One-Pot, Multicomponent, Diastereoselective, Green Synthesis of 3,4-Dihydro‑2<i>H</i>‑benzo[<i>b</i>][1,4]oxazine Analogues

A novel green and efficient catalyst-free, mild one-pot, multicomponent synthetic strategy has been developed to construct substituted 3,4-dihydro-2H-benzo­[b]­[1,4]­oxazine. This reaction proceeds via in situ formation of Schiff-base followed by base mediated alkylation with phenacyl bromide/substituted phenacyl bromide, finally leading to intramolecular cyclization to give a mixture of diastereomers with excellent diastereoselectivity (up to dr = 99:1), which were isolated as a single diastereomer in moderate to excellent yields (41–92%). Besides, this new versatile methodology provides a wide scope for the synthesis of different functionally substituted benzoxazine scaffolds and can be further exploited as building blocks for the synthesis of multifaceted molecular structures, especially for pharmaceutical applications.本研究开发了一种新型绿色高效、无催化剂且条件温和的多组分一锅法合成策略，用于构建取代型3,4-二氢-2H-苯并[b][1,4]噁嗪。该反应首先原位生成希夫碱（Schiff-base），随后在碱介导下与苯甲酰甲基溴（phenacyl bromide）/取代苯甲酰甲基溴发生烷基化反应，最终通过分子内环化得到一组非对映异构体混合物，其非对映选择性极佳（最高dr值可达99:1），且可分离得到单一非对映异构体，收率中等至优异（41%~92%）。此外，该新型通用合成方法的底物适用范围广，可用于制备多种不同官能团取代的苯并噁嗪骨架，还可进一步作为合成砌块，用于构建多样分子结构，尤其适用于药物研发领域。