One-Pot Protocol To Synthesize 2-Aminophenols from Anilines via Palladium-Catalyzed C–H Acetoxylation

Abstract

This paper describes a facile one-pot protocol to synthesize 2-aminophenol derivatives via a palladium-catalyzed C−H acetoxylation strategy with 5-nitropyrimidine as a directing group (DG), which can be easily preinstalled and readily removed under mild condition after the coupling. In addition, the transformation is operationally simple, has high functional group tolerance, and is amenable to gram-scale. Moreover, several examples were shown that introduction/removal of 5nitropyrimidine and the C−H oxylation sequence could be integrated in one pot.

An Easy Access to Pyrogallol Derivatives Using a Practical Auxiliary

“…Gratifyingly, various substituent at para-position of the phenyl ring could deliver the final product.The halo-substituted (F, Cl, Br, I) phenol were well tolerated under the standard conditions (2 e-2 h, 57 %-58 % yields), allowing them for further transformation via transition-metal catalyzed CÀ C or C-heteroatom formation reactions. [13] At the same time, it is obvious that phenol with an electron-donating group on the benzene ring performed slightly better than the ones with an electron-withdrawing group.Substrates with an electron-withdrawing group, such as MeOOC-, -OCF 3 groups, afforded the desired products (2 i, 59 %, 2 j, 60 %) in low yield than those of phenols with electrondonating group, such as t-Bu, -OMe groups (2 c, 70 %, 2 d, 66 %).We found that the substrates with -Ph and -OPh at paraposition could also gave the desired products in moderate yields, 50 %, 55 % respectively. Furthermore, we have found that the synthetic outcomes could be well controlled by using different amount of the PhI (OAC) 2 .When 1.1 equiv.…”

“…For instance, phenol with a methyl group on the meta‐ position gave the corresponding product 2 b in 59 %, while the para ‐position with a tertiary butyl product 2 c were afforded in 70 % yield.These results showed that sterically hindered substituents on the phenol have a negative effect on the reaction yield. Gratifyingly, various substituent at para‐position of the phenyl ring could deliver the final product.The halo‐substituted (F, Cl, Br, I) phenol were well tolerated under the standard conditions ( 2 e – 2 h , 57 %‐58 % yields), allowing them for further transformation via transition‐metal catalyzed C−C or C‐heteroatom formation reactions [13] . At the same time, it is obvious that phenol with an electron‐donating group on the benzene ring performed slightly better than the ones with an electron‐withdrawing group.Substrates with an electron‐withdrawing group, such as MeOOC‐, ‐OCF 3 groups, afforded the desired products ( 2 i , 59 %, 2 j , 60 %) in low yield than those of phenols with electron‐donating group, such as t ‐Bu, ‐OMe groups ( 2 c , 70 %, 2 d , 66 %).We found that the substrates with ‐Ph and ‐OPh at para‐position could also gave the desired products in moderate yields, 50 %, 55 % respectively.…”

“…2) Readily removal of DG to obtain pyrogallol products under mild conditions. Our group has recently disclosed a Pd‐catalyzed C−H acetoxylation of aniline substrates, leading to the facile formation of a wide range of 2‐aminophenols and derivatives [13] . As part of our ongoing efforts for the development of efficient protocols in C−H functionalization of arenes, [14] we herein reported a practical method for preparation of pyrogallol derivatives through Pd‐catalyzed C−H acetoxylation assisted by directing group 5‐nitropyrimidine.…”

“…Our group has recently disclosed a Pd-catalyzed CÀ H acetoxylation of aniline substrates, leading to the facile formation of a wide range of 2aminophenols and derivatives. [13] As part of our ongoing efforts for the development of efficient protocols in CÀ H functionalization of arenes, [14] we herein reported a practical method for preparation of pyrogallol derivatives through Pd-catalyzed CÀ H acetoxylation assisted by directing group 5-nitropyrimidine. Our initial work was characterized by step-economic that the DG introduction/CÀ H functionalization, as well as the elimination of practical auxiliary, 5-nitropyrimidine, were successfullycombined in one step under mild condition.…”

Development of New Meridianin/Leucettine-Derived Hybrid Small Molecules as Nanomolar Multi-Kinase Inhibitors with Antitumor Activity

“…Moreover, overexpression of various types of protein kinases is found in different types of cancer, which encouraged medicinal chemists worldwide to develop numerous receptor tyrosine kinases inhibitors (RTKIs). In addition, the advent of protein kinase inhibitors in cancer research and therapy has led to a paradigm shift in how cancer is currently treated [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. As a result, the FDA has approved many protein kinase inhibitors in the last few decades.…”