PhSeBr-catalyzed selective addition of thiols to α,β-unsaturated carbonyl compounds: regioselective synthesis of thioacetals vs. β-mercapto ketones

Abstract

Apresentamos aqui nossos resultados da adição de tióis, catalisada por PhSeBr, a compostos carbonílicos α,β-insaturados sob condições brandas para obter regiosseletivamente β-mercapto cetonas ou tioacetais com altos rendimentos e seletividade. A reação foi principalmente controlada pela temperatura, na qual os produtos de adição 1,4 foram obtidos à temperatura de -20 o C. Inversamente quando a reação foi realizada sob refluxo, tioacetais foram obtidos como único produto. O método admite diversos grupos funcionais, como alquilicos, benzilicos e arilicos com substituintes neutros, deficientes e ricos em elétrons no anel aromático.We present herein results on the PhSeBr-catalyzed addition of thiols to α,β-unsaturated carbonyl compounds under mild conditions to afford regioselectivily β-mercapto ketones or thioacetals in high yields and selectivity. The reaction was highly controlled by the temperature in which, the 1,4-addition products were obtained when the temperature was -20 °C, conversely when the reaction was carried out at reflux, the thioacetals were obtained as a sole product. The developed protocol stands a wide range of functional groups, in which alkyl, benzyl and aryl with neutral, electron deficient and electron rich substituents on the aromatic ring. Keywords: thioacetals, β-mercapto ketones, chalcogenides IntroductionThioacetals are useful intermediates in organic synthesis and are often used as masked carbonyl groups, in particular α-lithiated thioacetals that are synthetic equivalents of carbonyl anions. [13][14][15] have been used for this purpose. Despite those methods reported in the literature, some problems were found as, difficulties in work-up, isolation, requirement of inert atmosphere, harsh reaction conditions, expensive and stoichiometric reagents, incompatibility with other protecting groups and failure to protect desactivated and hindered substrates. In contrast, none of the reported methods describe the selective catalytic preparation of β-mercapto ketones or thioacetals from α,β-unsaturated carbonyl compounds with thiols, catalyzed by PhSeBr. Therefore, it would be of interest to define a method in order to prepare selectively β-mercapto ketones or thioacetals starting from α,β-unsaturated carbonyl compounds and thiols (Scheme 1). Results and DiscussionOur initial studies have focused on the development of an optimum set of reaction conditions to obtain β-mercapto ketones in the absence of thioacetals. In Schneider et al. 2089 Vol. 21, No. 11, 2010 this way, cyclohex-2-enone 1a and benzenethiol 2a were used as standard substrates and the variation in the temperature, time, presence or absence of catalyst were investigated. At first, the reaction was tested under room temperature, using CH 2 Cl 2 as solvent in the presence of PhSeBr (2 mol%); thus after 10 min the product of 1,4-addition was obtained in 65% yield. However, under this reaction condition traces of the thioacetal were also obtained. In attempt to avoid the thioacetal by-product and to select the β-mercapto ketones...

Electrochemical Cascade Thia-Michael and Thioacetalization of Cyclic Enones

“…were reported. 15,16 However, the development of atom-economical, green and sustainable electrocatalytic synthetic protocols still has a place in this field. In our previous synthetic methodology, we envisioned that a specific electric current may be used to activate thiols to lead to C-S bond formation.…”

Bis(2-pyridyl)diselenoethers as versatile ligands for copper-catalyzed C–S bond formation in glycerol

“…11 Still, the use of organoselenium compounds have been shown as catalyst in organic transformations, such as the selective addition of thiols to α,β-unsaturated carbonyl compounds. 12 On the other hand, the development of green methodologies from renewable resources has grown because of the extensive use of solvents in chemical industries and the impact of these on the environment, health and safety. 13 Glycerol, an organic waste generated by the biodiesel industry, has been recently proposed by Gu and Jérôme as a valuable green solvent.…”