Palladium-Catalyzed Cyanation of Carbon-Carbon Triple Bonds Under Aerobic Conditions
Palladium-Catalyzed Cyanation of Carbon-Carbon Triple Bonds Under Aerobic Conditions
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DOI：
10.1002/anie.200900030
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Nishida, Atsushi
中科院分区：
文献类型：
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作者：
Arai, Shigeru;Sato, Takashi;Nishida, Atsushi
氰基已被公认为与羰基、氨基和羟甲基等同的有用官能团，在合成有机化学中主要通过简单的取代反应探索了将氰基有效地引入有机分子。虽然羰基型基团（如C= O， C= N和共轭C= C键[1]）的亲核氰化反应已被广泛研究，但过渡金属催化的简单和非共轭碳-碳多键氰化反应是目前的研究热点。[2 - 6]自炔的氢化反应首次报道以来，已经报道了许多用钯或镍催化将XÀCN （X= Si,[3a-c] Ge,[3d] Sn,[4a] S,[4b] C，[5]和[6]）加成到炔上的例子。三甲基硅氰（TMSCN）是目前应用最广泛的氰化剂之一。Chatani和Hanafusa首先在氩气气氛下将其用于末端炔的硅氰化反应。[3a]我们发现这种硅基氰化过程在氧气气氛下可以完全被抑制，而1,2 -二氰化过程则相当有效（方案1）。虽然查塔尼etal。在无氧条件下，用TMSCN从二苯乙炔中分离出1,2 -二氰化产物[3b]，对其机理和反应范围的进一步研究未见报道。本文报道了钯催化的1,2 -二氰化反应以及1,6 -二炔及其衍生物的氰化环化反应的初步结果。当端炔（1a-e）和TMSCN（2.5当量）在PdCl2 （2mol%）存在下与O2 （1atm）在甲苯（0.5 m）中1008C加热时，得到相应的反二氰烯（2a-e），产率较高（表1，第1 - 5项）由于立体因素似乎在反应的立体选择性中起着重要作用（比较表1，条目3和4），因此研究了在丙炔位置（1 f-k）具有四取代碳中心的底物。正如预期的那样，syn选择性得到了显著提高（表1，条目6-10），三乙炔1k完全转化为syn-2k，产率为72%（表1，条目11）。虽然这些反应条件都不适合生成内炔，但经过仔细的考察，发现TMSOTf [8]（50 mol%）和Pd (CN) 2 （5 mol%）的加入可以生成更强的Lewis酸性钯（II），这是最有效的。例如，syn-2m和2n是唯一的产物，产率分别为67%和45%（表1，第12和13项）。然而，对于末端炔，TMSOTf不影响2的产率和非对映选择性。同时，简单烯烃在上述反应条件下不发生反应。在钯催化的炔的氰化反应[5]或芳基卤化物与氰化物的交叉偶联反应[9]中，通过还原消除CÀPdÀCN安装了CN基团。由于这种简单的机制建议不足以解释我们的1,2 -二氰化，因此我们提出了两种不同的氰化模式，亲核氰化和还原消除，作为催化反应的关键步骤。一般来说，钯上的CN基团作为伪卤化物（亲核性较差），因此在钯催化下，通过还原消除引入CN基团是有利的。本文提出外部氰基源和钯（II）促进炔烃的亲核氰化反应。结果表明：1)分子氧是必需的；2)在氧气氛下，单独使用Pd （CN) 2 （100 mol%）而不使用TMSCN的反应不产生双氰加合物；3）其他氰化剂如n-Bu3SnCN或Me2C (OH) CN均不起作用。
The cyano group has been recognized as a useful functional group that is equivalent to carbonyl, amino-, and hydroxymethyl groups: Its efficient introduction into organic molecules has been explored in synthetic organic chemistry mainly using simple substitution reactions. Although nucleophilic cyanation of carbonyl-type groups such as C= O, C= N, and conjugated C= C bonds [1] has been widely investigated, cyanation of simple and nonconjugated carbon–carbon multiple bonds by transition-metal catalysis is of current interest.[2–6] Since the first report of the hydrocyanation of alkynes,[2] many examples of the addition of XÀCN (X= Si,[3a–c] Ge,[3d] Sn,[4a] S,[4b] C,[5] and B [6]) to alkynes by using palladium or nickel catalysis have been reported. Trimethylsilylcyanide (TMSCN) is one of the most widely used cyanating agents because of its ready availability. Chatani and Hanafusa were the first to use it in the silylcyanation of terminal alkynes under an argon atmosphere.[3a] We discovered that this silylcyanation process can be completely inhibited under an oxygen atmosphere, while 1, 2-dicyanation proceeded quite effectively (Scheme 1). Although Chatani etal. isolated a 1, 2-dicyanated product from diphenylacetylene with TMSCN under oxygen-free conditions,[3b] no further investigation of its mechanism or reaction scope was reported. We report herein our preliminary results of palladium-catalyzed 1, 2-dicyanation of alkynes as well as cyanative cyclization of 1, 6-diyne and enyne derivatives.When terminal alkynes (1a–e) and TMSCN (2.5 equiv) were heated in the presence of PdCl2 (2mol%) with O2 (1 atm) in toluene (0.5 m) at 1008C, the corresponding synand anti-dicyano alkenes 2a–e were obtained in good yield (Table 1, entries 1–5).[7] Since steric factors seemed to play an important role in the stereoselectivity of the reaction (compare Table1, entries3 and 4), substrates bearing a tetrasubstituted carbon center at the propargylic position (1 f–k) were investigated. As expected, syn selectivity was dramatically improved (Table 1, entries 6–10) and tritylacetylene 1k was exclusively converted into syn-2k in 72% yield (Table 1, entry 11). Although these reaction conditions were not suitable for internal alkynes, the addition of TMSOTf [8](50 mol%) with Pd (CN) 2 (5 mol%), which would generate a more Lewis acidic palladium (II) species, was found to be most effective after a careful survey of the conditions. For example, syn-2m and 2n were obtained as the sole products in 67% and 45% yield, respectively (Table 1, entries 12 and 13). However, for terminal alkynes, TMSOTf did not affect the yield or diastereoselectivity of 2. Meanwhile, simple alkenes did not react under the reaction conditions described. In palladium-catalyzed cyanation of alkynes [5] or crosscoupling reactions [9] between aryl halides with cyanide, a CN group is installed by reductive elimination from CÀPdÀCN. As this simple mechanistic proposal is not sufficient to explain our 1, 2-dicyanation, we therefore propose two different modes of cyanation, nucleophilic cyanation and reductive elimination, as the key steps in this catalytic reaction. In general, a CN group on Pd acts as a pseudo halide (less nucleophilic) therefore introduction of the CN group through reductive elimination is favored under palladium catalysis. Herein we propose that an external cyano source and palladium (II) promote nucleophilic cyanation of alkynes. Based on the findings that 1) molecular oxygen is essential, 2) the reaction using Pd (CN) 2 (100 mol%) alone without TMSCN under an oxygen atmosphere gave no dicyano adducts, 3) other cyanating agents such as n-Bu3SnCN or Me2C (OH) CN did not work …