1,3,5‐Oxadiazine Framework by Oxygen vs. Nitrogen Trapping of an N‐Acyliminium Ion Derived from N,O‐bis‐TMS Pyroglutamic Acid

Abstract

We report that the reaction of N,O-bis-TMS pyroglutamic acid with aldehydes, under basic or acid catalysis leads to O-bis-TMS adducts. Treatment of these N,O-acetals by TfOH affords azalactones or N,N'-substituted methylene-bis-pyroglutamic acids from the trapping of N-acyliminium species, respectively, with oxygen or nitrogen atom intramolecularly versus intermo-lecularly. Anodic oxidation of the amido acids, followed by diastereoselective oxa-cyclisation of new N-acyliminium salts, provides exclusively fused meso-1,3,5-oxadiazines with the stereochemistry secured by X-ray analysis. The reactivity of these skeletons under both alkaline and acid conditions was also envisioned and discussed.

DMSO as a Dual Carbon Synthon and Water as Oxygen Donor for the Construction of 1,3,5-Oxadiazines from Amidines

“…There are several types of oxadiazines such as 1,2,4-, 1,3,4-, 1,2,3-, 1,2,5-, 1,2,6-, and 1,3,5-oxadiazines. Only the first two are frequently explored, and the latter four are little explored up to the present . Among these oxadiazines, the 1,3,5-analogues are a promising class of heterocycles applied as effective drugs, agrochemicals, and new materials (Figure ).…”

“…However, only a very few reports have been concerned for the synthesis of 1,3,5-oxadiazines. For example, fused meso-1,3,5-oxadiazines were synthesized from l -pyroglutamic acid with aldehydes by electrochemical oxidation under acid catalysis (Scheme A-i) . Novikov synthesized 1,3,5-oxadiazines from 1,2,4-oxadiazoles with α-diazo esters catalyzed by Rh­(II) or Cu­(II) (Scheme A-ii) .…”

“…Only the first two are frequently explored, and the latter four are little explored up to the present. 2 Among these oxadiazines, the 1,3,5-analogues are a promising class of heterocycles applied as effective drugs, agrochemicals, and new materials (Figure 1). 3 However, only a very few reports have been concerned for the synthesis of 1,3,5-oxadiazines.…”

“…For example, fused meso-1,3,5-oxadiazines were synthesized from Lpyroglutamic acid with aldehydes by electrochemical oxidation under acid catalysis (Scheme 1A-i). 2 Novikov synthesized 1,3,5-oxadiazines from 1,2,4-oxadiazoles with α-diazo esters catalyzed by Rh(II) or Cu(II) (Scheme 1A-ii). 3 A Mannich-type reaction of N-methyl-N′-nitgroguanidine with two moles of aldehyde provided 4-nitroimino-tetrahydro-1,3,5-oxadiazines (Scheme 1A-iii).…”