Orbital-overlap control of the reactivity of a bicyclic 1-hydroxy-1,4-biradical.
Orbital-overlap control of the reactivity of a bicyclic 1-hydroxy-1,4-biradical.
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DOI：
10.1002/anie.200500983
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发表时间：
2005-08
影响因子：
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通讯作者：
C. Yang;W. Xia;J. Scheffer;M. Botoshansky;M. Kaftory
中科院分区：
文献类型：
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作者：
C. Yang;W. Xia;J. Scheffer;M. Botoshansky;M. Kaftory
1, 4-双自由基是有机化学中最普遍的反应中间体之一，在多种反应中形成或涉及，包括 [2+ 2] 光环加成、[1] Paterno-Büchi 反应（氧杂环丁烷形成）、[2] Norrish-Yang II 型反应、[3] 以及环状偶氮化合物中氮的消除。 [4]一旦形成，1, 4-双自由基会遭受两个主要命运：闭合形成含有四元环的化合物，以及中心键裂解产生一对含有双键的片段。 [5]基于半经验计算支持的有机直觉，[6]并得到各种产品研究的支持，[1-4]普遍接受的双自由基反应性定性图像是，当构象允许位置1和4处的含自由基轨道与位置2和3之间的西格玛键重叠时，裂解是有利的。只要自由基末端彼此之间的键合距离合理，随着这种重叠的减少，可以观察到环化量的增加。然而，这一假设的定量实验测试很少，部分原因是难以建立流体介质中构象移动系统的结构-反应性关系。在三重态 1, 4-双自由基的情况下，情况变得复杂，因为双自由基行为反映了单重态双自由基由三重态的系间交叉 (isc) 形成的几何形状，这可能与构象平衡物种的几何形状显着不同。 [7]出于这些原因，我们选择使用结晶态的化合物，其中分子构象是固定的并可通过 X 射线晶体学确定，并且由 isc 形成的单线态双自由基具有与其三线态前体相同的几何形状。我们已经证明，通过 Norrish-Yang II 型反应可以在固态下方便地生成 1-羟基-1, 4-双自由基，并且由于氢原子转移发生时相关重原子的运动非常少，因此双自由基的结构和构象可以直接从其基态前体的 X 射线晶体结构推断出来。 [8]在此，我们比较和对比一般结构 1 和 2 的 1-羟基-1, 4-双自由基的行为。这些双自由基很有趣，因为与之前研究的大多数双自由基不同，它们只有一个显着的构象自由度，即围绕 C1-C2 键的旋转。关于这些双自由基，我们希望回答的问题包括：1）C1位置的p轨道方向如何影响环化与裂解的比率； 2）我们能否将 C1 轨道的方向与 C2-C3 或 C2-C3' 键的优先裂解联系起来？如下所述，通过生成晶态双自由基 1 和 2 并将它们在该介质中的行为与 X 射线晶体学测定的构象相关联，获得了这些问题的满意答案。我们并不是第一个研究 1 型和 2 型双自由基的人。1972 年 Padwa 和 Eisenberg 报道了双自由基 2 (Ar= Ph) 的溶液相行为，结果显示由 66% 裂解和 30% 环化组成。 [9]同样，Alexander 和 Uliana 在 1976 年证明，在溶液中，C2 位带有苯基取代基的双自由基 1 (Ar= Ph) 会发生 100% 环化。 [10]在这两种情况下，双自由基都是通过相应酮的 Norrish-Yang II 型光反应形成的。在目前的工作中，我们选择研究芳基在对位带有羧酸取代基的酮，即通式结构 3 和…的酮。
1, 4-Biradicals are among the most ubiquitous reactive intermediates in organic chemistry, and are formed or implicated in a variety of reactions including [2+ 2] photocycloaddition,[1] the Paterno–Büchi reaction (oxetane formation),[2] the Norrish–Yang type II reaction,[3] and the elimination of nitrogen from cyclic azo compounds.[4] Once formed, 1, 4-biradicals suffer two main fates: closure to form compounds containing a four-membered ring, and cleavage of the central bond to produce a pair of double-bond-containing fragments.[5] Based on organic intuition backed by semiempirical calculations,[6] and supported by a wide variety of product studies,[1–4] the generally accepted qualitative picture of biradical reactivity is that cleavage is favored when the conformation allows the radical-containing orbitals at positions 1 and 4 to overlap with the sigma bond between positions2 and 3. Increasing amounts of cyclization are observed as this overlap diminishes, provided that the radical termini are within reasonable bonding distance of one another. However, quantitative experimental tests of this hypothesis are rare, in part as a result of the difficulty of establishing structure–reactivity relationships for conformationally mobile systems in fluid media. In the case of triplet 1, 4-biradicals, the picture is complicated by the likelihood that biradical behavior reflects the geometry in which the singlet biradical is formed by intersystem crossing (isc) from the triplet, which may differ significantly from the geometry of the conformationally equilibrated species.[7] For these reasons, we have elected to work with compounds in the crystalline state, where molecular conformation is fixed and determinable by X-ray crystallography, and where the singlet biradical formed by isc has the same geometry as its triplet precursor. We have shown that 1-hydroxy-1, 4-biradicals can be generated conveniently in the solid state by the Norrish–Yang typeII reaction, and that because hydrogen-atom transfer occurs with very little movement of the associated heavy atoms, the structure and conformation of the biradicals can be inferred directly from the X-ray crystal structures of their ground-state precursors.[8] Herein, we compare and contrast the behavior of 1-hydroxy-1, 4-biradicals of general structures 1 and 2. These biradicals are interesting because, unlike the majority of biradicals studied previously, they have only one significant degree of conformational freedom, namely, rotation about the C1ÀC2 bond. Among the questions we wished to answer about these biradicals were: 1) how does the orientation of the p orbital at the C1 position affect the ratio of cyclization to cleavage; and 2) can we correlate the orientation of the porbital at C1 with preferential cleavage of either the C2ÀC3 or C2ÀC3’bond? As described below, satisfactory answers to these questions were obtained by generating biradicals 1 and 2 in the crystalline state and correlating their behavior in this medium with their conformations as determined by X-ray crystallography. We are not the first to study biradicals of types 1 and 2. The solution-phase behavior of biradical 2 (Ar= Ph) was reported in 1972 by Padwa and Eisenberg and shown to consist of 66% cleavage and 30% cyclization.[9] Similarly, Alexander and Uliana showed in 1976 that, in solution, biradical 1 (Ar= Ph) bearing a phenyl substituent at the C2 position undergoes 100% cyclization.[10] In both cases, the biradicals were formed by a Norrish–Yang typeII photoreaction of the corresponding ketone. In the present work, we chose to investigate ketones in which the aryl group bears a carboxylic acid substituent in the para position, that is, ketones of general structures 3 and …