Palladium- and Nickel-Catalyzed Cross-Couplings of Unsaturated Halides Bearing Relatively Acidic Protons with Organozinc Reagents

Abstract

A wide range of polyfunctional aryl, heteroaryl, alkyl, and benzylic zinc reagents were coupled with unsaturated aryl halides bearing an acidic NH or OH proton, using Pd(OAc)2 (1 mol %) and S-Phos (2 mol %) as catalyst without the need of protecting groups. A similar nickel-catalyzed reaction is described. The relative kinetic basicity of organozinc compounds as well as their stability toward acidic protons is also described.

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

“…[160] In 2008, Knochel and co-workers reported an extensive study of the Negishi cross-coupling reactions of functionalized of aryl, alkyl, and benzylzincates with bromoarenes bearing acidic OH and NH 2 groups. [161] Here, the chemoselectivity was strongly influenced by the kinetic basicity of the various zincated species. For example, the relatively low kinetic basicity of PhCH 2 ZnCl·LiCl 2 (194), prepared by zinc insertion in the presence of LiCl, allowed for chemoselective coupling with bromoarenes bearing unprotected NHR and OH groups (Scheme 81).…”

One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol

“…• C and a solution of KHF 2 (117 g in 300 cm 3 of water, 1.5 mol) was added dropwise via a dropping funnel. The reaction mixture was stirred at room temperature overnight, then the solvent and water were removed under reduced pressure to reveal a white solid.…”

“…The reaction mixture was stirred at room temperature overnight, then the solvent and water were removed under reduced pressure to reveal a white solid. The crude product was extracted into hot acetone (5 ¥ 100 cm 3 ) and hot filtered. Removal of acetone under reduced pressure revealed an orange solid that was recrystallised from acetone; trifluoroborate 8 (17.79 g, 55%) was collected by filtration as fine colourless needles.…”

Coupling reactions with haloaromatic amines and alcohols for a practical synthetic route to 2-substituted aminophenyl and hydroxyphenyl pyridines

“…A similar outcome has also been reported in another study. 12 In the case of bromophenolic alcohols, no coupling reaction took place with the Pd(0)-catalyst. Instead, the Pd(II)-catalyst was more efficient for the coupling reaction.…”