Direct Arylation of Benzyl Ethers with Organozinc Reagents

Abstract

A novel C(sp)-H bond arylation of benzyl ethers with Knochel-type arylzinc reagents has been developed. This transition-metal-catalyst-free reaction proceeds well under mild conditions in a simple and effective manner and enables the synthesis of a wide range of potentially biologically active benzyl ethers by using highly functionalized organozinc reagents as a carbon nucleophile.

Transition-Metal-Free Cross-Coupling of Acetals and Grignard Reagents To Form Diarylmethyl Alkyl Ethers and Triarylmethanes

“…), octane 880 uL, the crude product was purified by column chromatography (hexanes/ethyl acetate = 30:1) to obtain the target product 5a as a light-yellow liquid in 71% yield (28.0 mg). [10] Following the GP2, using 1-methoxyisochromane (32.8 mg, 0.2 mmol, 1.0 eq. ), phenylmagnesium bromide (120 uL, 2.5 M in 2-Me-THF, 0.3 mmol, 1.5 eq.…”

“…9 Our group recently developed a series of bulky chiral Nheterocyclic carbenes (NHCs), namely ANIPE and SIPE-type ligands, and successfully applied them to enantioselective metalcatalyzed cross-coupling reaction. 10 At the outset, we wondered whether our chiral NHCs would be applied to develop enantioselective nickel-catalyzed coupling of acetals with organomagnesium to afford enantioenriched diarylmethyl alkyl ethers and triarylmethanes. We thus commenced our study by employing benzylic acetal 1a and commercially available Grignard reagent PhMgBr 2a (2.5 M in 2-Me-THF) as model substrates, and coupling reactions proceeded smoothly to give diarylmethyl methyl ether 3a in moderate yields in the presence of nickel catalyst Ni(cod)2 and our NHC ligands (ANIPE or SIPE) in toluene at 80 o C (see Supporting Information, SI).…”

Synthesis of diarylmethyl thioethersviaa DABCO-catalyzed 1,6-conjugate addition reaction ofp-quinone methides with organosulfur reagents

“…However, the problem of using strong-smelling thiols must be solved, but some reaction systems are complex and have limited applications ( Scheme 1a ). In 2014 and 2018, Walsh and colleagues 11 and Peng and coworkers 12 reported the direct arylation of benzyl thioethers with aryl bromides or Knochel-type arylzinc reagents, respectively, to realize the synthesis of diarylmethyl thioethers. However, a complex reaction system (such as a catalytic system of NiXantPhos/[PdCl(allyl)] 2 in the presence of LiN(SiMe 3 ) 2 or NaN(SiMe 3 ) 2 (2.0 equiv), using Knochel-type arylzinc reagents and a stoichiometric oxidant) is needed ( Scheme 1b ).…”

Electrochemical α-C(sp3)–H/O–H cross-coupling of isochromans and alcohols assisted by benzoic acid

“…Many methods have been developed for converting isochromans into α-substituted derivatives, including catalyst-free oxidation, 9 catalysis by small molecules, 10 catalysis by transition metals, 11 and photochemistry. 12 These reactions generally proceed by one of two paths (Scheme 1B).…”