Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
College of Pharmacy, Third Military Medical University, Chongqing, 400038, China.
Chem Rec. 2020 Jun;20(6):541-555. doi: 10.1002/tcr.201900058. Epub 2019 Oct 14.
The development of synthetic protocols to access architectures with broad structural and functional diversity from readily available starting materials is very attractive in both organic and medicinal chemistry fields. Toward this objective, the multifunctional isatin-derived Morita-Baylis-Hillman (MBH) adducts provide opportunities to construct a variety of complex scaffolds containing a "privileged" oxindole motif through several catalytic pathways. By forming the ammonium or phosphonium salts with Lewis bases, isatin-derived MBH adducts can undergo allylic substitutions with a range of nucleophiles, usually in a S 2'-S 2' pattern. Besides, assisted by Brønsted bases, the corresponding onium salts can be converted into the allylic ylide intermediates, which can undergo various annulation reactions or even 1,3-difunctionalizations. Moreover, recent cooperative catalysis of Lewis bases and transition metal complexes further puts forward the application of isatin-derived MBH adducts. This tutorial review covers the significant transformations of isatin-derived MBH adducts, mostly in an asymmetric version, catalyzed by various Lewis bases over the past decade.
从易得的起始原料出发，开发能够获得具有广泛结构和功能多样性的合成方案，这在有机化学和药物化学领域都非常有吸引力。为此，多功能色胺衍生的 Morita-Baylis-Hillman（MBH）加合物提供了通过几种催化途径构建包含“特权”吲哚啉结构的各种复杂支架的机会。通过与路易斯碱形成铵盐或鏻盐，色胺衍生的 MBH 加合物可以与一系列亲核试剂进行烯丙基取代，通常遵循 S 2′-S 2′模式。此外，在布朗斯台德碱的辅助下，相应的翁盐可以转化为烯丙基叶立德中间体，其可以经历各种环化反应甚至 1,3-双官能化反应。此外，近年来路易斯碱和过渡金属配合物的协同催化进一步提出了色胺衍生的 MBH 加合物的应用。本综述涵盖了过去十年中，在各种路易斯碱的催化作用下，以不对称形式对色胺衍生的 MBH 加合物进行的重要转化。
