Nickel-Catalyzed Reductive Electrophilic Ring-Opening of Benzofurans with Alkyl Halides
Decai Ding, Haiyan Dong, Chuan Wang
Abstract
Open AccessCCS ChemistryCOMMUNICATION1 Feb 2022Nickel-Catalyzed Reductive Electrophilic Ring-Opening of Benzofurans with Alkyl Halides Decai Ding, Haiyan Dong and Chuan Wang Decai Ding Hefei National Laboratory for Physical Science at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026 , Haiyan Dong Hefei National Laboratory for Physical Science at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026 and Chuan Wang *Corresponding author: E-mail Address: [email protected] Hefei National Laboratory for Physical Science at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026 Center for Excellence in Molecular Synthesis of CAS, Hefei, Anhui 230026 https://doi.org/10.31635/ccschem.021.202000620 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail In this paper, we developed an electrophilic ring-opening reaction, which is beyond the strained small ring system. Under reductive nickel catalysis, ring-opening of diverse benzofurans via endocyclic inert carbon–oxygen bond cleavage can be achieved with an array of inactivated secondary and tertiary alkyl halides as coupling partners, allowing for the preparation of a series of (E)-o-alkenylphenols with excellent E/Z-selectivity and high functional tolerance. The utility of this method was further demonstrated through derivatizations of the ring-opening products using the o-hydroxyl group as a functional handle, providing various organic compounds in good to high efficiency. Download figure Download PowerPoint Introduction Transition metal-catalyzed electrophilic ring-opening reactions provide a unique reaction pathway to induce ring-opening progress, in which diverse electrophiles are engaged as coupling partners.1 In comparison with classic nucleophilic ring-opening reactions, the reductive strategy is particularly desirable for C–C bond forming ring-opening reactions, because readily available electrophiles, including organohalides, Michael acceptors, aldehydes, and imines, could be used as precursors instead of highly reactive and air-sensitive pregenerated organometallics. The challenge of realizing electrophilic ring-opening reactions lies in overturning the intrinsic electrophilic nature of ring molecules. To date, the most successful examples of catalytic electrophilic ring-opening reactions are limited to epoxides2–14 with a few exceptions of other small, strained rings, such as aziridines,15–19 oxetanes,20 azetidinones,21,22 cyclobutanones,23 and cyclobutanone oxime esters.24 Therefore, it is highly desirable to develop a new methodology to allow electrophilic ring-opening reactions to go beyond the small ring system. Heteroarenes are among the most abundant and useful building blocks in organic synthesis. The ring-opening of heteroaromatic compounds via endocyclic carbon–heteroatom bond cleavage leads to skeletal transformation, enabling the novel use of heteroarenes as precursors in organic reactions. However, this process is highly challenging due to high bond energy and aromatic stabilization. Until now, all ring-opening reactions of heteroarenes, including benzofurans and indoles, rely on the utilization of diverse C-,25–33 B-,34,35 Si-nucleophiles,36,37 or hydrides38,39 under the catalysis of transition metals (Ni,26–29,34 Mn,31,35 Rh,32 Fe,33 or Cu37,38), borane,39 or catalyst-free conditions (Figure 1a).30,36 In the case of C-nucleophiles, the use of reactive pregenerated organometallics like Grignard reagents and organolithiums results in narrow substrate scope and low compatibility of sensitive functionalities.25–33 To overcome the disadvantages of the nucleophilic ring-opening strategy, we envisioned an electrophilic ring-opening of benzofurans with secondary and tertiary halides as the coupling partner under reductive nickel catalysis,40–47 to break the heteroaromatic core requiring no pregenerated organometallics (Figure 1b). Figure 1 | (a) Nucleophilic ring-opening of benzofurans. (b) Electrophilic ring-opening of benzofurans with alkyl halides. Download figure Download PowerPoint Results and Discussion Optimization To optimize reaction conditions, benzofuran ( 1a) and cyclohexyl iodide ( 2a) were selected as benchmark substrates (Table 1). Initially, a series of pyridine- and phosphine-based ligands were tested using Ni(dme)Br2 as a precatalyst (10 mol %) in a N,N-dimethylacetamide (DMA) at 60 °C for 12 h. It turned out that only the reaction using 1,2-bis(diphenylphosphino)ethane (dppe) as a ligand could afford the desired ring-opening product 3aa in 12% yield (entry 1). Importantly, only the E-isomer was formed according to the 1H NMR spectroscopy. Encouraged by this result, various Ni precatalysts were examined for the studied reaction (entries 2–5), and the best outcome was achieved in the case of NiCl2 (entry 5). Furthermore, the same result was obtained when the pregenerated Ni(dppe)Cl2 was employed (entry 6). Next, a brief solvent screening was undertaken under the catalysis of Ni(dppe)Cl2 (entries 7–9). In the case of dimethylformamide (DMF) as a solvent, the yield diminished to 9% (entry 7), whereas no desired reaction occurred in either tetrahydrofuran (THF) or MeCN (entries 8 and 9). When the reaction was performed at 100 °C, the yield could be elevated to 28% (entry 10). However, raising the temperature further to 120 °C slightly deteriorated the reaction efficiency (entry 11). Notably, the use of MgBr2 as an additive gave rise to a dramatically increased yield (entry 12). Increasing the catalyst loading to 15 mol % resulted in lower efficiency because the homocoupling of cyclohexyl iodide ( 2a) was significantly benefited in this case (entry 13). In contrast, the yield could be improved to 63% when the catalyst loading was reduced to 1 mol % (entry 14). Finally, conducting the reaction with 3 equiv of cyclohexyl iodide ( 2a) and an extended reaction time (48 h) increased the yield to 73% with an E/Z ratio higher than 98:2 (entry 15). Replacing Zn with Mn as the reducing agent completely stopped the ring-opening reaction (entry 16). Table 1 | Optimization of Reaction Conditionsa Entry Ni-Precatalyst Solvent T (°C) Yield (%)b,c 1 NiBr2(dme) DMA 60 12 2 Ni(acac)2 DMA 60 0 3 NiBr2 DMA 60 10 4 Ni(COD)2 DMA 60 13 5 NiCl2 DMA 60 18 6d Ni(dppe)Cl2 DMA 60 18 7d Ni(dppe)Cl2 DMF 60 9 8d Ni(dppe)Cl2 THF 60 0 9d Ni(dppe)Cl2 MeCN 60 0 10d Ni(dppe)Cl2 DMA 100 28 11d Ni(dppe)Cl2 DMA 120 26 12d,e Ni(dppe)Cl2 DMA 100 58 13d–f Ni(dppe)Cl2 DMA 100 37 14d,e,g Ni(dppe)Cl2 DMA 100 63 15d,e,g,h Ni(dppe)Cl2 DMA 100 73 16d,e,g–i Ni(dppe)Cl2 DMA 100 0 aUnless otherwise specified, reactions were performed on a 0.4 mmol scale of benzofuran ( 1a) using 2 equiv of cyclohexyl iodide ( 2a), 10 mol % of Ni-precatalyst, 10 mol % of dppe, 3 equiv of Zn in 1 mL DMA at 60 °C for 12 h. bYields of the isolated product after column chromatography. cThe product was obtained in <98:2 E/Z-selectivity, which was determined by 1H NMR spectrocopy. dNo additional ligand was added. eReaction was performed with 1 equiv of MgBr2. fReaction was performed with 15 mol % Ni(dppe)Cl2. gReaction was performed with 1 mol % Ni(dppe)Cl2. hReaction was performed with 3 equiv of cyclohexyl iodide (2a) for 48 h. iReaction was performed with Mn as a reductant. Substrate scope With optimal reaction conditions determined, we started to evaluate the substrate spectrum of this Ni-catalyzed ring-opening reaction (Table 2). First, various benzofurans ( 1a– 1r) with a substituent on the C5, C6, or C7 position were reacted with cyclohexyl iodide ( 1a). To our delight, all these reactions proceeded smoothly under standard conditions, furnishing the corresponding products 3aa– 3ra in moderate to good yields and high E/Z-selectivities. It turned out that an array of functionalities, including aryl halides ( 3fa and 3ga), cyano ( 3ha), BPin ( 3ia), benzothiophene ( 3oa), and amide ( 3ra), were well tolerated in this reaction. Remarkably, the C–O bond cleavage selectively occurred on the C2-unsubstituted benzofuran, allowing the synthesis of the alkene containing a benzofuran subunit ( 3na). Furthermore, the reaction could be simply scaled up to 10 mmol, affording compound 3aa in 70% yield. We attempted to ring open 2- or 3-substituted benzofurans and benzothiophene with cyclohexyl iodide, which all failed to deliver the desired products. Table 2 | Substrate Scope Evaluation by Benzofuran Variationa–c aUnless otherwise specified, reactions were performed on a 0.4 mmol scale of benzofuran ( 1a) using 3 equiv of alkyl halides 2, 1 mol % of NiCl2(dppe), 3 equiv of Zn and 1 equiv of MgBr2 at 100 °C in 1 mL DMA for 48 h. bYields of the isolated products after column chromatography. cThe products were obtained in <98:2 E/Z-selectivity, which was determined by 1H NMR spectrocopy. dThe reaction was performed in a 10-mmol scale of 1a. Subsequently, we continued to study the scope of this reaction by varying the structure of alkyl halides (Table 3). Both cyclic and acyclic secondary alkyl iodides ( 2b– 2h) proved to be competent precursors, and the corresponding products 3ab– 3ak and 3cl were obtained in moderate to good yields wherein functional moieties, including carbamate ( 3ab), ketal ( 3ac), silyl ether ( 3ag), and ester ( 3ah), posed no problem. In the case of secondary alkyl bromides or chlorides, no desired ring-opening reaction occurred. To install the tertiary alkyl group to the products, relatively stable tertiary alkyl chlorides were utilized as the alkyl source instead of their bromo or iodo analogs. By increasing the catalyst loading to 10 mol %, the C–Cl bond cleavage could proceed smoothly, delivering a variety of coupling products ( 3am– 3as and 3ct) in moderate to good efficiencies. Again, complete E/Z control was achieved in all cases mentioned earlier. Unfortunately, this method is not applicable to primary alkyl halides due to its high propensity to undergo homocoupling. Table 3 | Substrate Scope Evaluation by Variation of the Alkyl Halidesa–c aUnless otherwise specified, reactions were performed on a 0.4 mmol scale of benzofuran ( 1a) using 3 equiv of alkyl halides 2, 1 mol % of NiCl2(dppe), 3 equiv of Zn and 1 equiv of MgBr2 at 100 °C in 1 mL DMA for 48 h. bYields of the isolated products after column chromatography. cThe products were obtained in <98:2 E/Z-selectivity, which was determined by 1H NMR spectrocopy. dReactions were preformed with 10 mol % NiCl2(dppe). Derivatization of the ring-opening products Since all our products contain an ortho-hydroxyl moiety, we turned our attention to use this group as a functional handle (Figure 2). First, the ring-opening product 3aa was smoothly converted into the corresponding triflate 4 in 98% yield, which could be subjected to a variety of Pd-catalyzed cross-coupling reactions with phenylboronic acid, 2,3-dihydrofuran,48 or aniline49 as the coupling partner, providing different ortho-substituted styrenes 5– 7 in good to excellent efficiency (Figure 2a). Moreover, we took advantage of both the hydroxyl and olefin moiety contained in compound 3aa to furnish the benzofuranone 8 via Pd-catalyzed hydroesterification in an excellent yield (Figure 2b).50 Figure 2 | (a and b) Derivatizations of ring-opening products. aTf2O (2 equiv), NEt3 (2.5 equiv), DCM, 0 °C, 3 h. bPd(PPh3)4 (5 mol %), PhB(OH)2 (1.5 equiv), Na2CO3 (2.5 equiv), DME/H2O (1:2), 100 °C, overnight. cPd(OAc)2 (5 mol %), BINAP (6 mol %), 2,3-dihydrofuran (5 equiv), DIPEA (3 equiv), THF, 80 °C, overnight. dPd(OAc)2 (10 mol %), XPHOS (15 mol %), PhNH2 (1.5 equiv), Cs2CO3 (1.5 equiv), toluene, 100 °C, overnight. DCM, dichloromethane; DME, dimethoxyethane; BINAP, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl; DIPEA, N,N-diisoproylethylamine; XPHOS, 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl. Download figure Download PowerPoint Control experiments Next, a set of experiments were carried out to disclose the mechanism of the studied reaction (Figure 3). First, a radical clock reaction was conducted using the alkyl iodide 2u bearing a pendant olefinic unit as the substrate. In this case, the reaction yielded only the cyclized product 3au (Figure 3a). Besides, an enantiopure secondary alkyl iodide 2v derived from estrone was engaged as a stereochemical probe in this Ni-catalyzed reaction, affording the ring-opening product 3av in a diastereomeric ratio of 1:1 (Figure 3b). The aforementioned results support the formation of alkyl radicals in the reaction. Furthermore, t-BuZnBr was used as the starting material under the redox-neutral conditions, and no ring-opening reaction occurred, ruling out the Negishi cross-coupling-like reaction pathway with in situ-generated organozincs (Figure 3c). In Yorimitsu's work34 on Ni-catalyzed boron-insertion to benzofurans, it was proposed that carbene-Ni(0) complex is able to undergo oxidative addition with benzofurans. To verify if the same process takes place in our case, a stoichiometric reaction between Ni(0) and benzofuran was performed (Figure 3d). It turned out that benzofuran was fully recovered under this condition, arguing against the oxidative insertion of Ni(0) into the C–O bond. In contrast, Ni(0) was capable of transforming the tertiary chloride 2k to the corresponding alkene, which likely proceeded in a sequence of oxidative addition and β-hydride elimination (Figure 3e). Moreover, no noticeable conversion of benzofuran was achieved in its stoichiometric reaction with Ni(0) and the tertiary chloride 2k. In contrast, the stoichiometric reaction with Ni(II) in the presence of Zn produced the ring-opening product 3ak in 31% yield. This result suggests that Zn should serve as an intermediate reductant instead of a terminal reducing agent in the studied reaction. Besides, we confirmed that no background ring-opening reaction occurred in the absence of Ni-catalyst (Figure 3f). Furthermore, we found out that the Z-alkene 3aa′ was able to completely isomerize to its E-analog 3aa under standard reaction conditions. In contrast, no isomerization occurred in the absence of the Ni-catalyst. Notably, only a small amount of the Z-configurated precursor was converted to the E-olefin when conducting the reaction without alkyl halides (Figure 3g). These results reveal that the primary product of our reaction could be Z-alkenes, which are transformed into E-alkenes under the catalysis of a Ni-species. In addition, no Heck reaction product 3ak was formed when o-vinyl phenol was reacted with the tertiary alkyl chloride 2k, excluding a reaction pathway consisting of NiH-mediated ring-opening of benzofurans and the following Heck reaction with alkyl halides (Figure 3h).51 Figure 3 | (a–h) Control experiments. Download figure Download PowerPoint Proposed reaction mechanism On the basis of the results of the control experiments, we tentatively proposed a mechanism exemplified by benzofuran ( 1a) and tert-butyl chloride ( 2i) (Figure 4). Initially, the reductive reaction conditions led to the generation of a Ni(0) species I, which undergoes oxidative addition with tert-butyl chloride ( 2i). The resultant Ni(II) complex II equilibrates with a cage III consisting of tert-butyl radical and Ni(I)Cl.52,53 Next, Zn-mediated reduction of the intermediate II provides a Ni(I) species IV, which performs migratory insertion to benzofuran ( 1a) followed by β-oxygen elimination from the resultant Ni(I) complex V, to afford the E-alkene VI.36,37 In the final step, Ni(0) I is regenerated via Zn-mediated reduction of the Ni(I) complex VI to close the catalytic cycle. After completion of the reaction, the protonation of the zinc phenolate VII provides the product 3ai. Figure 4 | Proposed catalytic cycle. Download figure Download PowerPoint Conclusions We described the nickel-catalyzed reductive ring-opening of benzofurans with alkyl halides as electrophilic coupling partners. In this process, the challenging inert endocyclic carbon–oxygen bond was successfully cleaved, leading to dearomatization and skeletal transformation of the benzofuran precursors. This reaction offers an efficient entry to (E)-o-alkenylphenols with high E-selectivity. The mild reaction conditions allow for compatibility of sensitive functional moieties, such as cyano, ester, and boronate. Taking advantage of the o-hydroxyl group, simple derivatizations of the ring-opening products result in the rapid construction of the framework of o-substituted alkenyl benzene and benzofuranone. Supporting Information Supporting Information is available and includes experimental procedures, characterization data, and 1H NMR, 13C NMR, and 19F NMR for the products. Conflict of Interest The authors declare no competing interests. Acknowledgments This work is supported by National Natural Science Foundation of China (grant no. 21772183), the Fundamental Research Funds for the Central Universities (grant no. WK2060190086), and "1000-Youth Talents Plan" start-up funding as well as the University of Science and Technology of China. References 1. Wang C.Electrophilic Ring Opening of Small Heterocycles.Synthesis2017, 49, 5307–5319. Google Scholar 2. Gansäuer A.; Bluhm H.; Pierobon M.Emergence of a Novel Catalytic Radical Reaction: Titanocene-Catalyzed Reductive Opening of Epoxides.J. Am. Chem. Soc.1998, 120, 12849–12859. Google Scholar 3. Lautens M.; Ouellet S. G.; Raeppel S.Amphoteric Character of 2-Vinyloxiranes: Synthetic Equivalents of β,λ-Unsaturated Aldehydes and a Vinylogous Enolate.Angew. Chem. Int. Ed.2000, 39, 4079–4082. Google Scholar 4. Araki S.; Kameda K.; Tanaka J.; Hirashita T.; Yamamura H.; Kawai M.Umpolung of Vinyloxiranes: Regio- and Stereoselectivity of the In/Pd-Mediated Allylation of Carbonyl Compounds.J. Org. Chem.2001, 66, 7919–7921. Google Scholar 5. Gansäuer A.; Bluhm H.; Lauterbach T.Titanocene‐Catalysed Enantioselective Opening of Meso‐Epoxides.Adv. Synth. Catal.2001, 343, 785–787. Google Scholar 6. Lautens M.; Tayama E.; Nguyen D.Direct Vinylogous Mannich-Type Reactions via Ring Opening and Rearrangement of Vinyloxiranes.Org. Lett.2004, 6, 345–347. Google Scholar 7. Friedrich J.; Walczak K.; Dolg M.; Piestert F.; Lauterbach T.; Worgull D.; Gansäuer A.Titanocene Catalyzed 4-Exo Cyclizations: Mechanism, Experiment, Catalyst Design.J. Am. Chem. Soc.2008, 130, 1788–1796. Google Scholar 8. Gansäuer A.; Lauterbach T.; Geich-Gimbel D.Polarity Matching of Radical Trapping: High Yielding 3‐Exo and 4‐Exo Cyclizations.Chem. Eur. J.2004, 10, 4983. Google Scholar 9. Gansäuer A.; Worgull D.; Knebel K.; Huth I.; Schnakenburg G.4‐Exo Cyclizations by Template Catalysis.Angew. Chem. Int. Ed.2009, 48, 8882–8885. Google Scholar 10. Feng J.; Garza V. J.; Krische M. J.Redox-Triggered C–C Coupling of Alcohols and Vinyl Epoxides: Diastereo- and Enantioselective Formation of All-Carbon Quaternary Centers via tert-(Hydroxy)Prenylation.J. Am. Chem. Soc.2014, 136, 8911–8914. Google Scholar 11. Zhao Y.; Weix D. J.Nickel-Catalyzed Regiodivergent Opening of Epoxides with Aryl Halides: Co-Catalysis Controls Regioselectivity.J. Am. Chem. Soc.2014, 136, 48–51. Google Scholar 12. Zhao Y.; Weix D. J.Enantioselective Cross-Coupling of Meso-Epoxides with Aryl Halides.J. Am. Chem. Soc.2015, 137, 3237–3240. Google Scholar 13. Lin Z.; Lan Y.; Wang C.Titanocene-Catalyzed Reductive Domino Epoxide Ring Opening/Defluorinative Cross-Coupling Reaction.Org. Lett.2020, 22, 3509–3514. Google Scholar 14. Lin Z.; Lan Y.; Wang C.Ligand-Free Nickel-Catalyzed Reductive Allylic Defluorinative Cross-Coupling of α-Trifluoromethyl Alkenes with Epoxides.Synlett2020, 31. Google Scholar 15. Ohno F H.; Hamaguchi H.; Tanaka T.Umpolung of Chiral 2-Ethynylaziridines: Indium(I)-Mediated Stereoselective Synthesis of Nonracemic 1,3-Amino Alcohols Bearing Three Chiral Centers, Catalyzed by Palladium(0).Org. Lett.2000, 2, 2161–2163. Google Scholar 16. Takemoto Y.; Anzai M.; Yanada R.; Fujii N.; Ohno H.; Ibuka T.Stereoselective Synthesis of Nonracemic 1,3-Amino Alcohols from Chiral 2-Vinylaziridines by InI–Pd(0)-Promoted Metalation.Tetrahedron Lett.2001, 42, 1725–1728. Google Scholar 17. Zhang Y.-Q.; Vogelsang E.; Qu Z.-W.; Grimme S.; Gansäuer A.Titanocene-Catalyzed Radical Opening of N-Acylated Aziridines.Angew. Chem. Int. Ed.2017, 56, 12654–12657. Google Scholar 18. Hao W.; Wu X.; Sun J. Z.; Siu J. C.; MacMillan S. N.; Lin S.Radical Redox-Relay Catalysis: Formal [3+2] Cycloaddition of N-Acylaziridines and Alkenes.J. Am. Chem. Soc.2017, 139, 12141–12144. Google Scholar 19. Woods B. P.; Orlandi M.; Huang C.-Y.; Sigman M. S.; Doyle A. G.Nickel-Catalyzed Enantioselective Reductive Cross-Coupling of Styrenyl Aziridines.J. Am. Chem. Soc.2017, 139, 5688–5691. Google Scholar 20. Sugiyama Y.-K.; Heigozono S.; Okamoto S.Iron-Catalyzed Reductive Magnesiation of Oxetanes to Generate (3-Oxidopropyl)magnesium Reagents.Org. Lett.2014, 16, 6278–6281. Google Scholar 21. Klimczak K.; B. in Reactions of Chiral with Entry into Nonracemic Google Scholar S.; J.; B. Control by an in the Reactions of with Google Scholar Ding D.; Dong H.; Wang Domino Ring Reaction of via a Reductive Google Scholar Ding D.; Wang Reductive Electrophilic Ring Opening of with Google Scholar E.; of into of into and Aryl into Am. Chem. Google Scholar E.; S.; of into by Org. 49, Google Scholar J.; Stereoselective of C–O at Google Scholar M.; C.; Catalyzed Coupling Synthesis of from Google Scholar M.; T.; T.; Cross-Coupling of with Grignard via C–O Am. Chem. Google Scholar Nguyen T.; Negishi Formation by the Reaction of with Stereoselective Synthesis of and and Google Scholar 31. H.; R.; H.; of or with 56, Google Scholar K.; Tanaka S.; K.; G.; of to by the of a J. Org. Google Scholar T.; R.; H.; Cross-Coupling Reaction of with Aryl Grignard Google Scholar H.; S.; K.; into the of Am. Chem. Soc.2017, Google Scholar S.; H.; K.; Ring Opening of Benzofurans and to of into the Google Scholar P.; G.; Ring-Opening of and Benzofurans with Chem. Int. Ed.2017, 56, Google Scholar H.; K.; Ring-Opening of Benzofurans with Chem. Int. Google Scholar Zhang X.; Ring Opening of Benzofurans and an Enantioselective Chem. Int. Google Scholar N.; S.; Ring Opening and of to Synthetic Google Scholar D. A.; Weix D. of and Org. Google Scholar T.; A.; Reductive Coupling Reactions of Halides with Eur. Google Scholar J.; Wang X.; W.; Reductive Coupling of Alkyl Halides with and Chem. 2, Google Scholar Weix D. and for Coupling of Halides with Alkyl Chem. 48, Google Scholar Wang X.; Y.; Reductive Google Scholar E.; in by Google Scholar E.; S. E.; S. Enantioselective Reductive Cross-Coupling 10, Google Scholar Y.; Wang Coupling Google Scholar H.; in on Eur. Google Scholar T.; S.; S.; S.; Fujii N.; Ohno Synthesis of by and Google Scholar Wang H.; Dong Wang Y.; J.; of to with as Lett.2014, 16, Google Scholar S.; C.; Novel 49, Google Scholar R.; M.; A.; G.; P.; M. C.; of the Ni(0) with Alkyl Halides: Reactions Radical and Google Scholar J. J.; C.; of Alkyl or Am. Chem. 1788–1796. Google Scholar Information work is supported by National Natural Science Foundation of China (grant no. 21772183), the Fundamental Research Funds for the Central Universities (grant no. WK2060190086), and "1000-Youth Talents Plan" start-up funding as well as the University of Science and Technology of China.