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

Abstract

The switchable synthesis of 3-non, 3-mono, 3,3′-disubstituted 3,4-dihydroquinolin-2­(1H)-ones was developed through a redox-neutral hydride-transfer/N-dealkylation/N-acylation strategy from o-aminobenzaldehyde with 4-hydroxycoumarin, and Meldrum’s acid, respectively. The unprecedented strategy for the synthesis of 3,3′-highly functionalized 3,4-dihydroquinolin-2­(1H)-one has been realized with the in situ utilization of the released HCHO via the o-QM involved Michael addition. In addition, the synthetic utility of this protocol has been well illustrated via concise synthesis of CYP11B2 inhibitor.

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.…”

Synthesis of Dihydroquinolinone Derivatives via the Cascade Reaction of o-Silylaryl Triflates with Pyrazolidinones

“…As a further aspect, 3,4-dihydroquinolin-2(1H)ones are also bestowed with diverse reaction patterns and have thus been used as convenient and flexible synthetic intermediates for the preparation of biologically valuable alkaloids and multipurpose fine chemicals. 3 Owing to its significance, several methods for the construction of the dihydroquinolinone scaffold, such as trifluoroacetic acid-catalyzed Friedel−Crafts reaction of phenols with cinnamic acids, 4 Pd-catalyzed sequential C-(sp 3 )−H/C(sp 2 )−H bonds functionalization of ortho-halogenated acetilides, 5 radical initiated cyclization of Narylcinnamamides with aliphatic carboxylic acids, 6 Pd/Cucatalyzed C−N/C−C bonds coupling of N-(2-bromophenyl)-N-methyl methacrylamides, 7 Friedlander reaction of o-aminobenzaldehyde with 4-hydroxycoumarin and Meldrum's acid, 8 and [4 + 2] cyclization of aza-o-quinone methides with azlactones, 9 have been developed. While these literature methods are generally effective and reliable, some of them still suffer from lengthy steps, harsh reaction conditions incompatible with susceptible functional groups, and limited substitution patterns of products.…”

3-Vinyl oxindole-chromone synthon as a skeletal reconstruction reactant for the synthesis of 2-hydroxy benzoyl pyridones

“…The molecular complexity of natural molecules has stimulated generations of organic chemists to design novel strategies for the creation of combinatorial libraries from commercially available starting materials. 1 2-Hydroxydiarylmethanones 2 are privileged scaffolds found in numerous natural products and bioactive molecules. As functionalized 2-hydroxydiarylmethanone molecules, 2-hydroxy benzoyl pyridone molecules are also particularly intriguing and exhibit good inhibitory activity including against HBV DNA replication.…”

“…Vinyl indoles and oxindole-derived alkenes have gained considerable prominence because of their versatility as building blocks in the synthesis of the library of collections of bioactive compounds. 5 Against this background 1,5 and in continuation of our subject on oxindole-chromone 4C synthon-directed tandem reaction for the facile access of diverse and functionalized hexahydroxanthones (Scheme 1a), 6 we envisioned that the readily available 3-vinyl oxindole-chromone synthons 1 may be a valuable substrate, which reacts with ammonia or primary aliphatic amines as binucleophiles at the 3-vinyl functional group and C-2 position of synthons 1 , resulting in the construction of diverse 2-hydroxy benzoyl pyridone molecules 3 with structural complexity through directed ring-opening and recyclization reaction process 7 (Scheme 1b).…”