Beng Timothy K, Eichwald Jane, Fessenden Jolyn, Quigley Kaiden, Sharaf Sapna, Jeon Nanju, Do Minh
Department of Chemistry, Central Washington University Ellensburg WA 98926 USA
RSC Adv. 2023 Jul 13;13(31):21250-21258. doi: 10.1039/d3ra03800a. eCollection 2023 Jul 12.
Sulfone-tethered lactones/amides/amines display a diverse spectrum of biological activities, including anti-psychotic and anti-hypertensive. Sulfones are also widely present in functional materials and fragrances. We therefore reasoned that a regiodivergent and stereocontrolled strategy that merges the sulfone, lactone, and lactam motifs would likely lead to the discovery of new pharmacophores and functional materials. Here, we report mild conditions for the sulfonyllactonization of γ-lactam-tethered 5-aryl-4()-pentenoic acids. The annulation is highly modular, chemoselective, and diastereoselective. With respect to regioselectivity, trisubstituted alkenoic acids display a preference for 5- cyclization whereas disubstituted alkenoic acids undergo exclusive 6- cyclization. The lactam-fused sulfonyllactones bear angular quaternary as well as four contiguous stereocenters. The products are post-modifiable, especially through a newly developed Co-catalyzed reductive cross-coupling protocol.
砜连接的内酯/酰胺/胺具有多种生物活性，包括抗精神病和抗高血压活性。砜也广泛存在于功能材料和香料中。因此，我们推测一种将砜、内酯和内酰胺基序结合起来的区域发散和立体控制策略可能会导致发现新的药效基团和功能材料。在此，我们报道了γ-内酰胺连接的5-芳基-4()-戊烯酸进行砜基内酯化的温和条件。环化反应具有高度模块化、化学选择性和非对映选择性。关于区域选择性，三取代链烯酸倾向于5-环化，而二取代链烯酸则专一性地进行6-环化。内酰胺稠合的砜基内酯带有角形季碳以及四个相邻的立体中心。这些产物可进行后期修饰，特别是通过新开发的钴催化还原交叉偶联方案。
