NHC-Catalyzed [3 + 3] Annulation of Thioamides and Modified Enals for the Enantioselective Synthesis of Functionalized Thiazinones

Abstract

Unless otherwise specified, all reactions were carried out under an atmosphere of argon in flame-dried reaction vessels with Teflon screw caps. Mesitylene was purchased from commercial sources and stored under argon over 4 Å molecular sieves. The 2-bromoenals were synthesized from the corresponding -unsaturated aldehydes following the literature procedure. 1 All the thioamide derivatives were prepared following the literature procedure. 2 The triazolium salt C was synthesized following the literature procedure. 3 K2CO3 was purchased from SD-Fine. Analytical thin layer chromatography was performed on TLC Silica gel 60 F254. Visualization was accomplished with short wave UV light or KMnO4 staining solutions followed by heating. Flash chromatography was performed on silica gel (230-400 mesh) by standard techniques eluting with Pet. Ether-EtOAc solvent system. All compounds were fully characterized. 1 H and 13 C NMR spectra were recorded on Bruker AV 400 and Bruker Ultra shield spectrometer in solvents as indicated. Chemical shifts (δ) are given in ppm. The residual solvent signals were used as references and the chemical shifts converted to the TMS scale (CDCl3: δH = 7.26 ppm, δC = 77.16 ppm). Infrared (FT-IR) spectra were recorded on a Perkin Elmer Spectrum BX spectrophotometer, ν-max in cm-1. Optical rotations were measured on JASCO P-2000 polarimeter at room temperature using 50 mm cell of 1 mL capacity. HRMS (ESI) data were recorded on a Micromass Q-TOF Micro instrument. HPLC analysis was performed on Agilent Technologies 1260 Infinity II with UV detector.

Recent Advances in Enantioselective Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes (NHCs) Containing Triazolium Motifs

“…This method provided high yield and selectivity up to 94% ee using 10 mol% NHC-Mes catalyst AM10 (Scheme 50). 147…”

Recent advances of N-heterocyclic carbenes in the applications of constructing carbo- and heterocyclic frameworks with potential biological activity

“… 94 In 2019, Biju and co-workers reported their [3 + 3] cycloaddition between enals and thioamides 142 catalyzed by chiral NHC C21, resulting in a variety of functionalized thiazinones 143 with high stereoselectivities ( Scheme 46b ). 95 Thirty-two reactions were carried out to prove the good functional group applicability.…”

Organocatalytic Name Reactions Enabled by NHCs

“…Hetero-Michael reactions catalyzed by NHCs are also possible. A peculiar example of NHC catalysis also involving sulfur constituted the most recent research of Ghosh et al, in which thia-Michael addition is the first step of [3+3] annulation, starting from 2-bromoenals and thioamides [161] (Scheme 20). Nitrogen can also take part in a Michael reaction like aza-Michael addition in, for example, [3+4] annulation [94,162].…”