The diene-transmissive hetero-Diels–Alder reaction of 2-vinyl α,β-unsaturated aldimines: stereoselective synthesis of hexahydroquinazolin-2-ones

Abstract

Stereoselective synthesis of hexahydroquinazolin-2(1H)-ones has been achieved through the application of the diene-transmissive hetero-Diels-Alder methodology to 2-vinyl-1-aza-1,3-butadienes. The cross-conjugated 1-azatriene underwent an initial hetero-Diels-Alder reaction on the 1-aza-1,3-butadiene system with tosyl isocyanate to afford the [4 + 2] mono-cycloadduct pyrimidinone. The second Diels-Alder reaction on the electron-rich 1-amino-1,3-diene unit of the mono-cycloadduct with dienophiles provided hexahydroquinazolin-2(1H)-ones with high stereoselectivity.

Transformations of Di‐ and Tetrahydropyrimidine Derivatives into Condensed Heterocycles with Retention of their Partially Saturated Structure

“…Diverse bi‐ and tricyclic scaffolds can be synthesized even without prefunctionalization at the positions 5 and 6 of the reduced pyrimidine core. T. Saito and coworkers reported the stereoselective synthesis of hexahydroquinazolin‐2‐ones as a result of Diels–Alder reaction of 3,4‐dihydro‐1 H ‐pyrimidin‐2‐one derivatives 169 containing the electron rich 1‐amino‐1,3‐diene unit with some dienophiles (Scheme ).…”

[3]‐1‐Azadendralenes as Versatile Building Blocks for the Stereoselective Synthesis of Polysubstituted Hexahydroquinazolin‐2‐ones and Hexahydrobenzothiazine‐2‐­imines

“…Herein, we report the extension of this attractive methodology by the use of cross‐conjugated 1‐azatrienes ([3]‐1‐azadendralenes) to synthesize a variety of ring‐fused nitrogen‐containing heterocyclic systems (Figure 2). 9…”

Regiospecific inverse electron demand Diels–Alder reactions of 7-methylcoumarin-4-azadienes

“…More recently Saito et al reported the Diels-Alder reaction of [3]-1-azadendralenes in which cross-conjugated 1azatriene underwent an initial hetero Diels-Alder reaction on the 1-aza-1,3-butadiene system with tosyl isocyanate to afford the mono-cycloadduct pyrimidinone which on further subsequent Diels-Alder reaction with dienophiles provides hexahydroquinazolin-2(1H)-ones with high stereoselectivity. 13 As a part of our interest in the Diels-Alder reaction of coumarins containing diene component, we thought that coumarin-4-azadienes (1) which contain a 3,4-double bond of coumarin ring conjugated to phenylimino group, would be an interesting diene system to study the Diels-Alder reaction; targeting coumarin containing polycyclic compounds.…”

“…disappeared and DHO peak appeared at 4.7 d. Hence, the structures 11c and 11d were ruled out, as they do not contain NH proton. Based on 13 C NMR spectra structure 11c was ruled out, as it contains a carbon atom which is anked by two electronegative atoms, oxygen and nitrogen, and is expected to give a peak around 80-85 d. Such a peak was not observed in both the spectra. To throw more light on the structure, DQF-COSY spectra of A and B were recorded and the spectra supported structure 11a.…”

“…1 H NMR spectra were recorded on 300 MHz or 500 MHz spectrometers. 13 C NMR spectra were recorded on 75 MHz or 100 MHz. Chemical shis are reported in parts per million relative to the central line of the multiplet at 77.0 ppm for CDCl 3 , 39.5 ppm for DMSO.…”