Comprehensive and Facile Entry into Substituted Amidines via the Condensation of N-Pmc-Substituted Thioamides with Amines Using Mukaiyama Reagent as a Thiophile

Abstract

A convenient approach is presented for the preparation of substituted amidines through the fusion of N-Pmc-substituted thioamides with amines, facilitated by a variety of thiophilic reagents. Assorted thiophiles were evaluated for their effectiveness as condensation reagents between the two partners, with the Mukaiyama reagent emerging as the optimal candidate for this process. The scope and limitations of this method were explored, revealing interesting synthetic challenges and constraints. Many of these limitations were overcome through the application of alternative reaction pathways in the construction of troublesome products. Treatment of the resultant Pmc-amidines with trifluoroacetic acid and trimethylsilyl trifluoromethanesulfonate cleanly afforded the deprotected substituted amidines.

Condensation of Amines with S-Methyl Thiouronium Salts: Another Entry for the Synthesis of Amidines

“…Interestingly, one-pot reactions have been reported for the synthesis of amidines from amides, but these suffer from a restricted substrate scope. [16][17][18] Amidines have also been synthesized by the reactions of amines with thioamides 19,20 or of thioimidates with ammonia or amines. 21,22 However, N,N,N′-trisubstituted amidines cannot be synthesized by these methods.…”