Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Catalytic sp3C−CN Bond Cleavage: Ni-Mediated Phosphorylation of Alkylnitriles Ji-Shu Zhang,† Tieqiao Chen,*,†,‡ Yongbo Zhou,† Shuang-Feng Yin,† and Li-Biao Han*,§ †
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State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China ‡ Key Laboratory of Ministry of Education for Advanced Materials in Tropical Island Resources, College of Materials and Chemical Engineering, Hainan University, Haikou, Hainan 570228, China § National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan S Supporting Information *
ABSTRACT: A direct phosphorylation of the sp3C−CN bond catalyzed by a nickel catalyst is disclosed. A wide range of primary nitriles readily coupled with secondary phosphine oxides to produce the corresponding phosphorylated products in high yields. As a key step, this new method was applied to the synthesis of anticancer drug Combretastatin-A4, significantly shortening its synthetic path.
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Scheme 1. Carbon−Carbon/Carbon−Heteroatom Bond Formation via C−CN Bond Cleavage
elective activation of nonstrained carbon−carbon single bonds by a transition metal catalyst is one of the most challenging topics in organic chemistry.1 This is not only because it constitutes fundamental academic value but also because it holds significant potential application in industrial manufacturing.2 The successful carbon−carbon bond cleavages reported so far are usually accompanied by either the release of ring strain or aromatization; thus, they lack generality.1b The activation of the strong C−CN bonds (∼550 kJ mol−1) is a hot topic that has been extensively studied in recent years.3,4 In 2001, Miller et al. reported a nickel-catalyzed cross-coupling reaction of benzonitriles with ArMgX that affords biaryl compounds (Scheme 1a, path 1).5 Later, similar cross-coupling reactions were successfully developed to construct sp2C−Z bonds (e.g., sp2C−Si, sp2C−B, and sp2C−P bonds) (Scheme 1a, path 2).6 In addition, the direct decyanation of nitriles was also achieved using a transition metal catalyst with a reductant (Scheme 1a, path 3).7 Although only being limited to electrondeficient (heteroatom)aryl nitriles, a novel photoredox/ organic-cocatalyzed C−CN/C−H cross-coupling was achieved (Scheme 1a, path 4).8 Moreover, C−CN bond transfer insertion into alkynes and olefins mediated by nickel/Lewis acid cocatalyst was also disclosed (Scheme 1a, path 5).9,10 Recently, Morandi et al. reported an elegant protocol for catalytic reversible alkene-nitrile interconversion through controllable transfer hydrocyanation to form a new nitrile and a new alkene in which HCN was a shuttle reagent (Scheme 1b).11 Likewise, a Rh-catalyzed anti-Markovnikov hydrocyanation of terminal alkynes using 2-hydroxy-2-methylpropanenitrile as CN source was reported.12 Despite these advances, the substrates were usually limited to sp2C−CN compounds or active benzylic nitriles.5−10,13 Only limited examples on inactive sp3C−CN activation were © XXXX American Chemical Society
reported.11 Therefore, a general catalytic transformation of an inert sp3C−CN bond by a low-price metal catalyst is still highly challenging.1,9,10b,11 Received: September 7, 2018
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DOI: 10.1021/acs.orglett.8b02854 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Scheme 2. Substrate Scopea
Herein, we communicate a new phosphorylation reaction of nonstrained alkylnitriles sp3C−CN with [P]-H compounds under mild conditions catalyzed by a nickel catalyst (Scheme 1c). Organophosphorous compounds play a vital role in organic synthesis, catalysis, pharmaceutical chemistry, agrochemistry, material science, and coordination chemistry, and their synthesis is of current interest.14,15 This reaction was accidently found during extensive studies on the nickel-catalyzed phosphorylation of aryl nitriles.6h When 4-(2-cyanoethyl)benzonitrile was allowed to couple with Ph2P(O)H in the presence of 2.5 mol % NiCl2 and 1.5 equiv of t-BuOK in dioxane at 120 °C for 16 h, a new phosphorylated product via sp3C−CN cleavage was produced in 41% yield. Encouraged by the result, we attempted to achieve the novel phosphorylation of sp3C−CN bonds by optimizing the reaction conditions and chose the reaction of 3-phenyl propanenitrile with Ph2P(O)H as a model. It was found that nickel catalyst was essential to this reaction. When the reaction was conducted at 100 °C in the absence of nickel catalyst, only a trace amount of 3a was detected by GC (Table 1, entry 1). Table 1. Optimization of the Reaction Conditionsa
entry
cat. Ni
base
1 2 3 4 5 6 7 8 9 10 11 12
− Ni(cod)2 Ni(cod)2 NiCl2 glyme NiCl2 NiCl2 NiCl2 NiCl2 NiCl2 NiCl2 NiCl2 NiCl2
t-BuOK t-BuOK t-BuOK t-BuOK t-BuOK t-BuONa t-BuOLi Cs2CO3 t-BuOK t-BuOK t-BuOK t-BuOK
solvent dioxane dioxane dioxane dioxane dioxane dioxane dioxane dioxane toluene DMF NMP cyclohexane
temp (°C)
yield (%)b
100 100 120 120 120 120 120 120 120 120 120 120
