Gold-catalyzed cycloaromatization of 2,4-dien-6-yne carboxylic acids: synthesis of 2,3-disubstituted phenols and unsymmetrical bi- and terphenyls.
Gold-catalyzed cycloaromatization of 2,4-dien-6-yne carboxylic acids: synthesis of 2,3-disubstituted phenols and unsymmetrical bi- and terphenyls.
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DOI：
10.1002/anie.200901269
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发表时间：
2009-07
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通讯作者：
P. García-García-P.-García-García-1443629201;M. A. Fernández-Rodríguez;E. Aguilar
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文献类型：
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作者：
P. García-García-P.-García-García-1443629201;M. A. Fernández-Rodríguez;E. Aguilar
共轭多烯体系的环芳化反应，如Bergman（烯二炔）、Saito-Myers（烯-烯）或Moore（烯-烯）环化反应，已成为生成芳香化合物的可靠方法（方案1）起始材料的特定和有限的取代模式以及这些转化传统上所需的苛刻反应条件可以通过化学计量学、金属基触发反应部分克服钌和钨通过金属偏乙烯催化的6π环芳构化也有报道此外，Rh、Fe和Pt催化剂能够促进含有内炔单元的共轭炔的环化然而，所有这些过程都局限于特定的取代或需要高温、高催化剂负载或长反应时间。众所周知，金衍生物具有激活三键以抵抗不同亲核试剂攻击的能力，这导致了一系列令人印象深刻的有机转化的发展，主要是分子内环化一个这样的例子是在温和的条件下，由6-内切金(I)催化的芳香1,5 -烯的环芳化反应合成取代萘，在它们的炔端有一个取代基我们最近描述了一种高效和简单的方法来合成捕获二烯1和2，[9]，它们可以作为金属催化转化的合适底物。从这个意义上说，在分子间杂脱氢- diols - alder反应中，非活化的腈选择性地攻击1的金属络合三键，在环化后导致四取代吡啶3然而，当类似的二乙烯羧酸2a在非常相似的反应条件下处理时，得到相应的吡啶3b和2,3 -二取代苯酚4a[11]的混合物（方案2）。值得注意的是，2a的环芳构化形成4a与上述涉及6π电子的环芳构化有很大不同。在本例中，在π共轭体系的碳原子2和7之间形成了一个新的CÀC键，而不是更常见的碳原子1和6之间形成的键（方案1）。在这里，我们报告了我们对这种新转化的研究，以及与非俘获性二乙烯羧酸发生的相关环化-脱羧序列。最初的实验是用二烯2a进行的，以便对几个参数进行优化。与在乙腈中的情况相反，在其他溶剂中，在室温下反应，只生成苯酚衍生物4a。因此，CH2Cl2比甲苯、四氢呋喃、乙醚、己烷或甲醇产生更好的结果用银盐原位生成的阳离子金(I)配合物也能催化该反应（表1，条目3-11）。银盐的反作用力被发现是重要的：提供了AgSbF6
Cycloaromatization reactions of conjugated polyenyne systems, such as the Bergman (enediynes), Saito–Myers (enyne–allene), or Moore (enyne–ketene) cyclizations, have become reliable methods for the formation of aromatic compounds (Scheme 1).[1] The specific and limited substitution pattern of the starting materials as well as the harsh reaction conditions traditionally required for these transformations can be partially overcome by stoichiometric, metal-based triggering reactions.[2] Ruthenium-and tungsten-catalyzed 6π cycloaromatizations via metal vinylidene species have also been reported.[3] Furthermore, Rh, Fe, and Pt catalysts are able to promote the cyclization of conjugated enynes containing internal alkyne units.[4] However, all of these processes are limited to a specific substitution or require high temperatures, high catalyst loadings, or long reaction times. The notorious ability of gold derivatives to activate triple bonds for attack by different nucleophiles [5] has resulted in the development of an impressive array of organic transformations [6]—predominantly intramolecular cyclizations.[7] One such example is the synthesis of substituted naphthalenes under mild conditions by a 6-endo-dig gold (I)-catalyzed cycloaromatization of aromatic 1, 5-enynes bearing a substituent on their alkyne terminus.[8] We have recently described an efficient and simple procedure for the synthesis of captodative dienynes 1 and 2,[9] which could be appropriate substrates for metal-catalyzed transformations. In this sense, non-activated nitriles regioselectively attack the metal-complexed triple bond of 1 which leads, after cyclization, to tetrasubstituted pyridines 3 in an intermolecular hetero-dehydro-Diels–Alder reaction.[10] However, when the analogous dienyne carboxylic acid 2a was treated under very similar reaction conditions, a mixture of the corresponding pyridine 3b and 2, 3-disubstituted phenol 4a [11] was obtained (Scheme 2). Remarkably, the cycloaromatization of 2a to form 4a is very different from the abovementioned cyclizations involving 6π electrons. In the present case, a new CÀC bond is formed between carbon atoms 2 and 7 of the π-conjugated system, instead of the more common creation of a bond between carbon atoms 1 and 6 (Scheme 1). Herein we report our study of this novel transformation as well as a related cyclization-decarboxylation sequence that occurs with noncaptodative dienyne carboxylic acids. The initial experiments were carried out with dienyne 2a to allow optimization of several parameters. In contrast to the situation in acetonitrile, reaction takes place at room temperature in other solvents to exclusively form phenol derivative 4a. Thus, CH2Cl2 led to better results than toluene, THF, diethyl ether, hexane, or methanol.[12] Cationic gold (I) complexes, generated in situ with silver salts, were also able to catalyze the reaction (Table 1, entries 3–11). The counterion of the silver salt was found to be important: AgSbF6 provided