Facile Construction of 3,4‐dihydro‐2H‐1,2,4‐Benzothiadiazine 1,1‐Dioxides via Redox‐Neutral Cascade Condensation/[1,7]‐Hydride Transfer/Cyclization

Abstract

The benzothiadiazine 1,1-dioxides were highly efficiently constructed via a BF 3 * Et 2 O promoted redoxneutral cascade condensation/[1,7]-hydride transfer/cyclization, which featured novel substrate skeletons, broad substrate scope, [1,7]-hydride transfer manner, metal-free conditions and the facile introduction of aryl, heteroaryl, allyl and propargyl groups etc.

The Cascade [1,5]-Hydride Shift/Intramolecular C(sp3)–H Activation: A Powerful Approach to the Construction of Spiro-Tetrahydroquinoline Skeleton

“…These valuable spirocyclic molecules have been well categorized according to the structural type of final products. Despite the significant developments that have been made in this growing field, some challenges still need to addressed: (1) The limitation of substrate scope, structural diversity of product, complex reaction conditions, and problem of large-scale capacity still limit its potential in organic synthesis ( Mori et al, 2014 ; Liu et al, 2018 ; Xing et al, 2020 ; Yuan et al, 2020 ; Guo et al, 2021 ; Sakai et al, 2021 ; Yang X. et al, 2021 ; Xie et al, 2022 ). (2) The current application of the cascade [1,5]-hydride shift/cyclization strategy mainly focuses on the construction of five- and six-membered spiro-tetrahydroquinoline.…”

Diastereoselective construction of structurally diverse 2,3-dihydroquinolin-4-one scaffolds via redox neutral cascade [1,7]-hydride transfer/cyclization

“…However, a series of challenges still persist for constructions of all-carbon quaternary stereocenters carrying allylic or propargyl groups, such as low atomeconomy 7b and very rare general protocols available for allylation and propargylation. 9 Until now, the cascade [1,n]-hydride transfer/cyclization strategy has been well established for the straightforward construction of aza-heterocycles, which features redox-neutrality and inherent high step-and atom-economy. 9,10 Remarkably, however, the protocol still suffers from intolerable disadvantages, such as limited product skeleton restricted to tetrahydroquinolines in most cases (Scheme 1a), 10f-k and in contrast, other aza-heterocycles are rarely accessed.…”

“…9 Until now, the cascade [1,n]-hydride transfer/cyclization strategy has been well established for the straightforward construction of aza-heterocycles, which features redox-neutrality and inherent high step-and atom-economy. 9,10 Remarkably, however, the protocol still suffers from intolerable disadvantages, such as limited product skeleton restricted to tetrahydroquinolines in most cases (Scheme 1a), 10f-k and in contrast, other aza-heterocycles are rarely accessed. As to the patterns of hydride transfer, [1,5]-HT is the major manner of hydride transfer in most cases, 10 and remarkably, [1,4]-HT, 11 [1,6]-HT, 12 [1,8]-HT 13 and [1,9]-HT 14 are sparsely reported.…”

“…15b We also reported a BF 3 •Et 2 O promoted cascade condensation/[1,7]-hydride transfer/cyclization for the efficient construction of pharmaceutically significant benzothiadiazine 1,1-dioxides featuring novel substrate skeletons and facile introduction of allyl and propargyl groups (Scheme 1e). 9 Very recently, the borane-catalyzed [1,7]-hydride transfer has been elegantly employed by Paradies et al to construct dihydroquinoline-4-ones in high yields and with excellent diastereoselectivities (Scheme 1f ). 15c Considering the significance of the privileged 2,3-dihydroquinolin-4-one, various heterocycles, 3-spirocyclic 3,4-dihydrocoumarin and allylic/propargyl groups as important pharmacophores and synthetic handles and according to the privileged structure-based diversity-oriented synthesis strategy, 16 the development of an efficient and general protocol for direct assembly of the hybrid of these pharmacophores is highly desirable, which might possess novel and promising bioactivities.…”

Redox-Triggered Switchable Synthesis of 3,4-Dihydroquinolin-2(1H)-one Derivatives via Hydride Transfer/N-Dealkylation/N-Acylation

“…Recently, hydride transfer strategy has received considerable attention, and made great progress in creation of polycyclic compounds . However, chemists tend to focus on its powerful ability of α-C­(sp 3 )–H functionalization, and nearly no new reaction modes spring up in the past few years. , As a continuation of our research interest in hydride transfer reactions, we expect to expand the reaction modes of hydride transfer. Thus, we rationally designed a multiple-step cascade reaction, with the application of Meldrum’s acid and 4-hydroxycoumarin as C2 synthons, through the cascade hydride transfer/ N -dealkylation/ N -acylation process for expedient synthesis of 3,4-dihydroquinolin-2­(1 H )-ones (Scheme a and b).…”