Nickel-Catalyzed Negishi Coupling of Cyclobutanone Oxime Esters with Aryl Zinc Reagents

Bin Shuai Zhao-Ming Li Hui Qiu Ping Fang Tian-Sheng Mei

Citation:  Shuai Bin, Li Zhao-Ming, Qiu Hui, Fang Ping, Mei Tian-Sheng. Nickel-Catalyzed Negishi Coupling of Cyclobutanone Oxime Esters with Aryl Zinc Reagents[J]. Chinese Journal of Organic Chemistry, 2020, 40(3): 651-662. doi: 10.6023/cjoc201911016 shu

镍催化环丁酮肟酯与芳基锌试剂的Negishi偶联反应

    通讯作者: 方萍, pfang@sioc.ac.cn
    梅天胜, mei7900@sioc.ac.cn
  • 基金项目:

    中国科学院战略性先导科技专项(No.XDB20000000)、国家自然科学基金(Nos.21572245,21772222,21772220)、上海市科委(Nos.17JC1401200,18JC1415600)资助项目

    上海市科委 18JC1415600

    上海市科委 17JC1401200

    中国科学院战略性先导科技专项 XDB20000000

    国家自然科学基金 21772222

    国家自然科学基金 21772220

    国家自然科学基金 21572245

摘要: 发展了一种镍催化环丁酮肟酯和芳基锌试剂之间Negishi偶联的方法.镍既作为亚胺自由基的引发剂,也作为芳基锌试剂与烷基自由基偶联反应的催化剂在反应中起作用.本方法可避免使用剧毒的氰化物,且具有很广的底物适应性和官能团兼容性,因此可能是一种具有潜在吸引力的高效合成烷基腈类化合物的新策略.初步的机理研究显示,该反应极可能经历自由基历程.

English

  • In contrast to the classical polar reaction pathway (two electron pathway), radicals can serve as both nucleophile and electrophile, and radical mediated transformations have higher functional group compatibility.[1] Thereby, the merger of radical and transition metal catalysis is an attractive strategy in organic synthesis.[2] Owing to the diverse readily available oxidation states (Ni0, Ni, Ni, Ni, and Ni) and less prone to β-H elimination, [3] Ni-catalyzed cross-couplings via alkyl radical has been developed as a powerful tool to forge carbon-carbon (C—C) and carbon-heteroatom (C—Y) bonds, including asymmetric variants.[4]

    Alkyl halides, sulfones, and redox-active esters are widely used as alkyl radical precursors for Ni-catalyzed cross-coupling.[5~7] Alternatively, cycloketone oximes are attractive alkyl radical precursors, wherein the N—O bond of oximes can be activated upon single-electron-transfer (SET) to generate alkyl radicals via C—C bond cleavage from resulting iminyl radicals.[8] For instance, Zard and co-workers[9] reported a ring opening of iminyl radicals when sulphenylimines was irradiated by UV or initiated by organotin reagent in 1991. Subsequently, they disclosed that oxime esters could also be activated to generate iminyl radicals by iron and nickel powder.[10] Since then, much efforts have been devoted to develop new transformations based on cycloketone oxime esters, wherein various valuable alkyl nitriles can be obtained, avoiding the use of extremely toxic NaCN or KCN.[11~15] Alkyl nitriles not only widely exist in natural products, pharmaceuticals and agrochemicals, but are also versatile intermediate in organic synthesis and can be easily converted to amides, ketones, imidazoles, and oxazoles.[16]

    Recently, Selander and co-workers[17] reported a nickel catalyzed Suzuki coupling, wherein only three examples were shown (left, Scheme 1a). However, the reaction requires super stoichiometric amount (10 equiv.) of Et3N as the base under elevated temperature (90 ℃). Later, Wang and Ding[18] reported a Ni-catalyzed cross-coupling of cycloketone oxime esters with aromatic acid chlorides using metal Mn as the reductant (right, Scheme 1a). As part of our continuing interest in Ni-catalyzed reactions and radical chemistry, [19] we wondered whether alkyl radicals generated from oxime esters by Ni catalysis could be captured by aryl nickel species and thus providing an efficient and mild protocol to prepare alkyl nitriles (Scheme 1b).[20] Herein, we report a Ni-catalyzed Negishi coupling of cyclobutanone oxime esters with aryl zinc reagents, in which Ni catalysis servers as dual roles for iminyl radical generation and cross-coupling of an alkyl radical with an aryl zinc reagent (Scheme 1c). The protocol provides an efficient method for the syntheses of various aliphatic nitriles in good yield, avoiding the use of poisonous cyanide. The broad substrate scope and good functional group compatibility make this method attractive for the synthesis of valuable nitriles. Preliminary mechanistic studies indicate that a radical pathway is involved in the product formation.

    Scheme 1

    Scheme 1.  Nickel-catalyzed transformations of oxime esters

    To test our hypothesis, cyclobutanone oxime ester 1a was initially selected as the substrate. However, no desired product was observed (Table 1, Entry 1). To our delight, changing acetate 1a to benzoate 1a' afforded 3a in 46% yield (Entry 2). Replacement of 1a' with p-trifluoromethyl-benzoate 1a'' further improved the yield to 96% (Entry 3), indicating a significant electronic effect of the acyl group on the reaction. Other metal catalyst such as Co(acac)2 was not effective for the reaction (Entry 4). While with FeCl3 as catalyst, it afforded only 19% yield of 3a (Entry 5). The inferior yield of FeCl3 was attributed to the formation of the halogenation side product. A brief ligand screening revealed obvious ligand effects, and 4, 4'-di-tert-butyl-2, 2'-bipyridine (L5) was found to be optimal (Entries 6~12). Notably, solvents were also critical, reaction carried out in tetrahydrofuran (THF) furnished product 3a in 53% yield, which was much lower than that of in N, N'-dimethyl-formamide (DMF) (Entry 13). Switching catalyst from NiBr2(glyme) to NiCl2(glyme) and reducing the catalyst loading to 5 mol% slightly decreased the yield (Entries 14, 15). Further reducing the catalyst loading to 1 mol% decreased the yield to 73% (Entry 16). The amount of 2a was also investigated, increasing the amount of 2a did not improve the yield, decreasing it led to the low yield.

    Table 1

    Table 1.  Optimization of reaction conditionsa
    下载: 导出CSV
    Entry Oxime ester Catalyst Ligand Yieldb/%
    1 1a NiBr2(glyme) L5 Trace
    2 1a' NiBr2(glyme) L5 46
    3 1a'' NiBr2(glyme) L5 96
    4 1a'' Co(acac)2 L5 Trace
    5 1a'' FeCl3 L5 19
    6 1a'' NiBr2(glyme) L1 66
    7 1a'' NiBr2(glyme) L2 93
    8 1a'' NiBr2(glyme) L3 71
    9 1a'' NiBr2(glyme) L4 82
    10 1a'' NiBr2(glyme) L6 44
    11 1a'' NiBr2(glyme) L7 79
    12 1a'' NiBr2(glyme) L8 93
    13c 1a'' NiBr2(glyme) L5 53
    14d 1a'' NiBr2(glyme) L5 86
    15e 1a'' NiCl2(glyme) L5 91
    16f 1a'' NiCl2(glyme) L5 73
    a Reaction conditions: 10 mol% NiBr2(glyme), 10 mol% L5, 1a (0.2 mmol, 1.0 equiv.), 2a (0.2 mmol, 1.0 equiv.) in DMF (0.2 mL), r.t., 12 h. b Yield determined by HNMR using 1, 4-dimethoxybenzene as internal standard. c THF as solvent. d 5 mol% NiBr2(glyme) was used. e 5 mol% NiCl2(glyme) was used. f 1 mol% NiCl2(glyme) was used.

    With the optimized conditions in hand, we further investigated the substrate scope of oxime esters (Table 2). A variety of 3-substituted cyclobutanone oxime esters react smoothly to afford the corresponding alkyl nitriles in good yields (3a~3n). Substrates bearing functional groups including fluoro, chloro, bromo, and CF3 groups were well-tolerated under the standard reaction conditions. For 2-substituted oxime esters, C—C bond cleavage selectively occurs on the more substituted side, affording a thermodynamically favorable secondary radical intermediate. The corresponding product was obtained in 64%~94% yield (3o~3q). The oxime ester derived from benzocyclobutenone was also efficient substrate and product 3r was obtained in 91% yield. Notably, alkenyl groups were also compatible, 3s and 3t were obtained in 90% and 81% yields, respectively. This result indicated that the capture of alkyl radicals by aryl nickel species was much faster than the intermolecular addition of radicals to alkenes. Substrates bearing 5- and 6-membered rings gave products 3u and 3v in trans-configuration.

    Table 2

    Table 2.  Substrate scope of oxime esters
    下载: 导出CSV

    Next, we turned our attention to examine the scope of organozinc reagents (Table 3). Under the standard conditions, organozinc reagents bearing chloro, bromo and iodo substituent gave the desired products in moderate to good yields (4b~4d). Organozinc reagents with electron withdrawing group such as CF3 and OCF3 groups were well-tolerated (4e, 4f, 4q). Ortho-substituted zinc reagents successfully afforded 4g and 4r in 94% and 85% yields, respectively. It was noteworthy that sulfur and nitrogen containing organozinc reagents reacted smoothly with 1a'' to afford the corresponding products in 66%~85% yields (4j, 4k, 4r~4t). However, alkenyl zinc or alkynyl zinc reagents delivered no cross-coupling products. But 23% yield of 4u was obtained when 3-phenyl propyl zinc reagent was used.

    Table 3

    Table 3.  Substrate scope of organozinc reagents
    下载: 导出CSV

    To gain insights into the reaction mechanism, control experiments was performed. When oxime ester 1x reacted with 2a under standard condition, 29% of 3x was isolated. Theoretically, the direct capture of ring opening radical intermediate Int Ⅰ by aryl nickel species could form 3y. Int Ⅰ could produce Int Ⅱ through an intramolecular cyclization, and trapping Int Ⅱ by aryl nickel could deliver 3z. However, 3y and 3z were not detected and 3x was isolated instead. We speculated that Int Ⅲ was formed from Int Ⅱ via a fast 1.5-hydrogen atom transfer process. The more stable radical in the α-position of cyano group then reacted with aryl nickel to produce 3x (Scheme 2a). Moreover, stoichiometric amount of TEMPO was added to the reaction system of 1a and 2a, formation of the desired product 3a was inhibited and radical trapping product 5 was isolated in 16% yield (Scheme 2b). Stoichiometric experiment was also carried out with an in-situ formed nickel complex. And the corresponding product 4v was isolated in 60% yield (Scheme 2c).

    Scheme 2

    Scheme 2.  Mechanistic experiments

    Based on these aforementioned results and related literature, [21] a possible mechanism is proposed in Scheme 3. First, oxime ester is activated by nickel catalyst via SET and furnishing iminyl radical which is further converted to radical by fragmentation. Aryl nickel species is formed by transmetalation of aryl zinc reagents to a Ni(Ⅱ) intermediate . Then the radical is trapped by aryl nickel species , affording a trivalent nickel intermediate . Subsequent reductive elimination gives the desired product 3 and regenerates the catalyst.

    Scheme 3

    Scheme 3.  Proposed reaction mechanism

    Overall, we have developed a nickel catalyzed crosscoupling of cyclobutanone oxime esters with organozinc reagents. The mild reaction conditions, wide substrate scope and excellent functional group compatibility made this protocol an efficient method to prepare a wide variety of alkyl nitriles. Preliminary mechanistic experiments suggest that the reaction proceeds through a radical intermediate.

    Unless otherwise stated, all reagents and solvents were purchased from commercial suppliers and used without further purification. 1H NMR and 13C NMR spectra were recorded at 400 MHz NMR spectrometer using CDCl3 as solvent and TMS as an internal standard.

    Cyclobutanone O-(4-(trifluoromethyl)benzoyl) oxime (1a): According to the literature, [22a] 1a was prepared from the commercially available cyclobutanone as a white solid (73% yield). The data is consistent with the literature report.

    3-Benzylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1b): According to the literature, [22a] 1b was prepared from the commercially available allylbenzene as a white solid (64% yield). The data is consistent with the literature report.

    3-Methyl-3-phenylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1c): According to the literature, [22b] 1c was prepared from the commercially available prop-1-en-2-ylbenzene as a yellow solid (81% yield). The data is consistent with the literature report.

    3-Phenylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1d): According to the literature, [22b] 1d was prepared from the commercially available styrene as a white solid (86% yield). The data is consistent with the literature report.

    3-(4-Fluorophenyl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1e): According to the literature, [22a] 1e was prepared from the commercially available 1-fluoro-4-vinylbenzene as a white solid (77% yield). m.p. 111.3~114.3 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.17 (d, J=8.1 Hz, 2H), 7.74 (d, J=8.2 Hz, 2H), 7.26 (m, 2H), 7.06 (m, 2H), 3.77~3.53 (m, 3H), 3.23 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 166.44, 162.80, 160.55 (d, J=246 Hz), 138.53 (d, J=3 Hz), 134.65 (q, J=33 Hz), 132.20, 130.06, 127.86 (d, J=8 Hz), 125.59 (q, J=4 Hz), 124.89 (q, J=271 Hz), 115.55 (q, J=21 Hz), 39.73, 39.71, 31.92; 19F NMR (376 MHz, CDCl3) δ: -63.18, -115.53; IR (neat) v: 1739, 1687, 1323, 1262, 1221, 1125, 1076, 825, 528 cm-1. HRMS (ESI) cacld for C18H13F4NO2Na [M+Na]+ 374.0775, found 374.0783

    3-(2-Fluorophenyl)cyclobutan-1-one O-(4-(trifluoromethyl) benzoyl) oxime (1f): According to the literature, [22b] 1f was prepared from the commercially available 1-fluoro-2-vinylbenzene as a white solid (69% yield). m.p. 70.6~71.5 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.16 (d, J=8.2 Hz, 2H), 7.72 (d, J=8.2 Hz, 2H), 7.24 (m, 2H), 7.14 (td, J=7.5, 1.3 Hz, 1H), 7.09~7.02 (m, 1H), 3.86 (p, J=8.4 Hz, 1H), 3.69~3.53 (m, 2H), 3.40~3.25 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 166.71, 162.78, 161.21 (d, J=244 Hz), 134.73 (q, J=33 Hz), 132.25, 130.06, 129.19 (d, J=14 Hz), 128.74 (d, J=8 Hz), 127.62 (d, J=4 Hz), 125.57 (q, J=4 Hz), 124.30 (d, J=4 Hz), 123.61 (q, J=273 Hz), 115.60 (d, J=22 Hz), 38.51 (d, J=2 Hz), 38.32 (d, J=2 Hz), 27.44 (d, J=2 Hz); 19F NMR (376 MHz, CDCl3) δ: -63.19, -116.78; IR (neat) v: 1739, 1492, 1323, 1262, 1164, 1075, 872, 753 cm-1. HRMS (ESI) cacld for C18H13F4NO2Na [M+Na]+ 374.0775, found 374.0769

    3-(3-Bromophenyl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1g): According to the literature, [22b] 1g was prepared from the commercially available 1-bro-mo-3-vinylbenzene as a white solid (83% yield). m.p. 67.3~72.7 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.18~8.13 (d, J=8.1 Hz, 2H), 7.72 (d, J=8.1 Hz, 2H), 7.43~7.37 (m, 2H), 7.26~7.18 (m, 2H), 3.75~3.53 (m, 3H), 3.30~3.17 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 166.03, 162.73, 145.10, 134.65 (q, J=33 Hz), 132.16, 130.39, 130.16, 130.06, 129.62, 125.59 (q, J=3 Hz), 124.98, 122.91, 122.18, 39.37, 32.17; 19F NMR (376 MHz, CDCl3) δ: -63.18; IR (neat) v: 1740, 1408, 1321, 1256, 1126, 1067, 844, 767, 687 cm-1. HRMS (ESI) cacld for C18H13-BrF3NO2Na [M+Na]+ 433.9974, found 433.9984

    3-(4-Chlorophenyl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1h): According to the literature, [22b] 1h was prepared from the commercially available 1-chloro-4-vinylbenzene as a white solid (88% yield). m.p. 137.2~140.4 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.19 (d, J=8.0 Hz, 2H), 7.76 (d, J=8.0 Hz, 2H), 7.35 (d, J=1.7 Hz, 2H), 7.30~7.23 (d, J=1.7 Hz, 2H), 3.79~3.58 (m, 4H), 3.25 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 166.23, 162.77, 141.28, 134.67 (q, J=33 Hz), 132.83, 132.17, 130.07, 128.94, 127.75, 125.60 (q, J=3 Hz), 123.60 (q, J=274 Hz), 39.57, 39.55, 32.03; 19F NMR (377 MHz, CDCl3) δ: -63.15; IR (neat) v: 1738, 1687, 1323, 1261, 1181, 1124, 1074, 1011, 867, 818, 698 cm-1. HRMS (ESI) cacld for C18H13ClF3NO2Na [M+Na]+ 390.0479, found 390.0483

    3-(4-(Trifluoromethyl)phenyl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1i): According to the literature, [22b] 1i was prepared from the commercially available 1-(trifluoromethyl)-4-vinylbenzene as a white solid (80% yield). m.p. 156.3~158.5 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.15 (d, J=8.1 Hz, 2H), 7.72 (d, J=8.2 Hz, 2H), 7.61 (d, J=8.0 Hz, 2H), 7.39 (d, J=8.0 Hz, 2H), 3.78 (p, J=7.9 Hz, 1H), 3.72~3.57 (m, 2H), 3.34~3.18 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 165.84, 162.73, 146.77, 135.02 (q, J=33 Hz), 132.12, 130.06, 129.26 (q, J=33 Hz), 126.78, 125.82 (q, J=3 Hz), 125.60 (q, J=3 Hz), 124.87 (q, J=53 Hz), 122.16 (q, J=54 Hz), 39.40, 32.35; 19F NMR (376 MHz, CDCl3) δ: -62.52, -63.21; IR (neat) v: 2935, 1738, 1511, 1323, 1244, 1159, 1109, 1064, 827, 584 cm-1. HRMS (ESI) cacld for C19H13F6N-O2Na [M+Na]+ 424.0743, found 424.0748

    3-(4-(Tert-butyl)phenyl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1j): According to the literature, [22c] 1j was prepared from the commercially available 1-(tert-butyl)-4-vinylbenzene as a white solid (89% yield). The data is consistent with the literature report.

    3-Methyl-3-(3-(trifluoromethyl)phenyl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1k): According to the literature, [22b] 1k was prepared from the commercially available 1-(prop-1-en-2-yl)-4-(trifluoromethyl)benzene as a white solid (78% yield). m.p. 87.5~89.6 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.21 (d, J=8.0 Hz, 2H), 7.77 (d, J=8.0 Hz, 2H), 7.59~7.46 (m, 4H), 3.52 (m, 2H), 3.41~3.25 (m, 2H), 1.65 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 165.03, 162.72, 148.73, 134.68 (q, J=33 Hz), 132.15, 130.94 (q, J=32 Hz), 130.08, 129.31, 128.62, 125.62 (q, J=4 Hz), 125.15 (q, J=50 Hz), 123.47 (q, J=3 Hz), 122.44 (q, J=50 Hz), 121.89 (q, J=3 Hz), 44.71, 44.67, 44.67, 38.11, 30.74; 19F NMR (377 MHz, CDCl3) δ: -62.55, -63.14; IR (neat) v: 1743, 1325, 1264, 1127, 1064, 862, 696 cm-1. HRMS (ESI) cacld for C20H15F6-NO2Na [M+Na]+ 438.0899, found 438.0888

    3-(Naphthalen-2-yl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1l): According to the literature, [22d] 1l was prepared from the commercially available 2-vinylnaphthalene as a white solid (75% yield). The data is consistent with the literature report.

    3-Propylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1m): According to the literature, [22b] 1m was prepared from the commercially available cyclobutanone as an oil (68% yield), m.p. 42.8~44.8 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.16 (d, J=8.1 Hz, 2H), 7.72 (d, J=8.2 Hz, 2H), 3.23 (m, 2H), 2.76~2.64 (m, 2H), 2.45 (p, J=7.4 Hz, 1H), 1.56 (qd, J=7.2, 3.3 Hz, 3H), 1.34 (h, J=7.3 Hz, 2H), 0.94 (t, J=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 168.40, 162.89, 134.82 (q, J=32 Hz), 132.41, 130.02, 125.48 (q, J=3 Hz), 122.21 (q, J=271 Hz), 38.24, 37.46, 28.14, 20.51, 13.90; 19F NMR (376 MHz, CDCl3) δ: -63.17; IR (neat) v: 1740, 1323, 1261, 1160, 1113, 1065, 1013, 891, 837, 740, 698 cm-1. HRMS (ESI) cacld for C15H16F3NONa [M+Na]+ 322.1025, found 322.1024

    Spiro[3.11]pentadecan-2-one O-(4-(trifluoromethyl)benzoyl) oxime (1n): According to the literature, [22b] 1n was prepared from the commercially available cyclobutanone as a white solid (75% yield). m.p. 125.4~132.2 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.18 (d, J=8.1 Hz, 2H), 7.75 (d, J=8.1 Hz, 2H), 2.81 (m, 4H), 1.61 (m, 4H), 1.38 (s, 18H); 13C NMR (101 MHz, CDCl3) δ: 167.78, 162.90, 134.50 (q, J=33 Hz), 132.45, 130.02, 125.50 (q, J=3 Hz), 123.50 (q, J=274 Hz), 42.49, 36.71, 33.41, 26.26, 25.93, 22.44, 22.18, 19.44; 19F NMR (377 MHz, CDCl3) δ: -63.13; IR (neat) v: 2932, 1744, 1322, 1252, 1127, 1078, 1013, 882, 696 cm-1. HRMS (ESI) cacld for C23H30F3NO2 [M+Na]+ 432.2121, found 432.2130

    (Z)-2-Benzylcyclobutan-1-one O-(4-(trifluoromethyl)-benzoyl) oxime (1o): According to the literature, [22e] 1o was prepared from the commercially available cyclobutanone as a yellow oil (54% yield), The spectrum was a mixture of cis and trans isomers. The data is consistent with the literature report.

    3-Phenethylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1p): According to the literature, [22b] 1p was prepared from the commercially available cyclobutanone as a yellow oil (83% yield). 1H NMR (400 MHz, CDCl3) δ: 8.08 (d, J=8.1 Hz, 2H), 7.65 (d, J=8.2 Hz, 2H), 7.22 (dd, J=8.1, 6.7 Hz, 2H), 7.17~7.08 (m, 3H), 3.25~3.10 (m, 2H), 2.72~2.59 (m, 2H), 2.60~2.53 (m, 2H), 2.38 (tt, J=9.5, 7.0 Hz, 1H), 1.88~1.77 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 167.95, 162.85, 141.24, 134.51 (q, J=33 Hz), 132.39, 130.03, 128.52, 128.36, 126.11, 125.53 (q, J=4 Hz), 123.59 (q, J=274 Hz), 37.70, 37.39, 37.34, 33.67, 27.85; 19F NMR (377 MHz, CDCl3) δ: -63.12; IR (neat) v: 1743, 1323, 1258, 1166, 1125, 1067, 1014, 859, 767, 697 cm-1. HRMS (ESI) cacld for C20H18F3-NO2Na [M+Na]+ 384.1182, found 384.1183

    (Z)-2-Pentylcyclobutan-1-one O-(4-(trifluoromethyl)-benzoyl) oxime (1q): According to the literature, [22b] 1q was prepared from the commercially available cyclobutanone as a yellow oil (43% yield). The spectrum was a mixture of cis and trans isomers. 1H NMR (400 MHz, CDCl3) δ: 8.17 (d, J=8.0 Hz, 2H), 7.74 (d, J=8.4 Hz, 2H), 3.47~2.96 (m, 2H), 2.57~2.20 (m, 2H), 1.94~1.58 (m, 3H), 1.49~1.25 (m, 6H), 0.91 (t, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 173.55, 162.90, 134.57 (q, J=33 Hz), 132.56, 129.97, 125.49 (q, J=3 Hz), 123.57 (q, J=273 Hz), 45.77, 32.28, 31.59, 29.09, 26.51, 22.49, 20.95, 14.02; 19F NMR (377 MHz, CDCl3) δ: -63.15; IR (neat) v: 2931, 1746, 1323, 1258, 1166, 1127, 1066, 1014, 860, 769, 699 cm-1. HRMS (ESI) cacld for C17H20F3-NO2Na [M+Na]+ 350.1338, found 350.1334.

    (E)-Bicyclo[4.2.0]octa-1(6), 2, 4-trien-7-one O-(4-(trifluoromethyl)benzoyl) oxime (1r): According to the literature, 22b 1r was prepared from the commercially available cyclobutanone as a white solid (85% yield). The spectrum was a mixture of cis and trans isomers. the data is consistent with the literature report.

    (Z)-2-(But-3-en-1-yl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1s): According to the literature, [22b] 1s was prepared from the commercially available cyclobutanone as a mixture of trans and cis isomers, yellow oil (39% yield). 1H NMR (400 MHz, CDCl3) δ: 8.17 (d, J=8.1 Hz, 2H), 7.74 (d, J=8.2 Hz, 2H), 5.83 (ddt, J=16.9, 10.2, 6.6 Hz, 1H), 5.15~4.97 (m, 2H), 3.54~3.39 (m, 1H), 3.21~2.95 (m, 2H), 2.37~2.11 (m, 3H), 2.00 (ddt, J=13.4, 8.5, 6.6 Hz, 1H), 1.83~1.73 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 173.29, 162.88, 137.59, 134.47, 132.51, 130.41, 129.98, 125.51, 115.32, 45.14, 31.41, 30.99, 29.12, 20.94; 19F NMR (377 MHz, CDCl3) δ: -63.15; IR (neat) v: 1745, 1323, 1258, 1166, 1126, 1066, 1014, 859, 768, 698 cm-1. HRMS (ESI) cacld for C16H16-F3NO2Na [M+Na]+ 334.1025, found 334.1029

    (Z)-2-Allylcyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1t): According to the literature, [22b] 1t was prepared from the commercially available cyclobutanone as a white solid (43% yield). The data is consistent with the literature report.

    (E)-2, 2a, 7, 7a-Tetrahydro-1H-cyclobuta[a]inden-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1u): According to the literature, [22b] 1u was prepared from the commercially available cyclobutanone as a white solid (71% yield), The spectrum was a mixture of cis and trans isomers. m.p. 114.2~123.7 ℃; 1H NMR (400 MHz, CDCl3) (major) δ: 8.10 (d, J=8.1 Hz, 2H), 7.69 (d, J=8.2 Hz, 2H), 7.33~7.17 (m, 4H), 4.25~4.13 (m, 1H), 4.05 (ddd, J=13.1, 8.4, 4.0 Hz, 1H), 3.66~3.27 (m, 3H), 3.12~2.88 (m, 1H); 1H NMR (400 MHz, CDCl3) (minor) δ: 8.21 (d, J=8.1 Hz, 2H), 7.78 (d, J=8.2 Hz, 2H), 7.33~7.17 (m, 4H), 4.25~4.13 (m, 1H), 4.05 (ddd, J=13.1, 8.4, 4.0 Hz, 1H), 3.66~3.27 (m, 3H), 3.12~2.88 (m, 1H). 13C NMR (101 MHz, CDCl3) δ: 172.59, 162.68, 144.02, 143.13, 142.37, 134.53 (q, J=33 Hz), 132.26, 130.00, 127.71, 127.49, 125.53 (q, J=4 Hz), 125.38, 124.97, 47.91, 40.45, 40.15, 36.96. 19F NMR (376 MHz, CDCl3) δ: -63.19; IR (neat) v: 1744, 1323, 1246, 1131, 1063, 1011, 838, 768, 681 cm-1. HRMS (ESI) cacld for C19H14F3NO2Na [M+Na]+ 368.0869, found 368.0863

    (E)-Bicyclo[3.2.0]hept-2-en-6-one O-(4-(trifluoromethyl)benzoyl) oxime (1v): According to the literature, [22b] 1v was prepared from the commercially available cyclobutanone as a yellow oil (67% yield), The spectrum was a mixture of cis and trans isomers. 1H NMR (400 MHz, CDCl3) δ: 8.13 (d, J=8.1 Hz, 2H), 7.71 (d, J=8.2 Hz, 2H), 5.88~5.77 (m, 2H), 3.95 (m, 1H), 3.52~3.39 (m, 1H), 3.28 (m, 1H), 2.94~2.63 (m, 3H); 13C NMR (101 MHz, CDCl3) δ: 173.80, 162.78, 134.47 (q, J=33 Hz), 132.57, 132.04, 129.99, 125.48 (q, J=3 Hz), 123.58 (q, J=274 Hz), 46.90, 40.83, 38.98, 37.66; 19F NMR (376 MHz, CDCl3) δ: -63.22; IR (neat) v: 1742, 1322, 1256, 1164, 1126, 1063, 976, 843, 768, 699 cm-1. HRMS (ESI) cacld for C15H12F3NONa [M+Na]+ 318.0712, found 318.0706

    (Z)-2-Methylcyclobutan-1-one O-(4-(trifluoromethyl)-benzoyl) oxime (1w): According to the literature, [22b] 1w was prepared from the commercially available cyclobutanone as a yellow oil (53% yield). The data is consistent with the literature report.

    (Z)-2-(Pent-4-en-1-yl)cyclobutan-1-one O-(4-(trifluoromethyl)benzoyl) oxime (1x): According to the literature, [22b] 1x was prepared from the commercially available cyclobutanone as an yellow oil (44% yield), 1H NMR (400 MHz, CDCl3) δ: 8.17 (d, J=8.1 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 5.82 (ddt, J=16.9, 10.2, 6.7 Hz, 1H), 5.08~4.95 (m, 1H), 3.43 (ddtd, J=9.4, 6.2, 4.3, 3.6, 2.2 Hz, 1H), 3.19~2.93 (m, 1H), 2.28 (dtd, J=11.2, 9.6, 5.9 Hz, 1H), 2.11 (qd, J=6.8, 1.5 Hz, 1H), 1.96~1.64 (m, 2H), 1.60~1.48 (m, 1H); 13C NMR (101 MHz, CDCl3) δ: 173.32, 162.87, 138.33, 134.43 (q, J=33 Hz), 132.52, 129.97, 125.49 (q, J=3 Hz), 123.41 (q, J=274 Hz), 114.87, 45.59, 33.48, 31.74, 29.11, 26.10, 20.91; 19F NMR (376 MHz, CDCl3) δ: -63.18; IR (neat) v: 1743, 1324, 1258, 1153, 1065, 983, 768, 687 cm-1. HRMS (EI) cacld for C17H18F3-NO2Na [M+Na]+ 348.1182, found 348.1177.

    To a 4 mL screwed-capped vial was added oxime ester 1 (0.2 mmol), NiCl2 glyme (2 mg, 0.01 mmol), ligand (3 mg, 0.01 mmol), DMF (0.2 mL) in Glove box. The resulting mixture was stirred for 15 min at room temperature. To the solution was added organo-zinc reagent (0.8 mL, 0.25 mol·L-1, 0.2 mmol). The vial was removed from Glove box and stirred at room temperature for 12 h. After this time, the reaction mixture was quenched with saturated ammonia chloride (1 mol·L-1), and diluted with ethyl acetate. The organic layer was separated and dried over anhydrous Na2SO4, filtered and removed under vacuum. The corresponding product 3 or 4 was obtained by flash chromatography.

    4-(4-Methoxyphenyl)butanenitrile (3a): Colorless oil, 29.8 mg, 85% yield. The data is consistent with the literature report.[22f]

    3-Benzyl-4-(4-methoxyphenyl)butanenitrile (3b): Colorless oil, 33.1 mg, 62% yield. 1H NMR (400 MHz, CDCl3) δ: 7.36~7.29 (m, 2H), 7.28~7.23 (m, 1H), 7.23~7.18 (m, 2H), 7.12 (d, J=8.5 Hz, 2H), 6.89~6.84 (m, 2H), 3.80 (s, 3H), 2.84 (ddd, J=19.0, 13.9, 5.7 Hz, 2H), 2.66 (td, J=13.3, 8.8 Hz, 2H), 2.26~2.18 (m, 1H), 2.15 (d, J=4.9 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 158.37, 138.89, 130.74, 130.00, 129.04, 128.74, 126.67, 118.43, 114.11, 55.30, 39.70, 38.87, 20.26; IR (neat) v: 2925, 1780, 1511, 1452, 1245, 1178, 1033, 741, 701 cm-1. HRMS (ESI) cacld for C18H19NONa [M+Na]+ 288.1359, found 288.1353.

    4-(4-Methoxyphenyl)-3-methyl-3-phenylbutanenitrile (3c): Colorless oil, 42.9 mg, 81% yield. 1H NMR (400 MHz, CDCl3) δ: 7.37 (m, 2H), 7.34~7.22 (m, 3H), 6.73 (m, 4H), 3.77 (s, 3H), 3.02 (s, 2H), 2.68 (s, 2H), 1.54 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 158.40, 143.98, 131.24, 128.56, 128.52, 126.96, 126.08, 118.51, 113.34, 55.18, 47.31, 41.31, 29.38, 25.52; IR (neat) v: 3031, 2242, 1721, 1609, 1510, 1245, 1178, 1030, 836, 812, 755, 698 cm-1. HRMS (ESI) cacld for C18H19NONa [M+Na]+ 288.1365, found 288.1359.

    4-(4-Methoxyphenyl)-3-phenylbutanenitrile (3d): Colorless oil, 25.1 mg, 50% yield. 1H NMR (400 MHz, CDCl3) δ: 7.32 (dd, J=8.1, 6.5 Hz, 2H), 7.29~7.23 (m, 1H), 7.21 (dd, J=7.1, 1.8 Hz, 2H), 7.03~6.97 (m, 2H), 6.82~6.76 (m, 2H), 3.76 (s, 3H), 3.17 (p, J=6.9 Hz, 1H), 2.99 (dd, J=7.6, 2.4 Hz, 2H), 2.63~2.46 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 158.34, 141.37, 130.33, 130.01, 128.79, 127.46, 127.25, 118.51, 113.94, 55.21, 43.99, 40.33, 23.47; IR (neat) v: 3004, 2242, 1720, 1610, 1511, 1244, 1176, 1032, 816, 699 cm-1. HRMS (EI) cacld for C17H17NO [M]+ 251.1310, found 251.1305.

    3-(4-Fluorophenyl)-4-(4-methoxyphenyl)butanenitrile (3e): Colorless oil, 45.7 mg, 85% yield. 1H NMR (400 MHz, CDCl3) δ: 7.20~7.13 (m, 1H), 7.05~6.94 (m, 2H), 6.83~6.76 (m, 2H), 3.76 (s, 3H), 3.17 (qd, J=7.4, 5.7 Hz, 1H), 2.96 (d, J=7.5 Hz, 2H), 2.61~2.46 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 163.23, 160.78, 158.40, 137.03, 130.04, 129.98, 128.80 (d, J=129 Hz), 118.32, 115.67 (d, J=21 Hz), 113.98, 55.21, 43.33, 40.46, 23.66; 19F NMR (376 MHz, CDCl3) δ: -114.99; IR (neat) v: 2915, 1606, 1508, 1242, 1177, 1031, 830, 535 cm-1. HRMS (EI) cacld for C17H16FNO [M]+ 269.1216, found 269.1210.

    3-(2-Fluorophenyl)-4-(4-methoxyphenyl)butanenitrile (3f): Colorless oil, 31.2 mg, 58% yield. 1H NMR (400 MHz, CDCl3) δ: 7.22~7.13 (m, 2H), 7.05 (m, 1H), 7.02~6.94 (m, 3H), 6.76~6.70 (m, 2H), 3.70 (s, 3H), 3.44 (dt, J=8.3, 6.7 Hz, 1H), 3.01~2.89 (m, 2H), 2.56 (d, J=6.5 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 160.66 (d, J=246 Hz), 158.45, 130.10, 130.00, 129.03 (d, J=8 Hz), 128.65 (d, J=4 Hz), 127.99 (d, J=14 Hz), 124.49 (d, J=3 Hz), 118.32, 115.78 (d, J=22 Hz), 114.03, 55.26, 38.83, 37.66, 22.09; 19F NMR (376 MHz, CDCl3) δ: -118.03; IR (neat) v: 2933, 1722, 1611, 1511, 1490, 1245, 1033, 821 cm-1. HRMS (EI) cacld for C17H16FNO [M]+ 269.1216, found 269.1212.

    3-(3-Bromophenyl)-4-(4-methoxyphenyl)butanenitrile (3g): Colorless oil, 49.7 mg, 75% yield. 1H NMR (400 MHz, CDCl3) δ: 7.39 (dt, J=7.8, 1.5 Hz, 1H), 7.35 (s, 1H), 7.27~7.09 (m, 2H), 7.03~6.95 (m, 2H), 6.83~6.74 (m, 2H), 3.77 (s, 3H), 3.14 (p, J=7.0 Hz, 1H), 3.02~2.87 (m, 2H), 2.61~2.43 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 158.48, 143.64, 130.67, 130.38, 130.35, 129.98, 129.75, 126.02, 122.83, 118.10, 114.06, 55.24, 43.73, 40.21, 23.30; IR (neat) v: 2933, 1611, 1511, 1490, 1245, 1033, 821, 756 cm-1. HRMS (EI) cacld for C17H16BrNO [M]+ 329.0415, found 329.0410.

    3-(4-Chlorophenyl)-4-(4-methoxyphenyl)butanenitrile (3h): Yellow solid, 41.4 mg, 73% yield. m.p. 56.2~58.6 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.25~7.19 (m, 2H), 7.09~7.03 (m, 2H), 6.94~6.87 (m, 2H), 6.75~6.70 (m, 2H), 3.69 (s, 3H), 3.09 (m, 1H), 2.89 (d, J=7.5 Hz, 1H), 2.55~2.39 (m, 1H); 13C NMR (101 MHz, CDCl3) δ: 158.46, 139.79, 133.28, 130.03, 129.91, 129.00, 128.70, 118.30, 114.05, 55.27, 43.50, 40.32, 23.52; IR (neat) v: 2930, 1610, 1511, 1244, 1177, 1032, 784, 694 cm-1. HRMS (EI) cacld for C17H16ClNO [M]+ 285.0920, found 285.0915.

    4-(4-Methoxyphenyl)-3-(4-(trifluoromethyl)phenyl)butanenitrile (3i): Colorless oil, 41.1 mg, 64% yield. 1H NMR (400 MHz, CDCl3) δ: 7.58 (d, J=8.1 Hz, 2H), 7.32 (d, J=8.1 Hz, 2H), 7.04~6.94 (m, 2H), 6.80 (d, J=8.6 Hz, 2H), 3.76 (s, 3H), 3.24 (td, J=7.5, 5.8 Hz, 1H), 3.00 (d, J=7.5 Hz, 2H), 2.65~2.51 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 158.51, 145.26, 129.96, 129.58, 127.72, 125.81 (q, J=3 Hz), 123.98 (q, J=273 Hz), 118.01, 115.38 (q, J=123 Hz), 114.08, 55.22, 43.86, 40.15, 23.26; 19F NMR (376 MHz, CDCl3) δ: -62.52; IR (neat) v: 2935, 1613, 1511, 1323, 1245, 1162, 1109, 1067, 833 cm-1. HRMS (EI) cacld for C18H16F3NO [M]+ 319.1184, found 319.1179.

    3-(4-(tert-Butyl)phenyl)-4-(4-methoxyphenyl)butanenit-rile (3j): Yellow solid, 48.8 mg, 79% yield. m.p. 102.7~104.9 ℃, 1H NMR (400 MHz, CDCl3) δ: 7.28 (d, J=8.4 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 6.97 (d, J=8.6 Hz, 2H), 6.74 (d, J=8.6 Hz, 2H), 3.70 (s, 3H), 3.13~3.02 (m, 1H), 2.92 (qd, J=13.8, 7.5 Hz, 2H), 2.52–2.37 (m, 2H), 1.24 (s, 9H); 13C NMR (101 MHz, CDCl3) δ: 158.38, 150.34, 138.49, 130.64, 130.06, 126.89, 125.72, 118.73, 114.00, 55.28, 43.45, 40.23, 34.52, 31.37, 23.44; IR (neat) v: 2917, 1661, 1508, 1235, 1175, 1089, 1028, 827, 572 cm-1. HRMS (EI) cacld for C21H25NO [M]+: 307.1936, found 307.1931.

    4-(4-Methoxyphenyl)-3-methyl-3-(3-(trifluoromethyl)-phenyl) butanenitrile (3k): Yellow oil, 48.1 mg, 72% yield. 1H NMR (400 MHz, CDCl3) δ: 7.55 (d, J=7.6 Hz, 1H), 7.51~7.38 (m, 3H), 6.75~6.67 (m, 4H), 3.76 (d, J=0.9 Hz, 3H), 2.99 (m, 2H), 2.75~2.61 (m, 2H), 1.56 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 158.61, 145.04, 131.20, 130.65, 129.54 (q, J=1 Hz), 129.03, 127.78, 125.41, 123.90 (q, J=4 Hz), 122.94 (q, J=4 Hz), 117.94, 113.52, 55.19, 47.29, 41.54, 29.26, 25.34; 19F NMR (376 MHz, CDCl3) δ: -62.53; IR (neat) v: 2933, 1683, 1511, 1321, 1248, 1162, 1119, 1069, 1033, 802, 701 cm-1. HRMS (EI) cacld for C19H18F3NO [M]+ 333.1340, found 333.1335.

    4-(4-Methoxyphenyl)-3-(naphthalen-2-yl)butanenitrile(3l): Yellow solid, 52.4 mg, 87% yield. m.p. 143.1~144.5 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.74 (td, J=9.7, 9.1, 4.4 Hz, 3H), 7.58 (d, J=1.8 Hz, 1H), 7.45~7.34 (m, 2H), 7.28 (dd, J=8.5, 1.9 Hz, 1H), 6.99~6.93 (m, 2H), 6.76~6.66 (m, 2H), 3.69 (s, 3H), 3.29 (p, J=7.0 Hz, 1H), 3.10~2.96 (m, 2H), 2.66~2.51 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 158.39, 138.78, 133.43, 132.75, 130.30, 130.08, 128.66, 127.88, 127.69, 126.33, 126.20, 126.00, 125.23, 118.57, 114.01, 55.25, 44.18, 40.36, 23.57; IR (neat) v: 2925, 1610, 1510, 1243, 1176, 1032, 817, 747, 477 cm-1. HRMS (EI) cacld for C21H19NO [M]+ 301.1467, found 301.1461.

    3-(4-Methoxybenzyl)hexanenitrile (3m): Yellow oil, 36.1 mg, 83% yield. 1H NMR (400 MHz, CDCl3) δ: 7.07–6.97 (m, 2H), 6.82~6.75 (m, 2H), 3.72 (s, 3H), 2.69 (dd, J=13.9, 5.6 Hz, 1H), 2.44 (dd, J=13.9, 9.0 Hz, 1H), 2.24~2.05 (m, 2H), 1.96–1.73 (m, 1H), 1.43~1.23 (m, 4H), 0.87 (t, J=7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 158.25, 131.02, 130.00, 118.71, 114.01, 55.28, 38.90, 37.18, 35.53, 20.91, 19.98, 14.04; IR (neat) v: 2923, 1610, 1512, 1453, 1322, 1245, 1033, 745, 699 cm-1. HRMS (EI) cacld for C14H19NO [M]+ 217.1467, found 217.1460.

    2-(1-(4-Methoxybenzyl)cyclododecyl)acetonitrile (3n): White solid, 45.6 mg, 70% yield. m.p. 85.7~87.5 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.20~7.14 (m, 2H), 6.88~6.82 (m, 2H), 3.80 (s, 3H), 2.63 (s, 2H), 2.00 (s, 2H), 1.37 (m, 22H); 13C NMR (101 MHz, CDCl3) δ: 158.30, 131.29, 128.95, 118.94, 113.69, 55.22, 41.86, 39.97, 32.08, 26.66, 26.02, 25.57, 22.80, 22.25, 19.14; IR (neat) v: 2933, 1608, 1467, 1246, 1181, 1031, 841, 585 cm-1. HRMS (ESI) cacld for C22H33NONa [M+Na]+ 350.2460, found 350.2454.

    4-(4-Methoxyphenyl)-5-phenylpentanenitrile (3o): Yellow oil, 50.3 mg, 95% yield. 1H NMR (400 MHz, CDCl3) δ: 7.29~7.13 (m, 3H), 7.09~7.01 (m, 4H), 6.90~6.80 (m, 2H), 3.80 (s, 3H), 3.01~2.78 (m, 3H), 2.27~2.10 (m, 1H), 2.09~1.94 (m, 2H), 1.91~1.77 (m, 1H); 13C NMR (101 MHz, CDCl3) δ: 158.49, 139.55, 134.14, 129.08, 128.53, 128.31, 126.20, 119.59, 114.15, 55.24, 45.99, 43.56, 31.05, 15.38; IR (neat) v: 2930, 1610, 1511, 1422, 1246, 1177, 1031, 830, 699 cm-1. HRMS (EI) cacld for C18H19NO [M]+ 265.1467, found 265.1461.

    3-(4-Methoxybenzyl)-5-phenylpentanenitrile (3p): Yellow oil, 35.8 mg, 64% yield. 1H NMR (400 MHz, CDCl3) δ: 7.38~7.30 (m, 2H), 7.27~7.17 (m, 3H), 7.14~7.07 (m, 2H), 6.87 (dd, J=8.3, 1.6 Hz, 2H), 3.82 (s, 3H), 2.87 (m, 1H), 2.73 (m, 2H), 2.59 (m, 1H), 2.40~2.20 (m, 2H), 1.99 (m, 1H), 1.92~1.77 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 158.33, 141.17, 130.69, 130.01, 128.58, 128.34, 126.17, 118.49, 114.07, 55.30, 38.72, 36.72, 34.92, 33.02, 21.00; IR (neat) v: 2923, 1610, 1510, 1453, 1244, 1177, 1032, 835, 699 cm-1. HRMS (ESI) cacld for C19H21NONa [M+Na]+ 302.1515, found 302.1513.

    4-(4-Methoxyphenyl)nonanenitrile (3q): Colorless oil, 36.2 mg, 74% yield. 1H NMR (400 MHz, CDCl3) δ: 7.06 (d, J=8.5 Hz, 2H), 6.86 (d, J=8.5 Hz, 2H), 3.79 (s, 3H), 2.59 (m, 1H), 2.23~2.09 (m, 2H), 2.09~1.93 (m, 1H), 1.84~1.71 (m, 2H), 1.65~1.49 (m, 6H), 1.31~1.08 (m, 3H), 0.87–0.78 (m, 1H); 13C NMR (101 MHz, CDCl3) δ: 158.31, 134.99, 128.41, 119.82, 114.08, 55.22, 44.05, 36.62, 32.41, 31.75, 27.09, 22.50, 15.38, 14.03; IR (neat) v: 2926, 1610, 1511, 1459, 1245, 1177, 1034, 829 cm-1. HRMS (ESI) cacld for C16H23NONa [M+Na]+ 268.1672, found 268.1271.

    2-(4-Methoxybenzyl)benzonitrile (3r): Colorless oil, 40.5 mg, 91% yield. The data is consistent with the literature.[22g]

    4-(4-Methoxyphenyl)oct-7-enenitrile (3s). Colorless oil, 41.2 mg, 90% yield. 1H NMR (400 MHz, CDCl3) δ: 7.11~7.04 (m, 2H), 6.90~6.84 (m, 2H), 5.74 (ddt, J18.1, 9.4, 6.6 Hz, 1H), 5.00~4.87 (m, 2H), 3.80 (s, 3H), 2.70~2.51 (m, 1H), 2.25~2.10 (m, 1H), 2.09~1.97 (m, 2H), 1.91 (m, 2H), 1.78 (m, 1H), 1.74~1.62 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 158.44, 138.11, 134.37, 128.51, 119.71, 114.92, 114.17, 55.24, 43.38, 35.72, 32.36, 31.48, 15.37; IR (neat) v: 2928, 1639, 1511, 1245, 1177, 1034, 911, 829 cm-1. HRMS (EI) cacld for C15H19NO [M]+ 229.1467, found 229.1461.

    (E)-4-(4-Methoxyphenyl)oct-6-enenitrile (3t): Colorless oil, 35.8 mg, 64% yield. 1H NMR (400 MHz, CDCl3) δ: 7.14~6.98 (m, 2H), 6.88~6.79 (m, 2H), 5.64 (ddt, J=17.2, 10.2, 7.0 Hz, 1H), 5.07~4.89 (m, 2H), 3.78 (s, 3H), 2.69 (m, 1H), 2.35 (m, 2H), 2.25~2.14 (m, 1H), 2.11~1.96 (m, 2H), 1.87~1.68 (m, 1H): 13C NMR (101 MHz, CDCl3) δ: 158.44, 135.97, 134.28, 128.43, 119.62, 116.72, 114.13, 113.70, 55.22, 43.76, 41.04, 31.40, 15.27; IR (neat) v: 2930, 1610, 1511, 1443, 1245, 1177, 1033, 915, 830 cm-1. HRMS (ESI) cacld for C14H17NONa [M+Na]+ 238.1202, found 238.1206.

    2-(2-(4-Methoxyphenyl)-2, 3-dihydro-1H-inden-1-yl)acetonitrile (3u): Colorless oil, 48.2 mg, 92% yield. 1H NMR (400 MHz, CDCl3) δ: 7.44~7.36 (m, 1H), 7.31 (m, 5H), 7.01~6.83 (m, 2H), 3.85 (s, 3H), 3.52 (m, 1H), 3.44~3.28 (m, 2H), 3.14 (m, 1H), 2.82 (ddd, J=17.0, 5.0, 1.4 Hz, 1H), 2.63 (ddd, J=17.0, 6.5, 1.3 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ: 158.75, 142.39, 142.11, 134.12, 128.53, 128.00, 127.19, 124.72, 123.25, 118.48, 114.25, 55.36, 51.77, 48.99, 40.19, 20.49; IR (neat) v: 2934, 1609, 1510, 1466, 1248, 1180, 1029. 829, 776 cm-1. HRMS (ESI) cacld for C18H17NONa [M+Na]+ 286.1202, found 286.1203.

    2-(2-(4-Methoxyphenyl)cyclopent-3-en-1-yl)acetonitrile (3v): Colorless oil, 39.8 mg, 94% yield. 1H NMR (400 MHz, CDCl3) δ: 7.23~7.03 (m, 2H), 6.89~6.77 (m, 2H), 5.99~5.84 (m, 1H), 5.72 (m, 1H), 3.78 (s, 3H), 3.01 (m, 2H), 2.95~2.79 (m, 1H), 2.58~2.40 (m, 2H), 2.39 (m, 1H); 13C NMR (101 MHz, CDCl3) δ: 158.38, 136.17, 132.71, 130.58, 128.14, 118.58, 114.09, 55.28, 50.87, 49.41, 41.84, 22.22; IR (neat) v: 2963, 1611, 1512, 1441, 1245, 1024, 824, 725 cm-1. HRMS (ESI) cacld for C14H15NONa [M+Na]+ 236.1046, found 236.1045.

    4-(4-Methoxyphenyl)pentanenitrile (3w): Colorless oil, 33.7 mg, 89% yield. The data is consistent with the literature.[22h]

    2-(4-Methoxyphenyl)-3-(2-methylcyclopentyl)propane-nitrile (3x): Colorless oil, 14.1 mg, 29% yield. 1H NMR (400 MHz, CDCl3) δ: 7.28~7.23 (m, 2H), 6.92 (m, 2H), 3.84 (s, 3H), 3.75~3.67 (m, 1H), 2.17~1.99 (m, 2H), 1.97~1.51 (m, 6H), 1.42~1.23 (m, 2H), 0.83 (dd, J=7.0, 1.9 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 159.26, 128.39, 128.34, 121.72, 114.44, 55.37, 40.76, 37.81, 36.15, 35.66, 33.45, 29.29, 22.54, 15.00; IR (neat) v: 2934, 1609, 1511, 1229, 1032, 842, 729 cm-1. HRMS (EI) cacld for C16H21NO [M]+: 243.1618, found 243.1616

    4-Phenylbutanenitrile (4a): Colorless oil, 24.3 mg, 84% yield. The data is consistent with the literature.[22f]

    4-(4-Chlorophenyl)butanenitrile (4b): Colorless oil, 31.5 mg, 88% yield. The data is consistent with the literature.[22h]

    4-(4-Bromophenyl)butanenitrile (4c): Colorless oil, 36.4 mg, 82% yield. The data is consistent with the literature.[22h]

    4-(4-Iodophenyl)butanenitrile (4d): White solid, 33.6 mg, 62% yield. m.p. 80.5~82.2 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.71~7.61 (m, 2H), 7.03~6.90 (m, 2H), 2.75 (t, J=7.5 Hz, 2H), 2.34 (t, J=7.0 Hz, 2H), 1.98 (p, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 139.35, 137.76, 130.55, 119.31, 91.71, 33.88, 26.70, 16.41; IR (neat) v: 2930, 2244, 1483, 1399, 1059, 1005, 824, 786, 501 cm-1. HRMS (EI) cacld for C10H10IN [M]+ 270.9858, found 270.9852.

    4-(4-(Trifluoromethyl)phenyl)butanenitrile (4e): Colorless oil, 30.7 mg, 72% yield. The data is consistent with the literature.[22h]

    4-(4-(Trifluoromethoxy)phenyl)butanenitrile (4f): Colorless oil, 38.6 mg, 84% yield. 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, J=8.6 Hz, 2H), 7.14 (d, J=8.4 Hz, 2H), 2.78 (t, J=7.5 Hz, 2H), 2.32 (t, J=7.0 Hz, 2H), 1.96 (p, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 147.86, 138.45, 129.74, 121.27, 120.45 (q, J=258 Hz), 119.28, 33.65, 26.80, 16.41; 19F NMR (376 MHz, CDCl3) δ: -57.98; IR (neat) v: 2933, 1509, 1253, 1218, 1155 cm-1. HRMS (EI) cacld for C11H10F3NO [M]+ 229.0714, found 229.0709.

    4-([1, 1'-Biphenyl]-2-yl)butanenitrile (4g): Yellow solid, 41.5 mg, 94% yield. m.p. 182.6~185.4 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.48~7.22 (m, 9H), 2.82–2.75 (t, J=7.2 Hz, 2H), 2.17 (t, J=7.2 Hz, 2H), 1.81~1.71 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 142.05, 141.35, 137.29, 130.41, 129.39, 129.05, 128.34, 127.70, 127.15, 126.53, 119.49, 31.97, 26.51, 16.63; IR (neat) v: 2933, 2244, 1478, 1435, 1008, 749, 702 cm-1. HRMS (EI) cacld for C16H15N [M]+ 221.1204, found 221.1199.

    4-([1, 1'-Biphenyl]-3-yl)butanenitrile (4h): Yellow solid, 39.2 mg, 89% yield. m.p. 187.8~190.1 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.60–7.55 (m, 2H), 7.49–7.31 (m, 6H), 7.16 (m, 1H), 2.83 (t, J=7.4 Hz, 2H), 2.33 (t, J=7.1 Hz, 2H), 2.01 (p, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 141.72, 141.00, 140.29, 129.17, 128.86, 127.46, 127.42, 127.37, 127.21, 125.46, 119.57, 34.51, 27.00, 16.50; IR (neat) v: 2926, 2244, 1599, 1501, 1478, 1453, 754, 698 cm-1. HRMS (EI) cacld for C16H15N [M]+ 221.1204, found 221.1199

    4-(4-(tert-Butyl)phenyl)butanenitrile (4i): Colorless oil, 34.4 mg, 86% yield. The data is consistent with the literature.[22h]

    4-(4-(Methylthio)phenyl)butanenitrile (4j): Colorless oil, 28.6 mg, 75% yield. The data is consistent with the literature.[22i]

    4-(4-(Dimethylamino)phenyl)butanenitrile (4k): Yellow solid, 24.9 mg, 66% yield. m.p. 68.4~70.8 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.11~7.05 (m, 2H), 6.78~6.68 (m, 2H), 2.95 (s, 6H), 2.71 (t, J=7.3 Hz, 2H), 2.33 (t, J=7.1 Hz, 2H), 1.96 (p, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 149.43, 129.14, 127.57, 119.82, 112.99, 40.80, 33.37, 27.24, 16.31; IR (neat) v: 2925, 1614, 1523, 1445, 1349 cm-1. HRMS (EI) cacld for C12H16N2 [M]+ 188.1314, found 188.1308.

    4-(4-Cyclopropylphenyl)butanenitrile (4l): Colorless oil, 31.4 mg, 84% yield. 1H NMR (400 MHz, CDCl3) δ: 7.10 (m, 2H), 7.07~7.02 (m, 2H), 2.76 (t, J=7.4 Hz, 2H), 2.33 (t, J=7.1 Hz, 2H), 1.98 (p, J=7.2 Hz, 2H), 1.90 (tt, J=8.4, 5.1 Hz, 1H), 1.01~0.93 (m, 2H), 0.70 (dt, J=6.6, 4.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 142.25, 136.67, 128.42, 125.94, 119.65, 33.92, 27.01, 16.38, 15.05, 9.22; IR (neat) v: 3006, 2928, 2244, 1516, 1457, 1424, 1047, 1018, 898, 810 cm-1. HRMS (EI) cacld for C13H15N [M]+ 185.1204, found 185.1199.

    4-(Naphthalen-2-yl)butanenitrile (4m): Colorless oil, 35.3 mg, 90% yield. The data is consistent with the literature.[22h]

    4-(2-Fluoro-[1, 1'-biphenyl]-4-yl)butanenitrile (4n): White solid, 41.2 mg, 86% yield. m.p. 175.4~177.7 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.58 (dt, J=8.1, 1.5 Hz, 2H), 7.51~7.38 (m, 2H), 7.08 (dd, J=7.8, 1.7 Hz, 2H), 7.03 (dd, J=11.4, 1.7 Hz, 1H), 2.85 (t, J=7.5 Hz, 2H), 2.40 (t, J=7.1 Hz, 2H), 2.05 (p, J7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 159.85 (d, J=247 Hz), 141.30 (d, J=4 Hz), 135.55, 130.95 (d, J=4 Hz), 128.97 (d, J=4 Hz), 128.52, 127.69, 127.24 (d, J=13 Hz), 124.54 (d, J=3 Hz), 119.38, 115.55 (q, J=23 Hz), 33.85, 26.64, 16.47; 19F NMR (400 MHz, CDCl3) δ: -117.88; IR (neat) v: 2933, 2246, 1624, 1483, 1416, 1126, 765, 697 cm-1. HRMS (EI) cacld for C16H14FN [M]+ 239.1110, found 239.1105

    4-(3a, 7a-Dihydrobenzo[d][1, 3]dioxol-5-yl)butanenitrile (4o): Colorless oil, 28.5 mg, 75% yield. The data is consistent with the literature.[22j]

    4-(2, 3-Dihydrobenzo[b][1, 4]dioxin-6-yl)butanenitrile (4p): Colorless oil, 35.4 mg, 87% yield. 1H NMR (400 MHz, CDCl3) δ: 6.78 (d, J=8.1 Hz, 1H), 6.68~6.60 (m, 2H), 4.23 (s, 4H), 2.65 (t, J=7.3 Hz, 2H), 2.29 (t, J=7.1 Hz, 2H), 1.91 (p, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 143.49, 142.14, 132.93, 121.38, 119.61, 117.34, 117.05, 64.39, 64.31, 33.61, 26.98, 16.29; IR (neat) v: 2932, 2245, 1588, 1505, 1284, 1204, 884, 812 cm-1. HRMS (EI) cacld for C12H13NO2 [M]+ 203.0946, found 203.0941.

    4-(3, 5-Bis(trifluoromethyl)phenyl)butanenitrile (4q): Colorless oil, 40.4 mg, 72% yield. 1H NMR (400 MHz, CDCl3) δ: 7.79 (s, 1H), 7.68 (s, 2H), 3.00~2.92 (t, J=6.9, 2H), 2.44 (t, J=6.9, 2H), 2.07 (p, J=7.0 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 142.25, 131.85 (q, J=33 Hz), 128.60, 123.38 (q, J=274 Hz), 120.77 (p, J=4 Hz), 118.81, 34.15, 26.57, 16.69; 19F NMR (377 MHz, CDCl3) δ: -62.89; IR (neat) v: 2935, 1381, 1275, 1167, 1121, 895, 681 cm-1. HRMS (EI) cacld for C12H9F6N [M]+ 281.0639, found 281.0634.

    4-(Dibenzo[b, d]thiophen-4-yl)butanenitrile (4r): Yellow solid, 42.8 mg, 85% yield. m.p. 232.5~235.8 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.18~8.09 (m, 1H), 8.04 (dd, J=7.9, 1.2 Hz, 1H), 7.90~7.82 (m, 1H), 7.50~7.38 (m, 3H), 7.31~7.22 (m, 1H), 3.05 (t, J=7.4 Hz, 2H), 2.37 (t, J=7.1 Hz, 2H), 2.17 (p, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 139.01, 138.86, 136.04, 135.98, 133.94, 126.92, 126.53, 125.02, 124.59, 122.87, 121.84, 120.09, 119.48, 33.71, 24.74, 16.71; IR (neat) v: 2933, 2244, 1441, 1400, 797, 748 cm-1. HRMS (EI) cacld for C16H13NS [M]+ 251.0769, found 251.0763.

    4-(4-Morpholinophenyl)butanenitrile (4s): Yellow solid, 36.5 mg, 79% yield. m.p. 123.4~125.8 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.10 (d, J=8.5 Hz, 2H), 6.87 (d, J=8.5 Hz, 2H), 3.89~3.83 (m, 4H), 3.16~3.10 (m, 4H), 2.70 (t, J=7.3 Hz, 2H), 2.30 (t, J=7.1 Hz, 2H), 1.94 (p, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 149.91, 131.13, 129.22, 119.68, 115.98, 66.93, 49.49, 33.42, 27.04, 16.30; IR (neat) v: 2930, 2856, 1453, 746, 898 cm-1. HRMS (EI) cacld for C14H18N2O [M]+ 230.1419, found 230.1414.

    4-(5-Methylthiophen-3-yl)butanenitrile (4t): Colorless oil, 23.0 mg, 69% yield. 1H NMR (400 MHz, CDCl3) δ: 6.71 (s, 1H), 6.57 (s, 1H), 2.69 (t, J=7.3 Hz, 2H), 2.44 (s, 3H), 2.31 (t, J=7.1 Hz, 2H), 1.93 (p, J7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 140.52, 139.78, 126.06, 119.57, 118.89, 29.01, 26.05, 16.40, 15.34; IR (neat) v: 2934, 2244, 1441, 1400, 1054, 1020, 748 cm-1. HRMS (EI) cacld for C9H11NS [M]+ 165.0612, found 165.0607

    7-Phenylheptanenitrile (4u): Colorless oil, 10.0 mg, 23% yield. The data is consistent with the literature.[22f]

    4-((2, 2, 6, 6-Tetramethylpiperidin-1-yl)oxy)butanenitrile (5): Yellow oil, 7.0 mg, 16% yield. The data is consistent with the literature report.[22c]

    To a 4 mL screwed-capped vial were added bromide 2v (34 mg, 0.2 mmol), Ni(cod)2 (55 mg, 0.2 mmol), dtbbpy (54 mg, 0.2 mmol) and THF (0.4 mL) in Glove box. The resulting mixture was stirred for 2 h at room temperature to prepare nickel complex solution. To another 4 mL screwed-capped vial were added oxime ester 1a (52 mg, 0.2 mmol) and DMF (0.2 mL) in Glove box. Then the aforementioned in-situ formed nickel complex solution was added. The vial was removed from Glove box and stirred at room temperature for 12 h. After this time, the reaction mixture was quenched with saturated ammonia chloride (1 mol·L-1), and diluted with ethyl acetate. The organic layer was separated and dried over anhydrous Na2SO4, filtered and removed under vacuum. The corresponding product 4-(o-tolyl)butanenitrile (4v) was obtained as a colorless oil by flash chromatography with 60% yield (19.2 mg). The data is consistent with the literature.[22h]

    Supporting Information The optimization details, experimental procedures for the preparation of oxime esters and spectra of reported compounds is available free of charge via the Internet at http://sioc-journal.cn/.


    1. [1]

      (a) Wu, X.; Zhu, C. Chin. J. Chem. 2019, 37, 171.
      (b) Li, C.; Zhu, C. Acta Chim. Sinica 2019, 77, 771 (in Chinese).
      (李超忠, 朱晨, 化学学报, 2019, 77, 771.)
      (c) Smith, J. M.; Harwood, S. J.; Baran, P. S. Acc. Chem. Res. 2018, 51, 1807.
      (d) Yan, M.; Lo, J. C.; Edwards, J. T.; Baran, P. S. J. Am. Chem. Soc. 2016, 138, 12692.
      (e) Studer, A.; Curran, D. P. Angew. Chem., Int. Ed. 2016, 55, 58.

    2. [2]

      For selected reviews on merger of transition metal catalysis with alkyl radical, see:
      (a) Feng, Z.; Xiao, Y.-L.; Zhang, X. Acc. Chem. Res. 2018, 51, 2264.
      (b) Wang, F.; Chen, P.; Liu, G. Acc. Chem. Res. 2018, 51, 2036.
      (c) Green, S. A.; Crossley, S. W. M.; Matos, J. L. M.; Shevick, S. L.; Shenvi, R. A. Acc. Chem. Res. 2018, 51, 2628.
      (d) Crossley, S. W. M.; Obradors, C.; Martinez, R. M.; Shenvi, R. A. Chem. Rev. 2016, 116, 8912.
      (e) Liang, K.; Xia, C. Chin. J. Chem. 2017, 35, 255.
      (f) Jahn, U. Radicals in Transition Metal Catalyzed Reactions? Transition Metal Catalyzed Radical Reactions? A Fruitful Interplay Anyway. In Radicals in Synthesis III, Eds.: Heinrich, M.; Gansäuer, A., Springer Berlin Heidelberg, Berlin, Heidelberg, 2012, p. 323.
      (g) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417.
      (h) Kochi, J. K. Acc. Chem. Res. 1974, 7, 351.
      (i) Zhao, J.; Duan, X.; Guo, L.-N. Chin. J. Org. Chem. 2017, 37, 2498 (in Chinese).
      (赵景峰, 段新华, 郭丽娜, 有机化学, 2017, 37, 2498.)
      (j) Chen, D.; Yang, W.; Yao, Y.; Yang, X.; Deng, Y.; Yang, D. Chin. J. Org. Chem. 2018, 38, 2571 (in Chinese).
      (陈董涵, 杨文, 姚永祺, 杨新, 邓颖颖, 杨定乔, 有机化学, 2018, 38, 2571.)

    3. [3]

      (a) Bour, J. R.; Ferguson, D. M.; McClain, E. J.; Kampf, J. W.; Sanford, M. S. J. Am. Chem. Soc. 2019, 141, 8914.
      (b) Camasso, N. M.; Sanford, M. S. Science 2015, 347, 1218.
      (c) Tasker, S. Z.; Stanley, E. A.; Jamison, T. F. Nature 2014, 509, 299.
      (d) Takahashi, T.; Kanna, K. Modern Organonickel Chemistry, Wiley-VCH, Weinheim, Germany, 2005, pp. 41.

    4. [4]

      (a) Wang, K.; Kong, W. Chin. J. Chem. 2018, 36, 247.
      (b) Fu, G. C. ACS Cent. Sci. 2017, 3, 692.
      (c) Cherney, A. H.; Kadunce, N. T.; Reisman, S. E. Chem. Rev. 2015, 115, 9587.
      (d) Hu, X. Chem. Sci. 2011, 2, 1867.
      (e) Netherton, M. R.; Fu, G. C. Adv. Synth. Catal. 2004, 346, 1525.

    5. [5]

      For selected recent examples on Ni-catalyzed cross-coupling with alkyl halides, see:
      (a) Wang, X.; Ma, G.; Peng, Y.; Gong, H. J. Am. Chem. Soc. 2018, 140, 14490.
      (b) Biswas, S.; Weix, D. J. J. Am. Chem. Soc. 2013, 135, 16192.
      (c) Zultanski, S. L.; Fu, G. C. J. Am. Chem. Soc. 2013, 135, 624.
      (d) Saito, B.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 6694.
      (e) Fischer, C.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 4594.
      (f) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 14726.
      (g) Devasagayaraj, A.; Stüdemann, T.; Knochel, P. Angew. Chem., Int. Ed. 1995, 34, 2723.

    6. [6]

      For selected recent examples on Ni-catalyzed cross-coupling with sulfones, see:
      (a) Merchant, R. R.; Edwards, J. T.; Qin, T.; Kruszyk, M. M.; Bi, C.; Che, G.; Bao D-H.; Qiao, W.; Sun, L.; Collins, M. R.; Gallego, G. M.; Mousseau, J. J.; Nuhant, P.; Baran, P. S. Science 2018, 360, 75.
      (b) Ariki, Z. T.; Maekawa, Y.; Zambo, M.; Crudden, C. M. J. Am. Chem. Soc. 2018, 140, 78.
      (c) Liu, M.; Zheng, Y.; Qiu, G.; Wu, J. Org. Chem. Front. 2018, 5, 2615.
      (d) Wu, J.-C.; Gong, L.-B.; Xia, Y.; Song, R.-J.; Xie, Y.-X.; Li, J.-H. Angew. Chem., Int. Ed. 2012, 51, 9909.

    7. [7]

      For selected recent examples on Ni-catalyzed cross-coupling with redox active esters, see:
      (a) Ni, S.; Padial, N. M.; Kingston, C.; Baran, P. S. J. Am. Chem. Soc. 2019, 141, 6726.
      (b) Chen, T.; Zhang, H.; Mykhailiuk, P. K.; Baran, P. S. Angew. Chem., Int. Ed. 2019, 58, 2454.
      (c) Edwards, J. T.; Merchant, R. R.; McClymont, K. S.; Knouse, K. W.; Qin, T.; Malins, L. R.; Vokits, B.; Shaw, S. A.; Bao, D.-H.; We, F.-L.; Zhou, T.; Eastgate, M. D.; Baran, P. S. Nature, 2017, 545, 213.
      (d) Cornella, J.; Edwards, J. T.; Qin, T. Baran, P. S. J. Am. Chem. Soc. 2016, 138, 2174.
      (e) Qin T.; Cornella, J.; Li, C.; Baran, P. S. Science 2016, 352, 801.
      (f) Ye, Y.; Chen, H.; Sessler, J. H.; Gong, H. J. Am. Chem. Soc. 2019, 141, 820.
      (g) Huihui, K. M.; Caputo, J. A.; Melchor, Z.; Weix, D. J. J. Am. Chem. Soc. 2016, 138, 5016.
      (h) Wang, P.; Zhao, B.; Yuan, Y.; Shi, Z. Chem. Commun. 2019, 55, 1971.
      (i) Yang, L.; Zhang, J-Y.; Duan, X-H.; Gao, P.; Jiao, J.; Guo, L-N. J. Org. Chem. 2019, 84, 8615.

    8. [8]

      For selected reviews on cycloketone oximes, see:
      (a) Morcillo, S. P. Angew. Chem., Int. Ed. 2019, 58, 14044.
      (b) Stateman, L. M.; Nakafuku, K. M.; Nagib, D. A. Synthesis 2018, 50, 1569.
      (c) Davies, J.; Morcillo, S. P.; Douglas, J. J.; Leonori, D. Chem.- Eur. J. 2018, 24, 12154.
      (d) Zard, S. Z. Chem. Soc. Rev. 2008, 37, 1603.

    9. [9]

      Boivin, J.; Fouquet, E.; Zard, S. Z. J. Am. Chem. Soc. 1991, 113, 1055. doi: 10.1021/ja00003a057

    10. [10]

      Boivin, J.; Schiano, A. M.; Zard, S. Z. Tetrahedron Lett. 1992, 33, 7849. doi: 10.1016/S0040-4039(00)74760-5

    11. [11]

      For selected examples on Ni-catalyzed ring cleavage of cyclobutanone oximes, see:
      (a) Angelini, L.; Davies, J.; Simonetti, M.; Leonori, D. Angew. Chem., Int. Ed. 2019, 58, 5003.
      (b) Tang, Y.-Q.; Yang, J.-C.; Wang, L.; Guo, L.-N. Org. Lett. 2019, 21, 5178.
      (c) Gu, Y.-R.; Duan, X.-H.; Yang, L.; Guo, L.-N. Org. Lett. 2017, 19, 5908.
      (d) Ding, D.; Lan, Y.; Lin, Z.; Wang, C. Org. Lett. 2019, 21, 2723.

    12. [12]

      For selected examples on Cu-catalyzed ring cleavage of cyclobutanone oximes, see:
      (a) Liu, Z.-L.; Shen, H.-G.; Xiao, H.-W.; Li, C.-Z. Org. Lett. 2019, 21, 5201.
      (b) Wang, P.-P.; Zhao, B.-L.; Yuan, Y.; Shi, Z.-Z. Chem. Commun. 2019, 55, 1971.
      (c) Zhao, B.; Shi, Z.-Z. Angew, Chem., Int. Ed. 2017, 56, 12727.
      (d) Yu, X.-Y.; Zhao, Q.-Q.; Chen, J.; Xiao, W.-J. Angew. Chem., Int. Ed. 2018, 57, 15505.
      (e) Zhang, J. Y.; Duan, X. H.; Yang, J. H.; Guo, L. N. J. Org. Chem. 2018, 83, 4239.
      (f) Ai, W.-Y; Liu, Y.-Q; Wang, Q.; Liu, Q. Org. Lett. 2018, 20, 409.

    13. [13]

      For selected examples on other metal-catalyzed ring cleavage of cyclobutanone oximes, see:
      (a) Zhao, J.-F.; Guo, P.; Duan, X.-H.; Guo, L.-N. Adv. Synth. Catal. 2018, 360, 1775.
      (b) Nishimura, T.; Yoshinaka, T.; Nishiguchi, Y.; Uemura, S. Org. Lett. 2005, 7, 2425.
      (c) Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 2000, 122, 12049.

    14. [14]

      For selected examples on ring cleavage of cyclobutanone oximes via photocatalysis, see:
      (a) Lu, B.; Cheng, Y.; Chen, L.-Y.; Xiao, W.-J. ACS Catal. 2019, 9, 8159.
      (b) Yu, X.-Y.; Chen, J.-R.; Wang, P.-Z.; Xiao, W.-J. Angew. Chem., Int. Ed. 2018, 57, 738.
      (c) He, Y.; Anand, D.; Sun, Z.; Zhou, L. Org. Lett. 2019, 21, 3769.
      (d) Li, L.-M.; Chen, H.-G.; Mei, M.-J.; Zhou, L. Chem. Commun. 2017, 53, 11544.
      (e) Xia, P.-J.; Ye, Z.-P.; Hu, Y.-Z.; Yang, H. Org. Lett. 2019, 21, 2658.
      (f) Zhao, B.; Tan, H. Chen, C.; Jiao, N. Shi, Z.-Z. Chin. J. Chem. 2018, 36, 995.
      (g) Zhao, B.-L.; Chen, C.; Lv, J.-H.; Shi, Z.-Z. Org. Chem. Front. 2018, 5, 2719.
      (h) Shen, X.; Zhao, J.-J.; Yu, S.-Y. Org. Lett. 2018, 20, 5523.
      (i) Jiang, H.; Studer, A. Angew. Chem., Int. Ed. 2018, 57, 10707.
      (j) Davies, J.; Sheikh, N. S.; Leonori, D. Angew. Chem., Int. Ed. 2017, 56, 13361.

    15. [15]

      (a) Zhang, J.-J.; Duan, X.-H.; Wu, Y.; Guo, L.-N. Chem. Sci. 2019, 10, 161.
      (b) Yin, Z.-P.; Rabeah, J.; Brückner, A.; Wu, X.-F. Org. Lett. 2019, 21, 1766.

    16. [16]

      (a) Shang, R.; Ji, D.-S.; Chu, L.; Liu, L. Angew. Chem., Int. Ed. 2011, 50, 4470.
      (b) Dalziel, M.-E.; Chen, P.-H.; Carrera, D. E.; Gosselin, F. Org. Lett. 2017, 19, 3446.
      (c) López, R.; Palomo, C. Angew. Chem., Int. Ed. 2015, 54, 13170.

    17. [17]

      Yang, H.-B.; Pathipati, S. R.; Selander, N. ACS Catal. 2017, 7, 8441. doi: 10.1021/acscatal.7b03432

    18. [18]

      Ding, D.; Wang, C. ACS Catal. 2018, 8, 11324. doi: 10.1021/acscatal.8b03930

    19. [19]

      (a) Chen, Y.-G.; Shuai, B.; Xu, X.-T.; Li, Y.-Q.; Yang, Q.-L.; Qiu, H.; Zhang, K. Fang, P.; Mei, T.-S. J. Am. Chem. Soc. 2019, 141, 3395.
      (b) Liu, D.; Ma, H.-X.; Fang, P.; Mei, T.-S. Angew. Chem., Int. Ed. 2019, 58, 5033.
      (c) Ma, C.; Zhao, C.-Q.; Xu, X.-T.; Li, Z.-M.; Wang, X.-Y.; Zhang, K.; Mei, T.-S. Org. Lett. 2019, 21, 2464.
      (d) Chen, Y.-G.; Shuai, B.; Ma, C.; Zhang, X.-J.; Fang, P.; Mei, T.-S. Org. Lett. 2017, 19, 2969.

    20. [20]

      During preparing our manuscript, a nickel catalyzed Negishi coupling of oximes using 20% nickel catalyst was recently published: Angelini, L.; Sanz, L. M.; Leonori, D. Synlett 2019, DOI: 10.1055/s-0039-1690690

    21. [21]

      (a) Tellis, J. C.; Kelly, C. B.; Primer, D. N.; Molander, G. A. Acc. Chem. Res. 2016, 49, 1429.
      (b) Xu, H.-W.; Diccianni, J. B.; Katigbak, J.; Diao, T.-N. J. Am. Chem. Soc. 2016, 138, 4779.
      (c) Schley, N. D.; Fu. G. C. J. Am. Chem. Soc. 2014, 136, 16588.
      (d) Phapale, V. B.; Cardenas, D. J. Chem. Soc. Rev. 2009, 38, 1598.
      (e) Casares, J. A.; Espinet, P.; Fuentes, B.; Salas, G. J. Am. Chem. Soc. 2007, 129, 3508.

    22. [22]

      (f) Anderson, T. J.; Jones, G. D.; Vicic, D. A. J. Am. Chem. Soc. 2004, 126, 8100.

    23. [23]

      (a) Yin, Z.; Rabeah, J.; Brückner, A.; Wu, X.-F. ACS Catal. 2018, 8, 10926.
      (b) Yu, X.-Y.; Chen, J.-R.; Wang, Z.-P.; Yang, M.-N.; Liang, D.; Xiao, W.-J. Angew. Chem., Int. Ed. 2018, 57, 738.
      (c) He, B.-Q.; Yu, X.-Y.; Wang, P.-Z.; Chen, J.-R.; Xiao, W.-J. Chem. Commun. 2018, 54, 12262.
      (d) Wang, P.-Z.; Yu, X.-Y.; Li, C.-Y.; He, B.-Q.; Chen, J.-R.; Xiao, W.-J. Chem. Commun. 2018, 54, 9925.
      (e) Ai, W.; Liu, Y.; Wang, Q.; Lu, Z.; Liu, Q. Org. Lett. 2018, 20, 409.
      (f) Nakata, K.; Feng, C.; Tojo, T.; Kobayashi, Y. Tetrahedron Lett. 2014, 55, 5774.
      (g) Zhang, L.; Ang, G. Y.; Chiba, S. Org. Lett. 2011, 13, 1622.
      (h) Suga, T.; Shimazu, S.; Ukaji, Y. Org. Lett. 2018, 20, 5389.
      (i) Guiard, J.; Rahali, Y.; Praly, J.-P. Eur. J. Org. Chem. 2014, 21, 4461.
      (j) Ghosh, A. K.; Martyr, C. D.; Xu, C.-X. Org. Lett. 2012, 14, 2002.

  • Scheme 1  Nickel-catalyzed transformations of oxime esters

    Scheme 2  Mechanistic experiments

    Scheme 3  Proposed reaction mechanism

    Table 1.  Optimization of reaction conditionsa

    Entry Oxime ester Catalyst Ligand Yieldb/%
    1 1a NiBr2(glyme) L5 Trace
    2 1a' NiBr2(glyme) L5 46
    3 1a'' NiBr2(glyme) L5 96
    4 1a'' Co(acac)2 L5 Trace
    5 1a'' FeCl3 L5 19
    6 1a'' NiBr2(glyme) L1 66
    7 1a'' NiBr2(glyme) L2 93
    8 1a'' NiBr2(glyme) L3 71
    9 1a'' NiBr2(glyme) L4 82
    10 1a'' NiBr2(glyme) L6 44
    11 1a'' NiBr2(glyme) L7 79
    12 1a'' NiBr2(glyme) L8 93
    13c 1a'' NiBr2(glyme) L5 53
    14d 1a'' NiBr2(glyme) L5 86
    15e 1a'' NiCl2(glyme) L5 91
    16f 1a'' NiCl2(glyme) L5 73
    a Reaction conditions: 10 mol% NiBr2(glyme), 10 mol% L5, 1a (0.2 mmol, 1.0 equiv.), 2a (0.2 mmol, 1.0 equiv.) in DMF (0.2 mL), r.t., 12 h. b Yield determined by HNMR using 1, 4-dimethoxybenzene as internal standard. c THF as solvent. d 5 mol% NiBr2(glyme) was used. e 5 mol% NiCl2(glyme) was used. f 1 mol% NiCl2(glyme) was used.
    下载: 导出CSV

    Table 2.  Substrate scope of oxime esters

    下载: 导出CSV

    Table 3.  Substrate scope of organozinc reagents

    下载: 导出CSV
  • 加载中
计量
  • PDF下载量:  9
  • 文章访问数:  108
  • HTML全文浏览量:  16
文章相关
  • 发布日期:  2020-03-25
  • 收稿日期:  2019-11-08
  • 修回日期:  2019-12-11
  • 网络出版日期:  2019-12-19
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章