Four-Component Synthesis of Polysubstituted Pyrazin-2(1H)-ones through a Ugi/Staudinger/Aza-Wittig/Isomerization Sequence

Abstract

A new efficient synthesis of polysubstituted pyrazin-2­(1H)-ones via the sequential Ugi/Staudinger/aza-Wittig/isomerization reaction has been developed. The four-component Ugi reactions of arylglyoxals 1, primary amines 2, α-azidovinyl acids 3, and isocyanides 4 produced the azides 5, which were treated with triphenylphosphine to give pyrazin-2­(1H)-ones 6 in good yields through domino Staudinger/aza-Wittig/isomerization reactions.

2(1H)-Pyrazinones from acyclic building blocks: methods of synthesis and further derivatizations

“…After the Ugi condensation, the resulting intermediate was treated with PPh 3 leading to a one-pot Staudinger/Aza-Wittig/isomerization cascade giving 2(1 H )-pyrazinones in an efficient way. 125…”

In situ generation of imines by the Staudinger/aza-Wittig tandem reaction combined with thermally induced Wolff rearrangement for one-pot three-component β-lactam synthesis

“…Recent examples of combining this approach with well-established MCRs include the Ugi reaction 8–10 giving acyclic peptide-like products and preparation of diverse 5 to 7-membered N-heterocycles 11 such as quinolines, 12 imidazoles, 13 pyrazines, 14 and benzodiazepines 15 (Fig. 2a).…”

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

“…Recently we have reported the synthesis of 3H-2-benzoxepin-1-ones, 4H-3,1-benzoxazines and oxazoles by combination of a Passerini with an intramolecular aza-Wittig reaction [33][34][35]. Continuing our interest in the synthesis of N-heterocycles via the aza-Wittig reaction and multicomponent reactions [36][37][38], we wish to report herein a facile synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reactions. Compared with the synthetic method to 4H-3,1-benzothiazines in Scheme 1f, we provide another new sequential synthetic route to 4H-3,1-benzothiazines, especially for N,N-disubstituted 2-amino-4H-3,1-benzothiazines.…”