2009 级 专业：无机化学 姓名：孙静 学号：2009000647 专业： 姓名： 学号：
Investigation on carbon-carbon bond forming
Abstract: Carboxylic acid and carboxyl functional groups present in various ty
organic compounds in a wide range. Active functional groups of carboxylic acid derivatives in the conversion and building C-C bond occupies a very important position. Carboxyl-containing compounds have the characteristics of cheap and easily prepared by decarboxylation to form a new C-C bonds for organic synthesis provides a new reaction pathway. Decarboxylation reaction is highly selective and the main by-products of carbon dioxide, so by decarboxylation to build a new chemical bond is a cheap, environmental friendly synthetic route. A mechanistically unprecedented transition-metal-catalyzed cross-coupling of thioesters with boronic acids to produce ketones under neutral conditions, Cu is a key metal in new pH-neutral, desulfitative carbon-carbon bond forming processes that take palce between thioorganic substrates and boronic acids or organostannanes.
1 2 3 4 5 6 7 8 Introduction Decarboxylative cross-coupling reaction Decarboxylative Heck-type reaction Decarboxylative allylation Decarboxylative aldol and Mannich reaction Decarboxylative Claisen rearrangement reaction Decarboxylative addition Conclusion and outlook
Carbon-carbon bond formation and the conversion of functional groups, Simple small molecules can be made into complex molecules, C-C bond formation reaction has been the focus of organic chemistry research. In the past few decades, transition metal-catalyzed coupling reaction has become to build new C-C bond of the most effective way[1-4]. A large number of transition metal catalyzed carbon-carbon bond formation reaction has been developed, including: Suzuki-Miyaura, Negishi, Still, Kumada and so on. Suzuki-Miyaura reaction which is widely used in organic synthetic chemistry, especially small and medium-volume laboratory synthesis of chemicals. Based on previous literatures, in 2000, Liebeskind and Srogl described a mechanistically unprecedented transition-metal-catalyzed cross-coupling of thioesters with boronic acids to produce ketones under neutral conditions. In this Minireview, we highlight recent applications of this intriguing cross-coupling reaction in modern organic synthesis, with an emphasis on cases in which traditional methods for C-C bond formation have failed. Based on this, the first generation and the second generation about C-C bond forming catalysis in the presence of thiolate are reported, and we are searching the way which is predominant. A common feature of these reactions is that you need to activate the substrate in the reaction, usually converted to organic metal compounds, the chemical equivalent of the metal needs to consume, while you get the product, you will also have a lot of metal waste. From an environmental point of view, these reactions do not meet the requirements of green chemistry. So Organic chemists have been looking for other effective ways of generating new carbon-carbon bond and avoid the use of chemical equivalent of the metal. Such as the rise of C-C bond formation reaction in recent years based on C-H activation, which provides a new way for the synthesis of new C-C bond[7-9]. The reaction of these substrates do not need to be functional, but based on the C-H activation, this C-C bond formation method is difficult to face the controlled and selective reactivity and low challenges, through groups such as decarboxylation to generate new C-C bond provides another option. Carboxylic acid or organic molecules in one of the most common functional groups, carboxylic acid compounds had a lot of large-scale industrial production. If necessary, they can be easily prepared by other groups, and many methods have been very mature, such as aromatic carboxylic acids with side chains by aromatic compounds easily prepared by oxidation[10,11] And
can use oxygen as a green oxidant, as the water main by-product, because of these characteristics of carboxylic acids, Carboxylic acid used in organic synthesis as a promising starting material. Carboxylic acid compounds can be easily converted into other derivatives, such as ester, chloride, anhydride, can be very easy to reduction reaction occurs to produce the corresponding alcohol, in no time it can also be removed by decarboxylation. Carboxylic acid in the catalyst can occur under many types of conversion reaction, according to the location of reaction can be broadly grouped into the following four categories(Scheme 1):
The first type of reaction: After the O-H bond broke, caboxylic acid as a whole in response, such as carboxylic acid and acetylene addition reaction catalyzed acrylate. The second type of reaction: Carboxylate ions and metal coordination catalyst decarboxylation occurs to form an organic metal intermediates. Organometallic intermediates that can be reaction of hydrogen protons in the reaction of the corresponding alkanes or aromatics, which is commonly referred to as decarboxylation; It can also occur further and olefin Heck reaction or coupling reaction occurs with alkyl halides to generate a new C-C bond. Such decarboxylation reactions often require very stringent reaction conditions, but also use chemical equivalents of metal such as silver or copper, mercury at high temperatures. After decarboxylation reaction, system is easy to make action with hydrogen protons to form the corresponding alkanes and aromatic compounds, it is generally difficult to be captured for further transformation. So in most cases, the decarboxylation reaction is just to remove the excess carboxyl groups as a response, there are very few successful examples used to build the new C-C bond. Until recent
years based on decarboxylation of C-C bond formation reaction has made significant breakthroughs in the field. The third type of reaction: Carboxylic acid derivatives into a more lively, such as ester or amide anhydride chloride, then place C-O single bond breaking reaction of acyl intermediates. Acyl intermediate can be of further acylation reaction, and with boric acid compounds to product such as ketones, and can occur aldehyde by hydrogenation reaction with the reducing agent. The fourth type of reaction: This type of reaction is based on the third one, in the catalyst, acyl carbonyl compounds take off the carbonyl to form an organic metal intermediates, The intermediates and olefins can occur Heck reaction, and can also occur coupling reaction with other nucleophiles such as the occurrence of organic boric acid to generate a new C-C bond. With the continuous development of the transition metal catalyzed reactions and the constant discovery of new catalyst system, efficient and high-selective decarboxylation could become very real and possible. In recent years a large number based on decarboxylation of C-C bond and C-reactive hybrid bond was reported out of paper, the catalytic decarboxylation of the past few years a new method to generate some C-C bond to make a simple overview of research, and in accordance with reaction type classification.
2. Decarboxylative cross-coupling reaction
Miyaura-Suzuki reaction is one of the most common methonds to generate C-C bond, especially in the laboratory. The reaction is very convenient and need mild conditions, but the reaction requires the use of chemical equivalent of organic boric acid compounds as raw materials, expensive, and boric acid compounds difficult to save. These shortcomings in the response to the application in industrial production has been greatly limited. As early as 1966, Nilsson trid on the coupling reaction of decarboxylation, they found that o-nitro benzoic acid and the chemical equivalent of cuprous iodide carboxyl off at a high temperature reaction of organometallic intermediates are formed that can be captured and further reaction with iodobenzene to biphenyl (Scheme 2). However, the extremely harsh conditions of the reaction, the reaction temperature up to 250 ℃, need to use expensive iodo compounds as reactants, and less than 20% yield. These shortcomings greatly limit the type of reactions in organic synthesis.
Until 2006, Goossen research study group and Bilodeau groups almost simultaneously discovered the high rate of decarboxylation coupling method. Goossen and his collaborators’ idea is the use of bimetallic catalysts: copper and palladium together to achieve the target response (Scheme 3)[18,19].
They used copper and palladium bimetallic catalyst system is mainly based on the following reasons: Copper is the most commonly used and very cheap decarboxylation catalyst, and palladium coupling reaction is the most commonly used transition metal catalysts. Two metals in such reactions in the division of labor is different: copper mainly involved in decarboxylation, copper and carboxylic acid take off carboxylic by heating, in the non-proton solvent under the conditions of the formation of organic copper intermediates; palladium and halogenated Suzuki reaction occurred with a similar oxidative addition and reductive elimination reaction, the two metals together with the coupling reaction to complete decarboxylation. O-nitro benzoic acid and Bromo-chloro-benzene were chosen as model substrate (Scheme 4), mainly based on the following considerations: the introduction of the ortho-carboxyl strong electron-withdrawing nitro group can make it easier for decarboxylation; coupling product of 2 - nitro -4-- PCBs is an important intermediate for synthetic pesticides Boscalid.
The study found that the N-methyl pyrrolidone (NMP) as solvent, Pd (acac)
isopropyl diphenyl phosphine as a ligand, potassium fluoride (KF) as a base, using 1.5 equivalent of copper carbonate in the lower temperature (120 ℃) corresponding biphenyl compound. However, from the environmental and cost point of view that the reaction is far from perfect, because the reaction requires the use of chemical equivalent of toxic heavy metals copper and potassium fluoride reagents, the reaction conditions need to be further optimized. By re-screening of a large number, a new catalytic system was found (Scheme 5), Re-optimized reaction conditions using only 1 mol% of palladium acetylacetonate (Pd (acac) 2) and 3mol% of cuprous iodide, using 5mol% of the 1,10 - phenanthroline as a ligand, potassium carbonate as base. Since the reactants are very cheap and only use of catalytic amount of palladium and copper transition metal catalyst, so the reaction has great value for industrial applications.
Further research found that if the catalyst system in a small amount of phosphine ligand as a common, low-reactivity can also be chlorinated benzene and the carboxylic acid coupling decarboxylation reaction occurs. With this dual metal / dual-ligand catalyst system, low aromatic and chlorinated benzene carboxylic acid decarboxylation coupling reaction occurs, you can get high yields biphenyl compounds. The reaction also can occur trifluoromethanesulfonate compounds decarboxylation coupling reaction, the same can be synthesized in high yield biphenyl compounds (Scheme 6).
Moreover, Goossen also found that the use of α-keto acid as the reactants, through decarboxylation reactions can occur and halogenated aromatic coupling reaction synthesis of the corresponding diaryl acetone (Scheme 7). The reaction mechanism and reaction conditions are the same as the decarboxylation of aromatic acids, also use double-metal catalyst system and 1,10 phenanthroline / phosphine ligand dual system. Off by the copper catalyst to form aromatic carboxylic acyl, then place in the palladium-catalyzed coupling reaction. For the reaction of phosphine ligands yield a significant effect, 3 - (o - tolyl) phosphine showed the best reactivity. The discovery of the reaction for the synthesis of double-aryl ketones provides a new way.
Goossen found in other copper and bimetallic palladium-catalyzed coupling reaction of decarboxylation, at the same time, Forgione and Bilodeau et al accidentally discovered heterocyclic carboxylic acid compounds (including pyrrole, furan, thiophene and thiazole, etc.) and the palladium catalyst Bromo-decarboxylation coupling reaction occurred (Scheme 9). The reaction using palladium as a catalyst, cesium carbonate as base, tetrabutylammonium chloride as an additive, the equivalent of twice the heterocyclic carboxylic acid at 170 ℃ in a microwave reactor reaction 8min, biphenyl compounds in 23% yield -88%. Possible reaction mechanism is: the first and brominated aromatic compounds, palladium oxidative addition, followed by palladium in heterocyclic carboxylic acid of 3 to electrophilic addition, after decarboxylation and reductive elimination step has been the target coupling product, while releasing catalyst.
Crabtree et al found that the use of microwave reactor as a catalyst of palladium acetate, o-no electron-withdrawing groups of non-complex aromatic acid and iodine benzene compounds can also occur decarboxylation coupling reaction, the product of medium yield to be diphenyl more importantly, after decarboxylation to form organometallic intermediates can also be directly and C-H bond by the reaction of new biphenyl compounds. The decarboxylation reaction and C-H activation of organically combined. But the response is also very obvious shortcomings: the need for expensive and the use of chemical equivalent of silver carbonate as base, the reaction temperature up to 200 ℃, the yield of less than 50%, and the reaction regioselectivity is not very good, get a number of products ( scheme 10).
Similarly, Glorius et al developed a class of molecule-based carboxyl and C-H bond of the direct coupling decarboxylation reaction (Scheme 11).
The reaction conditions mentioned above is slightly different, the reaction system only added 5 mol% of DMSO, using conventional heating at 150 ℃ reaction. The target product yield of double-benzofuran up to 85% and selectivity increased significantly. For the reaction
mechanism is generally believed that the first decarboxylation to form carbonic acid in the organic silver silver and then through the metal exchange reaction intermediates (transmetallation) and C-H activation step, and finally reductive elimination reaction by the target product, while releasing Pd0, Pd0 be silver carbonate oxidation of Pd order to achieve the cycle (Scheme 12).
re-involved in the reaction, the catalyst in
In most cases, decarboxylation reactions are coupled need to use the precious metal palladium as a catalyst. Fu Yao and Liu Lei research group recently found a need to use the decarboxylation catalyst of palladium metal coupling reaction. Fluorinated aromatic acids, especially full-fluorinated aromatic acid in the CuI and 1,10 - phenanthroline catalytic next generation of aromatic compounds with iodine bromide or decarboxylation of aromatic compounds, biphenyl coupling reaction, the reaction at 130 ℃ can be smooth (Scheme 13).
The study found that the choice of solvent on the reaction yield have a critical influence, the best solvent is diethylene glycol dimethyl ether (diglyme), reaction yield of 99%. However, for non-full-fluorinated aromatic acid decarboxylation reactions coupling is more difficult, even if the reaction temperature to 150-160 ℃, reaction yields are still significantly lower, such as 2 fluoro-coupled decarboxylation of benzoic acid reactions have little access to the target product. Therefore, the method is mainly applied in the carboxyl containing two ortho-fluorine atoms of aromatic acid decarboxylation coupling reaction.
Decarboxylation mentioned earlier, most of the use of coupling reactions with aromatic acid or electron-withdrawing group of fatty acids, mainly the product of biphenyl compounds; and decarboxylation of fatty acids based on relatively few studies coupling reaction. Chao-Jun Li et al found a proline derivatives based on coupling decarboxylation reaction (Scheme 14).
3. Decarboxylative Heck-type reaction
Heck reaction is an important class of the formation of unsaturated double C-C bond formation reaction by Mizoroki and Heck, respectively in 1971 and 1972 found. Heck reaction usually halogenated aromatics and electron-containing α-olefin group in the palladium-catalyzed reaction of aromatic generation of olefins, in the past 30 years has evolved into a widely used in building the new C-C bond synthesis (type 3)
In 2002, Myers et al[28?30] reported that a decarboxylation Heck coupling reaction of halogenated aromatic raw materials were replaced by aromatic carboxylic acid (Scheme 15).
Recently, Li et al reported a intramolecular Heck reaction of decarboxylation, the conversion of synthesis through a series of complex multi-ring compounds, but the key step is the formation of organometallic intermediates after decarboxylation and then through the Heck type of reaction (Scheme 16).
4. Decarboxylative allylation
Allylation especially carbonyl allylation reaction is a very important class of C-C bond formation reaction, the addition product is an important intermediate in organic synthesis. General reaction mechanism of these reactions is shown in Scheme 17. First, the metal catalyst (in most cases the use of palladium as a catalyst) into the C-O ester in touch, then remove part of CO2, the formation of organometallic intermediates R1-M-R2, the final product obtained after reductive elimination and release the metal catalyst.
Tunge, etc. as early as this method is used to Csp-Csp3 decarboxylation allylation (Scheme 18). Esters (with alkynyl side, the side with allyl) in toluene solvent, using Pd (PPh3) 4 as catalyst, 75 ℃ response 2h, you can get the target product, the only reaction by-product is carbon dioxide .
5. Decarboxylative aldol and Mannich reaction
Aldol Reaction and Mannich reaction are important C-C bond formation methods, which are through the C-O and C-N nucleophilic addition to build a wide variety of organic molecules. Shair et al to maleic acid ester as raw material of a single sulfur-based decarboxylation of the aldol reaction, they tried a variety of metal catalysts such as Mg (Ⅱ), Zn (Ⅱ), Ni (Ⅱ) and Cu (Ⅰ) and imidazole complexes, but are not able to get the product. When using other equivalent of Cu (OAc) 2 and imidazole complexes as a catalyst to get a small amount of target product. Further optimize the reaction showed that Cu (2 - ethylhexanoate) 2 (2-ethylhexyl acid copper) / 5 - methoxy benzimidazole catalytic system has the best catalytic activity (Scheme 19).
In most cases, the decarboxylation reaction requires adding metal catalysts, especially transition metal catalyst to obtain a higher yield, in the absence of metal catalyst reaction conditions are usually difficult. Decarboxylation reaction can be used in aldol addition reactions and outside the Mannich reaction. Shibasaki et al reported the use of copper and a chiral phosphine complexes as catalysts for decarboxylation Asymmetric Mannich type reaction (Scheme 20). Studies have shown that the reaction mechanism is: the decarboxylation reaction of copper in a nucleophilic carbon, chiral catalysts in place of the imine induced nucleophilic addition reaction, to afford the target product.
6. Decarboxylative Claisen rearrangement reaction
Claisen rearrangement is a class of reactions based on intramolecular migration, usually occurs in the molecular structure with the allyl ether. Since 1972 has been found, a large number of Claisen rearrangement was reported out, and now the response is still synthesis of new C-C bond is one effective method. Craig et al reported by the decarboxylation of a Claisen rearrangement (Scheme 21). Allyl ester with the structure of organic silicon substrate in the reagent BSA (N, O-double top three silicon-acetamide) and under the action of alkali at room temperature decarboxylation Claisen rearrangement reaction occurs (Ts is tosyl). Reaction mechanism is as follows: the substrate under the action of alkali and silicon reagent to form enol transition state, enolase occur [3,3] migration reaction, after decarboxylation reaction and the reaction of silicon reagents to leave the target product.
7. Decarboxylative addition
Rhodium metal is a commonly used transition metal catalysts, are widely used C-C bond formation reaction and hydrogenation of unsaturated bonds. Rhodium-catalyzed organic acid reagent for unsaturated bond conjugate addition can be carried out under mild conditions, the reaction has high regioselectivity and enantioselectivity. Zhao et al reported a rhodium-based catalyst of the decarboxylation conjugate addition (Scheme 22).
The reaction in strong alkaline conditions, the presence of sodium hydroxide to BIPHEP [2, 2'-bis (diphenylphosphanyl) -1, 1'-biphenyl] as ligand, in toluene 120 ℃ to react. The reaction is
mainly applied to ortho with electron-withdrawing groups such as the aromatic carboxylic acid fluoride substrate, the reaction with high regioselectivity. The reaction is generally believed that the key to the smooth conduct because of the formation of carboxylic acid with a rhodium catalyst activity of the complex (Scheme 23). With electron-donating ortho-methoxy groups such as carboxylic acids can also react, but did not replace the base substrate, such as benzoic acid decarboxylation addition reaction can not occur.
8. Conclusion and outlook
Currently most use for decarboxylation of C-C bond formation reaction, in other types of reactions, such as C-S bond formation reaction and C-O bond formation reaction has also been applied. Carboxylic acid and its derivatives (such as acetate, chloride, acid anhydride) is a class of easily prepared, inexpensive synthetic organic materials. Through off carboxyl (CO2) can be an effective aryl, alkyl, acyl source. Decarboxylation of the main by-products of carbon dioxide, which is a pollution of organic synthesis. These features make the decarboxylation reaction aroused, especially in green chemistry research scientists' attention. In the past few years, a large number of synthetic methods based on decarboxylation reactions have been reported out. Decarboxylation coupling reaction has proven to be an effective method of carbon-carbon bond formation, but only a few years ago the idea was considered impossible to achieve. With the application of new catalyst, decarboxylation reaction conditions more moderate response to increasing yield and selectivity, the reaction substrate more extensive range of applications. I believe in the near future, based on decarboxylation of carbon-carbon bond formation reaction will be more complete, more and more will be used in organic synthesis decarboxylation.
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