Stereoselective Synthesis of 12-Tetrazolyl Substituted (E)-5H-Quinazolino[3,2-a]quinazolines via Sequential Ugi-Azide/Staudinger/aza-Wittig/Addition/Ag(I)-Catalyzed Cyclization

Abstract

A new efficient and stereoselective synthesis of 12-tetrazolyl substituted (E)-5H-quinazolino[3,2-a]quinazolines via sequential Ugi-azide/Staudinger/aza-Wittig/addition/Ag(I)-catalyzed cyclization was developed. The four-component reactions of 2-azidobenzaldehyde, 2-(alkynyl)benzenamine, isocyanide, and trimethylsilyl azide gave Ugi-azide intermediates, which were subsequently treated with triphenylphosphine and isocyanate to produce 12-tetrazolyl substituted (E)-5H-quinazolino[3,2-a]quinazolines in the presence of Ag(I) catalyst and K2CO3.

Efficient and Sustainable Electrosynthesis of N-Sulfonyl Iminophosphoranes by the Dehydrogenative P–N Coupling Reaction

“…Iminophosphoranes, also referred to as phosphinimines, are nitrogen analogues of phosphonium ylides and represent powerful reagents in organic synthesis . They serve as nitrene donors in aziridine synthesis and in aza-Wittig reactions, ,− which are frequently used for the construction of N-heterocyclic compounds such as drugs (Scheme a). − Furthermore, they are utilized as superbasic organocatalysts for versatile transformations, − as ligands for transition metal catalysts, − and as intermediates for amino group protection and optical resolutions. , Moreover, several iminophosphoranes showed biological activity and were investigated as potential anticancer agents − and acetylcholinesterase (AChE) inhibitors targeting the treatment of Alzheimer’s disease (Scheme b) …”

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

“…The Ding group developed sequential Ugi-azide/Ag-catalyzed oxidative cycloisomerization reactions for the synthesis of 2-tetrazolyl-substituted 3-acylpyrroles ( Scheme 2C ) [ 42 ]. The Ding group also reported sequential Ugi-azide/Staudinger/aza-Wittig/addition/Ag-catalyzed cyclization reactions for obtaining 12-tetrazolyl-substituted ( E )-5 H -quinazolino[3,2- a ]quinazolines ( Scheme 2D ) [ 40 ].…”

“…By replacing the carboxylic acid with a nucleophilic azide reagent XN 3 (generally TMSN 3 ), the Ugiazide four-component reaction (UA-4CR) of an aldehyde, amine, isocyanide, and azide gives 1,5-disubstituted 1H-tetrazoles (1,5-DS-1H-Ts) B. The performance of post-condensation reactions of UA-4CR adducts has resulted in various 1,5-DS-1H-Ts containing heterocyclic compounds [28][29][30][31][32], such as bis-heterocyclic lactam-tetrazoles [33,34], 2-tetrazolylmethyl-2,3,4,9-tetrahydro-1H-β-carbolines [35], ketopiperazinetetrazoles [36], imidazotetrazolodiazepinones [37], tetracyclic tetrazolylpyridoimidazoquinolines [38], bis-heterocyclic 1,5-disubstituted tetrazoleindolizines [39] and (E)-12-tetrazolyl-5Hquinazolino [3,2-a]quinazolines [40]. Among them, the Hulme group reported a UA-4CR/post-condensation sequence to give fused imidazotetrazolodiazepinones (Scheme 2A) [37].…”

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

“…By replacing the carboxylic acid with a nucleophilic azide reagent XN3 (generally TMSN3), the Ugiazide four-component reaction (UA-4CR) of aldehyde, amine, isocyanide, and azide gives 1,5disubstituted 1H-tetrazoles (1,5-DS-1H-Ts) B. The performance of post-condensation reaction of UA-4CR adducts has resulted various 1,5-DS-1H-Ts containing heterocyclic compounds [28][29][30][31][32], such as bis-heterocyclic lactam-tetrazoles [33,34], 2-tetrazolylmethyl-2,3,4,9-tetrahydro-1H-β-carbolines [35], ketopiperazines-tetrazoles [36], imidazo-tetrazolodiazepinones [37], tetracyclic tetrazolyl pyridoimidazo quinolines [38], bis-heterocyclic 1,5-disubstituted tetrazole-indolizine [39] and (E)-12tetrazolyl-5H-quinazolino[3,2-a]quinazolines [40]. Among them, the Hulme group reported a UA-4CR/post-condensation sequence to give fused imidazo-tetrazolodiazepinones (Scheme 2, A) [37].…”