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The decarboxylation reaction

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Original title: The decarboxylation reaction, which has been studied for more than 200 years, can become a hot spot again in this way. Previously, we introduced the recent progress in the study of photoredox-catalyzed C (sp 3) -H arylation reactions (). This kind of reaction mainly involves the formation of the corresponding carbon-centered radicals from the C (SP3) -H bond at the α-position of aliphatic compounds containing heteroatoms (N, O, S, etc.), such as aliphatic amines, ethers, thioethers, etc., by hydrogen atom transfer (HAT), followed by coupling with halogenated aromatic hydrocarbons in the presence of Ni catalyst to obtain the target products. What we are going to discuss today is also an arylation reaction, but through another way, the decarboxylation of aliphatic carboxylic acids produces radical active species, which further completes the subsequent transformation. Carboxylic acids are diverse and abundant in nature, and many of these compounds have been commercialized. Decarboxylation of these compounds as raw materials into other synthons is an effective strategy to obtain a variety of structural units. Throughout the development of organic chemistry research, decarboxylation reaction can be regarded as a classical chemical transformation. As Early as in 1849, German chemist Adolph Kolbe discovered that high-concentration CH3COONa solution could undergo decarboxylation dimerization by electrolysis to form C2H6, in which CH3COO- could be oxidized at the anode and eliminate one molecule of CO2 to form · CH3. The Kolbe electrolysis reaction was born by coupling two molecules of · CH3 to form the final product. Later, this method was extended to other higher aliphatic carboxylic acids, and even two different carboxylic acids were mixed to prepare more complex hydrocarbons. Reaction Mechanism of Kolbe Electrolysis Reaction (Image Source: Reference [2]) Another well-known decarboxylation reaction is the Hunsdiecker reaction. In 1861, Russian chemist A. Borodine mixed CH 3COOAg with Br 2, and a molecule of CO 2 was eliminated under heating to give the decarboxylated brominated product. Until 1942, German chemist H. Hunsdiecker further studied the reaction process, extended the substrates involved in the reaction to aliphatic carboxylic acids, which were converted to the corresponding silver salts and then introduced Br 2, and then heated to obtain brominated hydrocarbons with one carbon atom reduced. This decarboxylation and bromination process is not only suitable for aliphatic carboxylic acids such as alkyl and alkenyl, but also for some aromatic carboxylic acids. Br2 can be replaced by other halogen sources such as Cl2 and I2, and even more mild halogenation reagents such as BrCCl3 and CHI3 can be used to complete the above transformation after the reaction conditions are improved. Hunsdiecker reaction (Image: Reference [3]) In addition, Derek Barton, a British chemist, also developed a series of reactions named after him, including Barton's radical decarboxylation reaction. The reaction starts from the aliphatic carboxylic acid and is converted into the thiohydroxamic acid ester, and then decarboxylation reduction is carried out to obtain the alkane product. To this day, many people continue to study reactions involving decarboxylation processes using carboxylic acids as raw materials, and the discussion is increasing. Barton Radical Decarboxylation (Image: Reference [4]) Expand the full text From the reactions mentioned above, we can find that most of the carboxylic acid substrates are decarboxylated through the free radical pathway to produce the corresponding free radical intermediates, which then participate in the subsequent chemical transformation. Photoredox catalysis has also been developed with the vigorous revival of free radical chemistry in recent years, so people will also think of using this way to design decarboxylation reactions. In this issue, we will introduce the achievements in the research of photoredox-catalyzed decarboxylation and arylation of aliphatic carboxylic acids, the protagonist of which is still Professor David W. C. MacMillan of Princeton University in the United States. In 2014, Professor David W. C. MacMillan's team used Ir [p-F (t Bu) -ppy] 3 as a photoredox catalyst to realize the decarboxylation coupling of α-amino acids modified by N-Boc protecting groups with terephthalonitrile, and finally obtained benzylamine products. Both cyclic and acyclic α-amino acids can participate in the reaction, and the source of arylation can be replaced by other electron-withdrawing substituents (4-cyanobenzoic acid methyl ester, 4-cyanophenyl diethyl phosphite, etc.) Or even heteroaromatic nitriles. Decarboxylative coupling of N-Boc protecting group-modified α-amino acids with terephthalonitrile (Image source: Reference [6]) Substrate range for N-Boc protecting group-modified α-amino acids (Image source: Reference [6]) Range of substrates for aromatic nitriles (Image source: Reference [6]) The reaction involves an Ir III/Ir IV/Ir III catalytic cycle, and the decarboxylation of the alpha-amino acid is mainly completed through the following way: the alpha-amino acid 5 modified by an N-Boc protecting group is deprotonated under the action of alkali CsF, One-electron oxidation by Ir IV photoredox-catalyzed active species gives the carboxyl radical intermediate, which is then rapidly decarboxylated (eliminating one molecule of CO2) to form the α-amino radical 6. 6 is further combined with aromatic nitrile free radical anion to obtain the target product. Possible catalytic cycles for the reaction (Image: Ref. [6]) In the same year, they cooperated with Professor Abigail G. Doyle of Princeton University in the United States, using NiCl2 coordinated by 4,4 '-di-tert-butyl-2, decarboxylation after extraction ,jacketed glass reactor,2' -bipyridine (dtbbpy) as a transition metal catalyst. Ir [dF (CF 3) ppy] 2 (dtbbpy) PF 6 was used as a photoredox catalyst to realize the decarboxylation coupling of N-Boc protecting group-modified α-amino acids with halogenated aromatic hydrocarbons. Ni/photoredox-catalyzed decarboxylation coupling of N-Boc protecting group-modified α-amino acids with halogenated aromatic hydrocarbons (Image source: Reference [7]) This dual catalytic system has also been seen in previous articles (see recommended reading at the end of this article [1] [2]), and in fact, the combination of Ni catalysts with photoredox catalysts to design C-C bond coupling reactions began with this work. The process of α-amino acid decarboxylation to form α-amino radical 4 is similar to the previous reaction, and 4 can be further coupled with bromine and iodobenzene through C (sp 3) -C (sp 2) bonds in the presence of Ni catalyst, thus obtaining decarboxylation arylation products. In addition, halogenated heteroaromatics can also be used as the source of arylation. Because of the low electron density of the aromatic ring of pyridine and pyrimidine, the corresponding chlorinated compounds also have good reactivity. The catalytic cycle involved in the dual catalytic system (Image source: Reference [7]) In 2016, Professor of David W. C. MacMillan cooperated with Professor of Gregory C. Fu of California Institute of Technology (California Institute of Technology). Chiral bisoxazoline ligand 6 modified NiCl2 was used as a transition metal catalyst. Based on the above biscatalytic system, the asymmetric decarboxylation coupling of N-Boc protected α-amino acids with bromoaromatic (hetero) hydrocarbons was designed, and chiral benzylamines were obtained with good enantioselectivity. Tetrabutylammonium iodide (TBAI) was used as an additive to increase the reaction rate. Asymmetric Decarboxylation Coupling of N-Boc Protecting Group Modified α-Amino Acids with Brominated (Hetero) Aromatic Hydrocarbons (Image Source: Reference [8]) In order to demonstrate the practical value of this method, they also synthesized two chiral benzylamines 7, 8, 7 and 8 from leucine modified by N-Boc protecting group, which can be used to obtain two bioactive molecules through C-C bond coupling of amide and Buchwald-Hartwig amination, respectively. Application of Asymmetric Decarboxylation Coupling to Chiral Benzylamine (Image Source: Reference [8]) Another work also involves the decarboxylation process, but the reaction materials are different. Professor David W. C. MacMillan also cleverly used oxalyl chloride to condense with alcohol to obtain the corresponding oxalyl monoester, which could be directly used in decarboxylation coupling reaction without purification, and could realize C (sp 3) -C (sp 2) bond coupling with bromoaromatic hydrocarbons by means of Ni/photoredox dual-catalytic system. In the meantime, oxalic acid monoester needs to eliminate two molecules of CO2 to form alkyl radicals. Decarboxylative coupling of oxalic acid monoesters with brominated aromatic hydrocarbons (Image source: Ref. [9]) These are the main works of photoredox-catalyzed decarboxylation and arylation of aliphatic carboxylic acids in recent years. At this point, you may ask, what is the advantage of photoredox catalytic system compared with the previous electrochemical and thermal reaction mode of decarboxylation process? The answer, of course, is that the reaction conditions are milder and the decarboxylation can proceed smoothly at room temperature, thus further expanding the scope of application of the substrate. In addition, with the development of transition metal-catalyzed reactions, the cross-coupling process is no longer limited to C-C bonds, C-N, C-O and C-X (X = Cl, Br, I) bonds and other coupling reactions have been reported, which means that in addition to the decarboxylation described in this paper, more other types of transformations can be achieved by combining photoredox catalysts with transition metal catalysts. I will continue to discuss this in subsequent articles. [1] C (SP3) -H bond activation: another window can be opened by closing the door of the directing group [2] Sp3-hybridized C-C bond coupling is too difficult? It is recommended that you use this method taught by MacMillan. References [1] Jonathan D. Bell et al., Recent advances in visible light-activated radical coupling reactions triggered by (i) ruthenium, (ii) iridium and (iii) organic photoredox agents. Chem. Soc. Rev. 2021, 50 , 9540. [2] A. K. Vijh et al., Electrode Kinetic Aspects of the Kolbe Reaction. Chem. Rev. 1967, 67 , 623. [3] Robert G. Johnson et al., The Degradation Of Carboxylic Acid Salts By Means Of Halogen - The Hunsdiecker Reaction. Chem. Rev. 1956, 56 , 219. [4] László Kürti, Barbara Czakó. Strategic Applications of Named Reactions in Organic Synthesis [M]: Elsevier, 2005. [5] Derek H. R. Barton et al., The invention of new radical chain reactions. Part VIII. Radical chemistry of thiohydroxamic esters; A new method for the generation of carbon radicals from carboxylic acids. Tetrahedron 1985, 41 , 3901. [6] Zhiwei Zuo et al., Decarboxylative Arylation of α-Amino Acids via Photoredox Catalysis: A One-Step Conversion of Biomass to Drug Pharmacophore. J. Am. Chem. Soc. 2014, 136 , 5257. [7] Zhiwei Zuo et al., Merging photoredox with nickel catalysis: Coupling of α-carboxyl sp 3 -carbons with aryl halides. Science 2014, 345 , 437. [8] Zhiwei Zuo et al., Enantioselective Decarboxylative Arylation of α-Amino Acids via the Merger of Photoredox and Nickel Catalysis. J. Am. Chem. Soc. 2016, 138 , 1832. [9] Xiaheng Zhang et al., Alcohols as Latent Coupling Fragments for Metallaphotoredox Catalysis: sp 3 -sp 2 Cross-Coupling of Oxalates with Aryl Halides. J. Am. Chem. Soc. 2016,wiped film evaporator, 138 , 13862. Return to Sohu , see more Responsible Editor:


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