Palladium‐Catalyzed Suzuki–Miyaura Reaction Involving a Secondary sp³ Carbon: Studies of Stereochemistry and Scope of the Reaction

Abstract

Palladium-catalyzed C--C bond formation involving secondary sp3-hybridized carbon is described. These reactions occur with secondary 1-bromoethyl arylsulfoxides and different arylboronic acids, to produce the corresponding arylated sulfoxides in moderate to high yields and with complete stereospecificity. Despite the presence of beta hydrogens in the substrate, the competitive beta-hydride elimination is not a significant side reaction when coordinating solvents are used. The reported cross-coupling involves secondary C(sp3)--C(sp2) bond formation: this is the first time that a mechanistic study has been carried out with such substrates. The reaction proceeds with inversion of configuration at the stereogenic C(sp3) carbon. The high stereospecificity of the coupling and the mildness of the reaction conditions allow for the preservation of the optical purities of reagents and products and the preparation of useful chiral targets.

Asymmetric transition metal-catalyzed cross-coupling reactions for the construction of tertiary stereocenters

“…xxviii They utilized bromosulfoxides as substrates, which were synthesized by bromination of enantioenriched ethyl- p -tolyl sulfoxide. During optimization of the reaction conditions, t -amyl alcohol was identified as the optimal solvent because it efficiently suppressed competing β-H elimination.…”

Secondary Alkyl Halides in Transition‐Metal‐Catalyzed Cross‐Coupling Reactions

“…Asensio and co‐workers reported a Suzuki coupling reaction of activated secondary bromo sulfoxides with aryl boronic acids 61. An array of boronic acids were coupled with bromo sulfoxides under standard Suzuki conditions (Scheme ).…”

At the Forefront of the Suzuki–Miyaura Reaction: Advances in Stereoselective Cross-Couplings

“…In order to explore the feasibility of stereoselective Suzuki-Miyaura cross-coupling reactions, Asensio and co-workers first examined diastereoselective variants using configurationally defined α-bromosulfoxides 69 as substrates (Scheme 19a) [83][84][85]. Using this method, either enantioenriched or racemic syn-α-bromosulfoxides 69 could be crosscoupled with arylboronic acids to furnish α-arylsulfoxide 70 with inversion of stereochemistry at the stereogenic α-carbon centre.…”