Palladium-Catalyzed Csp3–H Bond mono-Aroyloxylation of O-Alkyl Substituted 2,4,6-Trimethoxybenzaldoxime Ethers

Abstract

A palladium-catalyzed Csp3–H bond mono-aroyloxylation of O-alkyl substituted oxime ethers has been developed by using 2,4,6-trimethoxybenzaldoxime as an exo-type directing group with exclusive site-selectivity. With the wide range of masked aliphatic alcohol substrates and aromatic acid coupling partners, the protocol allows rapid access to various 2-alkyl substituted glycol derivatives in synthetically useful to good yields. The employed directing group is readily removed, accordingly affording valuable functionalized aliphatic alcohols. When the solvent from hybrid DCE/HFIP to CH3CN, non-directed oxidative cross-coupling is observed between the electron-rich aromatic ring of substrates and aromatic acid partners.

HFIP in Organic Synthesis

“…The site-selective C­(sp 3 )–H functionalization of O -alkyl substituted 2,4,6-trimethoxybenzaldoxime ethers with diverse (hetero)­aromatic and aliphatic acids provides 2-alkyl substituted glycol derivatives (Scheme ). The reaction is catalyzed by Pd­(OAc) 2 in the presence of K 2 S 2 O 8 /PIDA as oxidants; 2,4,6-trimethoxylbenzaldoxime served as a N , O -bidentate DG. Solvent screening identified a 3:1 DCE/HFIP to be more effective than DCE or HFIP alone.…”