Addition of nucleophiles to (E)-3-phenylsulfonylprop-2-enenitrile: a route to β-substituted α,β-unsaturated nitriles and to acetals of cyanoacetaldehyde

Abstract

Abstract(E)-3-Phenylsulfonylprop-2-enenitrile reacts with sulfur-, oxygen-and carbon-based nucleophiles to yield (E)-configured β-substituted α,β-unsaturated nitriles via a regiospecific addition-elimination sequence.

Design and Semisynthesis of Biselectrophile-Functionalized Ubiquitin Probes To Investigate Transthioesterification Reactions

“…Moreover, under these conditions, treatment with ethane-1,2-dithiol resulted only in single addition to E-Ac-Gly-PSAN (E-23a) as well as to BAY 11−7082 (8) (Figure S6b,c). In contrast, in organic solvent (4 equiv Et 3 N, CHCl 3 , rt, 2 h), BAY 11-7082 ( 8) underwent double addition to the corresponding dithiolane as previously reported, 19 while E-Ac-Gly-PSAN (E-23a) again underwent only single addition. 26 This indicates marked differences in reactivity between the disubstituted olefin BAY 11-7082 ( 8) and the trisubstituted olefin E-Ac-Gly-PSAN (E-23a), as well as solvent dependence of this reactivity.…”

Stereoselective formal alkenylation of β,β-disubstituted enesulfinamides for constructing 1,5- and 1,4-dicarbonyl derivatives bearing less-accessible acyclic α-quaternary stereocenters

“…Subsequently, we explored the transformation employing another electron-deficient alkene, ( E )-β-tosyl acrylonitrile ( 4a ), that also bears electron-withdrawing groups on both α- and β-carbons. 17 Rather than the 1,5-dicarbonyl product derived from addition at the β-carbon atom, the 1-cyanovinylated product ( R S , R )- 5a , formed via the addition at the α-carbon atom, was obtained in 90% yield with >20 : 1 dr (Scheme 2e), in which treatment of the initially formed Michael adduct with DBU in one-pot operation was performed to facilitate complete β-elimination. Similarly, the gram scale synthesis and the synthesis of other three stereoisomers produced excellent results (Scheme 2f–h).…”

Orthogonal Thiol Functionalization at a Single Atomic Center for Profiling Transthiolation Activity of E1 Activating Enzymes

“…An AVS could potentially serve as a novel thiol-reactive warhead and covalently label proximal cysteine residues yielding a stable and tetrahedral, geminal heterobisthioether. The first class of reaction involves thiol addition to a phenylsulfonyl substituted- or a tosyl substituted-doubly activated ene (TDAE) , which in aqueous buffer yields the trans AVS via an unexpected addition–elimination mechanism (Figure a). The second class of reaction involves nucleophilic thiol-yne addition to activated ynes, − which in aqueous buffer yields the cis AVS (Figure b).…”