Selective Synthesis of Tetrasubstituted Olefins by Copper‐Mediated Acetoxythiolation of Internal Alkynes: Scope and Mechanistic Studies

Abstract

The Cu-mediated synthesis of tetrasubstituted olefins by the addition of an acetate group and a thiolate to an unactivated internal alkyne is described. The reaction is fully stereoselective, because only the E alkene is obtained. If the alkyne is asymmetric, the reaction also shows a very high degree of regioselectivity. The mechanism of the reaction is elucidated by DFT methods, which show that it takes place through Cu-stabilized radical species. Calculations highlight the crucial role of the dimeric copper(II) diacetate in the process, as it generates the active species in which the sulfur center has an incipient thiyl radical character and accepting, through a series of changes in the oxidation states of the two copper centers, the two electrons released in the addition of two nucleophiles to the alkyne.

Sulfur-Centered Reactivity of Oxidized Iron-Thiolate Complex toward Unsaturated Hydrocarbon Addition

“…Because of the existence of highly covalent Fe–S bonds in oxidized intermediate A , an unpaired electron can be delocalized over iron and sulfur atoms to generate iron-stabilized thiyl radicals B , which are responsible for ethylene addition to form new C–S bond to produce adduct 2a­[BPh 4 ] . Similarly, the generation of the metal-stabilized thiyl radical as a key intermediate for further C–S bond formation with alkenes or alkynes was also observed in mononuclear ruthenium , and copper systems . Interestingly, in the absence of ethylene, iron-stabilized thiyl radical will self-assemble into reported diiron complex with a tpdt bridge in moderate yield .…”

“…Similarly, the generation of the metal-stabilized thiyl radical as a key intermediate for further C−S bond formation with alkenes or alkynes was also observed in mononuclear ruthenium 6,8a and copper systems. 32 Interestingly, in the absence of ethylene, iron-stabilized thiyl radical will self-assemble into reported diiron complex with a tpdt bridge in moderate yield. 15 This result is different from other metal complex systems involving thiyl radicals, such as those of Goh's 10 and Wieghardt's 33 work, which all involve the generation of a coordinated thiyl radical and then intermolecular coupling to give the corresponding disulfide complexes.…”

Recyclable Gold Catalyst for the Stereoselective Thioallylation of Alkynes

“…Matsubara et al reported the synthesis of tetrasubstituted ( Z )-β-aminocarbonyl vinyl sulfides via nickel-catalyzed thiocarbamoylation of internal alkynes with thiocarbamates . Urriolabeitia and co-workers described a copper-mediated acetoxythiolation of internal alkynes with thiols under microwave conditions for the synthesis of tetrasubstituted ( E )-β-acetoxyalkenyl sulfides . However, these reported methods generally suffer from some drawbacks such as the limited substrate scope, moderate yields, and poor regio- or stereoselectivities.…”

Computational Organometallic Catalysis: Where We Are, Where We Are Going

“…Reagents such as sodium tert-butoxide and copper diacetate keep aggregated structures in non-polar solvent environments, and their description as monomeric species in QM calculations could be misleading. [16,17] The same issue arises with iodosylbenzene (PhIO) a polymeric solid of low solubility. [18] To build up a reliable energy profile, all the species that can influence the energy of the system in each step of a catalytic cycle should be taken into account.…”

“…Attention should also be paid to the speciation of simple reagents, which can be very solvent dependent. Reagents such as sodium tert ‐butoxide and copper diacetate keep aggregated structures in non‐polar solvent environments, and their description as monomeric species in QM calculations could be misleading [16,17] . The same issue arises with iodosylbenzene (PhIO) a polymeric solid of low solubility [18] …”