Thermal Hetero-Diels–Alder Reaction of Benzocyclobutenones with Isatins To Form 2‑Oxindole Spirolactones

Benzocyclobutenones 1a–1g undergo cycloreversion at 150 °C in m-xylene solvent to form transient α-oxo-ortho-quinodimethanes or “ortho-quinoid ketene methides”, which engage in intermolecular [4+2] cycloadditions with isatins 2a–2f to form 2-oxindole spirolactones 3a–3l. This process tolerates an array of different functional groups and substitution patterns, and is applicable to unprotected isatins 2b–2f bearing free NH-functionalities. The superior performance of isatins compared to other carbonyl based dienophiles was demonstrated and rationalized with the aid of quantum chemical calculations.

苯并环丁烯酮（Benzocyclobutenones）1a–1g在间二甲苯溶剂中于150 ℃下发生逆环加成反应，生成瞬态α-氧代邻醌二甲烷（即“邻醌型烯酮甲化物”）；该中间体可与靛红（Isatins）2a–2f发生分子间[4+2]环加成反应，生成2-氧吲哚螺内酯（2-oxindole spirolactones）3a–3l。该反应具有宽泛的官能团兼容性与取代基普适性，可适用于带有游离NH官能团的未保护靛红2b–2f。研究人员通过量子化学计算，验证了靛红相较于其他羰基类亲双烯体的优异反应性能，并对其反应机理进行了合理化阐释。