Organocatalytic aza-Michael Reaction to 3-Vinyl-1,2,4-triazines as a Valuable Bifunctional Platform

Abstract

An unprecedented catalytic aza-Michael addition to substituted 3-vinyl-1,2,4-triazines, as original bifunctional platforms for domino conjugate addition-ihDA/rDA reaction, was achieved using the highly acidic triflimide as organocatalyst. Based on the use of alkoxyamine nucleophiles, this sequence not only highlights a rare example of catalytic aza-Michael reaction to alkenylazaarenes but proved to be useful for the elaboration of an array of biorelevant tetrahydro-[1,6]-naphthyridines. Medicinal chemistry and chemical biology are currently seeking original heterocyclic scaffolds as biological tools. Accordingly, the development of new synthetic methodologies aiming at exploring chemical space, while increasing molecular diversity and complexity, is a current concern in organic synthesis. 1 The construction of fused non-aromatic/heteroaromatic bicycles has emerged as a promising strategy furnishing unprecedented potent bioactive

Triflamides and Triflimides: Synthesis and Applications

“…Triflimide is used in some cyclization in Diels-Alder reactions of 4-oxopent-2-enoates [38], in Michael addition reactions to substitute 3-vinyl-1,2,4-triazines and the subsequent cyclization to tetrahydro- [1,6]-naphthyridines [39] and in the synthesis of 2,3-dihydro-1Hbenzo[e]indoles and 2,3-dihydrobenzofurans using Tf 2 NH. The yield of the latter was 64% (with Tf 2 NH) but while using In(OTf) 3 , the yield increased to 80% [40].…”

The Riveting Chemistry of Poly‐aza‐heterocycles Employing Microwave Technique: A Decade Review

“…The reaction started at ambient temperature in methanol (polar‐protic solvent) led to aza‐Micheal addition product 59 i without detection of domino product 60 for 24 h. Perhaps, the reaction in non‐polar solvents at room temperature was inappropriate, but heating at 180 °C under microwave irradiation for 3.5 h in THF exclusively afforded domino product 1,6‐naphthyridines ( 60 ) in good yields [32a] . In the reaction protocol, N ‐alkoxy propargyl amines were also efficiently used with trifluoromethanesulfonimide as an organocatalyst [32b] . Moreover, to implement thiol nucleophile (instead of amine) and to access the path for 7,8‐dihydro‐5 H ‐thiopyrano[4,3‐ b ]pyridines ( 61 ) an organo‐catalytic base (DBU) was required to in situ generate the required nucleophile from acetylated thiols (Scheme 24).…”