Nitroso Diels-Alder Cycloadducts Derived From N-Acyl-1,2-dihydropyridines as a New Platform to Molecular Diversity

Abstract

This review focuses upon the use of nitroso Diels–Alder reactions as a structural complexity generating reaction that has been so far a quite scarcely treated topic, despite its potential. In particular, the use of N-acyl-1,2-dihydropyridines as a non-symmetrical diene component in nitroso Diels–Alder reactions encompasses an initial diversification of pathways giving rise to different cycloadducts (direct and inverse). Selective elaborations of these cycloadducts, basically using a reagent-based approach, deliver a discrete number of structurally diverse compounds, including some original heterobicyclic scaffolds and functionalized heterocycles. This forward synthetic planning allowed the individuation of a new biologically active compound based on a novel oxadiaza-bicyclic-[3.3.1]-nonene scaffold which is still under preclinical evaluation.

Alternating Current Electrolysis as Efficient Tool for the Direct Electrochemical Oxidation of Hydroxamic Acids for Acyl Nitroso Diels–Alder Reactions

“…However, the 1,1-disubstituted diene 2 e gave a moderate yield of 36 % as a single regioisomer (distal). [11] The oxazine 3 f was synthesised from cycloocta-1,3-diene (2 f) and isolated in 82 % yield, confirming that cyclic 1,3-dienes can also be used for the electrochemical acyl NDA. On the other hand, electron-rich 1,3-dienes (2 g, 2 i and 2 j) with a phenyl-or oxygensubstituent attached to the 1,3-diene could not be used for this reaction, probably due to their low redox potential.…”

Highlighting the Underrated Side of the High Profile Nitroso Entity as a Nucleophile

“…The nitrosoarene, acting as a N-nucleophile, attacks the metal activated alkyne. It is the catalyst nature that selectively diverts the metathesis to 1,2- (23) or 1,4-imines (24) (Scheme 6) [47] .…”

Wechselstromelektrolyse als effizientes Instrument für die direkte elektrochemische Oxidation von Hydroxamsäuren für die Acyl‐Nitroso Diels‐Alder‐Reaktion

“…Die optimierten Reaktionsbedingungen wurden genutzt, um die Substratbreite der 1,3-Diene mit 1 a zu untersuchen (Schema 2). Das Oxazin [11] Das Oxazin 3 f wurde aus Cycloocta-1,3-dien (2 f) hergestellt und in 82 % Ausbeute isoliert -womit bestätigt wird, dass auch cyclische 1,3-Diene für die elektrochemische Acyl-NDA geeignet sind. Auf der anderen Seite eignen sich sehr elektronenreiche Diene (2 g, 2 i und 2 j) mit einem Phenyl-oder Oxysubstituenten an der Dieneinheit nicht für diese Reaktion, mçglichweise ist deren Redoxpotential zu niedrig.…”