Cobalt-Catalyzed Reductive Allylation of Alkyl Halides with Allylic Acetates or Carbonates
Cobalt-Catalyzed Reductive Allylation of Alkyl Halides with Allylic Acetates or Carbonates
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DOI：
10.1002/anie.201104390
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Gosmini, Corinne
中科院分区：
文献类型：
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作者：
Qian, Xin;Auffrant, Audrey;Gosmini, Corinne
过渡金属催化的烯丙基烷基化反应由于其在合成新的烯烃化合物，特别是全合成中的潜在应用而受到广泛的研究。[1]软亲核试剂通常用于Pd-，[1]Mo-，[2]Ir-，[3]Ru-，[4]Rh-，[5]铂，[6]，甚至铁催化的[7]烯丙基取代反应。镍、[8]钴、[9]和铜[10]催化剂允许使用烷基锌或格氏试剂等硬亲核试剂，但如果不仔细设计，可能会观察到有限的官能团兼容性和/或较差的区域选择性。为了避免处理空气和湿度敏感的有机镁和有机锌试剂，不需要有机金属试剂的简单程序是非常可取的，现在已经开发了许多。[11]据我们所知，使用原位生成的催化有机金属试剂直接进行过渡金属催化的烷基-烯丙基交叉偶联仍然未知。然而，几年前，我们报道了一个相关的Co催化的芳基卤化物和烯丙基乙酸酯的偶联反应；[12]这些反应在适当的还原剂存在下，得到了烯丙基化合物。这类烯丙基羧酸盐虽然比烯丙基卤化物活性低，但更环保。鉴于我们以前在直接共催化功能化方面的经验，包括烷基化，[11c]芳基卤化物[13]，我们有兴趣进一步的化学，在这里我们报告了一种新的和一般的方法，使用CoBr2/Mn体系和乙腈/吡啶混合溶剂直接还原交叉偶联烯丙基乙酸酯和烷基卤化物。该方法适应了各种简单和官能化的烷基卤化物和取代的烯丙基化合物，并且在实验上是直接的。事实上，它使用现成的试剂，没有任何特别的防止空气和潮湿的措施。首先，我们研究了易于获得但活性较差的4-溴丁酸乙酯与简单的乙酸烯丙酯作为电泳剂的使用。这里的主要挑战在于促进交叉耦合，而不是形成减少和同质耦合的产品。多种因素的综合作用使我们能够克服这些困难(表1)。以我们建立的反应条件为标准，在3小时内获得了良好的产率(表1，条目1)。5mol%的催化剂负载得到了相同的结果，但在16小时内(表1，条目2)和20mol%的CoBr2负载加速了反应(2小时)，但根据GC分析，得到了更高数量的烷基二聚体(表1，条目3)。Co(Acac)2没有催化活性(表1，条目4)。减少锰粉尘的量降低了反应速度和产率(表1，条目5)，而用锌粉尘取代锰导致没有交叉偶联产物的形成(表1，条目6)。同样，在将CH3CN改为DMF时没有检测到交叉偶联产物(表1，条目7)。由于形成了苯丙基钴络合物，需要过量的乙酸烯丙酯来完成反应(表1，条目8)；吡啶似乎在稳定低价钴中间体方面很重要，因为没有它，交叉偶联产率会降低(表1，条目9)。用联吡啶或三苯基膦取代吡啶的产率很低，50%以上的烷基卤化物仍未消费(表1，条目11和12)。钴/锰体系需要用三氟乙酸(TFA)活化以形成低价钴中间体，在没有这种活化剂的情况下尝试进行反应没有得到交叉偶联产物(表1，条目13)。在358℃时，…几乎没有反应
Transition-metal-catalyzed allylic alkylations, using a broad range of metal complexes, have been intensively studied because of their potential applications in the synthesis of new olefinic compounds in particular for total synthesis.[1] Soft nucleophiles are usually used in Pd-,[1] Mo-,[2] Ir-,[3] Ru-,[4] Rh-,[5] Pt-,[6] and even Fe-catalyzed [7] allylic substitutions. Ni,[8] Co,[9] and Cu [10] catalysts allow the use of hard nucleophiles such as alkylzinc or Grignard reagents, but limited functional group compatibility and/or poor regioselectivity can be observed if the system is not designed carefully. To avoid handling the air-and moisture-sensitive organomagnesium and organozinc reagents, straightforward procedures, which do not require organometallic reagents, are highly desirable and many have now been developed.[11] To the best of our knowledge, direct transition-metal-catalyzed alkyl–allyl cross-couplings using in situ generated catalytic organometallic reagents are still unknown. However, a few years ago, we reported a related Co-catalyzed coupling reaction of aryl halides with allylic acetates;[12] these reactions in the presence of an appropriate reducing reagent, gave allylaromatic compounds. Such allylic carboxylates, whilst less reactive than allyl halides, are much more environmentally friendly. Given our previous experience with the direct Cocatalyzed functionalization, including alkylation,[11c] of aryl halides [13] we were interested to take the chemistry further, and herein we report a new and general method for direct reductive cross-coupling of allylic acetates with alkyl halides using a CoBr2/Mn system with an acetonitrile/pyridine solvent mixture. The approach accommodates a variety of simple and functionalized alkyl halides and substituted allylic compounds and is experimentally straightforward. Indeed it uses off-theshelf reagents without any particular precautions against air and moisture. First, we investigated the use of the readily available yet poorly reactive ethyl 4-bromobutanoate with a simple allyl acetate as the electrophile. The major challenge here lies in promoting cross-coupling rather than the formation of reduction and homocoupling products. A combination of factors enabled us to overcome these difficulties (Table 1). The reaction conditions we established as standard afforded an excellent yield within 3 hours (Table 1, entry 1). A 5 mol% catalyst loading gave the same result but over a period of 16 hours,(Table 1, entry 2) and a 20 mol% CoBr2 loading accelerated the reaction (2 hours) but gave a higher quantity of the alkyl dimer according to GC analysis (Table 1, entry 3). Co (acac) 2 showed no catalytic activity (Table1, entry 4). Reducing the amount of Mn dust decreased the reaction rate and the yield (Table 1, entry 5), while replacing Mn by Zn dust resulted in no formation of cross-coupling product (Table 1, entry 6). Equally, no cross-coupling product was detected upon changing CH3CN for DMF (Table1, entry 7). An excess of the allyl acetate was required to drive the reaction to completion because of the formation of a pallyl Co complex (Table 1, entry 8); the pyridine appears to be important in stabilizing the low-valent Co intermediate because cross-coupling yields decreased in its absence (Table1, entry9). Replacing pyridine by bipyridine or triphenylphosphine gave poor yields, with more than 50% alkyl halide remaining unconsumed (Table 1, entries 11 and 12). The Co/Mn system requires activation by trifluoroacetic acid (TFA) for the formation of the low-valent Co intermediate, and attempts to run the reaction in the absence of this activator gave no cross-coupling product (Table1, entry 13). At 358C, almost no reaction …