Deoxygenative Suzuki–Miyaura arylation of tertiary alcohols through silyl ethers

Abstract

The coupling of tertiary alcohols with boronic esters is described, providing a direct access to quaternary carbon scaffolds without needing to proceed by a highly activated intermediate such as an alkyl halide. A dual catalyst system is employed with both Ni(0) and Bi(III) components playing a critical role along with a mild chlorosilane reactant that enhances the yield by alcohol silylation. This method was found to tolerate diverse functional groups including chloro, nitro, olefin, ketone, ester and phenol moieties, while also being applicable to the derivatization of heterocyclic scaffolds. Mechanistic studies suggest the combination of Lewis acid catalyst and organosilane promote heterolytic cleavage of the substrate C-O bond by an SN1-like reaction pathway, providing a powerful strategy for derivatizing readily available alcohols.

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

“…In 2023, the Newman group disclosed a method for the arylation of cyclic tertiary alcohols via Suzuki− Miyaura coupling (Scheme 46d). 284 A dual Lewis acid/ transition-metal-catalyzed system is employed, with the authors proposing that in situ silylation occurs to generate a silyl ether intermediate that is activated by the Lewis acid. The authors hypothesized that a carbocation might form that is trapped by nickel in an S N 1-type oxidative addition; however, kinetic studies revealed contrasting rate behavior that prevented a complete mechanistic picture from being developed.…”

Oxidative Dehydroxycyclization of Catechols with o-Mercaptoanilines to Access 1-Hydroxyphenothiazines

“…In comparison, the coupling reactions starting with hydroxyl compounds (Scheme b–d) have been less studied, even though the corresponding dehydroxycoupling is a more concise protocol to build new C–X bonds. The established reactions generally employ aliphatic alcohols as an alternative of organic halides and borates, up to now, rarely involving phenolic hydroxyl groups except the Pd-catalyzed dehydroxylative functionalization of phenols (Scheme d) mediated by toxic and unmanageable SO 2 F 2 for delivering arylamides and arylnitriles. …”

A Synthesis of α-Alkyl Cycloenones by Pd-Catalyzed Suzuki–Miyaura Coupling with Cyclic Morita–Baylis–Hillman Adducts

“…Since the earliest reports on transition-metal-catalyzed Suzuki–Miyaura coupling with allylic alcohols, much progress has been made involving the π-activated alcohols . Although several examples of Suzuki–Miyaura-type couplings with nonactivated alcohols have been disclosed, allylic alcohols, which are more advantageous than allyl halides, carbonates, and esters, are still the mostly employed alcoholic electrophiles. In the seminal work by Shi and coworkers, secondary cyclic MBH alcohols could react with aryl boronic acids by chiral palladium complex catalyzed β-arylations .…”