Authors: Ming Chen | Xucai Wang | Zhi‐Hui Ren | Zheng‐Hui Guan
Source: CCS Chemistry (article, 2021-01-08)
Field: Chemistry — Organic Chemistry

Palladium-Catalyzed Asymmetric Domino Heck/Carbocyclization/Suzuki Reaction: A Dearomatization of Nonactivated Naphthalenes Open AccessCCS ChemistryCOMMUNICATION1 Dec 2021Palladium-Catalyzed Asymmetric Domino Heck/Carbocyclization/Suzuki Reaction: A Dearomatization of Nonactivated Naphthalenes Ming Chen†, Xucai Wang†, Zhi-Hui Ren and Zheng-Hui Guan Ming Chen† Key Laboratory of Synthetic and Nature Molecule of Ministry of Education, Department of Chemistry and Materials Science, Northwest University, Xi'an 710127 , Xucai Wang† Key Laboratory of Synthetic and Nature Molecule of Ministry of Education, Department of Chemistry and Materials Science, Northwest University, Xi'an 710127 , Zhi-Hui Ren Key Laboratory of Synthetic and Nature Molecule of Ministry of Education, Department of Chemistry and Materials Science, Northwest University, Xi'an 710127 and Zheng-Hui Guan *Corresponding author: E-mail Address: [email protected] Key Laboratory of Synthetic and Nature Molecule of Ministry of Education, Department of Chemistry and Materials Science, Northwest University, Xi'an 710127 https://doi.org/10.31635/ccschem.021.202000596 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Herein, we report a novel palladium (Pd)-catalyzed asymmetric domino Heck/carbocyclization/Suzuki reaction of N-(2-bromoaryl)-2-naphthylacrylamides. The reaction involves a novel and enantioselective dearomative 1,2-insertion of the naphthalene group, thus providing a unique dearomatization strategy of nonactivated naphthalenes. A new phosphoramidite ligand L12, which displayed excellent reactivity and enantioselectivity in the reaction, has been developed. The reaction employs readily available starting materials, and provides straightforward access to a diverse array of spirooxindoles bearing three stereogenic centers in high yields under mild conditions. Download figure Download PowerPoint Introduction Dearomatization is an important reaction for the transformations of readily available planar aromatic compounds into complex three-dimentional (3D) structures such as spirocycles, polycycles, and bridged cycles.1–5 Recently, transition-metal-catalyzed dearomatization reactions of furans, pyrroles, indoles, pyridines, phenols, anilines, and naphthols have been developed as powerful strategies to construct complex structures,6–15 and catalytic asymmetric dearomatization (CADA) is an emerging concept in organic synthesis.16 However, due to the inherent stability and high resonance energy of nonactivated arenes, the dearomative transformation of nonactivated arenes remains an important challenge.1,17 Over the past years, several approaches, including high-pressure hydrogenations of arenes,18–20 photocycloadditions of arenes and alkenes,3 cyclopropanations of arenes and diazo compounds,21,22 stoichiometric reactions of transition-metal-arene complexes,2,23 and visible-light-mediated 1,4- and 1,2-cycloadditions of arenes with arenophiles,1,24,25 have been developed for the dearomatization of nonactivated arenes. Nevertheless, new protocols, especially for enantioselective dearomatization of nonactivated benzene or naphthalene, remain highly desirable. Palladium (Pd)-catalyzed asymmetric domino Heck reaction is one of the most powerful methods for the construction of quaternary stereocenters.26,27 Through trapping of the in situ generated alkyl-PdX intermediate, various enantioselective domino reactions, including Heck tandem coupling with azoles,28,29 (dearomative) Heck–Sonogashira reaction,30–32 Heck–Suzuki reaction,33,34 and Heck carbonylative reaction,35–38 have been developed for the synthesis of valuable structures (Scheme 1a). Alternatively, by switching the cross-coupling of alkyl-PdX to reductive elimination, intriguing reductive Heck and Heck carboiodination reactions have been reported (Scheme 1a).39–44 Recently, a dearomative rearrangement of biaryl phosphine ligated Pd(II) complexes, which was involved in a Pd(II)-mediated insertion of an aryl group into an unactivated arene, has been disclosed.45 Very recently, elegant examples of Pd-catalyzed dearomative 1,4-difunctionalization of naphthalenes for the diastereoselective formation of 1,4-dihydronaphthalene-based spirocycles have emerged (Scheme 1b).46,47 Based on our recent interest in the field,35,48 we hypothesized that the β-naphthyl group might be activated by the key alkyl-Pd species in domino Heck reaction through an intramolecular coordination interaction (Scheme 1c). As such, an intramolecular dearomative migratory insertion of the nonactivated naphthyl ring into the alkyl-Pd bond might be achieved in certain cases. If successful, the reaction would not only develop a new type of domino Heck reaction, but also open a complementary catalytic protocol for dearomatization of nonactivated naphthalenes. Herein, we report the development of a highly regio- and enantioselective Pd-catalyzed domino Heck/dearomative carbocyclization/Suzuki reaction of N-aryl-2-naphthylacrylamides (Scheme 1c). Scheme 1 | Pd-catalyzed asymmetric domino Heck reactions. Download figure Download PowerPoint Experimental Methods General procedure for Pd-catalyzed domino Heck/carbocyclization/Suzuki reaction: A 10 mL round-bottom flask was charged with acryamide 1 (0.1 mmol, 1.0 equiv), ArB(OH)2 (0.2 mmol, 2.0 equiv), Pd2(dba)3 (4 mol %), L12 (16 mol %), Cs2CO3 (3.0 equiv), H2O (50 equiv), and toluene (0.8 mL). The reaction in the flask was then heated in a 50 °C oil bath and stirred for 6–24 h under N2 atmosphere. After reaction completion, the mixture was cooled down to room temperature. The reaction was quenched with H2O (5 mL) and extracted with EtOAc (5 mL, three times). The combined organic layers were dried over anhydrous Na2SO4 and then evaporated in vacuo. The residue was purified by column chromatography on silica gel (hexanes:ethyl acetate = 10∶1 as the eluent) to afford the corresponding spirocycle 3. The enantiopurity of the product was analyzed by chiral high-performance liquid chromatography (HPLC). More experimental details and characterization are presented in the Supporting Information. Results and Discussion Reaction conditions and the outcome Initially, we conducted the Pd-catalyzed Heck dearomatization reaction of naphthyl-substituted acrylamide 1a with various trapping agents, including terminal alkynes, phenylboronic acids, amines, and alcohols. A variety of ligands were screened under different conditions. Happily, the Pd-catalyzed Heck dearomatization Suzuki coupling product 3a, an intriguing spirooxindole bearing three stereogenic centers, was observed in 5% yield when the P(2-MeC6H4)3 was used as the ligand (Table 1, entry 1), whereas no dearomatization product was obtained by using other coupling partners. Due to the vital role of the ligand, a series of monodentate ligands were further screened in the reaction (entries 2–7). Encouragingly, a phosphoramidite L4 showed improved yield and enantioselectivity in the reaction. Therefore, phosphoramidite ligands with different substituents on the 3,3′-position of H8-BINOL-framework ( L5– L10) were synthesized and tested in the reaction (entries 8–13). It was found that the 3,5-(CF3)2-aryl substituent ( L10) displays better results in terms of the reactivity and enantioselectivity.35 Next, fine-tuning the amino moiety of the phosphoramidite ligands suggested N-(3,5-dimethylbenzyl)-3-(trifluoromethyl)aniline ( L12) as optimal (entry 15). With L12 as the ligand, the corresponding dearomative coupling product 3a was obtained in 69% yield and 94% enantiomeric excess (ee). Finally, we found that the experiment result could be further improved to 90% yield and 96% ee by using water as the additive in 50 °C (entries 18 and 19).49 Table 1 | Optimization of the Reaction Conditionsa Entry Catalyst Ligand Yield (%) ee (%) 1 Pd2(dba)3 P(2-MeC6H4)3 5 — 2 Pd2(dba)3 P(2-MeOC6H4)3 0 — 3 Pd2(dba)3 P(2-CF3C6H4)3 0 — 4 Pd2(dba)3 L1 0 — 5 Pd2(dba)3 L2 0 — 6 Pd2(dba)3 L3 0 — 7 Pd2(dba)3 L4 8 17 8 Pd2(dba)3 L5 16 49 9 Pd2(dba)3 L6 19 41 10 Pd2(dba)3 L7 17 49 11 Pd2(dba)3 L8 45 84 12 Pd2(dba)3 L9 22 80 13 Pd2(dba)3 L10 52 85 14 Pd2(dba)3 L11 66 93 15 Pd2(dba)3 L12 69 94 16 Pd2(dba)3 L13 36 74 17 Pd2(dba)3 L14 51 68 18b Pd2(dba)3 L12 84 94 19bc Pd2(dba)3 L12 90 96 aConditions: 1a (0.1 mmol), 2a (2.0 equiv), Pd2(dba)3 (4 mol %), L1– L14 (16 mol %), Cs2CO3 (3.0 equiv), toluene (0.8 mL), 70 °C, 24 h, under N2. The ee is determined by HPLC analysis, isolated yield. bH2O (50 equiv) was added. c50 °C. Scope of the reaction With the optimal reaction conditions in hand, we have investigated the reaction scope of N-aryl acrylamides. As depicted in Table 2, this novel Pd-catalyzed asymmetric domino dearomatization reaction shows good functional-group tolerance. N-Aryl acrylamides bearing electron-donating groups, such as alkyl and alkoxyl, were tolerated under the conditions to afford the corresponding spirooxindoles 3a– 3k in 67–90% yields and 91–99% ee. N-(2-Bromoaryl)-N-acrylamides bearing an additional halide substituent, such as F and Cl, were also tolerated under the conditions to give the desired products 3l– 3n in 72–80% yields and 86–99% ee. Notably, the strong electron-withdrawing CF3 group was compatible with the conditions to produce 3o with 98% ee in 62% yield. Table 2 | Scope of N-Aryl Acrylamidesa aConditions: 1 (0.1 mmol), 2a (2.0 equiv), Pd2(dba)3 (4 mol %), L12 (16 mol %), Cs2CO3 (3.0 equiv), H2O (50 equiv), toluene (0.8 mL) at 50 °C for 6–24 h under N2. The ee is determined by chiral HPLC analysis, isolated yield. Furthermore, different arylboronic acids were investigated for extending the substrate scope. Arylboronic acids with methyl, sterically bulky isopropyl and t-butyl, and alkoxy groups on the phenyl ring reacted efficiently with 1a to afford the spirocycles 3p– 3u with 94–98% ee in 70–91% yields. Notably, 2-naphthyl boronic acid underwent the reaction smoothly to produce the spirocycle 3v with 96% ee in 73% yield. Halide-substituted arylboronic acids were compatible with the conditions to give the corresponding spirocycles 3w and 3x with 89–97% ee in high yields. And the absolute configuration of 3x was unambiguously confirmed by single-crystal X-ray crystallographic diffraction (see Supporting Information). Whereas the desired dearomative products 3y and 3z were obtained in very high ee values when strong electron-withdrawing group substituted arylboronic acids were employed in the reaction, the important Heck–Suzuki byproducts 3y′ and 3z′ were observed in 27–31% yield and 3–10% ee. Similar results were observed when 3-thiopheneboronic acid and cyclohexene-1-boronic acid were employed as the substrates in the reaction. In these cases, the Heck/carbocyclization/Suzuki products 3aa and 3ab accompanied by the Heck–Suzuki byproducts 3aa′ and 3ab′ were obtained. In this context, the significant difference in ee values between Heck/carbocyclization/Suzuki products ( 3y– 3ab) and Heck–Suzuki byproducts ( 3y′– 3ab′) indicated that the side reaction probably involved a different intermediate in the enantiodetermining alkenyl insertion step (Table 3). Table 3 | Scope of Arylboronic Acidsa aConditions: 1a (0.1 mmol), 2 (2.0 equiv), Pd2(dba)3 (4 mol %), L12 (16 mol %), Cs2CO3 (3.0 equiv), H2O (50 equiv), toluene (0.8 mL) at 50 °C for 6–24 h under N2. The ee is determined by chiral HPLC analysis, isolated yield. bThe data of Heck–Suzuki byproducts are shown within parentheses. Mechanistic investigation In principle, there are several possible mechanistic pathways for this domino Heck dearomatization reaction (Scheme 2, pathways a–d). First, the reaction is initiated by oxidative addition of the aryl bromide of acrylamide 1a to a Pd(0)/L* complex to generate the important intermediate A. Then, intramolecular migratory insertion of A forms the intermediate B. And intramolecular dearomative 1,2-insertion of the B forms the intermediate C. Transmetalation of the intermediate C and arylboronic acid sequential with reductive elimination of the D, gives the final product 3 (path a). The second pathway is that the intermolecular transmetalation of A and arylboronic acid for forming E occurred before the intramolecular Heck cyclization step ( A → E → F) (path b).50 In this way, the dearomative 1,2-insertion of the key intermediate F forms D, which proceeds through reductive elimination to give the final product 3. Alternatively, direct reductive elimination of the intermediate F generates the Heck–Suzuki coupling side-product 3′. The third plausible pathway lies in transmetalation of B and arylboronic acid to afford the intermediate F (path c). Apart from above pathways, the cationic mechanism should also be considered.45 Namely, the 1,2-insertion of naphthyl group might proceed through a cationic alkyl-Pd species G which is generated by the disassociation of Br anion from the intermediate B (path d). Scheme 2 | Possible pathways for the reaction. Download figure Download PowerPoint The path c should be ruled out principally because of the dramatic difference in ee between the Heck dearomative carbocyclization Suzuki products ( 3y– 3ab) and the Heck–Suzuki byproducts ( 3y′– 3ab′). Since the electron-withdrawing group on arylboronic acids might accelerate the rate of transmetalation,51,52 a reasonable assumption was that the domino dearomative reaction proceeded through path a or path d, while the side Heck–Suzuki reaction proceeded through path b. Indeed, the intermediate E could not have been involved in the formation of dearomative product 3 according to the halide effect investigation, because different ee values of 3a were observed when Br and I were employed in the reaction (Scheme 3, entries 2 and 3). To determine whether the dearomative reaction proceeded through a neutral or cationic mechanism (paths a and d), solvent effects on the reaction were examined. In comparison with toluene solvent, the same ee and lower yield of 3a were obtained in tetrahydrofuran (THF) (Scheme 3, entries 2 and 3). Because halide dissociation should be uniformly accelerated by the more coordinating THF solvent, these results are inconsistent with an ion-dissociation pathway (path d). Therefore, the domino Heck/dearomative/carbocyclization Suzuki reaction probably proceeded through path a ( 1 → A → B → C → D → 3). And path b ( 1 → A → E → F → 3′) was the possible route for the formation of the Heck–Suzuki byproducts 3y′– 3ab′. Scheme 3 | Control experiments. Download figure Download PowerPoint Further transformations were performed to demonstrate the synthetic utility of the reaction (Scheme 4). The alkenyl group on the spirooxindole 3a could be easily reduced by a Pd/C-catalyzed hydrogenation reaction with balloon pressure of H2. And the oxidative rearomatization of 3a can be easily achieved in high yield in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and catalytic p-toluenesulfonic acid (TsOH).53 In addition, the epoxidation of the alkenyl group on the spirooxindole 3a to form 6 was also achieved in 95% yield without loss of enantiomeric purity. Scheme 4 | Derivatization of spirocycle product. Download figure Download PowerPoint Conclusion We have developed an unprecedented Pd-catalyzed enantioselective domino Heck/dearomative carbocyclization/Suzuki reaction of naphthyl substituted acrylamides and arylboronic acids. A novel and effective phosphoramidite ligand L12 has been developed for this domino Heck dearomatization reaction. Mechanistic studies suggested that the reaction proceeded through an asymmetric Heck cyclization, 1,2-migratory insertion of the naphthyl group, transmetalation with arylboronic acid, and reductive elimination cascade steps. The reaction not only established a complementary catalytic protocol for dearomatization of nonactivated naphthalenes, but also provided a straightforward method for the synthesis of spirooxindoles bearing three stereogenic centers in high yields. Supporting Information Supporting Information is available and includes additional experimental procedures, characterization data, HPLC spectra, copies of NMR spectra, and X-ray data of 3x and 6. Conflict of Interest The authors declare no competing financial interests. Funding Information This work was supported by generous grants from the National Natural Science Foundation of China (nos. NSFC-21971204, 21622203, and 21702161) and the Innovation Capability Support Program of Shaanxi Province (no. 2020TD-022). References 1. Wertjes W. C.; Southgate E. H.; Sarlah D.Recent Advances in Chemical Dearomatization of Nonactivated Arenes.Chem. Soc. Rev.2018, 47, 7996–8017. Google Scholar 2. Liebov B. K.; Harman W. D.Group 6 Dihapto-Coordinate Dearomatization Agents for Organic Synthesis.Chem. Rev.2017, 117, 13721–13755. Google Scholar 3. Remy R.; Bochet C. G.Arene-Alkene Cycloaddition.Chem. Rev.2016, 116, 9816–9849. Google Scholar 4. Roche S. P.; Porco J. A.Dearomatization Strategies in the Synthesis of Complex Natural Products.Angew. Chem. Int. Ed.2011, 50, 4068–4093. Google Scholar 5. Pape A. R.; Kaliappan K. P.; Kündig E. P.Transition-Metal-Mediated Dearomatization Reactions.Chem. Rev.2000, 100, 2917–2940. Google Scholar 6. Xia Z.-L.; Xu-Xu Q.-F.; Zheng C.; You S.-L.Chiral Phosphoric Acid-Catalyzed Asymmetric Dearomatization Reactions.Chem. Soc. Rev.2020, 49, 286–300. Google Scholar 7. Huang G.; Yin B.Recent Developments in Transition Metal-Catalyzed Dearomative Cyclizations of Indoles as Dipolarophiles for the Construction of Indolines.Adv. Synth. Catal.2019, 361, 405–425. Google Scholar 8. Festa A. A.; Voskressensky L. G.; Van der Eycken E. V.Visible Light-Mediated Chemistry of Indoles and Related Heterocycles.Chem. Soc. Rev.2019, 48, 4401–4423. Google Scholar 9. Huang L.; Cai Y.; Zhang H.-J.; Zheng C.; Dai L.-X.; You S.-L.Highly Diastereo- and Enantioselective Synthesis of Quinuclidine Derivatives by an Iridium-Catalyzed Intramolecular Allylic Dearomatization Reaction.CCS Chem.2019, 1, 106–116. Abstract, Google Scholar 10. Gribble A. W.; Guo S.; Buchwald S. L.Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile.J. Am. Chem. Soc.2018, 140, 5057–5060. Google Scholar 11. Qin X.; Lee M. W. Y.; Zhou J. S.Nickel-Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Afford Indolines.Angew.Chem. Int. Ed.2017, 56, 12723–12726. Google Scholar 12. Mu X.; Yu H.; Peng H.; Xiong W.; Wu T.; Tang W.Construction of Various Bridged Polycyclic Skeletons by Palladium Catalyzed Dearomatization.Angew. Chem. Int. Ed.2020, 59, 8143–8147. Google Scholar 13. Zuo Z.; Wang J.; Liu J.; Wang Y.; Luan X.Palladium-Catalyzed [2+2+1] Spiroannulation via Alkyne-Directed Remote C-H Arylation and Subsequent Arene Dearomatization.Angew.Chem. Int. Ed.2020, 59, 653–657. Google Scholar 14. Zuo Z.; Wang H.; Diao Y.; Ge Y.; Liu J.; Luan X.Palladium-Catalyzed Aryne Insertion/Arene Dearomatization Domino Reaction: A Highly Chemoselective Route to Spirofluorenes.ACS Catal.2018, 8, 11029–11034. Google Scholar 15. Shen D.; Chen Q.; Yan P.; Zeng X.; Zhong G.Enantioselective Dearomatization of Naphthol Derivatives with Allylic Alcohols by Cooperative Iridium and Brønsted Acid Catalysis.Angew. Chem. Int. Ed.2017, 56, 3242–3246. Google Scholar 16. Zhuo C.-X.; Zhang W.; You S.-L.Catalytic Asymmetric Dearomatization Reactions.Angew. Chem. Int. Ed.2012, 51, 12662–12686. Google Scholar 17. Schleyer P. R.; PÜhlhofer F.Recommendations for the Evaluation of Aromatic Stabilization Energies.Org. Lett.2002, 4, 2873–2876. Google Scholar 18. Wang D.-S.; Chen Q.-A.; Lu S.-M.; Zhou Y.-G.Asymmetric Hydrogenation of Heteroarenes and Arenes.Chem. Rev.2012, 112, 2557–2590. Google Scholar 19. Wei Y.; Rao B.; Cong X.; Zeng X.Highly Selective Hydrogenation of Aromatic Ketones and Phenols Enabled by Cyclic (Amino)(alkyl)carbene Rhodium Complexes.J. Am. Chem. Soc.2015, 137, 9250–9253. Google Scholar 20. Wiesenfeldt M. P.; Nairoukh Z.; Li W.; Glorius F.Hydrogenation of Fluoroarenes: Direct Access to All-cis-(multi)fluorinated Cycloalkanes.Science2017, 357, 908–912. Google Scholar 21. Smith K. L.; Padgett C. L.; Mackay W. D.; Johnson J. S.Catalytic, Asymmetric Dearomative Synthesis of Complex Cyclohexanes via a Highly Regio- and Stereoselective Arene Cyclopropanation Using α-Cyanodiazoacetates.J. Am. Chem. Soc.2020, 142, 6449–6455. Google Scholar 22. Nani R. R.; Reisman S. E.α-Diazo-β-ketonitriles: Uniquely Reactive Substrates for Arene and Alkene Cyclopropanation.J. Am. Chem. Soc.2013, 135, 7304–7311. Google Scholar 23. Wilson K. B.; Myers J. T.; Nedzbala H. S.; Combee L. A.; Sabat M.; Harman W. D.Sequential Tandem Addition to a Tungsten-Trifluorotoluene Complex: A Versatile Method for the Preparation of Highly Functionalized Trifluoromethylated Cyclohexenes.J. Am. Chem. Soc.2017, 139, 11401–11412. Google Scholar 24. Bingham T. W.; Hernandez L. W.; Olson D. G.; Svec R. L.; Hergenrother P. J.; Sarlah D.Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene.J. Am. Chem. Soc.2019, 141, 657–670. Google Scholar 25. Southgate E. H.; Pospech J.; Fu J.; Holycross D. R.; Sarlah D.Dearomative Dihydroxylation with Arenophiles.Nat. Chem.2016, 8, 922–928. Google Scholar 26. A. D.; E. M.; B.; the Chem. Google Scholar Y.; Li Y.; J.; W.Construction of by Reactions.Angew. Chem. Int. Google Scholar W.; Wang Q.; Enantioselective Domino C-H and to the Synthesis of Am. Chem. Soc.2015, 137, Google Scholar S.; A.; Wang Q.; Wang Enantioselective Functionalization with of A Chem. Int. Ed.2017, 56, Google Scholar Liu Wang Li Huang Dearomative of Indoles by Chem. Int. Ed.2017, 56, Google Scholar X.; Wu C.; Ge S.; Lu Enantioselective Asymmetric Synthesis of Trifluoromethylated Chem. Int. Ed.2020, 59, Google Scholar Zhou L.; Li S.; B.; D.; Wu L.; Liu Y.; Zhang Zhang of by a Chem. Int. Ed.2020, 59, Google Scholar Zhang B.; Wu L.; Wu Y.; Y.; Zhou L.; Liu Y.; Zhang of by Tandem Chem. Int. Google Scholar Zhou B.; of by or Domino 2, Google Scholar Chen M.; Wang X.; P.; X.; Ren Guan Enantioselective Heck with a Asymmetric Synthesis of and Chem. Int. Ed.2020, 59, Google Scholar H.; Liu J.; W.; S.; Synthesis of and via Method and Chem. Int. Google Scholar Z.; Zeng Y.; Z.; Guan Z.; A.; via Asymmetric Tandem of Google Scholar R. C.; D.; C. R. Enantioselective Intramolecular by and Chem. Int. Google Scholar Shen C.; Liu Li Dearomatization of Indoles via Intramolecular Reductive Heck Am. Chem. Soc.2015, 137, Google Scholar W.; Wang Q.; as a in Enantioselective Reductive Heck Reactions.Angew. Chem. Int. Ed.2017, 56, Google Scholar Zhang B.; Y.; Wu L.; Wu Y.; Zhou L.; Liu Y.; Zhang Enantioselective Reductive Heck Access to Chem. Int. Google Scholar G.; K.; H.; Zhou Asymmetric Reductive Heck Reaction of Aryl Chem. Int. Google Scholar D. A.; H.; H.; in the of Chem. Int. Google Scholar Zhang B.; Wu L.; Zhou L.; D.; Liu Y.; Li Z.; Zhang Enantioselective of Aryl Am. Chem. Soc.2019, 141, Google Scholar P. J.; T. J.; M.; Chen J.; P.; Buchwald S. the Dearomative of Pd(II) Complexes.J. Am. Chem. Google Scholar P.; Zheng C.; You Dearomative of Google Scholar Zhou B.; Wang H.; X.; of Naphthalenes via Tandem Google Scholar Yu L.; Zhang Y.; X.; Ren Guan Enabled by Iridium and Brønsted Acid-Catalyzed Reductive 2, Google Scholar D. A.; M.; Dearomative of Google Scholar Z.; L.; C.; Chen J.; Wang D.; Construction of by of Google Scholar A. A.; Wang H.; A. S. and of the in the Am. Chem. Soc.2017, 139, Google Scholar T. T.; B. S. T.; C. General for the Construction of Functionalized via Domino Heck Google Scholar C.; R. via Google Scholar Wang Zhou C and Li G Remote of Nonactivated with via Reductive Information Chemical Heck Palladium ; Heck reaction ; Catalysis ; Domino ; Chemistry ; Combinatorial chemistry ; Organic chemistry Catalytic C–H Functionalization Methods ; Chemical synthesis and alkaloids ; Axial and Atropisomeric Chirality Synthesis