaction parameters were investigated to optimize the conditions (see Supporting Information Tables S1 and S2). To our delight, the desired acyloxylation product 3aa was formed in 50% yield with 82% ee using 10 mol % Co(SCN)2 as catalyst in DCM under air at 90 °C (entry 9 in Supporting Information Table S2). Previously, we found that the addition of external neutral ligand promoted the asymmetric self-assembly coordination around Co(III) center and led to superior reactivity and selectivity.65,70 In addition, because dual-ligand catalyst has found broad application in controlling reactivity and selectivity in C–H activation reactions,90–95 we then pursued the synergic effect of dual ligands. To our delight, the combination of Salox and 10 mol % tricyclohexylphosphine tetrafluroborate (PCy3•HBF4) significantly improved the enantioselectivity (see Supporting Information Tables S3 and S8, 96% ee). Lowering the temperature from 90 to 70 °C and prolonging reaction time to 24 h improved the yield from 48% to 56%. We next performed a systematic evaluation of structurally modified Salox ligands (Scheme 2). When Salox L5 with bromo substituted at para-position of phenol group, 3aa was obtained in 72% yield with 96% ee. Salox ligands bearing the electron-donating group at the para-position ( L6: p-OMe) or bulky substituents at the ortho-position ( L7: o-Br; L8: o-Me; L9: o-t-Bu) of phenol group resulted in reduced yields despite excellent enantioselectivities. Switching the residue of oxazoline in L5 to i-Pr ( L10), Cyclohexyl ( L11), and t-Bu ( L12) led to dramatically reduced reactivity and enantioselectivity. Salox ligand is crucial for the reaction, and no product was observed in the absence of Salox ligand. In addition, kinetic experiments indicated that PCy3•HBF4 significantly accelerated the reaction ( Supporting Information Figure S1). Finally, no desired product was observed when other commonly used bidentate directing groups, such as oxazoline-aniline ( 1h),96 2-pyridinylisopropyl ( 1i),97 and 2-aminopyridine-1-oxide ( 1j),98 were used ( Supporting Information Table S9). Scheme 2 | Optimization of Salox ligands. Reaction conditions: 1a (0.1 mmol), 2a (1.0 equiv), Co(SCN)2 (10 mol %), Ligand (15 mol %), PCy3•HBF4 (10 mol %), Ag2CO3 (2.0 equiv), Na2CO3 (2.0 equiv), DCM (1.0 mL), 70 °C, Air, 24 h. Isolated yield. The ee value was determined by chiral high performance liquid chromatography (HPLC). Download figure Download PowerPoint Evaluation of substrate scope The scope of acids was then evaluated under optimized reaction conditions (Scheme 3a, Conditions A). Aromatic acids bearing a methyl group at the 2-, 3-, and 4-positions were well tolerated, giving the corresponding planar chiral products 3ab– 3ad in moderate to good yields with excellent enantioselectivity (96–99% ee). A variety of aromatic acids bearing electron-rich groups such as methoxy, phenyloxy, and t-Bu at the meta- and para-positions were also investigated. In general, all the desired products 3ae– 3ah were obtained successfully (53–83% yield, 95–99% ee). The reaction of aromatic acids bearing electron-withdrawing groups, including fluoro, chloro, bromo, cyano, formyl, and ester, gave slightly lower yields (35–55%), however with excellent stereochemical control (94–99% ee). 2-Naphthoic acid ( 2p) delivered the desired product 3ap in 75% yield with excellent ee (97%). Notably, heteroaromatic acids, such as pyridine ( 2q), quinoline ( 2r), indole ( 2s), furan ( 2t), and thiophene ( 2u), also reacted and did not lead to deleterious effects on reactivity and enantioselectivity ( 3aq–3au, 48–72% yield, 96–97% ee). The absolute configuration of 3al (Cambridge Crystallographic Data Centre (CCDC) 2295994) and 3ar (CCDC 2295995) were assigned by X-ray diffraction analysis. Moreover, the efficiency of this protocol was further tested with pharmaceutical molecules ( 2v: PTC124; 2w: flavoxate) and food additives ( 2x: piperonylic acid; 2y: sorbic acid; and 2z: cinnamic acid), and the late-stage functionalization reactions furnished the oxy-substituted chiral ferrocenes with excellent enantioselectivity (90–98% ee). As shown in Scheme 3b, a variety of ferrocenecarboxamides bearing alkyl groups ( 1b: ethyl; 1c: benzyl; 1d: 2-phenyl-1-ethyl; and 1e: isopropyl) on the other cyclopentadienyl (Cp) ring were quite compatible. It should be noted that introducing a prop-1-en-2-yl on the other Cp ring largely retarded the reactivity, leading to 3fh in only 25% isolated yield with 98% ee. Furthermore, reaction with 1g-bearing acetyl substituent failed to provide the expected product. Scheme 3 | Reaction scope of aromatic acids and ferrocenecarboxamides. Conditions A: 1a–g (0.1 mmol), 2b–z (1.0 equiv), Co(SCN)2 (10 mol %), (R)-L5 (15 mol %), Ag2CO3 (2.0 equiv), Na2CO3 (2.0 equiv), DCM (1.0 mL), 70 °C, under air, 24 h. Isolated yield. The ee value was determined by chiral HPLC. aDCM (1.5 mL). Download figure Download PowerPoint The compability of aliphatic carboxylic acids was then investigated. We were delighted to find that the enantioselective C–H acyloxylation could be expanded to aliphatic carboxylic acids when sodium carboxylates were used as the coupling partners and (S)- L6 was used as the chiral ligand (Scheme 4, Conditions B; see Supporting Information Table S10 for details). Various sodium carboxylates generated from aliphatic carboxylic acids, such as acetic acid, propionic acid, butyric acid, 4-methylphenylacetic acid, and oleic acid, were well tolerated, delivering the acyloxylated planar chiral ferrocenes 3aaa– 3aee in moderate yields (41–68% yield) with excellent enantioselectivities (92–97% ee). Scheme 4 | Reaction scope of aliphatic carboxylic acids. Conditions B: 1a (0.1 mmol), 2aa–ee (1.0 equiv), Co(SCN)2 (10 mol %), (S)-L6 (15 mol %), Ag2CO3 (2.0 equiv), DCM (1.0 mL), 90 °C, under air, 12 h. Isolated yield. The ee value was determined by chiral HPLC. Download figure Download PowerPoint Mechanistic insight In order to shed light on the mechanism of this reaction, control experiments were performed (Scheme 5a). When 1a was subjected to the standard conditions without PCy3•HBF4, a significant loss of yield and enantioselectivity was observed (entry 2, 32%, 80% ee). Replacing PCy3•HBF4 with NaBF4 also gave dramatically decreased yield and enantioselectivity (entry 3). However, the use of tricyclohexyl phosphine oxide (O=PCy3) as the neutral ligand resulted in a comparable enantioselectivity (entry 4). Based on these results, we speculated that PCy3•HBF4 was oxidized to O=PCy3 under the basic aerobic conditions, which might act as the actual neutral ligand. O=PCy3 was proposed to facilitate the formation of the coordination environment with L5 and substrate 1a around the cobalt center during the C–H activation process (Scheme 5d, Int-2 and Int-3). To gain further mechanistic insights during the C–H activation process, deuterium-labeling studies were performed (Scheme 5b). The ortho-deuterated substrate 1a-d2 was subjected to the standard reaction conditions without 2a, and the 1a-d2 was recovered without any loss of deuterium. In contrast with the enantioselective C–H acyloxylation of 1a-d2, the ratio of deuterium at the ortho site in unreacted substrate 1a-d2 decreased to 80%, and notably the corresponding product 3aa-d was isolated without significant de-deuterium at the ortho position (Scheme 5b, entry 5). These observations illustrate three notable features of the C–H activation process: (1) the C–H activation is reversible; (2) C–H activation serves as the enantio-determining step; and (3) the benzoic acid is crucial for C–H activation through concerted metalation deprotonation.89 Neither deuterium incorporation of 1a-d2nor corresponding product 3aa-d was observed in the absence of Ag2CO3, suggesting that the oxidation process was required for the in situ generation of trivalent cobalt catalysts for C–H activation (entry 6). Moreover, as shown in entry 7, the enantioselectivity of the C–H acyloxylation of 1a-d2 dramatically decreased without Na2CO3, which further suggests that PCy3•HBF4 is crucial for stereocontrol, since the O=PCy3 was generated by the neutralization of PCy3•HBF4 with base followed by oxidation. On the other hand, kinetic isotope effect (KIE) experiments were conducted through intermolecular competition reactions under standard conditions for 3 h, and the KIE value was determined to be 1.27, which indicates that the enantioselective C–H cleavage might not be involved in the rate-determining step (Scheme 5c).99 Scheme 5 | Mechanistic studies. CMD, concerted metalation deprotonation. Download figure Download PowerPoint Based on the preliminary mechanistic investigations and previous results,65,66,70 a plausible mechanistic pathway was proposed (Scheme 5d). The coordination of Co(II) precatalyst with (R)- L5, followed by in situ oxidation gave chiral octahedral cobalt(III) catalyst Int-1. The π–π stacking interaction between the quinolyl moiety of 1a and the phenyl group of chiral oxazoline in L5 facilitated the asymmetric self-assembly to form Int-2, which can be suitably stabilized by in situ generated O=PCy3 by the coordination as a neutral ligand and thereby improve its efficiency. Subsequent C–H activation of Int-2 afforded the cobaltacycle Int-3, which was oxidized to high-valent Co(IV) complex Int-4 with the simultaneous ligand exchange of O=PCy3 with benzoate. Reductive elimination delivered the desired product (Sp)- 3aa and liberated the cobalt(II) species, which was oxidized to Int-1 and completed the cycle. We suggested that Int-2 is more favorable than intermediate Int-2′ to avoid the steric repulsion between the ferrocene skeleton and Salox ligand, which is quite consistent with the predominant formation of (Sp)-configuration products experimentally (Scheme 5e). Synthetic transformation As an extension, we demonstrated the synthetic utility of this strategy (Scheme 6). The gram-scale reaction between 1a (2.14 g, 6.0 mmol) and 2h (6.0 mmol) proceeded in the presence of 4 Å molecular sieve under the standard conditions for 60 h, delivering the desired product 3ah (2.27 g) in 71% yield with 98% ee. 3ah underwent hydrolysis reaction followed by Williamson ether synthesis with 2-(bromomethyl)naphthalene and iodoethane respectively, generating the corresponding chiral ferrocenyl alkyl ethers 4 and 6 in excellent yields (95% and 99%) without the erosion of enantiopurity. The directing group of compound 4 was readily removed to give ester 5 in 70% yield with 90% ee. A ferrum/iridium bimetallic complex 7 was prepared in 72% yield by the stoichiometric reaction of Cp*IrCl22 with ferrocene 6. O-Triflation of 3ah gave 8 in 78% yield with 95% ee, and the OTf group is a promising handle for further transformations. Furthermore, a sequence hydrolysis followed by SNAr substitution led to the formation of chiral ferrocene 9 in 70% yield with 94% ee. Scheme 6 | Gram-scale synthesis and synthetic transformations of product. (a) NaOH, EtOH −10 °C, N2; then 2-(bromomethyl)naphthalene. (b) LiHMDS, Boc2O, tetrahydrofuran; then LiOH, H2O2; then K2CO3, MeI. (c) NaOH, EtOH, −10 °C, N2; then iodoethane. (d) Cp*IrCl22, Na2CO3, DCM. (e) NaOH, EtOH −10 °C, N2; then N,N-bis(trifluoromethylsulfonyl)aniline. (f) NaOMe, 5-cyano-2-fluoropyridine, dimethylformamide, 50 °C. Cp* = pentamethylcyclopentadienyl. Download figure Download PowerPoint Conclusion In conclusion, the asymmetric synthesis of oxy-substituted planar chiral ferrocenes was achieved by cobalt-catalyzed enantioselective dehydrogenative C–H acyloxylation. The reaction proceeds with good yield with excellent enantioselectivity, enabled by the Salox/phosphine oxide dual-ligand catalyst. We anticipate that this protocol can boost the asymmetric synthesis of planar chiral ferrocenes by 3d-metal-catalyzed enantioselective C–H functionalization. Supporting Information Supporting Information is available and includes the experimental procedures and characterization of the compounds. All data supporting the findings of this study are available within this article and its Supporting Information. CCDC 2295994 ( 3al), CCDC 2295995 ( 3ar), and CCDC 2295996 ( 4) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint CCDC and Fachinformationszentrum Karlsruhe Access Structures service. Conflict of Interest There is no conflict of interest to report. Funding Information This work was supported by the National Key R Hayashi T.Ferrocenes: Homogeneous Catalysis, Organic Synthesis, Materials Science; Wiley-VCH: Weinheim, Germany, 1995. Google Scholar 2. Dai L.-X.; Hou X.-L.Chiral Ferrocenes in Asymmetric Catalysis; Wiley-VCH: Weinheim, Germany, 2010. Google Scholar 3. Hayashi T.; Kumada M.Asymmetric Synthesis Catalyzed by Transition-Metal Complexes with Functionalized Chiral Ferrocenylphosphine Ligands.Acc. Chem. Res.1982, 15, 395–401. Google Scholar 4. Togni A.Planar-Chiral Ferrocenes: Synthetic Methods and Applications.Angew. Chem. Int. Ed.1996, 35, 1475–1477. Google Scholar 5. Fu G. C.Enantioselective Nucleophilic Catalysis with "Planar-Chiral" Heterocycles.Acc. Chem. Res.2000, 33, 412–420. Google Scholar 6. Dai L.-X.; Tu T.; You S.-L.; Deng W.-P.; Hou X.-L.Asymmetric Catalysis with Chiral Ferrocene Ligands.Acc. Chem. Res.2003, 36, 659–667. Google Scholar 7. Fu G. C.Applications of Planar-Chiral Heterocycles as Ligands in Asymmetric Catalysis.Acc. Chem. Res.2006, 39, 853–860. Google Scholar 8. Štěpnička P.Forever Young: The First Seventy Years of Ferrocene.Dalton Trans.2022, 51, 8085–8102. Google Scholar 9. Laws D.; Poff C. D.; Heyboer E. M.; Blakey S. B.Synthesis, Stereochemical Assignment, and Enantioselective Catalytic Activity of Late Transition Metal Planar Chiral Complexes.Chem. Soc. Rev.2023, 52, 6003–6030. Google Scholar 10. Pietschnig R.Polymers with Pendant Ferrocenes.Chem. Soc. Rev.2016, 45, 5216–5231. Google Scholar 11. Muraoka T.; Kinbara K.; Aida T.Mechanical Twisting of a Guest by a Photoresponsive Host.Nature2006, 440, 512–515. Google Scholar 12. van Staveren D. R.; Metzler-Nolte N.Bioorganometallic Chemistry of Ferrocene.Chem. Rev.2004, 104, 5931–5986. Google Scholar 13. Jaouen G.; Vessiéres A.; Top S.Ferrocifen Type Anti Cancer Drugs.Chem. Soc. Rev.2015, 44, 8802–8817. Google Scholar 14. Patra M.; Gasser G.The Medicinal Chemistry of Ferrocene and Its Derivatives.Nat. Rev. Chem.2017, 1, 0066. Google Scholar 15. Blaser H.-U.; Brieden W.; Pugin B.; Spindler F.; Studer M.; Togni A.Solvias Josiphos Ligands: From Discovery to Technical Applications.Top. Catal.2002, 19, 3–16. Google Scholar 16. Blaser H.-U.; Pugin B.; Spindler F.Progress in Enantioselective Catalysis Assessed from an Industrial Point of View.J. Mol. Catal. A: Chem.2005, 231, 1–20. Google Scholar 17. Giri R.; Shi B.-F.; Engle K. M.; Maugel N.; Yu J.-Q.Transition Metal-Catalyzed C–H Activation Reactions: Diastereoselectivity and Enantioselectivity.Chem. Soc. Rev.2009, 38, 3242–3272. Google Scholar 18. You S.-L.Asymmetric Functionalization of C–H Bonds; RSC: Cambridge, UK, 2015. Google Scholar 19. Newton C. G.; Wang S.-G.; Oliveira C. C.; Cramer N.Catalytic Enantioselective Transformations Involving C–H Bond Cleavage by Transition-Metal Complexes.Chem. Rev.2017, 117, 8908–8976. Google Scholar 20. Saint-Denis T. G.; Zhu R.-Y.; Chen G.; Wu Q.-F.; Yu J.-Q.Enantioselective C(sp3)-H Bond Activation by Chiral Transition Metal Catalysts.Science2018, 359, eaao4798. Google Scholar 21. Wencel-Delord J.; Colobert F.Asymmetric C(sp2)–H Activation.Chem. Eur. J.2013, 19, 14010–14017. Google Scholar 22. Liao G.; Zhang T.; Liu Z.-K.; Shi B.-F.Transition Metal-Catalyzed Enantioselective C–H Functionalization via Chiral Transient Directing Group Strategies.Angew. Chem. Int. Ed.2020, 59, 19773–19786. Google Scholar 23. Achar T.; Maiti S.; Jana S.; Maiti D.Transition Metal Catalyzed Enantioselective C(sp2)–H Bond Functionalization.ACS Catal.2020, 10, 13748–13793. Google Scholar 24. Yoshino T.; Satake S.; Matsunaga S.Diverse Approaches for Enantioselective C–H Functionalization Reactions Using Group 9 CpxMIII Catalysts.Chem. Eur. J.2020, 26, 7346–7357. Google Scholar 25. Vyhivskyi O.; Kudashev A.; Miyakoshi T.; Baudoin O.Chiral Catalysts for Pd0-Catalyzed Enantioselective C–H Activation.Chem. Eur. J.2021, 27, 1231–1257. Google Scholar 26. Liang H.; Wang J.Enantioselective C–H Bond Functionalization Involving Arene Ruthenium(II) Catalysis.Chem. Eur. J.2023, 29, e202202461. Google Scholar 27. López L. A.; López E.Recent Advances in Transition Metal-Catalyzed C–H Bond Functionalization of Ferrocene Derivatives.Dalton Trans.2015, 44, 10128–10135. Google Scholar 28. Zhu D.-Y.; Chen P.; Xia J.-B.Synthesis of Planar Chiral Ferrocenes by Transition-Metal-Catalyzed Enantioselective C–H Activation.ChemCatChem2016, 8, 68–73. Google Scholar 29. Gao D.-W.; Gu Q.; Zheng C.; You S.-L.Synthesis of Planar Chiral Ferrocenes via Transition-Metal-Catalyzed Direct C–H Bond Functionalization.Acc. Chem. Res.2017, 50, 351–365. Google Scholar 30. Liu C.-X.; Gu Q.; You S.-L.Asymmetric C–H Bond Functionalization of Ferrocenes: New Opportunities and Challenges.Trends Chem.2020, 2, 737–749. Crossref, Google Scholar 31. Zhang Z.-Z.; Huang D.-Y.; Shi B.-F.Recent Advances in the Synthesis of Ferrocene Derivatives via 3d Transition Metal-Catalyzed C–H Functionalization.Org. Biomol. Chem.2022, 20, 4061–4073. Crossref, Google Scholar 32. Siegel S.; Schmalz H.-G.Insertion of Carbenoids into Cp–H Bonds of Ferrocenes: An Enantioselective-Catalytic Entry to Planar-Chiral Ferrocenes.Angew. Chem. Int. Ed. Engl.1997, 36, 2456–2458. Google Scholar 33. Gao D.-W.; Shi Y.-C.; Gu Q.; Zhao Z.-L.; You S.-L.Enantioselective Synthesis of Planar Chiral Ferrocenes via Palladium-Catalyzed Direct Coupling with Arylboronic Acids.J. Am. Chem. Soc.2013, 135, 86–89. Google Scholar 34. Pi C.; Li Y.; Cui X.; Zhang H.; Han Y.; Wu Y.Redox of Ferrocene Controlled Asymmetric Dehydrogenative Heck Reaction via Palladium-Catalyzed Dual C–H Bond Activation.Chem. Sci.2013, 4, 2675–2679. Google Scholar 35. Gao D.-W.; Yin Q.; Gu Q.; You S.-L.Enantioselective Synthesis of Planar Chiral Ferrocenes via Pd(0)-Catalyzed Intramolecular Direct C–H Bond Arylation.J. Am. Chem. Soc.2014, 136, 4841–4844. Google Scholar 36. Deng R.; Huang Y., Ma X., Li G.; Zhu R.; Wang B.; Kang Y.-B.; Gu Z.Palladium-Catalyzed Intramolecular Asymmetric C–H Functionalization/Cyclization Reaction of Metallocenes: An Efficient Approach Toward the Synthesis of Planar Chiral Metallocene Compounds.J. Am. Chem. Soc.2014, 136, 4472–4475. Google Scholar 37. Pi C.; Cui X.; Liu X.; Guo M.; Zhang H.; Wu Y.Synthesis of Ferrocene Derivatives with Planar Chirality via Palladium-Catalyzed Enantioselective C–H Bond Activation.Org. Lett.2014, 16, 5164–5167. Google Scholar 38. Gao D.-W.; Gu Q.; You S.-L.An Enantioselective Oxidative C–H/C–H Cross-Coupling Reaction: Highly Efficient Method to Prepare Planar Chiral Ferrocenes.J. Am. Chem. Soc.2016, 138, 2544–2547. Google Scholar 39. Zhang S.; Lu J.; Ye J.; Duan W.-L.Asymmetric C-H Arylation for the Synthesis of Planar Chiral Ferrocenes: Controlling Enantioselectivity Using Chiral Phosphoric Acids.Chin. J. Org. Chem.2016, 36, 752–759. Google Scholar 40. Xu J.; Liu Y.; Zhang J.; Xu X.; Jin Z.Palladium-Catalyzed Enantioselective C(sp2)–H Arylation of Ferrocenyl Ketones Enabled by a Chiral Transient Directing Group.Chem. Commun.2018, 54, 689–692. Google Scholar 41. Zhou L.; Cheng H.-G.; Li L.; Wu K.; Hou J.; Jiao C.; Deng S.; Li Z.; Yu J.-Q.; Zhou Q.Synthesis of Planar Chiral Ferrocenes via Enantioselective Remote C–H Activation.Nat. Chem.2023, 15, 815–823. Google Scholar 42. Shibata T.; Shizuno T.Iridium-Catalyzed Enantioselective C–H Alkylation of Ferrocenes with Alkenes Using Chiral Diene Ligands.Angew. Chem. Int. Ed.2014, 53, 5410–5413. Google Scholar 43. Liu L.; Song H.; Liu Y.-H.; Wu L.-S.; Shi B.-F.Achiral CpxIr(III)/Chiral Carboxylic Acid Catalyzed Enantioselective C–H Amidation of Ferrocenes under Mild Conditions.ACS Catal.2020, 10, 7117–7122. Google Scholar 44. Murai M.; Matsumoto K.; Takeuchi Y.; Takai K.; Rhodium-Catalyzed Synthesis of Benzosilolometallocenes via the Dehydrogenative Silylation of C(sp2)–H Bonds; Org. Lett.2015, 17, 3102–3105. Google Scholar 45. Zhao W.-T.; Lu Z.-Q.; Zheng H.; Xue X.-S.;