Etherification of Fluoroarenes with Alkoxyboronic Acid Pinacol Esters via C–F Bond Cleavage

Abstract

Potassium-base-mediated defluoroetherification of aryl and heteroaryl fluorides with alkoxyboronic acid pinacol esters under transition-metal-free conditions is reported. This protocol efficiently and safely provides a wide variety of aryl ethers in high yields without using metal catalysts, specific ligands, and harsh conditions to selectively forge Csp2–O bonds via the Csp2–F cleavage. This method can be applied to the late-stage etherification of structurally complex Csp2-fluorides and bioactive alcohols, such as β-estradiol, calciferol, and tocopherol.

Synthesis of triarylmethanes by silyl radical-mediated cross-coupling of aryl fluorides and arylmethanes

“…Based on both our experimental results and previous reports, 15,16 we proposed a reaction mechanism involving a radical-mediated defluorinative cross-coupling reaction (Fig. 5C).…”

“…in THF at room temperature; these conditions were also used in our previous defluorosilylation of aryl fluorides. 16 The reaction proceeded as expected, producing 4-benzhydrylbiphenyl ( 3aa ) in 37% yield accompanied by the defluorosilylated product, biphenyl-4-yltriethylsilane ( 4a ) (entry 1). Without Ni(COD) 2 , the yield of 3aa improved to 47% (entry 2).…”

“…29 We also confirmed the existence of intermediate I by 11 B NMR and 29 Si NMR spectroscopy. 15,16 In this step, due to the inherent steric repulsion of this ate complex I , the intermediate I splits into a sterically demanding and frustrated radical pair II 30 consisting of a triethylsilyl radical (˙SiEt 3 ) and boron-radical species via the homolytic scission of the Si–B bond. Hydrogen abstraction from diarylmethane 2 by ˙SiEt 3 affords a frustrated radical pair III accompanied by the formation of HSiEt 3 (detected by GC-MS).…”

“…Inspired by the studies mentioned above 14 and our studies on C–F bond activation, 15,16 we herein propose a silylboronate-mediated radical cross-coupling reaction of aryl fluorides 1 with arylalkanes 2 via the cleavage of both C–F and C–H bonds, which produces triarylmethanes 3 (Fig. 1D).…”

Transition-metal-free silylboronate-mediated cross-couplings of organic fluorides with amines

“…Figure 4c ). The reaction of 1 with the freshly prepared potassium salt of 3a in the presence of t BuOBpin 57 was attempted; however, no reaction occurred (Fig. 4d ).…”