Metal-free thioesterification of α,β-unsaturated aldehydes with thiols

Abstract

For the first time, the synthesis of thioesters starting from enals and thiols has been performed in the presence of a bulky N-heterocyclic carbene (NHC) as a catalyst.

Metal-free functionalization of SQs: a case of chemoselectivity and what ball-milling has got to do with it?

“…22 Because of the lack of literature reports on the use of mercapto-SQs as substrates in the thioesterification process, a preliminary experiment was carried out under the same conditions as those described for simple thiols in our previous work. 10 Addition of 10 mol% of bulky NHC (1,3-bis{2,6-bis(diphenylmethyl)-4-methoxy-phenyl}imidazole-2-ylidene, IPr* OMe ) to an equimolar solution of reagents in acetone, stirred at RT for 24 h, resulted in only 40% conversion of substrates and the formation of a mixture of 1,2- and 1,4-addition products at the ratio 55:45. The reaction also led to the formation of ca.…”

“…Based on the literature and our previous research concerning NHC-catalyzed thioester synthesis from α,β-unsaturated aldehydes with thiols, 10 we propose two possible complementary mechanisms depicted in Scheme 5.…”

“…Recently, we have designed and successfully tested a simple, chemoselective protocol for the synthesis of thioesters in thiol-enal addition, catalyzed by an in situ generated bulky NHC ligand. 10,11 This approach has led exclusively to thioesters in high yields without side-products originating from the Michael addition to the α,β-unsaturated system. Inspired by this work and bearing in mind the applications of thioester moieties in polymer chemistry, we turned our attention to polyhedral oligomeric silsesquioxanes (POSS®, SQ), which are well-defined, nanometric cage entities with the general formula [RSiO 1 .5 ] n with a robust and thermally stable siloxane framework.…”

Metal-free synthesis of unsymmetric bis(thioesters)

“…Recently, we have devised a new method for thioester synthesis, based on the reaction between enals and thiols in the presence of a bulky NHC carbene ( NHC-1 ). 8 We have proved that thioesterification allows efficient synthesis of mono- as well as bis-functionalized symmetrical organosulfur derivatives (Scheme 1).…”

“…We started our study by performing a number of catalytic tests in the same conditions as those described for the functionalization of thiols in our previous work. 8 Preliminary experiments, aimed at the optimization of the reaction conditions, were performed with the use of 1,4-benzenedithiol ( T1 ) as a source of sulfur. Addition of 20 mol% of bulky NHC carbene ( NHC-1 ) to an acetone solution of an equimolar ratio of T1 , cinnamaldehyde ( A1 ) and 4-methoxycinnamaldehyde ( B1 ) at 40 °C, resulted in a complete conversion of the substrates after 24 h. 1 H NMR analysis of the reaction mixture revealed the selective formation of the expected unsymmetrical bis-thioesterification product ( P1 ) in an almost quantitative yield (Scheme 3).…”