Brønsted acid catalyzed ortho-amination of azonaphthalene Brønsted酸催化的2-萘偶氮邻位胺化反应

Chen，Yiwei; Da，Bing Chao; Tan，Bin

2021-09-01

10.1360/TB-2020-1697

Chinese Science Bulletin-Chinese   影响因子和分区

0023-074X

2095-9419

Because of the unique molecular structure as well as physical and chemical properties, organic compounds containing the N-arylcarbazole moiety exhibit significant potential in functional organic light-emitting diode (OLED) materials and the pharmaceutical chemistry domain. The direct construction of a C-N bond through cross-coupling reactions is undoubtedly the most effective way to synthesize N-arylcarbazole moieties. Conventional transition-metal-catalyzed cross-coupling reactions, including Ullmann, Buchwald-Hartwig, and Chan-Lam-Evans couplings, have become the most reliable and commonly used methodologies to construct C-N bonds directly. Nevertheless, there remain several unavoidable shortcomings of these practical protocols. For instance, functionalized aryl halides or aryl boronic acid substrates need to be preprepared, which may be impossible with different functional groups. Besides, excessive waste production, including detrimental byproducts, also heavily hamper their efficiencies, and there would inevitably be the problem of heavy-metal residues. To overcome these disadvantages, reactions through C-H/N-H oxidative dehydrogenation coupling have become hot areas to accomplish the construction of C-N bonds. Thus, hypervalent iodine reagents or transition metals are utilized to promote the vital oxidative amination process. In addition, recently, novel photocatalysis and electrocatalysis strategies put forward by Nicewizc and Ackermann to establish amine-arene coupling has also drawn much attention. However, the abovementioned protocols still face many problems in terms of the additional oxidant, harsh reaction conditions, restricted substrate generality, etc. In contrast, organocatalyzed reactions have been well-developed, giving the advantages of mild reaction conditions, good functional group compatibility, and transition-metal-free catalyzed process. Therefore, the organocatalyzed C-H amination reaction is considered an ideal manner to build C-N bonds. However, the low reactivity of C-H bonds in organic molecules presents a great challenge to the development of this strategy in direct C-H amination reactions. Therefore, based on the aromatics polarity reversal strategy, we designed a substrate with a conjugated system to accomplish the rapid transformation of the high energy of Meisenheimer intermediates, and a Brønsted acid-catalyzed aromatic C-H amination pathway for efficient construction of N-arylcarbazoles was developed. This method features mild conditions, a high atom economy, and avoids the use of transition metals. In the exploration of this reaction system, a series of experiments on the organocatalysts, reaction temperature, reaction time, and other parameters was investigated in detail. The experimental results showed that the noncovalent interactions, including multiple hydrogen-bond interactions and π-π-stacking effect between the catalyst and substrates, played essential roles for the chemoselectivity of this transformation. After screening for the optimal reaction conditions, the substrate generality was evaluated with various substitutions on both azonaphthalenes and arylcarbazoles. As a whole, the substituents on the azonaphthalene ring exhibited good functional group compatibility, and the N-arylcarbazole compounds could be obtained with a good yield. The experimental results showed that the steric hindrance and electron cloud density on the N atom of arylcarbazole with different electron-withdrawing substituents would have a notable impact on the yield of the transformations, and basically, these substituent groups reduced the yield to some extent. When the 3,6-position of the carbazole substrate was replaced by an electron-donating group, the yield was obviously boosted, and the highest yield reached 96%. In contrast, when arylcarbazoles modified by an electron-withdrawing group were tested, only moderate yields of the desired products were obtained due to the lower electron cloud density on the nitrogen atom as well as its corresponding nucleophilicity. Moreover, the steric hindrance effect of the substituent on the carbazole presented a more obvious impact on the reactivity of the nucleophilicity when 1-bromocarbazole was chosen as the nucleophile that could not participate in the reaction even though the reaction temperature and amount of catalyst were greatly increased. Furthermore, 2-tert-butylcarbazole and 2-phenylcarbazole were initially chosen to evaluate the stereoselectivity of the reaction system, and finally, corresponding products with moderate yield and enantioselectivity were obtained.

Arylazo Brønsted acid C-H amination N-arylcarbazole

EI

中文

第一 ; 通讯

20213910941963

Amines ; Aromatic compounds ; Chemical bonds ; Dehydrogenation ; Electrocatalysis ; Heavy metals ; Organic light emitting diodes (OLED) ; Organocatalyst ; Reaction intermediates ; Substrates

Metallurgy and Metallography:531 ; Semiconductor Devices and Integrated Circuits:714.2 ; Physical Chemistry:801.4 ; Electrochemistry:801.4.1 ; Chemical Reactions:802.2 ; Chemical Agents and Basic Industrial Chemicals:803 ; Chemical Products Generally:804 ; Organic Compounds:804.1

2-s2.0-85115441985

Scopus

Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis,Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China

Chen，Yiwei,Da，Bing Chao,Tan，Bin. Brønsted acid catalyzed ortho-amination of azonaphthalene Brønsted酸催化的2-萘偶氮邻位胺化反应[J]. Chinese Science Bulletin-Chinese,2021,66(25):3325-3332.

Chen，Yiwei,Da，Bing Chao,&Tan，Bin.(2021).Brønsted acid catalyzed ortho-amination of azonaphthalene Brønsted酸催化的2-萘偶氮邻位胺化反应.Chinese Science Bulletin-Chinese,66(25),3325-3332.

Chen，Yiwei,et al."Brønsted acid catalyzed ortho-amination of azonaphthalene Brønsted酸催化的2-萘偶氮邻位胺化反应".Chinese Science Bulletin-Chinese 66.25(2021):3325-3332.