Balanna Kuruva, Barik Soumen, Shee Sayan, Gonnade Rajesh G, Biju Akkattu T
Department of Organic Chemistry, Indian Institute of Science Bangalore-560012 India
Centre for Materials Characterization, CSIR-National Chemical Laboratory Dr Homi Bhabha Road Pune-411008 India.
Chem Sci. 2022 Aug 29;13(39):11513-11518. doi: 10.1039/d2sc03745a. eCollection 2022 Oct 12.
The ubiquity of ε-lactones in various biologically active compounds inspired the development of efficient and enantioselective routes to these target compounds. Described herein is the enantioselective synthesis of indole-fused ε-lactones by the N-heterocyclic carbene (NHC)-Lewis acid cooperative catalyzed dynamic kinetic resolution (DKR) of generated γ,γ-disubstituted indole 2-carboxaldehydes. The Bi(OTf)-catalyzed Friedel-Crafts reaction of indole-2-carboxaldehyde with 2-hydroxy phenyl -quinone methides generates γ,γ-disubstituted indole 2-carboxaldehydes, which in the presence of NHC and Bi(OTf) afforded the desired tetracyclic ε-lactones in up to 93% yield and >99 : 1 er. Moreover, preliminary studies on the mechanism of this formal [4 + 3] annulation are also provided.
ε-内酯在各种生物活性化合物中的广泛存在激发了人们开发高效且对映选择性合成这些目标化合物的路线。本文描述了通过N-杂环卡宾（NHC）-路易斯酸协同催化生成的γ,γ-二取代吲哚-2-甲醛的动态动力学拆分（DKR）对吲哚稠合ε-内酯进行对映选择性合成。Bi(OTf)催化吲哚-2-甲醛与2-羟基苯基醌甲基化物的傅克反应生成γ,γ-二取代吲哚-2-甲醛，其在NHC和Bi(OTf)存在下以高达93%的产率和>99:1的对映体过量得到所需的四环ε-内酯。此外，还提供了对这种形式上的[4 + 3]环化反应机理的初步研究。
