N‐Functionalization of 4‐amino‐2‐(trifluoromethyl)‐1H‐pyrroles: Synthesis of N‐alkyl derivatives and 1,2,3‐triazol‐4‐yl‐pyrrole scaffolds

Abstract

The N‐functionalization of 4‐amino‐2‐trifluoromethyl‐1H‐pyrroles using alkyl halides is reported. The selectivity of the alkylation reaction was highly dependent on the nature of the alkyl halide and the reaction conditions applied, that is, methyl iodide may furnish N‐methyl or N,N‐dimethyl pyrroles, while allyl bromide furnishes N‐allyl or N,C‐diallyl analogs and propargyl bromide furnishes exclusively N‐propargyl pyrroles. The alkylated products were obtained between 65%–90% yields and were subjected to CuAAC reactions, which furnished conjugated 1,2,3‐triazoles in good yields (72%–91%). The structures of the obtained compounds were unambiguously determined via 2D‐NMR experiments.

Regioselective synthesis of (Z)‐5‐methylene‐containing morpholin‐2‐ones

“…This work presents a methodology to prepare enantio-and regioisomerically pure (Z)-5-methylenemorpholin-2-ones using 5-brominated trifluoro(chloro) enones through a 1,4-conjugated addition followed by intramolecular nucleophilic substitution protocol. The reactivity of these enones toward nitrogen dinucleophiles has been well described [31][32][33][34][35][36][37]; however, the reactivity toward more complex nucleophiles, such as unprotected α-amino acids, is still unknown. One of the main advantages of using these enones as suitable starting materials for assembling the morpholin-2-ones of interest is that they have a very different 1,2-dielectrophilic center compared to simple 1,2-dihaloalkanes, given the high chemoselectivity when undergoing the initial aza-Michael addition (Scheme 2) [38][39][40].…”