Construction of Fused Heterocyclic Architectures by Formal [4+1]/[3+2] Cycloaddition Cascade of Sulfur Ylides and Nitroolefins
Construction of Fused Heterocyclic Architectures by Formal [4+1]/[3+2] Cycloaddition Cascade of Sulfur Ylides and Nitroolefins
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通过硫叶立德和硝基烯烃的形式[4 1]/[3 2]环加成级联构建稠合杂环结构
DOI：
10.1002/anie.200904766
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Xiao, Wen-Jing
中科院分区：
文献类型：
--
作者：
Lu, Liang-Qiu;Li, Fang;Xiao, Wen-Jing
在过去的50年里，Franzen,[1] Corey,[2] Trost,[3] Aggarwal，[4]和Dai[5]等人的开创性研究已经确定了硫酰基化合物[6]是合成化学中有价值的和通用的中间体。因此，硫酰化物被广泛用于环氧化物、叠氮和环丙烷的结构。最近，Tang及其同事[7]和其他人[8]的研究大大扩展了酰基引发反应的范围，并概述了由硫酰基引发的串联反应的第一个例子，以提供一系列超越三元环的功能化环化合物。尽管取得了这些进展，但对前所未有的基于ylide的多重级联反应的研究仍在继续，其目标是以阶梯经济的方式增加可能底物的多样性和产品的结构复杂性最近，我们的实验室实现了一种新的硫酰基与亚硝基烯烃的反应，得到了多种结构复杂的恶唑烷-2- 1，其中瞬态生成的环硝酸酯参与其中在此基础上，我们开始对使用上述环硝酸钠作为合适的1,3偶极子与缺电子成分原位反应的可能性产生兴趣，并在一次转化中产生多个键、环和立体中心。在这里，我们报道了这一想法的成功实施，并描述了硫酰和烯系亚硝基烯烃的第一个分子间[4+ 1]/分子内[3+ 2]环加成级联这种新颖的无催化剂策略允许以高度简洁的方式快速获得功能化的2,3,5 -三氧杂a-2 -氮杂二烯[1,6 -ab]萘、2,3 -二氧杂a-2 -氮杂二烯[1,6 -ab]萘和异恶唑[4,3,2 -hi][2,1]苯并恶唑（方案1）；这些产物是构建密集功能化铬、硫铬、氨基酸、氨基醇和其他重要杂环的多功能合成物。[12]我们首先研究了二甲基（2-氧-2-苯乙基）磺酰化（1a）与（E)-乙基3-（2-(E)-2-硝基）苯氧基）丙烯酸酯（2a）在乙腈中在08℃下反应12小时，然后将反应混合物加热到室温并再搅拌8小时。令我们高兴的是，所提出的环加成级联确实很容易，并提供了1-（苯基羰基）- 4,4a, 9b， 9c-四氢- 1h - 2,3,5 -三氧-2a-氮杂二烯-丙烯[1,6 -ab]萘-4-羧酸乙酯（4a）作为主要分离产物，收率为43%，具有很强的非对构性（表1）。
Over the last 50 years, seminal research from the groups of Franzen,[1] Corey,[2] Trost,[3] Aggarwal,[4] and Dai [5] have established sulfur ylides [6] as valuable and versatile intermediates in synthetic chemistry. As a consequence, sulfur ylides are widely utilized for the construction of epoxide, aziridine, and cyclopropane architectures. Recently, studies by Tang and co-workers [7] and others [8] have significantly extended the scope of the ylide-initiated reactions and outlined the first examples of tandem reactions initiated by sulfur ylides to furnish a range of functionalized cyclic compounds beyond three-membered rings. Despite the advances, the search for unprecedented ylide-based multiple cascade reactions continues, with the goal of increasing the diversity of possible substrates and the architectural complexity of products in a step-economical fashion.[9] Recently, our laboratory implemented a new reaction of sulfur ylides with nitroolefins to afford diverse and structurally complex oxazolidin-2-ones, wherein a transiently generated cyclic nitronate was involved.[10] On this basis, we became interested in the possibility of using the above mentioned cyclic nitronate as a suitable 1, 3-dipole to react with electron-deficient components in situ, and in doing so create multiple bonds, rings, and stereocenters in a single transformation. Herein, we report a successful execution of this idea and describe the first intermolecular [4+ 1]/intramolecular [3+ 2] cycloaddition cascade of sulfur ylides and alkene-tethered nitroolefins.[11] This novel and catalyst-free strategy allows rapid access to functionalized 2, 3, 5-trioxa-2a-azapentaleno [1, 6-ab] naphthalenes, 2, 3-dioxa-5-thia-2a-azapentaleno [1, 6-ab] naphthalenes, and isoxazolo [4, 3, 2-hi][2, 1] benzisoxazoles in a highly concise fashion (Scheme 1); and these products are versatile synthons for the construction of densely functionalized chromans, thiochromans, amino acids, amino alcohols, and other important heterocycles.[12]We initially studied the reaction of dimethyl (2-oxo-2-phenylethyl) sulfonium ylide (1a) with (E)-ethyl 3-(2-((E)-2-nitrovinyl) phenoxy) acrylate (2a) in acetonitrile at 08C for 12 hours, at which point the reaction mixture was warmed to room temperature and stirred for an additional eight hours. To our delight, the proposed cycloaddition cascade was indeed facile and afforded ethyl 1-(phenylcarbonyl)-4, 4a, 9b, 9c-tetrahydro-1H-2, 3, 5-trioxa-2a-azapent-aleno [1, 6-ab] naphthalene-4-carboxylate (4a) as a major isolable product in 43% yield with great diastereocontrol (Table1,