A Method for the Analysis of Free Carbenes Present after NHC‐Organocatalyzed Transformations

Abstract

In N‐heterocyclic carbene (NHC) based organocatalysis, usually, the free carbene is generated in situ by treatment of the azolium salt with a base. Described herein is a method for the analysis of the NHC present in the reaction flask after the NHC‐organocatalyzed reaction. For this, the reaction mixture was treated with elemental sulfur after the reaction and the thus‐formed thiourea/thione derivative was isolated. Common NHC‐catalyzed transformations such as benzoin reactions, Stetter reactions, homoenolate annulation reactions, and reactions proceeding via the α,β‐unsaturated acylazolium intermediate have been studied. The results indicate that after the reactions, 28–84 % of the initial carbenes exist in the free form.

N‐Heterocyclic Carbene Mediated Sulfur Extrusion of Disulfides

“…Because of this analogy, we considered the use of NHCs as a substitute for the highly carcinogenic phosphor‐based amines as an alternative and more harmless reagent for sulfur extrusion reactions. Furthermore, the reaction of NHCs with elemental sulfur to the corresponding thiourea derivative has previously been reported in the literature [15] . Based on these findings we initiated the investigation of NHCs as an alternative sulfur extrusion reagent for organic disulfides to obtain the corresponding thioether compounds, which is presented herein.…”

“…Furthermore, the reaction of NHCs with elemental sulfur to the corresponding thiourea derivative has previously been reported in the literature. [15] Based on these findings we initiated the investigation of NHCs as an alternative sulfur extrusion reagent for organic disulfides to obtain the corresponding thioether compounds, which is presented herein.…”

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

“…163 Enders created the triazolium salt P7 a derivative of pyroglutamic acid, that influenced benzoin reactions with comparable enantioselectivities (Scheme 14). 28,164 Scheme 14 Asymmetric benzoin reactions using a PhCHO with bis-triazolium catalyst Dhayalan, Milo et al introduce an approach for the in situ systematic modification of NHC-organocatalysts under mild reaction conditions at their secondary sphere via dynamiccovalent binding. 108 As a proof-of-concept, we harnessed the propensity of aryl boronic acids for binding with carbene hydroxyl groups to accomplish enantioselective NHC-catalyzed benzoin reactions of a challenging substrate class containing electron-withdrawing groups on the aryl ring of 3 and 4 positions.…”

“…The enantioselective intramolecular Stetter reaction with AM16 was carried out in the presence of aminoindane triazoliums NHC (10 mol%), KHMDS (10 mol%), toluene, at 23 ℃ for 4 h. The product yield, as well as the enantioselectivity, is excellent and up to 92% ee was found as shown in scheme 37. 164…”

Exploring the stability of the NHC–metal bond using thiones as probes

“…Specifically, we investigated a series of NHC metal complexes on their intrinsic stability, with a particular focus on potential carbene dissociation, which was monitored by trapping the released free carbene with elemental sulfur to form the corresponding thione † as a readily detectable indirect probe. [24][25][26] To this end, a range NHC complexes were prepared with group 8-11 metals, as these metals are by far the most frequently used in catalytic applications, including Au(I), Pd(II), Rh and Ir both in +1 and +3 oxidation states, Ru(II), Ni(II), and Ag(I), as well as less explored Pt(II) and Os(II) complexes (Fig. 1).…”