Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

Abstract

SummaryThe synthesis of 5-substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones via [4 + 2] imino-Diels–Alder cyclization from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3-hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the formation of 2-(2-substitued-aryl)-3-(2-(2-oxopyrrolidin-1-yl)vinyl)isoindolin-1-one analogues indicating steric hinderance as the cause of deviation. The probable mechanism of the reaction based on the results from X-ray crystallography and molecular modelling is discussed.

Progress in the Chemistry of Tetrahydroquinolines

“…Using the same type of dienophiles, Cameron and co-workers developed a method for the regioselective synthesis of isoindolo­[2,1- a ]­quinolone derivatives 482 starting from N -aryl-3-hydroxyisoindolinones 480 and dienophiles 481 via an in situ generated N -acyliminium ion intermediate in the presence of BF 3 ·OEt 2 (Scheme ). The reaction afforded exclusively the endo -products, where the hydrogen atoms on the stereogenic centers are in a cis -orientation with respect to each other.…”

“…242 Using the same type of dienophiles, Cameron and co-workers developed a method for the regioselective synthesis of isoindolo [ of BF 3 •OEt 2 (Scheme 130). 243 The reaction afforded exclusively the endo-products, where the hydrogen atoms on the stereogenic centers are in a cis-orientation with respect to each other.…”

Tertiary Enamides as Versatile and Valuable Substrates to Reach Chemical Diversity

“…17 This method relied on the use of an inexpensive organic triplet sensitizer (isopropylthioxanthone, ITX) as In(OTf) 3 In 2014, Jha and co-workers published their research on the aza-Diels-Alder between N-acyliminium ions and tertiary enamides. 20 The authors reported the synthesis of isoindoloquinoline derivatives 62 by reaction of N-aryl-3-hydroxyisoindolinones 60 and tertiary enamides 61 under anhydrous Lewis acid conditions using a stoichiometric amount of BF 3 •OEt 2 (Scheme 10A). It is interesting to note that only the endo-cycloadducts were obtained during the reaction in modest to good yields.…”

Synthesis of dihydroisoindolo[2,1-a]quinolin-11-ones, their in silico ADMET properties and in vitro antitumor activities

“…investigations support a non-concerted mechanism for the Lewis acid catalysed aza DA reaction. [33][34][35][36] In our previous work on AIIQ products 4a-m we mentioned that amide formation (g-lactamization) may occur directly aer aldimine formation and prior to [4 + 2] cycloaddition of the acyliminium intermediate. 15 In this present study, in order to elucidate this mechanistic route, we achieved isolation of Nphenyl-3-hydroxy-isoindolinone (A) under the same reaction conditions (see ESI †).…”