Carboxylation reactant, silyl alkyl carbonate compound, and carboxylated compound production method

Abstract

Provided are: a carboxylation reactant that includes a silyl alkyl carbonate compound represented by a specific formula; a silyl alkyl carbonate compound that is represented by a specific formula; and a carboxylated compound production method in which an aromatic compound or an organic boron compound and the aforementioned carboxylation reactant are reacted in the presence of fluoride anions.

Description

Carboxylation Reagent, Silyl Alkyl Carbonate Compound, and Method for Producing Carboxylated Compound

[0001] The present invention relates to a carboxylation reactant, a silyl alkyl carbonate compound, and a method for producing a carboxylated compound.

[0002] Carboxylic acid compounds containing an aromatic ring (also referred to as aromatic-containing carboxylic acid compounds) have important molecular structures as biologically active compounds or their precursors. For example, aromatic carboxylic acids such as aspirin and telmisartan, and aromatic ring-containing carboxylic acids such as atorvastatin are known as important pharmaceuticals. Therefore, there is a need for the development of a carboxylation reaction of organic molecules that can efficiently synthesize aromatic carboxylic acid compounds. In particular, attention has been focused on the development of a reaction system that targets readily available carbon-hydrogen bonds or carbon-boron bonds, rather than pre-functionalized bonds such as carbon-halogen bonds or carbon-metal bonds. Under these circumstances, the present inventors have been working on the development of a carboxylation reaction of carbon-hydrogen bonds using carbon dioxide as a one-carbon source, using complex Brønsted bases (LiO-t-Bu, CsF, 18-crown-6) (see, for example, Non-Patent Documents 4 to 7). As a result, for example, the carboxylation reaction of the carbon-hydrogen bond between the carbon atom and hydrogen atom constituting a (hetero)aromatic ring, and the dicarboxylation reaction of the carbon-hydrogen bond between the carbon atom and hydrogen atom constituting a 2-alkylheteroaromatic ring have been developed. Furthermore, as a method for synthesizing an aromatic-containing carboxylic acid by the carboxylation reaction of a carbon-boron bond, for example, a method in which a phenylboronic acid ester is reacted with carbon dioxide in the presence of a specific catalyst is also known (e.g., Non-Patent Document 3).

[0003] on the other hand, １２ Instead of C １３ Compounds having C ( １３ C-labeled compounds) are considered important for elucidating the mechanisms of in vivo or chemical reactions, especially for the above-mentioned biologically active compounds. １３ The importance of aromatic-containing carboxylic acid compounds with C introduced is great. １３ Methods for introducing C are being researched and developed. １３The C introduction method has problems such as low efficiency and the need for complex and advanced reaction processes. １３ There is a strong demand, particularly in the fields of medicine and agrochemicals, for the development of a chemical reactant that enables efficient and simple introduction of C into compounds. １３ Although chemical reactants capable of introducing C into compounds are expensive, the market is expanding rapidly. １３ Using potassium triphenylacetate (1-13) as a C-labeled compound １３ A method for introducing C into a compound has been proposed (Non-Patent Document 8). １３ Compared with C-labeled compounds １３ Since C-labeled carbon dioxide is inexpensive, the carboxylation reaction using carbon dioxide developed by the present inventors (Non-Patent Documents 4 to 7) can be used to １３ C can be introduced into the compound at a relatively low cost. １３ C-labeled carbon dioxide can be synthesized by the method described in Non-Patent Document 9, for example.

[0004] Silyl carbonate compounds (silicon-containing compounds) have been proposed as components to be added to non-aqueous electrolyte solutions for lithium ion batteries (e.g., Patent Documents 1 to 3). Also, silyl carbonate compounds such as tert-butyltrimethylsilyl carbonate are known as compounds for synthesizing silyl carbamates from amines (Non-Patent Documents 1 and 2).

[0005] US Patent Application Publication No. 2019 / 0348713 US Patent Application Publication No. 2020 / 0243905 JP Patent Publication No. 2022-529217

[0006] J. Org. Chem. , Vol. 36, No. 20, 1971, 2954-2956J. Org. Chem. , Vol. 38, No. 14, 1973, 2521-2525 Angew. Chem. Int. Ed. , 2008, 47, 5792-5795Chem. Eur. J. , 2019, 25, 3235-3239Org. Lett. , 2022, 24, 809-814Org. Lett. , 2022, 24, 4825-4830Org. Lett. , 2019, 21, 4515-4519 Angew. Chem. Int. Ed. , 2023, 62, e20221J. Am. Chem. Soc. ,2023,145,10451--10457

[0007] The carboxylation reaction method using carbon dioxide developed by the present inventors is advantageous in terms of reaction efficiency, etc. On the other hand, the carboxylation reaction method using gaseous carbon dioxide has room for improvement in terms of the ease of handling gaseous carbon dioxide, from the viewpoint of carrying out the carboxylation reaction with a simple operation. １３ Using C-labeled carbon dioxide １３ The same applies to the C introduction method.

[0008] The present invention provides a carboxylation reagent ( １３ C-labeled carboxylation reagents), and suitable silyl alkyl carbonate compounds ( １３ Another object of the present invention is to provide a method for producing a carboxylated compound using the above carboxylation reagent.

[0009] As described in Patent Documents 1 to 3 and Non-Patent Documents 1 and 2, the present inventors have focused on the fact that silyl alkyl carbonate compounds, which have conventionally been limited to use as additive components in non-aqueous electrolytes of secondary batteries, are generally liquid at room temperature and normal pressure (25°C, 0.1 MPa) and therefore have excellent handleability. As a result, they have continued to study the carboxylation reaction of carbon-hydrogen bonds and have found that, in the presence of a specific fluoride anion, the silyl alkyl carbonate compound activates the carbon-hydrogen bond and serves as a carboxy (-CO-O- group) source, thereby enabling the carboxylation of the carbon-hydrogen bond. Furthermore, the carbonyl carbon in the alkyl silyl carbonate compound １３ Replaced with C １３ By using C-labeled alkylsilyl carbonate compounds, carbon-hydrogen bonds can be １３ Furthermore, by selecting the catalyst used in the carboxylation reaction, it was found that the carbon-boron bond in the organoboron compound can be carboxylated ( １３ The present invention was completed through further investigations based on these findings.

[0010] The object of the present invention has been achieved by the following means: <1> A carboxylation reactant containing a silyl alkyl carbonate compound represented by the following formula (I): In formula (I), X is １２ C or １３ C indicates R １ ~R ３ represents an alkyl group or an aryl group, and R ４ represents an alkyl group. ４ <3> The carboxylation reagent according to <1>, wherein R represents a branched alkyl group. ４ -C(R ４Ａ ) ３ (R ４Ａ <4> The carboxylation reagent according to <1> or <2>, wherein R represents an alkyl group. １ ~R ３<5> A silyl alkyl carbonate compound represented by the following formula (II): In formula (II), X is １２ C or １３ Indicates C. R １１ ~R １３ represents an alkyl group or an aryl group, and R １４ represents an alkyl group. １２ If C, then R １１ ~R １３ At least one of R represents a branched alkyl group, and R １４ -C(R ４Ａ ) ３ (R ４Ａ represents an alkyl group containing an alkyl group. １２ When C, said R ４Ａ <7> The silyl alkyl carbonate compound according to <5>, wherein at least one of X represents an alkyl group having 2 or more carbon atoms. １３ When C, said R １１ ~R １３ At least one of R represents a branched alkyl group, or １４ is the -C(R ４Ａ ) ３ (R ４Ａ <8> A method for producing a carboxylated compound, comprising reacting an aromatic compound containing a carbon atom bonded to a hydrogen atom with the carboxylation reagent according to any one of <1> to <4> in the presence of a fluoride anion. <9> The method for producing a carboxylated compound according to <8>, wherein the aromatic compound is at least one selected from aromatic compounds containing a carbon atom bonded to a hydrogen atom as an aromatic ring-forming carbon atom and aromatic compounds having, as a substituent, an aliphatic group containing a carbon atom bonded to a hydrogen atom. <10> A method for producing a carboxylated compound, comprising reacting an organoboron compound with the carboxylation reagent according to any one of <1> to <4> in the presence of a fluoride anion. <11> The method for producing a carboxylated compound according to <10>, wherein the organoboron compound is a boronic acid ester.

[0011] The present invention provides a carboxylation reagent ( １３ C-labeled carboxylation reagents), and suitable silyl alkyl carbonate compounds ( １３ The present invention also provides a method for producing a carboxylated compound using the above-mentioned carboxylation reagent. The above and other features and advantages of the present invention will become more apparent from the following description.

[0012] In the present invention and this specification, the terms "carboxylation agent" and "silyl alkyl carbonate compound" respectively refer to compounds having a carbonyl carbon atom, unless otherwise specified. １３ Replaced with C " １３ C-labeled carboxylation reagent" and " １３ Unless otherwise specified, the term "carboxylation reaction" also includes "C-labeled silyl alkyl carbonate compound." １３ Furthermore, unless otherwise specified, the "method for producing a carboxylated compound" includes the following: １３ C-labeled carboxylation reagent １３ In the present invention and the present specification, １３ C-labeled compounds and １３ To clearly distinguish between compounds labeled with C and those not labeled with C, use the following: １３ C-labeled compound”, “ １３ C unlabeled compound (or １２ It is sometimes called "C compound". １３ C-unlabeled compounds are characterized by, for example, stable isotope ratios of naturally occurring carbon elements. １３ It may contain a C-labeled compound.

[0013] In the present invention and this specification, the silyl alkyl carbonate compound represented by formula (I) contained in the carboxylation reactant is a group of compounds including the silyl alkyl carbonate compound represented by formula (II), and unless otherwise specified, the silyl alkyl carbonate compounds represented by each formula are sometimes collectively referred to as the "silyl alkyl carbonate compounds of the present invention." When distinguishing between the two, the silyl alkyl carbonate compound represented by formula (I) is referred to as "silyl alkyl carbonate compound (I)," and the silyl alkyl carbonate compound represented by formula (II) is referred to as "silyl alkyl carbonate compound (II)." Furthermore, when formula (I) is mentioned, it is meant to include formula (II) unless otherwise specified.

[0014] In the present invention and this specification, a numerical range expressed using "to" means a range that includes the numerical values ​​written before and after "to" as the lower and upper limits. In this specification, when multiple numerical ranges are set in stages for the content of a component, physical properties, etc., the upper and lower limits that form the numerical range can be combined as appropriate.

[0015] [Carboxylation Reactant] The carboxylation reactant of the present invention contains one or more silyl alkyl carbonate compounds represented by the following formula (I). In formula (I), X is １２ C or １３ C indicates R １ ~R ３ represents an alkyl group or an aryl group, and R ４ represents an alkyl group.

[0016] [Silyl alkyl carbonate compound] The silyl alkyl carbonate compound of the present invention is a silyl alkyl carbonate compound having a silyl group (—Si(R １ ) (R ２ ) (R ３ )) and an alkyl group (-R ４ In the presence of a specific fluoride anion, this compound converts carbon-hydrogen bonds in organic compounds, particularly aromatic compounds, into carboxylated ( １３In addition, in the presence of a specific fluoride anion and a specific catalyst, it is also suitable for carboxylation of the carbon-boron bond in an organoboron compound ( １３ Although the details of how the silyl alkyl carbonate compound of the present invention functions as a carboxylation reactant are unclear, as will be described later, the silyl alkyl carbonate compound of the present invention decomposes in the presence of a specific fluoride anion to form a Bronsted base, for example, an alkoxide anion (R ４ By generating a silyl alkyl carbonate compound (X(═O-) and a one-carbon source (X(═O)O), it is believed that the silyl alkyl carbonate compound of the present invention functions as a carboxylation reagent that initiates a carboxylation reaction with a simple operation without impairing ease of handling. Therefore, the silyl alkyl carbonate compound of the present invention can be suitably used as a carboxylation reagent. In this respect, the carboxylation reagent of the present invention can also be said to be a carbon-carbon bond-forming agent that converts a carbon-hydrogen bond or a carbon-boron bond into a carbon-carbon bond. In terms of realizing easy handling, the silyl alkyl carbonate compound of the present invention is preferably liquid at room temperature and normal pressure (e.g., 20 to 25° C., 1 atm).

[0017] In formula (I), X is １２ C or １３ The carboxylation reagent of the present invention is １３ When used in the production method of a C-unlabeled carboxylated compound, X is １２ On the other hand, the carboxylation reagent of the present invention is selected １３ When used in the method for producing a C-labeled carboxylated compound, X is １３ In formula (I), X is selected from the group consisting of １２ C and １３ The mixture ratio is not particularly limited and can be determined appropriately, and may be, for example, the ratio of stable isotopes of naturally occurring carbon element.

[0018] In formula (I), R １ ~R ３ are respectively R １ ~R ３ represents an alkyl group or an aryl group.１ ~R ３ At least one of R is preferably an alkyl group, and all of R are preferably alkyl groups. １ ~R ３ The number of carbon atoms in the alkyl group R is not particularly limited and can be determined appropriately, for example, from 1 to 20. １ ~R ３ The number of carbon atoms in the alkyl group that can be taken as the carboxylation group is preferably 1 to 12, more preferably 1 to 6, even more preferably 2 to 6, and particularly preferably 3 to 5, from the viewpoint of the efficiency of the carboxylation reaction (hereinafter, sometimes simply referred to as "reaction efficiency").

[0019] R １ ~R ３ The alkyl group that can be used as R is not particularly limited and may be any of a linear alkyl group, a branched alkyl group, and a cyclic alkyl group, but from the viewpoint of reaction efficiency, a branched alkyl group is preferred. １ ~R ３ The branched alkyl group that can be R is preferably a branched alkyl group containing at least one tertiary or quaternary carbon atom. The number of tertiary or quaternary carbon atoms in the branched alkyl group may be one or more, and may be 1 to 4, with 1 or 2 being preferred. １ ~R ３ In the branched alkyl group which may be represented by R, the position of the tertiary or quaternary carbon atom in the carbon chain is not particularly limited, and may be a carbon atom other than the carbon atom directly bonded to the Si atom in formula (I), but it is preferable that the carbon atom directly bonded to the Si atom in formula (I) is a tertiary or quaternary carbon atom. In the present invention, when the carbon atom directly bonded to the Si atom in formula (I) is bonded to two or three carbon atoms, these carbon atoms are conveniently referred to as a tertiary carbon atom or a quaternary carbon atom, respectively. １ ~R ３Examples of the branched alkyl group that can be used include an isopropyl group, an isobutyl (3-methylpropyl) group, a 2-butyl group, a 3-butyl group, an isobutyl (3-methylpropyl) group, a tert-butyl group, a 2-pentyl group, a 3-pentyl group, a sec-pentyl (1-methylbutyl) group, a tert-pentyl (1,1-dimethylpropyl) group, a 2-methylbutyl group, a 3-methylbutyl group, a 1-methyl-2-butyl group, a 2-methyl-2-butyl group, a neopentyl (2,2-dimethyl-1-propyl) group, a 1,1-diethyl-1-propyl (-C(CH ２ CH ３ ) ３ ) group, 2,2-diethyl-1-butyl (—CH ２ C(CH ２ CH ３ ) ３ ) group, 2,3-dimethylbutan-2-yl group, etc. Among these, an isopropyl group, a tert-butyl group, a 2-butyl group, a 2-pentyl group, a 3-pentyl group, etc. are preferred.

[0020] R １ ~R ３ The alkyl groups that can be taken as R may be the same or different. １ ~R ３ In terms of reaction efficiency, it is preferable that at least one of R is a branched alkyl group, and it is more preferable that two or three of R are branched alkyl groups. １ ~R ３ When at least one of R is an alkyl group, in terms of reaction efficiency, １ ~R ３ Of the alkyl groups that can be represented by R, it is preferred that at least one is a branched alkyl group, and it is more preferred that two or three are branched alkyl groups. １ ~R ３ Among the groups that can be taken as R, the groups other than the branched alkyl group (the remaining groups) are alkyl groups other than the branched alkyl group or aryl groups, and the alkyl groups other than the branched alkyl group are preferably linear alkyl groups. １ ~R ３ When at least two of R are alkyl groups, R １ ~R ３Possible combinations of alkyl groups include appropriate combinations of the above alkyl groups, and for example, a combination of linear alkyl groups, a combination of a branched alkyl group and a linear alkyl group, or a combination of branched alkyl groups is preferred, and from the viewpoint of reaction efficiency, a combination of branched alkyl groups is more preferred. In each of the above combinations containing a branched alkyl group, the branched alkyl group preferably has 3 or more carbon atoms. １ ~R ３ Examples of possible combinations of alkyl groups include the combinations of trialkylsilyl groups, such as tert-butyldimethylsilyl group and triisopropylsilyl group, in the silyl carbonate compounds synthesized in the examples described below.

[0021] R １ ~R ３ Examples of aryl groups that can be used as R include aromatic hydrocarbon groups and aromatic heterocyclic groups. The aromatic hydrocarbon compounds that form the aromatic hydrocarbon groups and the aromatic heterocyclic compounds that form the aromatic heterocyclic groups are not particularly limited, and examples thereof include aromatic hydrocarbon compounds and aromatic heterocyclic compounds that are used as aromatic compounds as substrates in the method for producing a carboxylated aromatic compound of the present invention. １ ~R ３ The aryl group that can be used as R is preferably an aromatic hydrocarbon group, and more preferably a phenyl group. The number of carbon atoms constituting the aryl group (number of carbon atoms constituting the ring) is not particularly limited and can be, for example, 6 to 20. １ ~R ３ When at least two of R are aryl groups, R １ ~R ３ The combination of aryl groups that can be used as R is not particularly limited, and examples thereof include a combination of aromatic hydrocarbon groups, a combination of aromatic heterocyclic groups, and a combination of an aromatic hydrocarbon group and an aromatic heterocyclic group. １ ~R ３ When one or two of R １ ~R ３The combination of an alkyl group and an aryl group that can be used as R is not particularly limited, but a combination of an alkyl group and an aromatic hydrocarbon group is preferred. １ ~R ３ Examples of the silyl group in which at least one of the groups is an aryl group include a phenyldimethylsilyl group, a phenyldiisopropylsilyl group, a diphenylmethylsilyl group, a tert-butyldiphenylsilyl group, and a triphenylsilyl group.

[0022] In formula (I), R ４ represents an alkyl group. ４ The number of carbon atoms in the alkyl group R is not particularly limited and can be determined appropriately, for example, from 1 to 20. ４ The number of carbon atoms in the alkyl group is preferably 3 to 12, more preferably 4 to 10, and even more preferably 4 to 8, from the viewpoint of reaction efficiency.

[0023] R ４ The alkyl group that can be used as R is not particularly limited and may be any of a linear alkyl group, a branched alkyl group, and a cyclic alkyl group, but from the viewpoint of reaction efficiency, a branched alkyl group is preferred. ４ From the viewpoint of reaction efficiency, the branched alkyl group that can be used as R is preferably a branched alkyl group containing at least one tertiary or quaternary carbon atom, and more preferably a branched alkyl group containing at least one quaternary carbon atom. The number of tertiary or quaternary carbon atoms in the branched alkyl group may be one or more, and may be 1 to 9, and preferably 1 to 4. ４ In the branched alkyl group which can be represented by the formula (I), the position of the tertiary or quaternary carbon atom in the carbon chain is not particularly limited, and it may be a carbon atom other than the carbon atom directly bonded to the oxygen atom (O atom) in formula (I), but it is preferable that the carbon atom directly bonded to the O atom in formula (I) is a tertiary or quaternary carbon atom. In the present invention, when the carbon atom directly bonded to the O atom in formula (I) is bonded to two or three carbon atoms, these carbon atoms are conveniently referred to as a tertiary carbon atom or a quaternary carbon atom, respectively.

[0024] R４ The branched alkyl group that can be used as the alkyl group is —C(R ４Ａ ) ３ In terms of reaction efficiency, it is preferable that the alkyl group contains ４Ａ represents an alkyl group, preferably an alkyl group having 1 to 6 carbon atoms, and more preferably an alkyl group having 1 to 4 carbon atoms. ４Ａ The alkyl group that can be used as R may be any of a linear alkyl group, a branched alkyl group, and a cyclic alkyl group, but is preferably a linear alkyl group. ４Ａ The number of carbon atoms in the alkyl group that can be represented by R is preferably 2 or more, more preferably 2 to 6, and even more preferably 2 to 4. ４Ａ Of the three alkyl groups that can be taken as R, it is preferable that at least one is an alkyl group having two or more carbon atoms, and it is preferable that two or three are alkyl groups having two or more carbon atoms. ４Ａ The three alkyl groups that can be taken as R may be the same or different. ４Ａ Possible combinations of three alkyl groups include appropriate combinations of the above alkyl groups, and preferred examples include combinations of the same three straight-chain alkyl groups.

[0025] -C(R ４Ａ ) ３ The alkyl group containing -C(R ４Ａ ) ３ may be bonded to the O atom in formula (I) via an alkylene group, but is preferably bonded directly. The alkylene group may be any of a linear alkylene group, a branched alkylene group, and a cyclic alkylene group, and the number of carbon atoms in the alkylene group is not particularly limited, and may be, for example, 1 to 6, and preferably 1 to 4. -C(R ４Ａ ) ３ Examples of alkyl groups containing the formula include a tert-butyl group, a 1,1-diethyl-1-propyl group (a 3-ethylpentan-3-yl group), a 2,2-diethyl-1-butyl group (a —CH ２ C(CH ２ CH ３ )３ ) groups and the like.

[0026] R ４ Examples of branched alkyl groups that can be used as R are not particularly limited, and include １ ~R ３ Examples of the branched alkyl group include the groups mentioned above, and among these, a tert-butyl group, a 1,1-diethyl-1-propyl group, etc. are preferred.

[0027] In formula (I), R １ ~R ３ and R ４ As a combination with １ ~R ３ The alkyl group or the aryl group that can be taken as R ４ and R １ ~R ３ the preferred combinations of alkyl groups or aryl groups, or the preferred combinations of alkyl groups and aryl groups, which may be taken as R ４ The preferred combinations of R with alkyl groups are １ ~R ３ The above-mentioned preferred combinations of alkyl groups that can be taken as R ４ Suitable examples of the combination of R with a preferred alkyl group include: １ ~R ３ and R ４ A preferred combination of R in formula (II) described below is, for example, １１ ~R １３ and R １４ and further, the combinations in the silyl carbonate compounds synthesized in the examples described below.

[0028] In formula (I), R １ ~R ３ At least two of these may be bonded to form a ring containing a Si atom, but it is preferable that such a ring is not formed. １ ~R ３ At least one of and R ４may be bonded to each other to form a ring containing —O—CO—O—, but it is preferred that they do not form such a ring.

[0029] In formula (I), X and R １ ~R ３ and R ４ The combination with R is not particularly limited. １ ~R ３ or R ４ and X in the formula (II) described below. １１ ~R １３ and R １４ A combination of is preferred.

[0030] In one preferred embodiment, the silyl alkyl carbonate compound (I) represented by formula (I) is a silyl alkyl carbonate compound (II) represented by the following formula (II).

[0031] In formula (II), X is １２ C or １３ C, which is the same as X in the above formula (I).

[0032] In formula (II), R １１ ~R １３ each represents an alkyl group or an aryl group, and R １４ represents an alkyl group. １１ ~R １３ The alkyl group or aryl group that can be taken as R in the above formula (I) １ ~R ３ The alkyl group or aryl group that can be represented by R １４ The alkyl group that can be taken as is R in the above formula (I). ４ However, in formula (I), R １ ~R ３ The alkyl or aryl group that can be taken as R ４ Among the alkyl groups that can be taken as X, the following embodiments are preferred depending on X.

[0033] X is １２ If C, then R １１ ~R１３ At least one of R represents a branched alkyl group, and R １４ -C(R ４Ａ ) ３ (R ４Ａ represents an alkyl group containing an alkyl group. １１ ~R １３ In an embodiment in which at least one of R represents a branched alkyl group, １ ~R ３ This is the same as the embodiment in which at least one of R represents a branched alkyl group. １１ ~R １３ The branched alkyl group that can be used as the １ ~R ３ The branched alkyl groups are the same as those preferably taken as R １１ ~R １３ Among the alkyl groups that can be taken as the alkyl group other than the branched alkyl group or the aryl group, R １ ~R ３ The alkyl group or aryl group that can be represented by R １１ ~R １３ The number of branched alkyl groups among the alkyl groups that can be taken as R may be at least one, and is preferably two or three. １４ It can be taken as -C(R ４Ａ ) ３ The alkyl group containing ４ It can be taken as -C(R ４Ａ ) ３ is the same as an alkyl group containing R ４Ａ The alkyl group which can be taken as R in formula (I) ４Ａ The alkyl groups are the same as those that can be taken as

[0034] On the other hand, X １３ If C, then R １１ ~R １３ each represents an alkyl group or an aryl group, and R １ ~R ３ The alkyl group or aryl group that can be represented by R １４ represents an alkyl group, and R in the above formula (I)４ The alkyl groups are the same as those that can be taken as

[0035] In formula (II), R １１ ~R １３ and R １４ As a combination with １１ ~R １３ The alkyl group or the aryl group that can be taken as R １４ and the alkyl groups described above. For example, the alkyl groups X and R １１ ~R １３ and R １４ R in combination with １１ ~R １３ and R １４ and further, the combinations in the silyl carbonate compounds synthesized in the examples described below.

[0036] In formula (II), X and R １１ ~R １３ and R １４ The combination with R is not particularly limited. １１ ~R １３ The alkyl group or the aryl group or R １４ and X is an alkyl group selected from the group consisting of X and R. １１ ~R １３ and R １４ The following combinations are preferred:

[0037] In formula (II), X and R １１ ~R １３ and R １４ The combination of X and R in formula (I) is １ ~R ３ and R ４ Among the combinations of X and X, the following combinations are used. １２ If C, then R １１ ~R １３ and R １４ In terms of reaction efficiency, etc., １１ ~R １３ At least one of R is a branched alkyl group, and R １４ -C(R ４Ａ )３ (R ４Ａ represents an alkyl group), and R １１ ~R １３ at least one of R is a branched alkyl group; １４ -C(R ４Ａ ) ３ (R ４Ａ represents an alkyl group, and at least one R ４Ａ represents an alkyl group having 2 or more carbon atoms). １１ ~R １３ at least one of R is a branched alkyl group; １４ -C(R ４Ａ ) ３ (R ４Ａ represents an alkyl group, and at least one R ４Ａ The alkyl group containing X is as explained in formula (I). １２ R when C １１ ~R １３ and R １４ A preferred combination of is, for example, the combination in the silyl carbonate compound synthesized in the Examples described below.

[0038] On the other hand, X １３ If C, then R １１ ~R １３ and R １４ The combination with R is not particularly limited. １１ ~R １４ Examples include suitable combinations of the alkyl groups that can be taken as R １１ ~R １３ and R １４ As a combination with R in formula (I), １ ~R ３ and R ４ A combination of R １１ ~R １３ and R １４ A more preferred combination with R １１ ~R １３ At least one of R is a branched alkyl group, or １４ -C(R４Ａ ) ３ (R ４Ａ represents an alkyl group), and more preferred combinations are those in which X is １２ When C, R １１ ~R １３ At least one of R is a branched alkyl group, and R １４ -C(R ４Ａ ) ３ A specific example of the combination is the silyl carbonate compound ( １３ C-unlabeled silyl alkyl carbonate compounds).

[0039] In formula (I), X and R １ ~R ３ and R ４ and compounds in which X and R in formula (II) are combined. １１ ~R １３ and R １４ Examples of compounds in combination with the above include the compounds described in Patent Document 3 (wherein the carbonyl carbon in the compound is １３ The contents of Patent Document 3 are incorporated herein in their entirety as part of the present specification.

[0040] The silyl alkyl carbonate compound of the present invention may be a commercially available product or may be appropriately synthesized. The silyl alkyl carbonate compound of the present invention can be synthesized by an appropriate method, for example, from an alkoxide base, carbon dioxide, and a chlorosilane compound. The alkoxide base is not particularly limited, and includes alkoxy metal salts, and includes alkoxides of metal elements belonging to Group 1 or Group 2 of the periodic table. The alkyl group forming the alkoxide base is not particularly limited, and includes the above-mentioned R ４ As the chlorosilane compound, a compound corresponding to the trialkylsilyl group of the silyl alkyl carbonate compound to be synthesized may be used. The alkyl group possessed by the chlorosilane compound is the same as that described above for the alkyl group R １ ~R３ The synthesis conditions for the synthesis method using an alkoxide base, carbon dioxide, and a chlorosilane compound include conditions in which carbon dioxide and a chlorosilane compound are reacted in the presence of an alkoxide base under normal cooling, for example, at about -20°C to 10°C. Specific synthesis methods using an alkoxide base, carbon dioxide, and a chlorosilane compound include, for example, the synthesis methods described in Non-Patent Documents 1 and 2, and the synthesis methods in the Examples described below. １３ For the C-labeled silyl alkyl carbonate compound, １３ It can be synthesized using C-labeled carbon dioxide. １３ Carbon dioxide labeled with C can be commercially available or can be appropriately synthesized by the method described in Non-Patent Document 9.

[0041] The structure of the silyl alkyl carbonate compound of the present invention can be identified by known structural analysis methods and analytical methods for organic compounds. Known structural analysis methods and analytical methods include, for example, nuclear magnetic resonance spectroscopy ( １ H-NMR, １３ Examples of the analytical methods include spectroscopy (C-NMR), infrared absorption spectroscopy (IR), mass spectrometry (LRMS, HRMS), elemental analysis, and combinations of these.

[0042] [Other Components] The carboxylation reagent of the present invention may contain a silyl alkyl carbonate compound represented by formula (I) above, and may also contain other components as appropriate. The other components are not particularly limited and may include, for example, a dehydrating agent and a stabilizer. The content of the other components in the carboxylation reagent is not particularly limited and can be determined as appropriate. For example, when the carboxylation reagent is used in a method for producing a carboxylated compound, the content (abundance) of the other components contained in the carboxylation reagent can be 100 times or less by mass, or even 10 times or less by mass, relative to the total mass of the silyl alkyl carbonate compound, substrate, and compound that will produce fluoride ions contained in the carboxylation reagent. The carboxylation reagent of the present invention can also be used as a solution or dispersion in which it is dissolved or dispersed in a solvent or the like. The content of the carboxylation reagent in this case is not particularly limited and can be determined as appropriate.

[0043] [Method for Producing Carboxylated Compounds] The method for producing a carboxylated compound of the present invention (hereinafter, sometimes simply referred to as "the production method of the present invention") is a method for producing a carboxylated compound by reacting an aromatic compound or an organoboron compound described below with the carboxylation reagent of the present invention in the presence of fluoride anions. In the production method of the present invention, the carboxylation reagent of the present invention undergoes a decomposition reaction in the presence of fluoride anions, and the generated alkoxy ions (R ４ O-) activates the carbon-hydrogen bond of the aromatic compound (by abstracting a hydrogen atom) or coordinates to the boron atom in the organoboron compound to form a boron complex, which is then activated and carboxylated by a carbon source. The carboxylation reagent of the present invention used is generally liquid at room temperature and pressure, and is therefore easy to handle, allowing the production method of the present invention (carboxylation reaction) to be carried out with a simple procedure. In particular, preferred carboxylation reagents of the present invention (for example, R １ ~R ３ At least one of R is a branched alkyl group, and / or R ４ -C(R ４Ａ ) ３ (R ４ＡBy using a carboxylation reagent (wherein the carboxyl group is an alkyl group containing a carboxyl group, and the carboxyl group represents an alkyl group), carboxylated compounds can be produced with high efficiency (high yield) even at relatively low temperatures. In the production method of the present invention, the carboxylation reagent of the present invention, which is easy to handle, is used instead of carbon dioxide, so that the amount used can be precisely measured, the reaction system can be easily controlled, and the use of specialized production equipment can be avoided, allowing the carboxylation reaction to be carried out with a simple procedure. Furthermore, since the production method of the present invention is not substrate specific and can use a variety of substrates, it is a useful method for producing a library of diverse carboxylated compounds.

[0044] The production method of the present invention includes a method for producing a carboxylated aromatic compound using an aromatic compound described below as a reaction substrate, and a method for producing a carboxylated organic compound using an organoboron compound described below. The carboxylated compound produced by the production method of the present invention cannot be uniquely determined depending on the type of substrate, post-treatment method, etc., but examples include aromatic carboxylic acids, aromatic ring-containing carboxylic acids, and other aromatic-containing carboxylic acid compounds, and ester compounds thereof.

[0045] [Method for Producing Carboxylated Aromatic Compound] The method for producing a carboxylated aromatic compound of the present invention (hereinafter, sometimes referred to as "production method (A) of the present invention") is a method for producing a carboxylated aromatic compound by reacting an aromatic compound containing a carbon atom bonded to a hydrogen atom with the carboxylation reactant of the present invention in the presence of a fluoride anion.

[0046] <Aromatic Compound> The aromatic compound used as a substrate in the production method (A) of the present invention is a compound containing at least one carbon atom bonded to a hydrogen atom. It is preferable that at least one of the hydrogen atoms bonded to a carbon atom among the hydrogen atoms possessed by the aromatic compound is easily carboxylated (easily substituted with a carboxy group) by the carboxylation reagent of the present invention. In the present invention, pKa is used as an indicator of the susceptibility to carboxylation, and the pKa of a hydrogen atom that is easily carboxylated cannot be uniquely determined due to its relationship with other hydrogen atoms possessed by the aromatic compound. The pKa of the hydrogen atom is preferably, for example, 20 to 40, and more preferably 20 to 35 in terms of increasing reaction efficiency. The aromatic compound may contain hydrogen atoms other than the hydrogen atom that is easily carboxylated, for example, hydrogen atoms with a pKa outside the above range. The number of carbon atoms in the aromatic compound bonded to hydrogen atoms exhibiting a pKa within the above range (also referred to as carboxylatable carbon atoms), i.e., the number of hydrogen atoms that are easily carboxylated, needs only to be at least one, and is appropriately determined depending on the structure of the aromatic compound, the presence or absence of substituents, the number of substituents, etc. The number of carbon atoms to be carboxylated contained in the aromatic compound may be, for example, 1 to 3. In the present invention, the pKa is a value measured or calculated by the method described in the non-patent document "Fraser, R.R.; Mansour, T.S.; Savard, S. Can. J. Chem. 1985, 63, 3505-3509," or a value described in the non-patent document.

[0047] The aromatic compound is not particularly limited and various aromatic compounds can be used, for example, aromatic compounds containing a carbon atom to which a hydrogen atom is bonded as an aromatic ring carbon atom, and aromatic compounds having an aliphatic group containing a carbon atom to which a hydrogen atom is bonded as a substituent. The number of carbon atoms constituting the aromatic compound (number of ring carbon atoms) is not particularly limited and can be, for example, 6 to 20.

[0048] Aromatic compounds containing a carbon atom bonded to a hydrogen atom as an aromatic ring-forming carbon atom may be monocyclic or polycyclic, with monocyclic being preferred. Examples of such aromatic compounds include aromatic hydrocarbon compounds and aromatic heterocyclic compounds. Examples of aromatic hydrocarbon compounds include monocyclic aromatic hydrocarbon (benzene) compounds and polycyclic aromatic hydrocarbon compounds. Polycyclic aromatic hydrocarbon compounds are compounds formed by the condensation of multiple monocyclic aromatic hydrocarbon compounds, including aromatic hydrocarbon (acene) compounds having a structure in which benzene rings are condensed in a linear fashion, as well as aromatic hydrocarbon compounds having a structure in which a benzene ring is condensed with a ring of a compound whose conjugate base exhibits aromaticity (e.g., cyclopentadiene). The number of condensed rings is not particularly limited and can be, for example, 2 to 5. Examples of such polycyclic aromatic hydrocarbon rings include acene compounds such as naphthalene, anthracene, tetracene, and pentacene, as well as chrysene, pyrene, triphenylene, benzopyrene, and coronene. Monocyclic aromatic hydrocarbon compounds are preferred.

[0049] The aromatic heterocyclic compound may be an aromatic compound containing a monocyclic heterocycle having at least one heteroatom such as a nitrogen atom, oxygen atom, or sulfur atom, and may be monocyclic or polycyclic. The monocyclic heterocycle is preferably a five- or six-membered ring. The monocyclic heterocycle may be an aromatic ring or an aliphatic ring, as long as the aromatic heterocyclic compound exhibits aromaticity. Examples of the aromatic heterocyclic compound include monocyclic aromatic heterocycles and polycyclic aromatic heterocycles. The polycyclic aromatic heterocycle may be a compound containing at least one monocyclic heterocycle, and includes aromatic heterocycles having a structure in which multiple monocyclic heterocycles are fused, and aromatic heterocycles having a structure in which a monocyclic heterocycle is fused with one or more benzene rings or rings of a compound whose conjugate base exhibits aromaticity. The number of fused rings is not particularly limited and can be, for example, 2 to 5. The aromatic heterocyclic compound is preferably a monocyclic aromatic heterocycle or a bicyclic aromatic heterocycle having a structure in which a monocyclic heterocycle is fused with a benzene ring. Examples of monocyclic aromatic hetero compounds include furan, thiophene, pyrrole, pyridine, imidazole, pyrazole, pyrazine, pyrimidine, pyridazine, triazole, tetrazole, triazine, thiazole, isothiazole, oxazole, and isoxazole. Examples of polycyclic aromatic hetero compounds include benzofuran, benzothiophene, indole, isoindole, indolizine, carbazole, quinoline, isoquinoline, benzimidazole, benzopyrimidine, benzopyridazine, benzotriazole, indazole, purine, quinazoline, benzothiazole, and benzoxazole. Preferred aromatic hetero compounds are furan, thiophene, benzofuran, benzothiophene, and indole. In the present invention, the nitrogen atom of the aromatic hetero compound may have a substituent. The substituent that the nitrogen atom may have is not particularly limited, and examples thereof include the following substituents, among which alkyl groups and aryl groups are preferred.

[0050] The aromatic compound may have a substituent. The substituent is not particularly limited, and examples thereof include halogen atoms (e.g., fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc.), cyano groups, nitro groups, carboxy groups, alkoxy groups (including fluorinated alkyloxy groups, preferably alkoxy groups having 1 to 20 carbon atoms), acyl groups (including alkylcarbonyl groups, arylcarbonyl groups, and formyl groups, preferably acyl groups having 0 to 20 carbon atoms, more preferably acyl groups having 1 to 20 carbon atoms), aryloyloxy groups (preferably aryloyloxy groups having 7 to 23 carbon atoms), alkoxycarbonyl groups (preferably alkoxycarbonyl groups having 2 to 20 carbon atoms), aryloxycarbonyl groups (preferably aryloxycarbonyl groups having 7 to 26 carbon atoms), acyloxy groups (preferably acyloxy groups having 1 to 20 carbon atoms), alkyl groups (preferably alkyl groups having 1 to 20 carbon atoms), aryl groups (preferably aryl groups having 6 to 26 carbon atoms), and composite substituents combining two or more of these. Examples of composite substituents include groups combining an alkyl group or an aryl group with a halogen atom, a cyano group, a nitro group, an alkoxy group, or an acyl group, and specifically include halogenated aryl groups. The bonding position of the halogen atom in the composite substituent is not particularly limited. The number of substituents that the aromatic compound may have is not particularly limited and can be 1 to 5, preferably 1 to 3. In one preferred embodiment, the aromatic compound does not have a boron atom. The positions of the substituents (positions of the ring-constituting atoms) of the aromatic compound are not particularly limited and can be determined as appropriate, but are preferably determined taking into consideration the pKa of the hydrogen atom bonded to the carbon atom to be carboxylated.

[0051] Examples of aromatic compounds having an aliphatic group containing a carbon atom bonded to a hydrogen atom as a substituent include aromatic compounds obtained by introducing an aliphatic group containing a carbon atom bonded to a hydrogen atom as a substituent into the above-mentioned aromatic compound containing a carbon atom bonded to a hydrogen atom as an aromatic ring-forming carbon atom. The aliphatic group containing a carbon atom bonded to a hydrogen atom is not particularly limited, but is preferably an alkyl group. The alkyl group may be a linear alkyl group, a branched alkyl group, or a cyclic alkyl group, and the number of carbon atoms can be determined appropriately. For example, the number of carbon atoms in the alkyl group can be 1 to 20, preferably 1 to 12, more preferably 1 to 6, and even more preferably 1 to 4. The number of aliphatic groups introduced as substituents is not particularly limited, but is preferably 1 to 3. The aliphatic group may have the above-mentioned substituent. Examples of aromatic compounds having an aliphatic group containing a carbon atom bonded to a hydrogen atom as a substituent include alkylbenzene compounds such as toluene, ethylbenzene, and xylene, 2-alkylthiophene, 2-alkylbenzothiophene, 3-alkylthiophene, and 3-alkylbenzothiophene.

[0052] <Carboxylation Reactant of the Present Invention> The carboxylation reactant of the present invention used in production method (A) of the present invention contains a silyl alkyl carbonate compound represented by formula (I) above, and is advantageous in that it can achieve high reaction efficiency. １ ~R ３ At least one of R in formula (I) is a branched alkyl group. ４ is the above -C(R ４Ａ ) ３ Preferably, the compound contains a silyl alkyl carbonate compound, which is an alkyl group containing １ ~R ３ At least one of R in formula (I) is a branched alkyl group. ４ is the above -C(R ４Ａ ) ３ In the production method (A) of the present invention, it is more preferable that the silyl alkyl carbonate compound contains an alkyl group containing １３ When using a C-unlabeled carboxylation reagent, １３C unlabeled carboxylated compounds can be prepared, １３ When a C-labeled carboxylation reagent is used, １３ C-labeled carboxylated compounds can be prepared. １３ The production method (A) of the present invention using a C-labeled carboxylation reagent is highly efficient in reaction. １３ It is highly useful in that it can produce C-labeled carboxylated compounds.

[0053] <Fluoride anion> In the production method (A) of the present invention, fluoride anion is allowed to coexist. The method for allowing fluoride anion to coexist is not particularly limited, but it is preferable to use a fluoride, and it is more preferable to use an inorganic fluorine compound. Examples of inorganic fluorine compounds include fluorides of metal elements belonging to Group 1 or Group 2 of the periodic table, and fluorides of metal elements belonging to Group 1 of the periodic table are preferred. Examples of inorganic fluorine compounds include CsF and the like.

[0054] <Other Components> In Production Method (A) of the present invention, it is preferable to use a complexing agent that complexes the cation of the metal element generated from the inorganic fluorine compound. Examples of the complexing agent include clathrate compounds such as 18-crown-6 and chelating compounds such as N,N,N',N'-tetramethylethylenediamine, with 18-crown-6 being preferred.

[0055] <Reaction Conditions> In Production Method (A) of the present invention, an aromatic compound is reacted with the carboxylation reagent of the present invention in the presence of a fluoride anion, preferably further in the presence of a complexing agent. The amount of the carboxylation reagent of the present invention used is preferably 1 equivalent (1 molar equivalent) or more relative to the aromatic compound, and can be, for example, 1 to 7 equivalents. From the viewpoint of achieving high reaction efficiency, 1 to 3 equivalents is more preferable, and 2 to 3 equivalents is even more preferable. The amount of the fluoride anion used is preferably 1 equivalent or more relative to the aromatic compound, and can be, for example, 1 to 7 equivalents. From the viewpoint of achieving high reaction efficiency, 1 to 3 equivalents is more preferable, and 2 to 3 equivalents is even more preferable. The amount of the complexing agent used is preferably 1 equivalent or more relative to the fluoride anion (number of moles). From the viewpoint of achieving high reaction efficiency, 1 to 5 equivalents is more preferable, and 2 to 3 equivalents is even more preferable.

[0056] The reaction conditions are not particularly limited as long as the carboxylation reaction of the substrate occurs and proceeds, and can be set appropriately. For example, the reaction temperature cannot be uniquely determined depending on the type of aromatic compound, the type of carboxylation reactant, etc., and can be, for example, 80°C or higher. Generally, 100°C or higher is preferred. From the viewpoint of achieving high reaction efficiency, 120°C or higher is more preferred, and 160°C or higher is even more preferred. The upper limit of the reaction temperature is not particularly limited, but from the viewpoint of maintaining high reaction efficiency, 200°C or lower is preferred, and 180°C or lower is more preferred. When the above-mentioned preferred silyl alkyl carbonate compound is used, high reaction efficiency can be maintained even if the reaction temperature is set at a relatively low temperature within the above range. The reaction time is appropriately determined depending on the reaction temperature, etc. The reaction atmosphere may be any of air, dry air (dew point -20°C or lower), and inert gas (e.g., argon gas, helium gas, nitrogen gas), etc., but inert gas is preferred. The pressure during the reaction is not particularly limited and may be either open (atmospheric pressure) or pressurized, and can be set appropriately. The carboxylation reaction is preferably carried out in a solvent. As the solvent, various solvents can be used, and although there are no particular limitations, an aprotic polar solvent is preferred. Examples of aprotic polar solvents include 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), and dimethylformamide (DMF). When the carboxylation reaction is carried out in a solvent, the amount of the solvent used can be 3 to 13 times by mass the total amount of the aromatic compound and the carboxylation reactant.

[0057] In the production method (A) of the present invention, carboxylic acid compounds (aromatic carboxylic acid compounds, aliphatic carboxylic acid compounds having an aromatic ring), carboxylic acid ester compounds (aromatic carboxylic acid ester compounds, aliphatic carboxylic acid ester compounds having an aromatic ring), etc. can be obtained by post-treatment after the reaction of an aromatic compound with the carboxylation reagent of the present invention as described above. The post-treatment is preferably carried out continuously after the reaction of the aromatic compound with the carboxylation reagent of the present invention (one-pot reaction). Any appropriate method can be used for the post-treatment. When producing an ester compound, for example, an alkylation reaction is carried out after the reaction of an aromatic compound with the carboxylation reagent of the present invention. Various known alkylation reactions can be used for the alkylation reaction, such as a methylation reaction using methyl iodide. Conventional conditions for the methylation reaction can be used, for example, using 1 equivalent (1 molar equivalent) or more, preferably 3 to 5 equivalents, of methyl iodide relative to the aromatic compound, and the reaction can be carried out under heating, for example, at a reaction temperature of 30 to 60°C.

[0058] The carboxylated compound produced by Production Method (A) of the present invention is a compound having at least one carboxy group introduced into its molecule. The position at which the carboxy group is introduced is not particularly limited. For example, in the aromatic compound, the carboxy group is substituted at a carboxylatable carbon atom among the hydrogen atoms of the aromatic compound that is easily carboxylated by the carboxylation reagent of the present invention. The position at which the carboxy group is introduced can be appropriately determined depending on the structure of the aromatic compound, the presence or absence of a substituent, the type of the substituent, etc.

[0059] <Other Steps> In the production method (A) of the present invention, other steps may be carried out in addition to the reaction of the aromatic compound with the carboxylation reagent of the present invention and post-treatment. Examples of other steps include a step of purifying the reaction product.

[0060] [Method for Producing Carboxylated Organic Compound] The method for producing a carboxylated organic compound of the present invention (hereinafter, sometimes referred to as "production method (B) of the present invention") is a method for producing a carboxylated organic compound by reacting an organoboron compound with the carboxylation reactant of the present invention in the presence of fluoride anions.

[0061] <Organoboron Compound> The organoboron compound used as a substrate in Production Method (B) of the present invention may be any organic compound having a boron-carbon bond. Examples include alkylboron compounds and aromatic boron compounds, with boronate ester compounds being preferred. The alkylboron compounds and aromatic boron compounds are not particularly limited. For example, alkylboron compounds include compounds in which a boron-containing group has been introduced into a saturated aliphatic hydrocarbon (preferably having 1 to 20 carbon atoms). Aromatic boron compounds include compounds in which a boron-containing group has been introduced into the above-mentioned monocyclic or polycyclic aromatic hydrocarbon compounds or monocyclic or polycyclic aromatic heterocyclic compounds. Boronate ester compounds include alkylboronate ester compounds and arylboronate ester compounds, with alkylboronic acid glycol ester compounds and arylboronic acid glycol ester compounds being preferred. The glycol is not particularly limited, but glycols having 2 to 10 carbon atoms are preferred, such as ethylene glycol, 1,3-propylene glycol, neopentyl glycol, and pinacol. The alkylboronic acid glycol ester compound and the arylboronic acid glycol ester compound are preferably compounds having a 1,3,2-dioxaborinane structure, such as 2-alkyl-1,3,2-dioxaborinane compounds and 2-aryl-1,3,2-dioxaborinane compounds. The alkyl group in the alkylboronic acid ester compound may be a linear alkyl group, a branched alkyl group, or a cyclic alkyl group, and the number of carbon atoms in the alkyl group is not particularly limited and may be, for example, 1 to 20. The number of carbon atoms in the aryl group in the arylboronic acid ester compound is not particularly limited and may be, for example, 6 to 20. The organoboron compound may have a substituent, and examples of the substituent include the substituents that the aromatic compounds may have.

[0062] <Carboxylation Reactant of the Present Invention> The carboxylation reactant of the present invention used in Production Method (B) of the present invention is the same as the carboxylation reactant of the present invention used in Production Method (A) of the present invention.

[0063] <Fluoride Anion> In the production method (B) of the present invention, a fluoride anion is allowed to coexist. The method for allowing the fluoride anion to coexist is the same as in the production method (A) of the present invention.

[0064] <Other Components> In Production Method (B) of the present invention, it is preferable to use a copper catalyst as a catalyst. Examples of copper catalysts include, but are not limited to, inorganic copper salts and copper complexes. Examples of inorganic copper salts include copper halides. Examples of copper complexes include, but are not limited to, complexes composed of a copper atom and various ligands. The ligand is not particularly limited, and various ligands can be used, including halogen atoms, pyridine, and bipyridine. Examples of copper catalysts include a copper complex of copper(I) chloride and bipyridine, a copper complex of copper(I) chloride and 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, and a copper complex of copper(I) chloride and triphenylphosphine. A pre-prepared copper complex may be used, or it may be prepared in the reaction system.

[0065] <Reaction Conditions> In Production Method (B) of the present invention, an organoboron compound and the carboxylation reagent of the present invention are reacted in the presence of fluoride anions, preferably in the presence of a copper catalyst. The amount of the carboxylation reagent of the present invention used is preferably 1 equivalent (1 molar equivalent) or more relative to the number of boron atoms in the organoboron compound (substantially the number of moles of boron atoms), more preferably 1 to 3 equivalents, and even more preferably 1 to 1.1 equivalents, in order to achieve high reaction efficiency. The amount of fluoride anions used is preferably 1 equivalent or more relative to the number of boron atoms in the organoboron compound, more preferably 1 to 3 equivalents, and even more preferably 1 to 1.1 equivalents, in order to achieve high reaction efficiency. The amount of copper catalyst used may be a catalytic amount relative to the number of boron atoms in the organoboron compound, and is, for example, more preferably 1 to 10 mol %, and even more preferably 5 to 10 mol %, in order to achieve high reaction efficiency.

[0066] The reaction conditions are not particularly limited as long as the carboxylation reaction of the substrate occurs and proceeds, and can be set appropriately. For example, the reaction temperature cannot be uniquely determined depending on the type of organoboron compound, the type of carboxylation reagent, etc., but can be set to 30 to 120°C. From the viewpoint of achieving high reaction efficiency, 40 to 120°C is preferred, and 80 to 120°C is more preferred. The reaction time is appropriately determined depending on the reaction temperature, etc. The reaction atmosphere may be air, dry air (dew point -20°C or lower), or an inert gas (e.g., argon gas, helium gas, nitrogen gas), etc. The pressure during the reaction is not particularly limited and may be open (atmospheric pressure) or pressurized, and can be set appropriately. The carboxylation reaction is preferably carried out in a solvent. When a solvent is used, the type and amount of solvent used are the same as those described in Production Method (A) of the present invention.

[0067] In production method (B) of the present invention, a carboxylic acid compound (aromatic carboxylic acid compound, aliphatic carboxylic acid compound), a carboxylic acid ester compound (aromatic carboxylic acid ester compound, aliphatic carboxylic acid ester compound), etc. can be obtained by a post-treatment method after reacting an organoboron compound with the carboxylation reactant of the present invention as described above. The post-treatment is the same as the post-treatment described in production method (A) of the present invention.

[0068] The carboxylated compound produced by production method (B) of the present invention is a compound having at least one carboxy group introduced into the molecule, at a carbon atom to which a boron atom is bonded (carbon-boron bond).

[0069] <Other Steps> In the production method (B) of the present invention, other steps may be carried out in addition to the reaction of the aromatic compound with the carboxylation reagent of the present invention and post-treatment. Examples of other steps include a step of purifying the reaction product.

[0070] The present invention will be described in more detail based on examples. The present invention is not to be construed as being limited to the following examples except as defined in the present invention.

[0071] Example 1: Synthesis of silyl alkyl carbonate compounds The following silyl alkyl carbonate compounds were synthesized.

[0072] Example 1-1: 3-ethylpentan-3-yl(triisopropylsilyl)carbonate: TIPSOCO ２ CEt ３ (1a) was synthesized and characterized as follows: LiOCEt ３(4915.6 mg, 40.3 mmol) and THF (40 mL) were stirred at 0°C for 1 hour. A solution of triisopropylsilyl chloride (7.71 mg, 40.0 mmol) dissolved in THF (20 mL) was slowly added thereto, and the mixture was stirred at 0°C for an additional 1 hour. Hexane was then added to the resulting reaction mixture, and the resulting solution was filtered through Celite, after which the solvent was distilled off under reduced pressure. The resulting crude product was then purified by distillation (8 mmHg, 120°C) to obtain product 1a (7933.7 mg, 25.0 mmol, yield 63%) as a colorless, transparent liquid.

[0073] The obtained product 1a was subjected to NMR, accurate mass measurement (HRMS), infrared absorption spectrum and elemental analysis, and the results are shown below. From the results shown below, it is clear that the obtained product 1a is TIPSOCO ２ CEt ３ It was confirmed that it was (1a). １ H-NMR (400MHz, CDCl ３ / TMS): σ 1.82 (q, 6H, J = 7.3 Hz), 1.36-1.26 (m, 3H), 1.10 (d, 18H, J = 7.3 Hz), 0.85 (t, 9H, J = 7.3 Hz) １３ C-NMR (100MHz, CDCl ３ / TMS): σ151.5, 88.6, 26.3, 17.7, 12.0, 7.58. HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １７ H ３７ O ３ Si ＋ :317.2507, found:317.2518 IR(neat):2947,2870,1716,1460,1274,1137,883cm －１

[0074] Example 1-2: tert-butyl(triisopropylsilyl)carbonate: TIPSOCO ２LiO-t-Bu (1b) was synthesized as follows. Under a carbon dioxide atmosphere, LiO-t-Bu (801.4 mg, 10.0 mmol) and THF (15 mL) were stirred at 0°C for 1 hour in a two-necked eggplant flask. A solution of triisopropylsilyl chloride (1938.0 mg, 10.1 mmol) dissolved in THF (7 mL) was slowly added, and the mixture was stirred at 0°C for an additional 1 hour. Hexane was then added, and the resulting solution was filtered through Celite, after which the solvent was distilled off under reduced pressure. The resulting crude product was then purified by distillation (5 mmHg, 81°C) to obtain product 1b (1209.5 mg, 4.4 mmol, 44% yield) as a colorless, transparent liquid.

[0075] The obtained product 1b was analyzed in the same manner as the above product 1a, and the results are shown below. ２ -t-Bu(1b). １ H-NMR (400MHz, CDCl ３ / TMS): σ 1.48 (s, 9H), 1.35-1.25 (m, 3H, J = 7.8 Hz), 1.11 (s, 9H), 1.09 (s, 9H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ151.7, 81.0, 27.7, 17.7, 12.0 HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １４ H ３１ O ３ Si ＋ :275.2037, found:275.2037 IR(neat):2944,2870,1719,1369,1295,1162,884cm －１

[0076] <Example 1-3> tert-butyl (tert-butyldimethylsilyl) carbonate: TBSOCO ２LiO-t-Bu (1c) was synthesized as follows. Under a carbon dioxide atmosphere, LiO-t-Bu (804.2 mg, 10.0 mmol) and THF (15 mL) were stirred at 0°C for 1 hour in a two-necked recovery flask. A solution of tert-butyldimethylsilyl chloride (1565.6 mg, 10.4 mmol) dissolved in THF (7 mL) was slowly added, and the mixture was stirred at 0°C for an additional 1 hour. Hexane was then added, and the resulting solution was filtered through Celite, after which the solvent was distilled off under reduced pressure. The resulting crude product was then purified by distillation (5 mmHg, 49°C) to obtain product 1c (0.9010 mg, 3.88 mmol, 39% yield) as a colorless, transparent liquid.

[0077] The obtained product 1c was analyzed in the same manner as the above product 1a, and the results are shown below. ２ -t-Bu(1c). １ H-NMR (400MHz, CDCl ３ / TMS): σ 1.47 (s, 9H), 0.95 (s, 9H), 0.27 (s, 6H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ151.4, 81.2, 27.7, 25.6, 17.8, -4.70 IR (neat): 2953, 2861, 1756, 1721, 1370, 1294, 1253, 1163, 829 cm －１

[0078] Example 2 Reactivity of Silyl Alkyl Carbonates The benzo[b]thiophene compounds shown below were carboxylated using the silyl alkyl carbonate compounds synthesized in Example 1, and the results are shown below.

[0079] Example 2-1 Under an argon atmosphere, benzo[b]thiophene (27.0 mg, 0.201 mmol, pKa = 33.0 (THF)), CsF (60.7 mg, 0.400 mmol), 18-crown-6 (105.8 mg, 0.400 mmol, referred to as "18-c-6" in the above reaction formula), the silyl alkyl carbonate compound (1a) (126.6 mg, 0.400 mmol) synthesized in Example 1, and DMI (1 mL) were placed in a screw-cap test tube (φ = 1.65 cm, total length 10.5 cm) under an argon atmosphere. After sealing with a screw cap, the mixture was heated and stirred at 160°C for 15 hours using a heat block. Next, MeI (0.38 mL, 0.6 mmol) was added, and the mixture was heated and stirred at 60°C for 2 hours. After that, water (3 mL) was added, and the resulting solution was extracted three times with ethyl acetate (3 mL). The ethyl acetate solutions were combined and washed with water (3 mL) and saturated brine (3 mL), and then extracted with Na ２ SO ４ The mixture was dried at 75°C, and the solvent was distilled off under reduced pressure. The resulting crude product was then purified by silica gel chromatography (hexane:ethyl acetate=20:1) to obtain methyl benzo[b]thiophene-2-carboxylate (3a) (37.9 mg, 0.197 mmol, yield 98%) as a white solid. The pKa of the substrate is described in the non-patent document "Fraser, R.R.; Mansour, T.S.; Savard, S. Can. J. Chem. 1985, 63, 3505-3509."

[0080] Example 2-2 Methylbenzo[b]thiophene-2-carboxylate (3a) (37.5 mg, 0.195 mmol, yield 98%) was obtained in the same manner as in Example 2-1, except that the silyl alkyl carbonate compound (1b) was used instead of the silyl alkyl carbonate compound (1a).

[0081] Example 2-3 Methylbenzo[b]thiophene-2-carboxylate (3a) (26.7 mg, 0.139 mmol, yield 70%) was obtained in the same manner as in Example 2-1, except that the silyl alkyl carbonate compound (1c) was used instead of the silyl alkyl carbonate compound (1a).

[0082] The melting point, NMR, mass spectrometry (LRMS, HRMS), infrared absorption spectrum, and elemental analysis of the product 3a obtained in Examples 2-1 to 2-3 were performed, and the results are shown below. From the results shown below, the obtained product 3a was confirmed to be methylbenzo[b]thiophene-2-carboxylate. Mp: 69-70°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 8.07 (s, 1H), 7.89-7.86 (m, 2H), 7.48-7.39 (m, 2H), 3.95 (s, 3H) １３ C-NMR (150MHz, CDCl ３ / TMS): σ163.2, 142.2, 138.6, 133.3, 130.6, 126.9, 125.5, 124.9, 122.7, 52.4 LRMS (EI) m / z: 192 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １０ H ８ O ２ S: 192.02450, found: 192.02428 IR (neat): 2945, 1708, 1520, 1289, 1242, 1173, 760cm －１

[0083] Example 2-4 Methyl-5-methoxybenzo[b]thiophene-2-carboxylate (3b) (42.4 mg, 0.191 mmol, yield 96%) was obtained as a white solid from 5-methoxybenzo[b]thiophene (32.7 mg, 0.199 mmol) in the same manner as in Example 2-1, except that the obtained crude product was purified by silica gel chromatography (hexane:ethyl acetate=5:1).

[0084] Example 2-5 Methyl-5-methoxybenzo[b]thiophene-2-carboxylate (3b) (37.7 mg, 0.170 mmol, yield 85%) was obtained as a white solid from 5-methoxybenzo[b]thiophene (32.7 mg, 0.199 mmol) in the same manner as in Example 2-2, except that the obtained crude product was purified by silica gel chromatography (hexane:ethyl acetate=5:1).

[0085] Example 2-6 Methyl-5-methoxybenzo[b]thiophene-2-carboxylate (3b) (25.5 mg, 0.115 mmol, yield: 58%) was obtained as a white solid from 5-methoxybenzo[b]thiophene (32.6 mg, 0.199 mmol) in the same manner as in Example 2-3, except that the obtained crude product was purified by silica gel chromatography (hexane:ethyl acetate=5:1).

[0086] The results of analyzing the product 3b obtained in Examples 2-4 to 2-6 in the same manner as for the product 3a are shown below. From the results shown below, the product 3b obtained was confirmed to be methyl-5-methoxybenzo[b]thiophene-2-carboxylate. Mp: 102-104°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.98 (s, 1H), 7.72 (d, 1H, J = 8.8 Hz), 7.28 (s, 1H), 7.12 (dd, 1H, J = 9.3, 2.4 Hz), 3.94 (s, 3H), 3.88 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ163.3, 157.9, 135.0, 139.8, 134.4, 130.3, 123.5, 118.2, 106.6, 55.6, 52.5 LRMS (EI) m / z: 222 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １１ H １０ O ３S: 222.03506, found: 222.03437 IR (neat): 2962, 2931, 1706, 1517, 1456, 1423, 1289, 1077 cm －１

[0087] Example 2-7 Methyl-5-chlorobenzo[b]thiophene-2-carboxylate (3c) (43.2 mg, 0.191 mmol, yield 96%) was obtained as a white solid from 5-chlorobenzo[b]thiophene (33.7 mg, 0.200 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction in Example 2-1 was carried out at 160°C for 3 hours and the crude product was purified by preparative thin-layer chromatography (hexane:ethyl acetate=20:1).

[0088] Example 2-8 Methyl-5-chlorobenzo[b]thiophene-2-carboxylate (3c) (44.5 mg, 0.196 mmol, yield 98%) was obtained as a white solid from 5-chlorobenzo[b]thiophene (33.7 mg, 0.200 mmol) in the same manner as in Example 2-2, except that the carboxylation reaction in Example 2-2 was carried out at 160°C for 3 hours and the crude product was purified by preparative thin-layer chromatography (hexane:ethyl acetate=20:1).

[0089] Example 2-9 Methyl-5-chlorobenzo[b]thiophene-2-carboxylate (3c) (36.7 mg, 0.162 mmol, yield 81%) was obtained as a white solid from 5-chlorobenzo[b]thiophene (33.7 mg, 0.200 mmol) in the same manner as in Example 2-3, except that the carboxylation reaction in Example 2-3 was carried out at 160°C for 3 hours and the crude product was purified by preparative thin-layer chromatography (hexane:ethyl acetate=20:1).

[0090] The results of analyzing the product 3c obtained in Examples 2-7 to 2-9 in the same manner as for the product 3a are shown below. From the results shown below, the product 3c obtained was confirmed to be methyl-5-chlorobenzo[b]thiophene-2-carboxylate. Mp: 108-110°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.99 (s, 1H), 7.86 (d, 1H, J = 1.4), 7.79 (d, 1H, J = 6.0 Hz), 7.42 (dd, 1H, J = 6.0, 1.4 Hz), 3.96 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ162.9, 140.3, 139.8, 135.4, 131.3, 129.7, 127.6, 124.9, 123.9, 52.7 LRMS (EI) m / z: 226 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １０ H ７ ClO ２ S: 225.98553, found: 225.98592 IR (neat): 2933, 1720, 1559, 1517, 1251, 1175cm －１

[0091] [Example 3] Silylated compounds were produced using the following aromatic compounds. The silylated compounds produced in each example were analyzed in the same manner as for Product 3a, and were confirmed to be the desired carboxylated compounds shown below.

[0092] Example 3-1 Methyl-5-cyanobenzo[b]thiophene-2-carboxylate (3d) shown below was prepared as follows.

[0093] Methyl-5-cyanobenzo[b]thiophene-2-carboxylate (3d) (40.5 mg, 0.187 mmol, yield 94%) was obtained as a white solid from 5-cyanobenzo[b]thiophene (32.7 mg, 0.199 mmol) in the same manner as in Example 2-1, except that the obtained crude product was purified by silica gel chromatography (hexane:ethyl acetate=5:1). Mp: 168-170°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 8.22 (s, 1H), 8.10 (s, 1H), 7.98 (d, 1H, J = 8.8 Hz), 7.66 (dd, 1H, J = 8.8, 1.4 Hz), 3.98 (s, 3H) １３C-NMR (100MHz, CDCl ３ / TMS): σ162.3, 145.7, 138.4, 136.3, 130.1, 129.8, 128.4, 123.9, 118.7, 109.0, 52.9 LRMS (EI) m / z: 217 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １１ H ７ O ２ S: 217.01975, found: 217.01935 IR (neat): 3087, 2965, 2925, 2229, 1720, 1527, 1435, 1248, 1057 cm －１

[0094] Example 3-2 Methyl-5-bromobenzo[b]thiophene-2-carboxylate (3e) shown below was prepared as follows.

[0095] Methyl-5-bromobenzo[b]thiophene-2-carboxylate (3e) (51.2 mg, 0.190 mmol, yield 95%) was obtained as a white solid from 5-bromobenzo[b]thiophene (42.5 mg, 0.199 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction in Example 2-1 was carried out at 160°C for 3 hours. Mp: 112-114°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 8.03 (s, 1H), 7.98 (s, 1H), 7.73 (d, 1H, J = 8.8 Hz), 7.55 (dd, 1H, J = 8.8, 2.0 Hz), 3.95 (s, 3H) １３ C-NMR (150MHz, CDCl ３ / TMS): σ162.7, 140.6, 140.1, 135.0, 129.9, 129.4, 127.9, 124.0, 118.8, 52.6 LRMS (EI) m / z: 272 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １０ H ７ BrO ２S: 269.93501, found: 269.93552 IR (neat): 2967, 1718, 1516, 1283, 1248, 1065cm －１

[0096] Example 3-3 Methyl 2,4,6-trichlorobenzoate (3f) shown below was prepared as follows.

[0097] Methyl 2,4,6-trichlorobenzoate (3f) (45.1 mg, 0.156 mmol, yield 78%) was obtained as a white solid from 2,4,6-trichlorobenzene (36.5 mg, 0.201 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction was carried out at 100°C for 5 hours and the crude product was purified by silica gel chromatography (hexane:ethyl acetate = 40:1). Mp: 41-43°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.35 (s, 2H), 3.97 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ164.5, 136.2, 132.7, 132.1, 128.0, 53.1 LRMS (EI) m / z: 238 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C ８ H ５ Cl ３ O ２ :237.9355, found:237.935 IR(neat):2962,1744,1580,1383,1266,1115,846cm －１

[0098] Example 3-4 Methyl 2,4,6-tribromobenzoate (3 g) shown below was prepared as follows.

[0099] Methyl 2,4,6-tribromobenzoate (3 g) (61.0 mg, 0.164 mmol, yield 82%) was obtained as a white solid from 2,4,6-tribromobenzene (62.7 mg, 0.199 mmol) in the same manner as in Example 2-1, except that the amount of silyl alkyl carbonate compound (1a) used was changed to 3 equivalents, the carboxylation reaction was carried out at 100°C for 5 hours, and the crude product was purified by silica gel chromatography (hexane:ethyl acetate = 40:1). Mp: 65-66°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.71 (s, 2H), 3.97 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ166.0, 136.6, 134.0, 124.0, 120.2, 53.1 LRMS (EI) m / z: 372 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C ８ H ５ Br ３ O ２ :369.78397, found:369.7847 IR(neat):2960,1739,1540,1271,1193,1136,832cm －１

[0100] Examples 3-5 Methyl-5-benzoylthiophene-2-carboxylate (3h) shown below was prepared as follows.

[0101] In the same manner as in Example 2-1, methyl-5-benzoylthiophene-2-carboxylate (3h) (49.2 mg, 0.200 mmol, yield 99%) was obtained as a white solid from 1-benzoylthiophene (38.0 mg, 0.202 mmol). Mp: 69-70°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.89-7.87 (m, 2H), 7.80 (d, 1H, J = 3.88), 7.65-7.60 (m, 2H), 7.54-7.50 (m, 2H), 3.94 (s, 3H) １３C-NMR (150MHz, CDCl ３ / TMS): σ188.0, 162.0, 147.8, 139.7, 137.2, 133.8, 133.1, 133.0, 129.2, 128.6, 52.6 LRMS (EI) m / z: 246 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １３ H １０ O ３ S: 246.03506, found: 246.03568 IR (neat): 2950, ​​1715, 1635, 1525, 1283, 1102 cm －１

[0102] Examples 3-6 Methyl 2-cyano-6-fluorobenzoate (3i) shown below was prepared as follows.

[0103] Methyl 2-cyano-6-fluorobenzoate (3i) (23.8 mg, 0.133 mmol, yield 67%) was obtained as a white solid from 1-cyano-3-fluorobenzene (24.2 mg, 0.200 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction was carried out at 130°C and the crude product was purified by preparative thin-layer chromatography (hexane:ethyl acetate = 10:1). Mp: 70-75°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.61-7.58 (m, 2H), 7.43-7.40 (m, 1H), 3.94 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ 162.5 (d, ３ J ＣＦ =2.9Hz), 160.7(d, １ J ＣＦ =258.5Hz), 133.5(d, ３ J ＣＦ =10.1Hz), 130.1(d, ３ J ＣＦ =4.3Hz), 122.9(d, ２ J ＣＦ =15.8Hz), 121.6(d,２ J ＣＦ =23.0Hz), 116.1(d, ４ J ＣＦ =2.9Hz), 114.1(d, ４ J ＣＦ =2.9Hz), 53.3. LRMS (EI) m / z: 179 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C ９ H ６ FNO ２ :179.0383, found:179.03877 IR(neat):3090,2959,2243,1726,1578cm －１

[0104] Examples 3-7 Methyl-5-bromothiophene-2-carboxylate (3j) shown below was prepared as follows.

[0105] In the same manner as in Example 2-1, methyl-5-bromothiophene-2-carboxylate (3j) (37.2 mg, 0.169 mmol, yield 85%) was obtained as a white solid from 2-bromothiophene (32.6 mg, 0.200 mmol). Mp: 59-60°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.55 (d, 1H, J = 3.92 Hz), 7.07 (d, 1H, J = 4.4 Hz), 3.87 (s, 3H) １３ C-NMR (150MHz, CDCl ３ / TMS): σ161.5, 134.6, 133.6, 131.0, 120.2, 52.2 LRMS (EI) m / z: 220 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C ６ H ５ BrO ２ S: 219.9194, found: 219.91934 IR (neat): 2965, 1710, 1437, 1332, 1260, 1093 cm －１

[0106] Example 3-8 Methyl-3-methylbenzo[b]thiophene-2-carboxylate (3k) shown below was prepared as follows.

[0107] In the same manner as in Example 2-1, methyl-3-methylbenzo[b]thiophene-2-carboxylate (3k) (29.8 mg, 0.144 mmol, yield 72%) was obtained as a white solid from 3-methylbenzo[b]thiophene (29.8 mg, 0.201 mmol). Mp: 100-103°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.86-7.82 (m, 2H), 7.49-7.42 (m, 2H), 3.93 (s, 3H), 2.79 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ163.9, 141.2, 140.4, 140.1, 127.1, 126.4, 124.4, 123.6, 122.6, 52.0, 13.1 LRMS (EI) m / z: 206 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １１ H １０ O ２ S: 206.0402, found: 206.04050 IR (neat): 2929, 1707, 1441, 1268, 1237, 1107 cm －１

[0108] Example 3-9 Methyl-5-phenylthiophene-2-carboxylate (31) shown below was prepared as follows.

[0109] Methyl-5-phenylthiophene-2-carboxylate (31) (41.5 mg, 0.191 mmol, yield 96%) was obtained as a white solid from 2-phenylthiophene (32.0 mg, 0.200 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction in Example 2-1 was carried out at 180°C. Mp: 98-99°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.77 (d, 1H, J = 3.88 Hz), 7.65-7.63 (m, 2H), 7.43-7.35 (m, 3H), 7.29 (d, 1H, 3.92 Hz), 3.91 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ162.8, 151.4, 134.5, 133.5, 132.1, 129.2, 128.9, 126.3, 123.7, 52.3 LRMS (EI) m / z: 218 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １２ H １０ O ２ S: 218.04015, found: 218.03908 IR (neat): 2929, 1700, 1559, 1540, 1454, 1433, 1347, 1265, 1102 cm －１

[0110] Example 3-10 Methyl-benzofuran-2-carboxylate (3m) shown below was prepared as follows.

[0111] Methyl benzofuran-2-carboxylate (3m) (26.0 mg, 0.148 mmol, yield 74%) was obtained as a yellow solid from benzo[b]furan (23.8 mg, 0.201 mmol, pKa = 33.2 (THF)) in the same manner as in Example 2-1, except that the carboxylation reaction in Example 2-1 was carried out at 180°C. Mp: 51-53°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.69 (d, 1H, J = 7.8 Hz), 7.60 (d, 1H, J = 8.8 Hz), 7.54 (s, 1H), 7.46 (dt, 1H, J = 7.32, 1.48 Hz), 3.98 (s, 3H), 7.31 (t, 1H) １３ C-NMR (150MHz, CDCl ３ / TMS): σ159.9, 155.6, 145.3, 127.6, 126.9, 123.7, 122.8, 114.0, 112.3, 52.3 LRMS (EI) m / z: 176 (M ＋ ) HRMS (FAB) m / z: (MH＋ ) Calcd. for C １０ H ８ O ３ :176.04734, found:176.04628 IR(neat):2956,1734,1713,1564,1296,1175,1086cm －１

[0112] Example 3-11 Methyl-2-([1,1'-biphenyl]-4-yl)acetate (3o) shown below was prepared as follows.

[0113] Under an argon atmosphere, 4-methylbiphenyl (phenyltoluene) (33.5 mg, 0.199 mmol, pKa = 38.6 (THF)), CsF (152.2 mg, 1.00 mmol), the silyl alkyl carbonate compound (1a) (312.3 mg, 0.988 mmol) synthesized in Example 1, and DMI (1 mL) were added to a screw-cap test tube (φ = 1.65 cm, 10.5 cm). After sealing with a screw cap, the mixture was heated and stirred at 180°C for 15 hours using a heat block. Next, 1 M hydrochloric acid (4 mL) was added, and the mixture was heated and stirred at 80°C for 4 hours. After that, water (3 mL) was added, and the resulting solution was extracted three times with ethyl acetate (3 mL). The ethyl acetate solutions were combined and washed with water (3 mL) and saturated saline (3 mL), followed by addition of NaCl. ２ SO ４ The mixture was dried at 75°C, and the solvent was evaporated under reduced pressure. The resulting carboxylic acid product was purified by silica gel chromatography (dichloromethane:methanol = 6:1). Next, the carboxylic acid was dissolved in methanol, and a hexane solution of trimethylsilyldiazomethane (0.6 M, 1.25 mL, 0.75 mmol) was added at 0°C. The mixture was stirred at room temperature for 15 minutes. The solvent was then evaporated under reduced pressure. The resulting crude product was purified by preparative thin-layer chromatography (hexane:ethyl acetate = 20:1) and silica gel chromatography (hexane:ethyl acetate = 20:1) to obtain methyl-2-([1,1'-biphenyl]-4-yl)acetate (3o) (24.6 mg, 0.109 mmol, yield 55%) as a colorless, transparent liquid. １H-NMR (400MHz, CDCl ３ / TMS): σ 7.59-7.55 (m, 4H), 7.45, 7.41 (m, 2H), 7.37-7.32 (m, 3H), 3.72 (s, 3H), 3.67 (s, 2H) １３ C-NMR (150MHz, CDCl ３ / TMS): σ172.0, 140.8, 140.1, 133.0, 130.0, 128.7, 127.3, 127.2, 127.0, 52.1, 40.8 LRMS (EI) m / z: 226 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １５ H １４ O ２ :226.09938, found:226.09855 IR(neat):3031,1734,1009,822,755cm －１

[0114] Example 3-12 Methyl-2-(2-methoxy-2-oxoethyl)benzo[b]thiophene-3-carboxylate (3p) shown below was prepared as follows.

[0115] Methyl-2-(2-methoxy-2-oxoethyl)benzo[b]thiophene-3-carboxylate (3p) (35.3 mg, 0.134 mmol, yield 67%) was obtained as a white solid from 2-methylbenzo[b]thiophene (29.8 mg, 0.200 mmol) in the same manner as in Example 3-11, except that the carboxylation reaction in Example 3-11 was carried out at 160°C. Mp: 85-86°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 8.44, (d, 1H, J = 7.8 Hz), 7.79 (d, 1H, J = 7.8 Hz), 7.45 (dt, 1H, J = 8.3, 1.0 Hz), 7.37 (dt, 1H, J = 8.8, 1.0 Hz), 4.28 (s, 2H), 3.96 (s, 3H), 3.75 (s, 3H) １３ C-NMR (150MHz, CDCl ３ / TMS): σ170.0, 163.8, 146.9, 137.8, 137.7, 125.3, 124.90, 124.87, 124.1, 121.7, 52.3, 51.6, 35.8 LRMS (EI) m / z: 264 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １３ H １２ O ４ S: 264.04563, found: 264.04445 IR (neat): 2960, 1746, 1696, 1194, 1178, 1016, 749cm －１

[0116] Example 3-13 Methyl-3-bromobenzo[b]thiophene-2-carboxylate (3q) shown below was prepared as follows.

[0117] Methyl-3-bromobenzo[b]thiophene-2-carboxylate (3q) (53.5 mg, 0.198 mmol, yield 99%) was obtained as a white solid from 3-bromobenzo[b]thiophene (42.6 mg, 0.200 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction in Example 2-1 was carried out at 160°C for 1 hour. １ H-NMR (400MHz, CDCl ３ / TMS): σ 8.00-7.98 (m, 1H), 7.85-7.82 (m, 1H), 7.56-7.49 (m, 2H), 3.98 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ161.8, 139.2, 138.5, 128.1, 127.1, 125.6, 125.3, 122.6, 115.0, 52.5 LRMS (EI) m / z: 272 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C １０ H ７ BrO ２ S: 269.93501, found: 269.93560 IR (neat): 2962, 1723, 1517, 1228, 1058 cm －１

[0118] Example 3-14 Methyl 2-cyano-6-nitrobenzoate (3r) shown below was prepared as follows.

[0119] Methyl 2-cyano-6-nitrobenzoate (3r) (25.8 mg, 0.125 mmol, yield 63%) was obtained as a yellow solid from 1-cyano-3-nitrobenzene (29.4 mg, 0.200 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction was carried out at 90°C for 15 hours and the crude product was purified by silica gel chromatography (hexane:dichloromethane=1:10). １ H-NMR (400MHz, CDCl ３ / TMS): σ 8.34 (dd, 1H, J = 8.5, 1.0 Hz), 8.01 (dd, 1H, J = 7.8, 1.0 Hz), 7.77 (t, 1H, J = 8.3 Hz), 4.07 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ163.5, 146.7, 137.6, 132.9, 131.4, 128.2, 114.6, 113.2, 54.2 LRMS (EI) m / z: 206 (M ＋ ) HRMS (FAB) m / z: (MH ＋ ) Calcd. for C ９ H ６ N ２ O ４ :206.03276, found:206.03354 IR(neat):3104,2239,1733,1535,1363,1278cm －１

[0120] Example 3-15 Methyl-3-cyano-1-methylindole-2-carboxylate (3s) shown below was prepared as follows.

[0121] Methyl-3-cyano-1-methylindole-2-carboxylate (3s) (42.4 mg, 0.198 mmol, yield 99%) was obtained as a yellow solid from 3-cyano-1-methylindole (31.2 mg, 0.200 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction was carried out at 120°C and the crude product was purified by silica gel chromatography (hexane:ethyl acetate = 2:1). １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.84 (d, 1H, J = 8.3 Hz), 7.52-7.46 (m, 2H), 7.40-7.34 (m, 1H), 4.15 (s, 3H), 4.05 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ160.2, 137.9, 131.7, 126.9, 126.6, 123.3, 120.8, 114.7, 111.1, 92.0, 52.5, 32.4 LRMS (EI) m / z: 214 (M ＋ ) HRMS (EI) m / z: (M ＋ ) Calcd. for C １２ H １０ N ２ O ２ :214.0742, found:214.0736 IR(neat):2952,2223,1723,1250,759,752cm －１

[0122] Example 3-16 Methyl-3-formyl-1-methylindole-2-carboxylate (3t) shown below was prepared as follows.

[0123] Methyl-3-formyl-1-methylindole-2-carboxylate (3t) (35.7 mg, 0.164 mmol, yield 82%) was obtained as a yellow solid from 3-formyl-1-methylindole (31.8 mg, 0.200 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction was carried out at 150°C and the crude product was purified by silica gel chromatography (hexane:ethyl acetate=5:1). １ H-NMR (400MHz, CDCl ３ / TMS): σ 10.59 (s, 1H), 8.52 (d, 1H, J = 8.3 Hz), 7.48-7.43 (m, 2H), 7.39-7.35 (m, 1H), 4.10 (s, 3H), 4.06 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ188.3, ​​161.4, 138.2, 133.1, 126.2, 124.4, 124.0, 123.7, 119.8, 110.3, 52.6, 32.4 LRMS (EI) m / z: 217 (M ＋ ) HRMS (EI) m / z: (M ＋ ) Calcd. for C １２ H １１ NO ３ :217.0739, found:217.0741 IR(neat):2955,1714,1641,1260,1245cm －１

[0124] Example 3-17 Methyl-5-(4-chlorophenyl)furan-2-carboxylate (3u) shown below was prepared as follows.

[0125] Methyl-5-(4-chlorophenyl)furan-2-carboxylate (3u) (15.8 mg, 0.0669 mmol, yield 34%) was obtained as a yellow solid from 2-(4-chlorophenyl)furan (35.5 mg, 0.199 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction in Example 2-1 was carried out at 180°C. １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.72 (d, 2H, J = 8.8 Hz), 7.40 (d, 2H, J = 8.8 Hz), 7.24 (d, 1H, J = 3.4 Hz), 6.73 (d, 1H, 3.4 Hz), 3.92 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ159.1, 156.4, 143.8, 134.8, 129.1, 127.9, 126.0, 120.0, 107.2, 51.9 LRMS (EI) m / z: 236 (M ＋ ) HRMS (EI) m / z: (M ＋ ) Calcd. for C １２ H ９ ClO ３ :236.0240, found:236.0251 IR(neat):2947,1725,1472,1435,1298,1137cm －１

[0126] Example 3-18 Methyl-2-chloro-6-cyanobenzene-1-carboxylate (3v) shown below was prepared as follows.

[0127] Methyl-2-chloro-6-cyanobenzene-1-carboxylate (3v) (26.9 mg, 0.138 mmol, yield 68%) was obtained as a white solid from 3-chlorobenzonitrile (27.6 mg, 0.201 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction was carried out at 130°C and the crude product was purified by silica gel chromatography (hexane:ethyl acetate=10:1). Mp 72-75°C １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.67-7.64 (m, 2H), 7.50 (t, 1H, J = 7.8 Hz), 4.04 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ164.2, 135.7, 134.5, 133.1, 131.41, 131.35, 115.8, 112.9, 53.4 LRMS (EI) m / z: 195 (M ＋ ) HRMS (EI) m / z: (M ＋) Calcd. for C ９ H ６ ClNO ２ :195.0087, found:195.0078 IR(neat):3081,2238,1724,1561,1460,1282,1110cm －１

[0128] Example 3-19 Methyl-2,6-dicyanobenzene-1-carboxylate (3w) shown below was prepared as follows.

[0129] Methyl-2,6-dicyanobenzene-1-carboxylate (3w) (35.2 mg, 0.189 mmol, yield 94%) was obtained as a white solid from 1,3-dicyanobenzene (25.7 mg, 0.201 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction was carried out at 130°C and the crude product was purified by silica gel chromatography (dichloromethane). １ H-NMR (400MHz, CDCl ３ / TMS): σ 8.02 (d, 2H, J = 7.3 Hz), 7.78 (t, 1H, J = 7.8 Hz), 4.11 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ162.5, 137.8, 136.4, 132.4, 115.6, 114.5, 53.8 LRMS (EI) m / z: 186 (M ＋ ) HRMS (EI) m / z: (M ＋ ) Calcd. for C １０ H ６ N ２ O ２ :186.0429, found:186.0434 IR(neat):3073,2243,2237,1728,1582,1456,1440cm －１

[0130] Example 3-20 Methyl-2,3,4-trichlorobenzene-1-carboxylate (3x) shown below was prepared as follows.

[0131] In the same manner as in Example 2-1, methyl-2,3,4-trichlorobenzene-1-carboxylate (3x) (36.3 mg, 0.153 mmol, yield 76%) was obtained as a yellow solid from 1,2,3-trichlorobenzene (36.5 mg, 0.153 mmol). １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.63 (d, 1H, J = 8.8 Hz), 7.44 (d, 1H, J = 8.8 Hz), 3.94 (s, 3H) １３ C-NMR (100MHz, CDCl ３ / TMS): σ165.1, 137.5, 133.7, 133.5, 130.7, 128.9, 128.1, 52.8 LRMS (EI) m / z: 238 (M ＋ ) HRMS (EI) m / z: (M ＋ ) Calcd. for C ８ H ５ Cl ３ O ２ :237.9355, found:237.9359 IR(neat):3095,2959,1732,1576,1425,1361cm －１

[0132] Example 3-21 Methyl-2,3-dicyanobenzene-1-carboxylate (3y) shown below was prepared as follows.

[0133] Methyl-2,3-dicyanobenzene-1-carboxylate (3y) (29.6 mg, 0.159 mmol, yield 79%) was obtained as a yellow solid from 1,2-dicyanobenzene (25.8 mg, 0.201 mmol) in the same manner as in Example 2-1, except that the carboxylation reaction was carried out at 150°C and the crude product was purified by silica gel chromatography (hexane:ethyl acetate=2:1). １ H-NMR (400MHz, CDCl ３ / TMS): σ 8.39 (dd, 1H, J = 8.0, 1.0 Hz), 8.01 (dd, 1H, J = 8.0, 1.5 Hz), 7.84 (t, 1H, J = 7.8 Hz), 4.06 (s, 3H)１３ C-NMR (100MHz, CDCl ３ / TMS): σ162.9, 136.6, 134.8, 134.1, 132.9, 118.7, 116.2, 114.9, 114.0, 53.5 LRMS (EI) m / z: 186 (M ＋ ) HRMS (EI) m / z: (M ＋ ) Calcd. for C １０ H ６ N ２ O ２ :186.0429, found:186.0435 IR(neat):2236,1723,1579,1437,1290,776cm －１

[0134] The results of Examples 2 and 3 demonstrate that the use of the carboxylation reagent of the present invention allows aromatic compounds to be carboxylated with simple procedures, thereby producing carboxylated compounds. Furthermore, the carboxylation reagent of the present invention is easy to handle, allowing the amount used to be precisely measured, facilitating control of the reaction system and avoiding the need for specialized production equipment. In particular, the use of the preferred carboxylation reagent of the present invention as the carboxylation reagent allows the reaction temperature to be set relatively low, and carboxylated compounds can be produced with high reaction efficiency (yield).

[0135] [Example 4: １３ C-labeled carboxylation reagent was used １３ Preparation of C-labeled carboxylated compound] First, １３ A C-labeled carboxylation reagent was synthesized as follows. Example 4-1: １３ C-labeled carboxylation reagent ( １３ Synthesis of C-1a)> In Example 1-1, instead of carbon dioxide, １３ The carbonyl carbon was determined in the same manner as in Example 1-1, except that C-labeled carbon dioxide was used. １３ C-labeled 3-ethylpentan-3-yl(triisopropylsilyl)carbonate: TIPSO １３ CO ２ CEt ３ ( １３C-1a) was synthesized (yield 37%). １３ C-labeled carboxylation reagent is TIPSO １３ CO ２ CEt ３ It was confirmed in the same manner as in Example 1-1 that the carbonyl carbon １３ The C labeling was confirmed by qC NMR.

[0136] Example 4-2 １３ C-labeled carboxylation reagent ( １３ Synthesis of C-1b)> In Example 1-2, instead of carbon dioxide, １３ The carbonyl carbon was determined in the same manner as in Example 1-2, except that C-labeled carbon dioxide was used. １３ C-labeled tert-butyl(triisopropylsilyl)carbonate: TIPSO １３ CO ２ -t-Bu( １３ C-1b) was synthesized (yield 48%). １３ C-labeled carboxylation reagent is TIPSO １３ CO ２ It was confirmed in the same manner as in Example 1-2 that the carbonyl carbon was -t-Bu. １３ The C labeling was confirmed by qC NMR.

[0137] Example 4-3 In Example 2-1, instead of the silyl alkyl carbonate compound (1a), １３ C-labeled carboxylation reagent TIPSO １３ CO ２ CEt ３ ( １３ The carbonyl carbon was prepared in the same manner as in Example 2-1, except that C-1a) was used. １３ C-labeled methylbenzo[b]thiophene-2-carboxylate ( １３ C-3a) (yield 95%) was obtained as a white solid. １３ C-labeled methylbenzo[b]thiophene-2-carboxylate ( １３ It was confirmed in the same manner as in Example 2-1 that the carbonyl carbon was C-3a). １３It is labeled with C ( １３ The C ratio of 97%) was confirmed by qC NMR.

[0138] Example 4-4 In Example 2-2, instead of the silyl alkyl carbonate compound (1b), １３ C-labeled carboxylation reagent TIPSOCO ２ -t-Bu( １３ The carbonyl carbon was prepared in the same manner as in Example 2-2, except that C-1b) was used. １３ C-labeled methylbenzo[b]thiophene-2-carboxylate ( １３ C-3a) (yield 91%) was obtained as a white solid. １３ C-labeled methylbenzo[b]thiophene-2-carboxylate ( １３ It was confirmed in the same manner as in Example 2-2 that the carbonyl carbon was C-3a). １３ It is labeled with C ( １３ The C ratio of 97%) was confirmed by qC NMR.

[0139] <Examples 4-5> In Examples 3-12, instead of the silyl alkyl carbonate compound (1a), １３ C-labeled carboxylation reagent TIPSOCO ２ CEt ３ ( １３ The carbonyl carbon was prepared in the same manner as in Example 3-12, except that C-1a) was used. １３ C-labeled methyl-2-(2-methoxy-2-oxoethyl)benzo[b]thiophene-3-carboxylate ( １３ C-3p) (yield 67%) was obtained as a white solid. １３ C-labeled methyl-2-(2-methoxy-2-oxoethyl)benzo[b]thiophene-3-carboxylate ( １３ It was confirmed in the same manner as in Example 3-12 that the carbonyl carbon was １３ It is labeled with C ( １３ C ratio 96% (-C- １３ CO ２ Me) and 98% (-CH ２ -１３ CO ２ Me) was confirmed by qC NMR.

[0140] From the results of Example 4, １３ Instead of C-unlabeled carboxylation reagents １３ By using a C-labeled carboxylation reagent, the carbonyl carbon １３ It is understood that C-labeled carboxylated compounds can be prepared.

[0141] Example 5: Preparation of organic carboxylated compounds using organoboron compounds as substrates Silylated compounds were prepared using the following organoboron compounds: Methyl-4-methoxybenzoate (4) shown below was prepared as follows.

[0142] Under an argon atmosphere, 2-(4-methoxyphenyl)-5,5-dimethyl-1,3,2-dioxaborinane (88.0 mg, 0.400 mmol), CuCl (2.0 mg, 0.020 mmol), CsF (91.6 mg, 0.603 mmol), the silyl alkyl carbonate compound (1a) synthesized in Example 1 (190.9 mg, 0.603 mmol), and DMI (1 mL) were placed in a screw-cap test tube (φ=1.65 cm, 10.5 cm). After sealing with a screw cap, the mixture was heated and stirred at 50°C for 15 hours using a heat block. Next, iodomethane (76 μL, 1.22 mmol) was added, and the mixture was heated and stirred at 30°C for 2 hours. After adding water (3 mL), the resulting solution was extracted three times with ethyl acetate (3 mL). The ethyl acetate solutions were combined and washed with water (3 mL) and saturated saline (3 mL). After that, the mixture was diluted with NaCl and HCl. ２ SO ４ The solvent was evaporated under reduced pressure, and the resulting crude product was purified by silica gel chromatography (hexane:ethyl acetate=20:1) to obtain methyl 4-methoxybenzoate (4) (63.6 mg, 0.383 mmol, yield 96%) as a colorless, transparent liquid.

[0143] The results of melting point, NMR, mass spectrometry (LRMS, HRMS), infrared absorption spectrum, and elemental analysis of Product 4 obtained in Example 5 are shown below. From the results shown below, it was confirmed that Product 4 obtained was methyl 4-methoxybenzoate. １ H-NMR (400MHz, CDCl ３ / TMS): σ 7.94 (d, 2H, J = 8.6 Hz), 6.87 (d, 2H, J = 9.0 Hz), 3.83 (s, 3H), 3.81 (s, 3H) １３ C-NMR (150MHz, CDCl ３ / TMS): σ166.8, 163.3, 131.5, 122.5, 113.5, 55.3, 53.8 LRMS (EI) m / z: 166 (M ＋ ) HRMS (EI) m / z: (M ＋ ) Calcd. for C ９ H １０ O ３ :166.0630, found:166.0635 IR(neat):2955, 2845, 1708, 1607, 1511, 1456, 1428, 1319cm －１

[0144] Considering the results of Example 5 in light of the results of Examples 2 and 3, it can be seen that by using the carboxylation reagent of the present invention, organoboron compounds can be carboxylated with simple operations, and carboxylated compounds can be produced. Furthermore, since the carboxylation reagent of the present invention is easy to handle, the amount used can be precisely weighed, the reaction system can be easily controlled, and the use of specialized production equipment can be avoided. Furthermore, when the carboxylation reagent of the present invention, particularly the preferred carboxylation reagent of the present invention, is used as the carboxylation reagent, the reaction temperature can be set relatively low, as in Example 3 using an aromatic compound, and carboxylated compounds can be produced with high reaction efficiency (yield). Furthermore, considering the results of Example 5 in light of the results of Example 4, it can be seen that in the carboxylation reaction of organoboron compounds, １３ Instead of C-unlabeled carboxylation reagents １３ By using a C-labeled carboxylation reagent, the carbonyl carbon can be converted to a carboxyl group similar to that in Example 4. １３It is understood that C-labeled carboxylated compounds can be prepared.

[0145] While the present invention has been described in connection with embodiments thereof, we do not intend to limit our invention to any of the details of the description unless otherwise specified, and believe that the claims should be construed broadly without departing from the spirit and scope of the invention as set forth in the appended claims.

[0146] This application claims priority based on Japanese Patent Application No. 2024-091429, filed on June 5, 2024, the contents of which are incorporated herein by reference as part of the present specification.

Claims

1. A carboxylation reactant containing a silyl alkyl carbonate compound represented by the following formula (I): In formula (I), X is １２ C or １３ C indicates R １ ~R ３ represents an alkyl group or an aryl group, and R ４ represents an alkyl group.

2. The above R ４ The carboxylation reactant according to claim 1 , wherein represents a branched alkyl group.

3. The above R ４ -C(R ４Ａ ) ３ (R ４Ａ The carboxylation reagent according to claim 1, wherein R represents an alkyl group.

4. The above R １ ~R ３ The carboxylation reagent according to claim 1 , wherein at least one of the groups represents a branched alkyl group.

5. The above R １ ~R ３ At least one of R represents a branched alkyl group, and ４ -C(R ４Ａ ) ３ (R ４Ａ The carboxylation reagent according to claim 1, wherein R represents an alkyl group.

6. A silyl alkyl carbonate compound represented by the following formula (II): In formula (II), X is １２ C or １３ Indicates C. R １１ ~R １３ represents an alkyl group or an aryl group, and R １４ represents an alkyl group. １２ If C, then R １１ ~R １３ At least one of R represents a branched alkyl group, and R １４ -C(R ４Ａ ) ３ (R ４Ａ represents an alkyl group).

7. X is １２ When C, said R ４Ａ The silyl alkyl carbonate compound according to claim 6, wherein at least one of the above represents an alkyl group having two or more carbon atoms.

8. X is １３ When C, said R １１ ~R １３ At least one of R represents a branched alkyl group, or １４ is the -C(R ４Ａ ) ３ (R ４Ａ The silyl alkyl carbonate compound according to claim 6, wherein R represents an alkyl group.

9. A method for producing a carboxylated compound, comprising reacting an aromatic compound containing a carbon atom bonded to a hydrogen atom with the carboxylation reagent according to any one of claims 1 to 5 in the presence of a fluoride anion.

10. The production method according to claim 9, wherein the aromatic compound is at least one selected from aromatic compounds containing a carbon atom to which a hydrogen atom is bonded as an aromatic ring-forming carbon atom, and aromatic compounds having an aliphatic group containing a carbon atom to which a hydrogen atom is bonded as a substituent.

11. A method for producing a carboxylated compound, which comprises reacting an organoboron compound with the carboxylation reagent according to any one of claims 1 to 5 in the presence of a fluoride anion.

12. The method of claim 11, wherein the organoboron compound is a boronate ester.

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