Expansion by Contraction: Diversifying the Photochemical Reactivity Scope of Diazo-oxochlorins toward Development of <i>in Situ</i> Alkylating Agents

Irradiation of 2-diazo-3-oxochlorins (200 W, λ ≥ 345 nm, 10 °C) in the presence of nucleophilic and biomimetic substrates 1-butanol, tosylhydrazine, or tetrahydrofurfuryl alcohol generates Wolff-rearranged, pyrrole ring-contracted azeteoporphyrinoids in 11−34% yield, with the corresponding hydroxyporphyrins in up to 55% yield. For metalated diazo-oxochlorins, these products compete with intramolecular exocyclic ring formation by meso-phenyl ring addition, which occurs in up to 76% yield in the absence of substrate. The dependence of product distribution on substrate is established by photolysis in neat dichlorometane. Under these conditions, formation of the Wolff-rearranged product is inhibited and the phenyl addition product dominates (76%) due to the absence of a good nucleophile. A conceptually analogous dependence is also observed for the free-base derivative, with the exocyclic ring-containing dimerization product isolated in 42% yield. The third reaction pathway, formation of the hydroxyporphyrin, is enhanced by the presence of non-nucleophilic, oxidizable substrates such as 1,4-cyclohexadiene (M = Cu; 55%); however, in the presence of the bulky and oxidatively more stable tert-butyl alcohol, intramolecular exocyclic ring-quenching is observed in 51% yield with no detection of the hydroxyporphyrin. X-ray structure characterization of the azeteoporphyrinoids reveals a planar macrocycle, illustrating the strong influence of periphery contraction. Specifically, the copper-containing azeteoporphyrinoids show remarkably short Cu−Nazete distances of 1.88−1.90 Å. All porphyrinoid photoproducts possess intense absorption bands throughout the visible spectral region, indicating that ring-contracted substrate adducts, as well as phenyl ring addition products, maintain porphyrinoid aromaticity. Overall, the ability of these chromophores to photochemically react under substrate control may make unimolecular porphyrinoid photoreagents such as these useful for applications in photobiology or O2-independent photodynamic therapy.在亲核性仿生底物正丁醇、对甲苯磺酰肼或四氢糠醇存在下，对2-重氮-3-氧代二氢卟吩（2-diazo-3-oxochlorins）进行辐照（200 W，波长λ ≥ 345 nm，10 ℃），可生成经沃尔夫重排（Wolff rearrangement）、吡咯环收缩的氮杂环丁烯卟啉类化合物（azeteoporphyrinoids），产率为11%~34%，同时得到羟基卟啉，产率最高可达55%。对于金属化重氮氧代二氢卟吩而言，上述产物会与通过中位苯基环加成发生的分子外环外成环反应形成的产物相互竞争；在无底物的情况下，该环加成产物的产率最高可达76%。通过在纯二氯甲烷中进行光解实验，确立了产物分布对底物的依赖性。在此条件下，由于缺乏良好的亲核试剂，沃尔夫重排产物的生成被抑制，苯基加成产物占主导（产率76%）。游离碱衍生物也表现出概念上类似的依赖性，含外环的二聚产物分离产率为42%。第三条反应路径为羟基卟啉的生成，该路径可被非亲核性且可被氧化的底物（如1,4-环己二烯，金属中心M=Cu时产率55%）增强；然而，当使用位阻较大且氧化稳定性更高的叔丁醇时，仅观察到分子外环外猝灭产物，产率为51%，未检测到羟基卟啉。对氮杂环丁烯卟啉类化合物的X射线晶体结构表征（X-ray structure characterization）显示其为平面大环结构，印证了周边收缩的显著影响。具体而言，含铜的氮杂环丁烯卟啉类化合物展现出极短的铜-氮杂环丁烯氮原子（Cu−Nazete）间距，为1.88~1.90埃（Å）。所有卟啉类光产物在可见光光谱区域均具有强吸收带，表明环收缩的底物加合物以及苯基环加成产物均保留了卟啉类芳香性。总体而言，这些发色团可在底物调控下发生光化学反应，这一特性使得这类单分子卟啉类光试剂有望应用于光生物学或不依赖氧气的光动力疗法（O2-independent photodynamic therapy）中。