A dual role for acetohydrazide in Pd-catalyzed controlled C(sp³)–H acetoxylation of aldehydes

Abstract

The palladium catalyzed aldehyde directed acetoxylation of C(sp3)–H bonds was realized by a transient directing group approach for the first time.

Transient Directing Groups in Metal−Organic Cooperative Catalysis

“…In this process, acetylhydrazine was selected as the transient directing mediator of choice and acetic acid could be employed both as the solvent of the reaction and the source of the acetoxy group, in the presence of potassium peroxodisulfate oxidant, of which the lipophobicity could be overcome by the addition of a specific molecular sieve, to deliver the corresponding acetoxylated products in decent yields (Scheme 71). [124] A hydroxylation by the Yu group, which could extend the Schönecker's [125] and Baran's [126] copper-mediated C(sp 3 )À H aerobic oxidation to the use of transient directing groups for the site-selective hydroxylation of pentacyclic triterpenoids in fair to excellent yields, was also reported recently. [127] At this stage of this review article, the efficiency and synthetic usefulness of the transient imine directing group strategy for the directed functionalization of C(sp 3 )À H bonds in both aromatic and aliphatic aldehydes and ketones has been well documented.…”

Recent progress in catalytic acyloxylation of C(sp3)‐H bonds

“…Bao with coworkers also described palladiumcatalyzed C(sp 3 )-H acyloxylation of aromatic aldehydes using TDGs. [81] Among various DGs, acetohydrazide moiety displayed the best results and was used as both the TDG and aldehyde protecting group in combination with Pd(OAc) 2 , K 2 S 2 O 8 as oxidant and carboxylic acid as the OCOR source (Scheme 18). This synthetic approach allowed preparing acyloxylated aldehydes 121 with various functional groups (alkyl, alkoxy, halogen, trifluoromethyl, and nitro) in moderate to good yields (31-67 %).…”

Transient imine directing groups for the C–H functionalisation of aldehydes, ketones and amines: an update 2018–2020

“…The activation of benzylic C(sp 3 )-H has seen some key advances in the past two years, with both new directing groups and novel coupling partners being reported. [43][44][45][46][47][48][49][50] The benzylic C-H bonds are electronically activated by the presence of the aryl group, and are relatively constrained geometrically. Yi and Zhang reported a method to construct polyaromatic hydrocarbons from o-tolualdehydes and di/tri-iodoarenes (Scheme 13a).…”

“…Following Yu's work, Bao recently published an acetoxylation protocol using acetohydrazide as a transient directing group and potassium persulfate as the terminal oxidant (Scheme 15). 50 MCM-48, a type of silica based molecular sieve, is proposed to improve solubility of the potassium persulfate enabling acetoxylation. While good yields were obtained for relatively electron-neutral aldehydes, reduced yields were observed for both more electronrich and electron-poor substrates.…”