Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment.
Photochemically Mediated Ring Expansion of Indoles and Pyrroles with Chlorodiazirines: Synthetic Methodology and Thermal Hazard Assessment.
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DOI：
10.1002/anie.202305081
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发表时间：
2023-06
影响因子：
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通讯作者：
Ben W. Joynson;Graham R. Cumming;Liam T. Ball
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文献类型：
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作者：
Ben W. Joynson;Graham R. Cumming;Liam T. Ball
我们证明了芳基氯二嗪可以作为光活化的卤代烃前体，用于n -取代吡咯和吲哚选择性地向相应的吡啶和喹啉盐扩展单碳环。初步研究表明，同样的策略也使n取代吡唑转化为嘧啶盐。底物的n取代基在以下方面起着至关重要的作用：(1)通过防止产物降解来增加底物范围；(2)通过抑制副产物抑制来提高产量；(3)为随后的合成操作激活azinium产物。后一点可以通过对喹啉盐进行四次互补的部分还原来说明，这可以简明地获得具有不同程度增加C（sp3）特征的环膨胀产物。差示扫描量热法（DSC）对重氮嘧啶的热分析提供了对其能量特性的详细了解，并强调了光解而不是热解这些试剂的安全性。
We demonstrate that arylchlorodiazirines serve as photo-activated halocarbene precursors for the selective one-carbon ring expansion of N-substituted pyrroles and indoles to the corresponding pyridinium and quinolinium salts. Preliminary investigations indicate that the same strategy also enables the conversion of N-substituted pyrazoles to pyrimidinium salts. The N-substituent of the substrate plays an essential role in: (1) increasing substrate scope by preventing product degradation, (2) enhancing yields by suppressing co-product inhibition, and (3) activating the azinium products towards subsequent synthetic manipulations. This latter point is illustrated by subjecting the quinolinium salts to four complementary partial reductions, which provide concise access to ring-expanded products with different degrees of increased C(sp3) character. Thermal analysis of the diazirines by differential scanning calorimetry (DSC) provides detailed insight into their energetic properties, and highlights the safety benefits of photolyzing - rather than thermolyzing - these reagents.