The [3 + 3]-cycloaddition alternative for heterocycle syntheses: catalytically generated metalloenolcarbenes as dipolar adducts.
The [3 + 3]-cycloaddition alternative for heterocycle syntheses: catalytically generated metalloenolcarbenes as dipolar adducts.
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DOI：
10.1021/ar5000055
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发表时间：
2014-04-15
影响因子：
18.3
通讯作者：
Doyle, Michael P.
中科院分区：
文献类型：
--
作者：
Xu, Xinfang;Doyle, Michael P.
形成环状有机化合物的两个或更多个不饱和结构单元的组合通常被称为环加成，并且形成六元环的两个不饱和结构单元的组合形式上是[5 + 1]-、[4 + 2]-、[2 + 2 + 2]-或[3 + 3]-环加成。环加成反应是有机化学中最有用的合成结构之一，它是协同或逐步进行的反应。在这些转化中，协同的[4 + 2]-环加成反应，即Diels-Alder反应，是迄今为止最著名和应用最广泛的。然而，虽然对称性不允许作为一个协调的过程，并缺乏可证明的例子，直到最近，逐步[3 + 3]-环加成提供了大量的杂环化合物的合成的优势，他们正在受到相当大的关注。在本报告中，我们介绍了逐步[3 + 3]-环加成反应的发展，从20世纪90年代的虚拟隐形到今天快速发展的合成方法，涉及有机催化或过渡金属催化。由于起源于有机金属或乙烯基杂环离子化学，这一领域已经发展成为一个可行的合成转化，用于构建含有一个或多个杂原子的六元杂环化合物。[3 + 3]-环加成转化的发展已经通过鉴定合适的和相容的反应性偶极加合物和稳定的偶极实现。反应性偶极物质是在反应中最佳催化形成的高能偶极中间体。逐步的过程发生与反应性偶极加合物作为亲电试剂或亲核试剂反应，形成第一个共价键，这种协会提供了熵的第二个共价键的建设和整体的正式[3 + 3]-环加成援助。有机催化在分子间和分子内的合成转化中得到了很好的发展，但过渡金属催化[3 + 3]-环加成的潜力最近才出现。过渡金属基方法学快速发展的关键是认识到某些催化生成的乙烯基卡宾是与稳定偶极化合物（包括芳基和乙烯基叶立德）反应的有效偶极加合物。特别地，由方便制备的稳定的烯醇重氮乙酸酯或由供体-受体环丙烯催化生成的金属-烯醇卡宾是[3 + 3]-环加成的高效偶极加合物。甲硅烷基醚的给电子氧增强了乙烯基卡宾加成反应中初始加合物的金属键合碳的亲电闭环，这种增强作用抑制了乙烯基卡宾的碳-碳双键上的交替[3 + 2]-环加成反应。催化产生的金属-烯醇卡宾在温和条件下与广谱相容的稳定偶极反应，包括硝酮、甲亚胺亚胺、叶立德和稳定偶极的某些共价前体，以高产率形成具有β-酮酯官能团的[3 + 3]-环加成产物（例如，在二氢恶嗪、四氢哒嗪、吡唑烷酮和间苯二唑衍生物、二氢喹啉和喹嗪烷中）。获得这些金属-烯醇卡宾的两种方法，通过从烯醇重氮乙酸酯中挤出二氮或通过供体-受体环丙烯的重排，增强了该方法的通用性。[3 + 3]-环加成方法是合成六元环杂环化合物的[4 + 2]-环加成的补充策略。通过在过渡金属催化剂上使用手性配体，包括在铑（II）和银（I）上的那些，获得了高水平的对映选择性。
The combination of two or more unsaturated structural units to form cyclic organic compounds is commonly referred to as cycloaddition, and the combination of two unsaturated structural units that forms a six-membered ring is formally either a [5 + 1]-, [4 + 2]-, [2 + 2 + 2]-, or [3 + 3]-cycloaddition. Occurring as concerted or stepwise processes, cycloaddition reactions are among the most useful synthetic constructions in organic chemistry. Of these transformations, the concerted [4 + 2]-cycloaddition, the Diels–Alder reaction, is by far the best known and most widely applied. However, although symmetry disallowed as a concerted process and lacking certifiable examples until recently, stepwise [3 + 3]-cycloadditions offer advantages for the synthesis of a substantial variety of heterocyclic compounds, and they are receiving considerable attention. In this Account, we present the development of stepwise [3 + 3]-cycloaddition reactions from virtual invisibility in the 1990s to a rapidly growing synthetic methodology today, involving organocatalysis or transition metal catalysis. With origins in organometallic or vinyliminium ion chemistry, this area has blossomed into a viable synthetic transformation for the construction of six-membered heterocyclic compounds containing one or more heteroatoms. The development of [3 + 3]-cycloaddition transformations has been achieved through identification of suitable and compatible reactive dipolar adducts and stable dipoles. The reactive dipolar species is an energetic dipolar intermediate that is optimally formed catalytically in the reaction. The stepwise process occurs with the reactive dipolar adduct reacting as an electrophile or as a nucleophile to form the first covalent bond, and this association provides entropic assistance for the construction of the second covalent bond and the overall formal [3 + 3]-cycloaddition. Organocatalysis is well developed for both inter- and intramolecular synthetic transformations, but the potential of transition metal catalysis for [3 + 3]-cycloaddition has only recently emerged. The key to the rapid development of the transition metal-based methodology has been recognition that certain catalytically generated vinylcarbenes are effective dipolar adducts for reactions with stable dipolar compounds, including aryl and vinyl ylides. In particular, metallo-enolcarbenes that are generated catalytically from conveniently prepared stable enoldiazoacetates or from donor–acceptor cyclopropenes are highly effective dipolar adducts for [3 + 3]-cycloaddition. The electron-donating oxygen of the silyl ether enhances electrophilic ring closure to the metal-bound carbon of the initial adduct from vinylogous addition, and this enhancement inhibits the alternative [3 + 2]-cycloaddition across the carbon–carbon double bond of the vinylcarbene. Catalytically generated metallo-enolcarbenes react under mild conditions with a broad spectrum of compatible stable dipoles, including nitrones, azomethine imines, ylides, and certain covalent precursors of stable dipoles, to form [3 + 3]-cycloaddition products having the β-ketoester functionality (in dihydrooxazines, tetrahydropyridazines, pyrazolidinone and pyraxole derivatives, dihydroquinolines, and quinolizidines, for example) in high yield. Two ways to access these metallo-enolcarbenes, either by dinitrogen extrusion from enoldiazoacetate esters or by rearrangement of donor–acceptor cyclopropenes, enhance the versatility of the process. The [3 + 3]-cycloaddition methodology is a complementary strategy to [4 + 2]-cycloaddition for the synthesis of heterocyclic compounds having six-membered rings. High levels of enantioselectivity are obtained with the use of chiral ligands on transition metal catalysts that include those on dirhodium(II) and silver(I).
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影响因子：
5.2
作者：
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通讯作者：
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影响因子：
5.2
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