N-Fused Indolines through Non-Carbonyl-Stabilized Rhodium Carbenoid C-H Insertion of N-Aziridinyl Imines
N-Fused Indolines through Non-Carbonyl-Stabilized Rhodium Carbenoid C-H Insertion of N-Aziridinyl Imines
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DOI：
10.1002/chem.201103155
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发表时间：
2012-01-01
影响因子：
4.3
通讯作者：
Fillion, Eric
中科院分区：
文献类型：
--
作者：
Mahoney, Stuart J.;Fillion, Eric
最近，金属催化的官能化CCHOH键的方法取得了令人难以置信的进展，允许新的逆合成断开到否则不反应的键，并以高化学控制、区域控制和立体控制执行转化。[1]一个更成熟的CACHTUGTRENNUNG（SP3）CCH 3 H键的功能化领域是铑催化的羰基稳定的重氮底物的CCH 3 H插入，这已经达到了甚至具有高对映选择性的分子间CCH 3 H插入的水平。[2]分子间方法成功的关键是将重点从研究配体改变转移到底物设计，特别是转移到供体-受体类卡宾。[2a-b]尽管取得了进展，但由于控制反应性物质的选择性的固有困难，在没有受体（主要是羰基官能团）的情况下类卡宾的类似C2 OH插入仍然难以实现。另一方面，一种快速发展的氧化还原中性方法官能化CACHTUNGTRENNUNG（SP3）OH键已经催化了叔氨基效应的变体，[3]现在包括未活化的炔和丙二烯受体，[4]叔脂肪族氢化物供体，[5]多米诺反应，[6]和对映选择性方案。[7]为了寻求开发一种通过CACHTUNGTRENNUNG（sp3）OH键官能化直接进入特权N-稠合吲哚啉骨架[8]的方法，我们将注意力转向N-氮丙啶基亚胺1（氮丙啶酰腙）[9]，其可能提供两种不同的反应模式以实现所需的转化（方案1），即氢化物受体和分解为苄基卡宾。[10]借助于所提出的[1，5]氢化物移位/环化机制（方案1，路径A），苄基碳将充当偕受体/供体（有效地为1，1-偶极）而不是典型的邻位受体/供体;净结果将是形成五元环，而不是用传统使用的受体产生的六元环。[11-12]此外，认识到N-氮丙啶基亚胺作为卡宾前体的能力（方案1，路径B），必须考虑可能导致N-稠合二氢吲哚2的竞争途径。[13]在这篇手稿中，我们报道了一种非羰基稳定的铑类卡宾CNOH插入的通用催化方案，能够快速合成N-稠合吲哚啉和复杂的杂环。首先检查了腙1a通过CACHTUNGTRENNUNG（sp3）OH键官能化环化为三环2a的能力（表1）。在筛选刘易斯酸和Brøn-ACHTUNGTRENNUNGsted酸时，仅观察到不同量的起始物料和分解。然而，当加热反应（！708 C），卡宾途径通过形成所需产物2a（通过C2 H4插入）与醛3a、环丙烷4a [14]和二聚产物（吖嗪5a和烯烃6a;表1，条目1）一起沿着形成而明显。然后发现，在加入过量苯乙烯时，通过卡宾中间体的分子间清除，可以选择性地形成环丙烷（4a，反式/顺式比为1.6：1）（表1，条目2）。对用铑介导卡宾反应[15]的可能性持乐观态度，[16-17]进行了催化剂筛选。令人满意的是，与最近报道的甲苯磺酰腙分解相比，产物分布发生了显著变化，主要形成C3 OH插入产物（表1，条目3），甲苯磺酰腙分解仅通过二聚形成烯烃。[13e]dirhodium（II）carboxamidates的空间效应
Metal-catalyzed methods of functionalizing CÀH bonds have seen incredible advancements in recent times, allowing for new retrosynthetic disconnections to otherwise unreactive bonds and executing transformations with high chemo-, regio-, and stereocontrol.[1] A more established area of functionalizing CACHTUNGTRENNUNG (sp3) ÀH bonds has been rhodium-catalyzed CÀ H insertions from carbonyl-stabilized diazo substrates, which has reached a level at which even intermolecular CÀ H insertions with high enantioselectivity have been achieved.[2] Key to the success of the intermolecular methodology was shifting the focus from studying ligand alterations to substrate design, specifically in moving to donor–acceptor carbenoids.[2a–b] Despite the progression, analogous CÀH insertions of carbenoids without an acceptor (primarily carbonyl functionalities) have remained elusive due to the inherent difficulties with controlling selectivity of the reactive species. Alternatively, a rapidly developing redox-neutral method of functionalizing CACHTUNGTRENNUNG (sp3) ÀH bonds has been catalyzed variants of the tert-amino effect,[3] which now includes unactivated alkyne and allene acceptors,[4] tertiary aliphatic hydride donors,[5] domino reactions,[6] and enantioselective protocols.[7] Seeking to develop a methodology to give direct access to the privileged N-fused indoline scaffold [8] through CACHTUNGTRENNUNG (sp3) ÀH bond functionalization, we turned our attention to N-aziridinyl imines 1 (Eschenmoser hydrazones),[9] which potentially offered two distinct reactivity modes to achieve the desired transformation (Scheme 1), namely, hydride acceptor and decomposition to a benzylic carbene.[10] By virtue of the proposed [1, 5] hydride shift/cyclization mechanism (Scheme1, pathA), the benzylic carbon would act as a geminal acceptor/donor (effectively a 1, 1-dipole) instead of the typical vicinal acceptor/donor; the net result would be the formation of a five-membered ring as opposed to the six-membered ring created with traditionally employed acceptors.[11–12] Also, cognizant of the ability of the N-aziridinyl imine to function as a carbene precursor (Scheme 1, path B) a competing pathway that could lead to N-fused indoline 2 had to be considered.[13]In this manuscript, we report a general catalytic protocol of non-carbonyl-stabilized rhodium carbenoid CÀH insertions enabling rapid synthesis of N-fused indolines and complex heterocycles. The ability of hydrazone 1a to cyclize to tricycle 2a through CACHTUNGTRENNUNG (sp3) ÀH bond functionalization was first examined (Table 1). Upon screening Lewis and Brøn-ACHTUNGTRENNUNGsted acids, only varying amounts of starting material and decomposition were observed. However, when heating the reaction (! 708C) in the absence of a promoter, the carbene pathway was evident by the formation of the desired product 2a (by CÀH insertion) along with aldehyde 3a, cyclopropanes 4a,[14] and dimerization products (azine 5a and alkenes 6a; Table 1, entry 1). It was then found that the cyclopropanes could be selectively formed (4a, trans/cis ratio of 1.6: 1) by intermolecular scavenging of the carbene intermediate upon addition of an excess of styrene (Table1, entry 2). Optimistic about the possibility of mediating the carbene reaction [15] with rhodium,[16–17] a catalyst screen was performed. It was gratifying to see that the product distribution changed significantly to predominantly form the CÀH insertion product (Table 1, entry 3) in contrast to a recent report of tosyl hydrazone decomposition, which exclusively formed alkenes through dimerization.[13e] Steric effects of dirhodium (II) carboxamidates …