Base Mediated Synthesis of Alkyl-aryl Ethers from the Reaction of Aliphatic Alcohols and Unsymmetric Diaryliodonium Salts

Abstract

The base mediated coupling of aliphatic alcohol pronucleophiles with unsymmetric diaryliodonium salt electrophiles is described. This metal-free reaction is operationally simple, proceeds at mild temperature, and displays broad substrate scope to generate industrially important alkyl-aryl ethers in moderate to excellent yield. The synthetic utility of these reactions is demonstrated, and aspects of sustainability are highlighted by the use of unsymmetric aryl(mesityl)iodonium arylating reagents.

A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

“…However,when the iodonium salt contained an electron-rich aryl group (2)the combined yield of 4 and 6 was significantly lower (entry 3). Thep roduct distribution observed for the reaction of morpholine with either 1 or 2 is in stark contrast to our previous alkoxide arylation chemistry, [12] and to the best of our knowledge other recent O-arylation methods. [13] Thea pproximate 1:1r atio of ipso-and cine-substitution isomers formed in this reaction is, however, consistent with classic reactivity of a4 -substituted aryne intermediate.…”

“…On the basis of our recent success in the arylation of alkoxide nucleophiles with unsymmetrical aryl-(mesityl)iodonium salt electrophiles [12] we turned our attention to Nnucleophiles.M orpholine is ap rivileged motif in biologically active compounds and was selected as ar epresentative alicyclic amine nucleophile.T he compound 1, bearing an electron-deficient aryl ring, was used as the iodonium electrophile to survey reaction conditions.W e found that the combination of morpholine and sodium tertbutoxide produced the desired and expected ipso-substitution product 3 along with as econd and unexpected product 5 in equimolar quantity (Table 1, entry 1). Moreover,t he combined yield of ipso-a nd cine-substitution products was excellent (89 %).…”

Competing Pathways in O‐Arylations with Diaryliodonium Salts: Mechanistic Insights

“…In Stuart's recent methodology to arylate primary and secondary aliphatic alcohols, benzyl alcohol was arylated using aryl(mesityl)iodonium salts with only trace formation of benzaldehyde . However, submission of 3 b to these conditions, with either salt 1 d or unsymmetric Ph(Mes)IBr, delivered the oxidized product 9 as a major product and ether 4 c as a minor product (entries 5–6).…”

Diaryliodonium Salts in Organic Syntheses: A Useful Compound Class for Novel Arylation Strategies

“…Very recently, Stuart and co-workers reported a base mediated chemoselective synthesis of alkylaryl ethers 20 (10) starting from the reaction of aliphatic alcohols (9) and unsymmetric arylmesityliodonium bromides (Scheme 6). Primary, secondary, tertiary, allylic, and benzylic aliphatic alcohols were all suitable substrates for the transformation.…”