Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal (Westville), Durban 4000, South Africa.
J Org Chem. 2020 Jun 19;85(12):8221-8229. doi: 10.1021/acs.joc.0c00463. Epub 2020 Jun 1.
A novel green and efficient catalyst-free, mild one-pot, multicomponent synthetic strategy has been developed to construct substituted 3,4-dihydro-2-benzo[][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.
一种新颖的绿色、高效的无催化剂、温和的一锅多组分合成策略已被开发出来，用于构建取代的 3,4-二氢-2-苯并[][1,4]恶嗪。该反应通过原位形成席夫碱，然后与苯乙酮溴化物/取代的苯乙酮溴化物进行碱介导的烷基化反应，最后进行分子内环化，以优异的非对映选择性（高达 dr = 99:1）得到混合物的非对映异构体，这些非对映异构体可以以中等至优异的收率（41-92%）分离为单一非对映异构体。此外，这种新的多功能方法为不同功能取代的苯并恶嗪支架的合成提供了广泛的可能性，并可进一步作为合成多方面分子结构的构建块，特别是在药物应用方面。
