Acetohydrazone: A Transient Directing Group for Arylation of Unactivated C(sp³)–H Bonds

Abstract

A straightforward and efficient method has been developed for the synthesis of 2-benzylbenzaldehyde derivatives from 2-methylbenzaldehyde and iodobenzene via a C(sp(3))-H activation process. In the course of the activation reaction, acetohydrazone is formed between 2-benzylbenzaldehyde and acetohydrazine as a transient directing group. As a new kind of transient directing group, acetohydrazone exhibits a remarkable directing effect to give corresponding products in good to excellent yields.

Transient Ligand‐Enabled Transition Metal‐Catalyzed C−H Functionalization

“…In their work, a bulky amino amide ligand played a vital role in achieving high enantioselectivity and in promoting C−F reductive elimination (Scheme c) . Following those studies, the benzylic C(sp 3 )−H arylation of 2‐methylbenzaldehyde was also achieved by Ma, Lei, and Hu, who used acetohydrazide ( L23 ) as the transient ligand (Scheme d) . Very recently, Jung, Kim, and co‐workers demonstrated that an amino amide bearing a pendant hydroxy group L24 could also be used as the transient ligand for this process (Scheme e) …”

Palladium‐Catalyzed ortho C−H Arylation of Benzaldehydes Using ortho‐Sulfinyl Aniline as Transient Auxiliary

“…In these reaction systems, an imine directing group was in situ generated to facilitate metal‐catalyzed ortho C−H activation and subsequently hydrolyzed to release the functionalized products and the transient auxiliary. For example, Yu and Hu reported palladium‐catalyzed C−H arylation reactions of 2‐alkyl benzaldehydes using unprotected glycine or acetohydrazone as transient auxiliary, respectively (Scheme A). Notably, the arylation reactions preferentially take place at the benzylic C(sp 3 )−H bonds over the ortho ‐(Csp 2 )−H bonds.…”

“…Both HFIP solvent and Ag 3 PO 4 base were critical to obtain good yield (entries 1–11). Importantly, the addition of 1 equiv of concentrated aqueous HCl solution significantly improved the yield of 3 to 80 % (75 % isolated yield, entry 12) . The amount and type of acid was crucial, as the addition of 2 equiv of aq.…”

Semicarbazide: A Transient Directing Group for C(sp3)−H Arylation of 2‐Methylbenzaldehydes

“…This strategy was subsequently applied to the synthesis of polycyclic aromatic hydrocarbons by Zhang's and Kim′s groups. In addition, acetohydrazide as a transient directing group for C( sp 3 )−H arylation of 2‐methylbenzaldehydes was also reported by Hu′s group . These successful examples have proved that an efficient transient directing group is crucial for enabling C( sp 3 )−H activation.…”