Bromoallenes as allyl dication equivalents in the absence of palladium(0): synthesis of bicyclic sulfamides by tandem cyclization of bromoallenes.
Bromoallenes as allyl dication equivalents in the absence of palladium(0): synthesis of bicyclic sulfamides by tandem cyclization of bromoallenes.
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DOI：
10.1002/anie.200462557
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发表时间：
2005-02
影响因子：
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通讯作者：
H. Hamaguchi;Shohei Kosaka;H. Ohno;Tetsuaki Tanaka
中科院分区：
文献类型：
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作者：
H. Hamaguchi;Shohei Kosaka;H. Ohno;Tetsuaki Tanaka
近年来，溴烯的化学反应引起了人们的极大兴趣，因为它们与累积的双键和溴原子有关然而，除了我们最近对成环反应的研究外[2,3]，迄今为止报道的溴allenes的所有反应都是分子间反应，如有机铜介导的取代，[4]钯催化的交叉偶联反应，[5]和烯基金属试剂的形成。[6]最近，我们发现溴allenes在钯(0)的存在下可以作为烯丙基反应的等价物，这是一个非常有用的合成中型杂环（方案1）的过程因此，在钯(0)催化剂和醇的存在下，溴allene 1与醇钠的反应通过分子内的亲核攻击在异位体部分的中心碳原子上产生（η - 3-烯丙基）钯（ii）中间体2。第二亲核反应与醇氧化合物提供了良好的高收率。根据这种化学性质，我们预计溴allene 4可以通过（η - 3-烯丙基）钯（ii）中间体5串联环化（方案2）形成双环化合物6。在药物化学领域，氨基磺胺是存在于许多药用化合物中最重要的结构基序之一。例如，一些磺胺类，包括环类磺胺类，已知是有效的HIV[7]和丝氨酸蛋白酶抑制剂[8]，并且两者都是激动剂
Reactions of bromoallenes have attracted much interest in recent years because of the interesting chemical properties associated with their cumulated double bonds and bromine atom.[1] However, except for our recent study on ring-forming reactions,[2, 3] all the reactions of bromoallenes reported to date are intermolecular reactions, such as organocoppermediated substitutions,[4] palladium-catalyzed cross-coupling reactions,[5] and formation of allenyl–metal reagents.[6] Recently, we found that bromoallenes can act as allyl dication equivalents in the presence of palladium (0), which is an extremely useful process for the synthesis of medium-sized heterocycles (Scheme 1).[3] Thus, reaction of bromoallene 1 with sodium alkoxide in the presence of a palladium (0) catalyst and alcohol affords the (η3-allyl) palladium (ii) intermediate 2 by intramolecular nucleophilic attack at the central carbon atom of the allenic moiety. A second nucleophilic reaction with alkoxide provides 3 in good to high yields. In light of this chemistry, we expected that bicyclic compounds 6 could be formed by tandem cyclization of the bromoallene 4 via (η3-allyl) palladium (ii) intermediate 5 (Scheme 2). In the field of medicinal chemistry, a sulfamide is one of the most important structural motifs that exist in many pharmaceutically useful compounds. For example, some sulfamides, including cyclic ones, are known to be effective HIV [7] and serine protease inhibitors,[8] and as both agonists