Catalyst-Free Conjugated Addition of Thiols to α,β-Unsaturated Carbonyl Compounds in Water

Abstract

[reaction: see text] Catalyst-free conjugate addition of thiols to alpha,beta-unsaturated carbonyl compounds in water is reported. beta-Sulfido carbonyl compounds were formed at room temperature, in short times and with excellent chemoselectivity. Competitive dithiane/dithiolane formation, transesterification, and ester cleavage were not observed. Water played a dual role in simultaneously activating the alpha,beta-unsaturated carbonyl compound and the thiol. This new methodology constitutes an easy, highly efficient, and green synthesis of beta-sulfido carbonyl compounds.

Catalytic activation of pre-substrates via dynamic fragment assembly on protein templates

“…The third pre-substrate, N-acrylamido-AMC 3, was selected as a model for irreversible pre-substrate activation. Activation of 3 was investigated in the presence of thiol nucleophiles, which were expected to yield Michael addition products being stable under assay conditions 38,39 . Thus, pre-substrate 3 was incubated with one of three thiol nucleophiles, 2-mercaptoethyl-guanidine 6, cysteamine 10 and 4-amino benzenethiol in the assay buffer for 30 min at room temperature (20°C).…”

Catalyst‐free Multicomponent Synthesis of β‐Mercapto Diketones in Water

“…16 Moreover, water plays a dual role in simultaneously activating the intermediate (5) and the thiol. 17 Hydrogen bond formation between water and the carbonyl oxygen atom of the intermediate (5) increases the electrophilic character at the β-carbon of 5. On the other hand, hydrogen bond formation between water and thiol increases the nucleophilicity of the sulfur atom of the thiol via the transition state (6a).…”

Addition Reactions: Polar Addition

“…129 In the conjugate addition of thiols to α,β-unsaturated carbonyl compounds, carried out in aqueous conditions, water was found to play a dual role in simultaneously activating the α,β-unsaturated carbonyl compound and the thiol. 130 While the Michael-type addition of thiolates to α,β-conjugate systems is expected to proceed faster if the thio donor contains an electron-rich group or the enone acceptor is highly electron deficient, the hard-soft acid-base (HSAB) principle predicts that this reaction is favoured when a soft-soft interaction between the reactants takes place. To analyse the apparent discrepancy, the effect of charge transfer of a para-substituent on the softness of sulfur in thiophenols, as well as its impact in the conjugate addition to cyclohex-2-en-1-one, has been investigated.…”