Copper‐Catalyzed CC Coupling of Thiol Esters and Boronic Acids under Aerobic Conditions

Abstract

Getting rid of palladium: Thiol esters can be cross‐coupled with boronic acids to generate ketones at neutral pH by using a CuI‐oxygenate catalyst under aerobic and Pd‐free conditions (see scheme; S‐pendant=NHtBu thiosalicyclamide). The mechanistically unique coupling is likely to proceed by a preorganized, higher oxidation state Cu species that relies on appropriately positioned ligating S‐pendant groups on the thiol ester and on an additional equivalent of the boronic acid.

Mechanistic Insights into the Aerobic Copper(I)-Catalyzed Cross-Coupling of S-Acyl Thiosalicylamide Thiol Esters and Boronic Acids

“…We were not able to locate all required transition state structures because the barriers associated with these transition states are very small. Among the numerous barriers located, the highest ones, 19.1 and 15.5 kcal/mol, are that associated with the 3 TS1-2 (OO,OO) and the 1 TS2 (OO,OO) transition states, respectively. Even this barrier can be considered as moderate.…”

“…6 In the original anaerobic desulfitative chemistry, which spans a wide variety of thioorganic substrates, palladium is required to affect an oxidative addition with the C-S bond to activate the thioorganic, which produces an intermediate, R-PdL n -SR', able to undergo transmetalation with a boronic acid when mechanistically facilitated through the action of the Cu I carboxylate. 24 In comparison, the S-acyl thiosalicylamide substrates described herein do not require prior activation by Pd in order to participate in Cu-mediated cross-coupling with boronic acids.…”

“…1–4 Recently, Liebeskind and co-workers 5 reported an unprecedented reaction for the construction of C-C bonds: the Cu I -templated coupling of a thiol ester and a boronic acid that was rendered catalytic under aerobic conditions. This new reaction type evolved from a mechanistically distinct earlier anaerobic transformation 6 that required catalytic quantities of Pd and at least a stoichiometric quantity of a Cu I -carboxylate as a reaction mediator. The proposed 5 mechanism of this aerobic cross-coupling process includes several elementary reactions and an active catalyst containing only Cu-centers (Scheme 1).…”

Synthesis of 2-Aminoazoles from Thioesters via α-Heterosubstituted Ketones by Copper-Mediated Cross-Coupling

“…A mild synthesis of ketones from readily available thioesters and organostannanes has been reported by Liebeskind et al 9 This reaction relies on the palladium-catalyzed, copper-mediated coupling under neutral conditions. Furthermore, a palladium-free, copper-mediated cross-coupling of thioesters with α-alkoxystannanes to give α-alkoxyketones has been developed.…”

Groupware requirements evolution patterns

“…52 Modha et al 53 reported the successful application of Liebeskind-Srogl conditions towards the coupling of p-methoxybenzylthiopyrazines with arylboronic acids. Initially, coupling of pmethoxybenzylthio-bearing pyrazine with arylboronic acid in the presence of copper(I)-thiophene-2-carboxylate (CuTC) and Pd(PPh 3 ) 4 in THF under conventional heating as well as under microwave irradiation gave poor to average yields, possibly due to decomposition of the reagents during the long reaction time at high temperature.…”