Gold-Catalyzed Cyclopenta- and Cycloheptannulation Cascades: A Stereocontrolled Approach to the Scaffold of Frondosins A and B
Gold-Catalyzed Cyclopenta- and Cycloheptannulation Cascades: A Stereocontrolled Approach to the Scaffold of Frondosins A and B
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DOI：
10.1002/anie.201006105
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Nevado, Cristina
中科院分区：
文献类型：
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作者：
Garayalde, David;Krueger, Karolin;Nevado, Cristina
七元环碳环是广泛存在于各种天然产物中的基序，包括胍基萜、秋水仙碱、佛波酯和叶素等。[1]由于直接环化已被证明是低效的，以构建这种特定的环的大小，替代策略已被设计出来，主要集中在环加成反应。[2]铑离子介导的乙烯基环丙烷与不饱和环之间的[5+ 2]环加成反应已被成功地发展起来。[3]另一种广泛使用的方法是在形式[4+ 3]环加成中使用铑-乙烯基卡宾和二烯。[4]然而，这种方法仍然存在几个缺点：首先，金属卡宾是由相应的重氮化合物产生的，其需要预先合成，从而为整个过程增加了额外的步骤，其次，只有供体-受体卡宾提供高水平的选择性。近年来，多功能金配合物的发展表明，金催化是构建分子复杂性的有力工具。[5]作为一个代表性的例子，金催化的炔丙基酯的1，2-酰氧基迁移产生金卡宾，其可以经历广泛的转化，如亲核攻击，[6]成环，[7]随后的酰氧基重排，[8]和烯烃环丙烷化。[9]最近，报道了金催化的稳定环丙基环的扩环反应。[10]我们设想，涉及炔丙基酯和二烯的反应序列可以被编排，使得金不仅催化1，2-乙酰氧基迁移和随后的环丙烷化，而且还可以再活化原位产生的乙酸乙烯酯，从而触发正式的homo-Cope重排，以直接的方式得到七元环（方案1;路径a）。[11]此外，如果使用烯烃代替二烯烃，则在环丙基开环时可以获得高度取代的环戊烯基乙酸酯（方案1;路径B）。在此，我们报告了这些概念的实现和应用在海洋次级代谢产物frondosins A和B的正式的对映选择性合成。乙酸对甲氧基苯基炔丙酯（1a）和（E）-（2-甲基丁-1，3-二烯基）苯（A）在[IPrAu] NTf 2存在下的反应干净地得到1 ∶ 2比率的环丙烷2aA和乙酸环庚烯酯4aA（表1，条目1）。在更亲电的亚磷酸酯配体存在下，可以检测到五元和七元环3 aA和4 aA（表1，条目2）。三（2，4-二叔丁基苯基）亚磷酸酯-金络合物在加热至80 ℃时得到类似的结果（表1，条目3;条件I），而Ph 3 PAuSbF 6提供环丙基2aA和七元环4aA以1：2比率的混合物（表1，条目4）。2.5摩尔%[IPrAu] NTf 2和2.5摩尔%（PhO）3 PAuSbF 6的组合以69%产率递送4aA（表1，条目5;条件II）。最后，[（2-联苯基）二叔丁基膦]-金络合物以85%产率选择性地提供4aA，从而提供
Seven-membered ring carbocycles are ubiquitous motifs in a wide variety of natural products including guanascaterpenes, colchicines, phorbols, and frondosins among many others.[1] Since direct cyclizations have proved to be inefficient to construct this particular ring size, alternative strategies have been devised and mainly focus on cycloaddition reactions.[2] Both inter-and intramolecular rhodium-mediated [5+ 2] cycloadditions between vinylcyclopropanes and unsaturated moieties have been successfully developed.[3] Another widespread method uses rhodium–vinyl carbenoids and dienes in formal [4+ 3] cycloadditions.[4] However, this methodology still presents several drawbacks: first, the metal carbenes are generated from the corresponding diazo compounds, which need to be pre-synthesized, thus adding extra steps to the overall process, and secondly, only donor–acceptor carbenoids provide high levels of selectivity. The development of versatile gold complexes in recent years has revealed gold catalysis as a powerful tool to construct molecular complexity.[5] As a representative example, the gold-catalyzed 1, 2-acyloxy migration of propargyl esters generates a gold carbene, which can undergo a broad palette of transformations such as nucleophilic attack,[6] annulation,[7] subsequent acyloxy rearrangement,[8] and olefin cyclopropanation.[9] Recently, gold-catalyzed ring expansions of stabilized cyclopropyl rings were reported.[10] We envisioned that a reaction sequence involving propargyl esters and dienes could be orchestrated such that gold not only catalyzed the 1, 2-acetoxy migration and subsequent cyclopropanation, but could also reactivate the in situ generated vinyl acetate, thereby triggering a formal homo-Cope rearrangement to give sevenmembered rings in a straightforward manner (Scheme1; path a).[11] Furthermore, if alkenes instead of dienes were used, highly substituted cyclopentenyl acetates could be obtained upon cyclopropyl ring opening (Scheme 1; path b). Herein, we report the realization of these concepts and an application in the formal enantioselective synthesis of marine secondary metabolites frondosins A and B. The reaction of p-methoxyphenylpropargyl acetate (1a) and (E)-(2-methylbuta-1, 3-dienyl) benzene (A) in the presence of [IPrAu] NTf2 cleanly delivered cyclopropane 2 aA and cycloheptenylacetate 4 aA in a 1: 2 ratio (Table 1, entry 1). In the presence of a more electrophilic phosphite ligand, fiveand seven-membered rings 3 aA and 4 aA could be detected (Table 1, entry 2). The tris (2, 4-di-tertbutylphenyl) phosphite–gold complex afforded similar results upon heating to 808C (Table 1, entry 3; Conditions I), whereas Ph3PAuSbF6, provided a mixture of cyclopropyl 2 aA and the seven-membered ring 4 aA in a 1: 2 ratio (Table 1, entry 4). A combination of 2.5 mol%[IPrAu] NTf2 and 2.5 mol%(PhO) 3PAuSbF6 delivered 4 aA in a 69% yield (Table 1, entry 5; Conditions II). Finally, a [(2-biphenyl) di-tert-butylphosphine]–gold complex selectively afforded 4 aA in a 85% yield, thereby providing