[2+2+1+1] Cycloaddition Reaction of 1,3,5‐Triazinanes with Methylene Compounds: Approach to Hexahydropyrimidines

Abstract

An acetic acid‐catalyzed [2 + 2 + 1 + 1] cycloaddition of 1,3,5‐triazinanes with methylene compounds was developed. This protocol provides an access to hexahydropyrimidines (HHPs) (25 examples) in 35‐99% yields under mild conditions in 2 hours. The potential application of this method was demonstrated by gram‐scale synthesis. Preliminary mechanistic investigation was conducted to elucidate the possible mechanism. This work represents the yet unknown example of [2 + 2 + 1 + 1] cycloaddition reaction between 1,3,5‐triazinanes and active methylene compounds.

Reaction of 1,3,5-Triazinanes with Phosphoryl Diazomethanes: Access to 5-Phosphoryl-1,2,3,4-tetrahydropyrimidines

“…1,3,5-Triazinanes are a class of important synthetic building blocks and have been widely utilized in organic synthesis, especially as formaldimine precursors . They can be prepared from primary amines and formaldehyde easily and used as the precursors of unstable formaldimines .…”

Substituent-controlled divergent cyclization reactions of benzo[c][1,2]dithiol-3-ones and hexahydro-1,3,5-triazines

“…4 Apart from the assembly of amines, hexahydro-1,3,5-triazines are frequently harnessed as prominent two-, 5 three-, 6 and four-atom 7 building blocks in cycloaddition reactions to forge a vast array of N-heterocycles in a single-vessel reaction. Moreover, hexahydro-1,3,5-triazines were also sporadically utilized as five- 8 and six-atom 9 synthons to produce hexahydropyrimidines under mild conditions. Given the versatile properties of hexahydro-1,3,5-triazines for incorporation of different quantities of atoms into the final product, it would be highly desirable to develop a practical synthetic strategy for divergent construction of structurally discrepant cyclic molecules by taking advantage of 1,3,5-triazines as the robust precursors.…”