(4 + 2) cyclization of aza-o-quinone methides with azlactones: construction of biologically important dihydroquinolinone frameworks

Abstract

A base-promoted (4 + 2) cyclization of N-(o-chloromethyl)aryl amides with azlactones was established, which helped construct biologically important dihydroquinolinone frameworks in good yields.

Transition-metal-free approach to quinolines via direct oxidative cyclocondensation reaction of N,N-dimethyl enaminones with o-aminobenzyl alcohols

“…However, such attractive synthetic strategies required expensive transition-metal (TM) pincer complexes, such as Ir ( Wang et al, 2016 ; Genc et al, 2019 ), Ru ( Maji et al, 2018 ; Wan et al, 2019 ), Ni ( Das et al, 2018 ; Das et al, 2018 ; Singh et al, 2018 ), Mn ( Mastalir et al, 2016 ; Barman et al, 2018 ; Das et al, 2019 ), Cu ( Tan et al, 2018 ), or Re ( Wei et al, 2019 ) complexes. In addition, aza- ortho -quinone methides (aza- o -QMs), in situ generated from o -aminobenzyl alcohols as short-lived and highly reactive diene species, have been extensively investigated and applied in organic synthesis ( Huang and Kang., 2017 ; Mei et al, 2017 ; Lee et al, 2019 ; Wang et al, 2021 ). In 2016, a KOH-promoted regioselective synthesis of quinolones via [4 + 2]-cycloaddition of aza- o -QMs with internal alkynes was disclosed by Verma and co-workers ( Saunthwal et al, 2016 ) ( Scheme 1b ).…”

Synthesis of Benzo[e][1,4]thiazepines by Base-Induced Formal [4+3] Annulation Reaction of Aza-o-quinone Methides and Pyridinium 1,4-Zwitterionic Thiolates

“…The recently discovered [4+3] annulation reaction of in situ-generated aza- o -quinone methides (aoQMs) with 1,3-zwitterionic intermediates for the synthesis of seven-membered nitrogen-containing heterocycles has attracted a great deal of attention owing to the high efficiency and step economy (Scheme a) . AoQMs, which contained exocyclic alkylidene and an imine unit, were envisioned to be effective four-atom synthons for [4+ n ] annulation reactions due to the driving force of aromatization. , In 2015, the Chen group presented a facile approach for accessing an azaspirocycloheptane oxindole scaffold through a [4+3] cycloaddition reaction with aoQMs and isatin-derived Morita–Baylis–Hillman (MBH) adducts . Later, Enders and co-workers developed an elegant NHC-catalyzed enantioselective [4+3] annulation of aoQMs with isatin-derived enals affording pharmaceutically important spirobenzazepinones .…”

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.…”