Li Yang research group of Xi'an Jiaotong University: visible light catalyzed decarboxylation and dehydrogenation of heteroaromatics and carboxylic acids

The author of this paper: Li Yang, a researcher in the research group, has paid more attention to the decarboxylation of carboxylic acids, which are cheap, non-toxic and relatively stable Decarboxylation Minisci reaction has been reported as early as 1870's (Fig 1, EQ 1) Visible light induced catalysis has also been used in decarboxylation Minisci reaction due to its green, mild and other characteristics (Fig 1, EQ 1-2) In these transformations, equivalent strong oxidants or pre activation of carboxylic acids are needed Recently, Professor Ackermann's research group reported that visible light induced catalytic decarboxylation of adamantane formic acid was Minisci reaction By releasing hydrogen, the use of equivalent oxidant was avoided, but three equivalent bases were added to promote conversion (Fig 1, EQ 3) Li Yang, researcher group of Xi'an Jiaotong University, is committed to the research of hydrogen catalytic system and carboxylic acid conversion (org Lett 2016, 18, 2840-2843; angel Chem Int ed 2017, 56, 3080-3084; angel Chem Int ed 2017, 56, 13809-13813; org Lett 2018, 20, 1421-1425; nature catalyst, 2018, 1, 332-338) Recently, the research group has developed a visible light induced Minisci reaction for decarboxylation of alkylcarboxylic acids (Fig 1, EQ 4) By releasing hydrogen and CO2, the use of oxidants is avoided, and only 0.3 equivalent base is needed, which provides an efficient way for arylheterocycloalkylation (Fig 1, EQ 4) Relevant research results were published in org Lett (DOI: 10.1021/acs.orglett 9b0539) The first authors of the research work are Dr Tian Wanfa (now working in Jiangxi Normal University of science and Technology) and Dr Hu Chunhong The corresponding author is Li Yang, researcher of Xi'an Jiaotong University Figure 1 Decarboxylation Minisci alkylation reaction (source: org Lett.) firstly, the author explored the reaction conditions with benzothiazole and adamantanic acid as substrates By optimizing the conditions, the author found that the target product can be obtained with 92% separation yield with 1 mol% IR [DF (CF 3) PPy] 2 (dtbbpy) pf 6 as photosensitizer, 3 mol% CO (dmgh) 2PY 2] pf 6 as proton reduction catalyst and 0.3 equivalent n-Bu 4 noac as base It was found that a series of heteroaryl derivatives, such as thiazole, oxazole, imidazole, benzofuran, thiophene, phenanthridine and so on, could be successfully obtained Halogen, aldehyde, cyano and other functional groups can also be compatible in the system (Fig 2) Fig 2 Heteroaryl ring substrate expansion (source: org Lett.) after that, the author investigated the substrate range of various alkyl carboxylic acids (Fig 3), and found that the third-order and the second-order and the first-order carboxylic acids with heteroatom activation in the neighborhood had better reaction effect In addition, good yield was also obtained Figure 3 Carboxylic acid substrate expansion (source: org Lett.) finally, the reaction mechanism was studied When tempo or BHT were added to the system, the reaction was completely inhibited When 2p is used as the substrate, ring opening products are detected in the reaction, which further supports that the catalytic process involves free radical reaction process (Fig 4) Figure 4 Mechanism study (source: org Lett.) further through UV-Vis absorption, fluorescence quenching experiment (Figure 5), quantum yield calculation and measurement of redox potential, the author proposed two possible reaction paths (Figure 6) In the light condition, the photosensitizer is excited to obtain excited state * IR III, and the excited state photosensitizer is reduced and quenched by carboxyl anion 4 to obtain IR II and carboxyl radical 5 5 and then remove CO 2 to obtain alkyl radical 6 The final target product 3AA was obtained by nucleophilic substitution of heteroaromatic ring The single electron transfer between IR II and co III resulted in re generation of IR III and co II species at the same time Co II continues to get an electron to produce CO I, while combining a proton to produce a Co-H species The Co-H species combines with another proton to generate hydrogen and returns to co III (path a) Another possible way is that the excited photosensitizer, IR III, is oxidized and quenched by CO III to produce IR IV and co II The single electron transfer between IR IV and carboxyl anion 4 returns to IR II, and the alkyl radical 5 is formed at the same time Then the final target product is obtained by a similar way to path a and hydrogen (path B) is released Fig 5 UV-Vis absorption spectrum and fluorescence quenching curve (source: org Lett.) Fig 6 Possible reaction mechanism (source: org Lett.) Summary: the visible light-induced catalytic decarboxylation reaction does not need to add any oxidant, and the amount of alkali is reduced to 0.3 equivalent, which benefits from H 2 and CO 2 Direct release from the system In addition, the reaction conditions were mild, which showed good substrate and functional group adaptability, and achieved gram level reaction with high yield, which provided an efficient way for alkylation of heteroaromatic rings.