Copper(II)-Mediated ortho-Selective C(sp²)–H Tandem Alkynylation/Annulation and ortho-Hydroxylation of Anilides with 2-Aminophenyl-1H-pyrazole as a Directing Group

Abstract

2-Aminophenyl-1H-pyrazole has been identified as a viable directing group to promote copper(II)-mediated ortho-selective sp C-H bond tandem alkynylation/annulation of anilides with terminal alkynes to offer arylmethylene isoindolinones. Meanwhile, copper(II)-mediated ortho-selective sp C-H hydroxylation of anilides has also been optimized as the major reaction pathway by using Cu(OAc) as the promoter and 1,1,3,3-tetramethylguanidine as an organic base. Recovery of the directing group was achieved by hydrazinolysis for arylmethylene isoindolinones and basic hydrolysis for the hydroxylation products.

Recent Advancements on Transition‐Metal‐Catalyzed, Chelation‐Induced ortho‐Hydroxylation of Arenes

“…established Cu(II) mediated ortho-hydroxylation of anilides using 2amino-1H-pyrazole as a removable directing group in 2018. [43] Tetramethyl guanidine (TMG) was used as an organic mild base to promote the hydroxylation in DMSO at 80°C (Scheme 27). The protocol successfully afforded a number of desired phenols in good yields when different functional groups like Me, F, CF 3 , Br etc.…”

“…al . established Cu(II) mediated ortho ‐hydroxylation of anilides using 2‐amino‐1 H ‐pyrazole as a removable directing group in 2018 [43] . Tetramethyl guanidine (TMG) was used as an organic mild base to promote the hydroxylation in DMSO at 80 °C (Scheme 27).…”

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

“…The 3-methyleneisoindolin-1-one moiety represents a key structure motif in natural products [20][21][22][23] or important pharma- cophores [24]. In this context, You [25], Huang [26], Liu [27], Li [28], and co-workers elegantly disclosed copper-mediated/ catalyzed cascade C−H alkynylation and annulation with terminal alkynes to afford 3-methyleneisoindolinone derivatives, through the assistance of 8-aminoquinoline [29] or 2-aminophenyl-1H-pyrazole [30] auxiliaries (Figure 1a). Besides, the cobalt(II)- [31] or nickel(II)-catalyzed [32,33], pyridine oxide (PyO)-directed tandem alkynylation/annulation was realized by Niu and Song et al, which also provided the 3-methyleneisoindolin-1-one scaffolds (Figure 1b).…”

Copper-Mediated Oxidative C−H/N−H Activations with Alkynes by Removable Hydrazides

“…The 3-methyleneisoindolin-1-one moiety represents key structure motif in natural products [20][21][22][23] or important pharmacophores [24]. In this context, You [25], Huang [26], Liu [27] and Jack Li [28] elegantly disclosed copper-mediated/catalyzed cascade C−H alkynylation and annulation with terminal alkyne to afford 3methyleneisoindolinone derivatives, through the assistance of 8-aminoquinoline [29] or 2-aminophnyl-1H-pyrazole [30] auxiliaries (Figure 1a). Besides, the cobalt(II) [31] or nickel(II) [32,33] catalyzed, pyridine oxide (PyO) directed tandem alkynylaiton/annulation were realized by Niu and Song, which also provided the 3-methyleneisoindolin-1-one scaffolds (Figure 1b).…”