JP2013155138A - Novel metalated-borated alkene compound, method of producing the same, and use of the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel metalated-borated alkene compound having a metal moiety and a boron moiety different in reactivity, a method of producing the same, and an application technology of the same.SOLUTION: Since reactivity of a metal moiety is different from that of a boron moiety in a metalated-borated alkene compound having a metal atom (e.g., tin and the like) and boron at a carbon-carbon double bond of alkene, a compound represented by formula (2) wherein different functional groups are introduced respectively to the metal moiety and the boron moiety can be produced. In the formula: R1-R7 are each hydrogen, an alkyl group or the like; and M is Sn or the like.

Description

  The present invention relates to a novel metal-borated alkene compound, a production method thereof and use thereof.

  Organoboron compounds are used not only as intermediates in organic synthesis, but also as functional molecules with Lewis acid catalytic ability and sugar recognition ability, and as pharmaceuticals in neutron capture therapy for cancer. Has been recognized again. In particular, the addition of diboron to a carbon-carbon unsaturated bond has attracted attention as an attractive reaction for simultaneously introducing two boron groups into an organic molecule.

  The present inventors have so far developed a method for synthesizing an orthodiborated arene compound by reacting aline with bis (pinacolato) diboron in the presence of fluoride ion using a platinum-isocyanide complex as a catalyst. (Patent Document 1, Non-Patent Document 1). In addition, it has been reported that addition of diboron to carbon-carbon unsaturated multiple bonds such as alkyne proceeds efficiently by using a platinum catalyst, and the corresponding diboronated alkene can be produced regioselectively and stereoselectively ( Non-patent document 2).

JP 2008-44893 A (published February 28, 2008)

H. Yoshida et. Al., Chem. Commun., 46, 1763 (2010) T. Ishiyama et.al., Organometallics, 15, 713 (1995)

  By converting the boron moiety in the above-described diboronated alkene to another functional group, compounds having a complicated structure and various structures can be obtained. However, the two boron sites of the diboronated alkene are not different in reactivity. For this reason, there is a problem that it is difficult to produce a compound in which different functional groups are introduced into each boron site.

  The present invention has been made in view of the above problems, and an object of the present invention is to provide a novel metal-boronated alkene compound having a metal having different reactivity and a boron moiety, a method for producing the same, and a technique for using the same. There is.

  As a result of intensive studies in order to achieve the above object, the present inventors have obtained a metal-borated alkene compound in which a metal (for example, tin) and boron are introduced into a carbon-carbon unsaturated triple bond of an alkyne. As a result of the production, the reactivity was different between the metal site and the boron site in the compound, and therefore, a new finding that a different functional group can be introduced into each site was found, and the present invention was completed. That is, the present invention includes the following configurations.

  1. A metal-borated alkene compound represented by the following general formula (1).

(In formula (1), M represents a metal atom of Sn, Si, or Ge. R1 to R7 are each independently hydrogen, an optionally substituted alkyl group having 1 to 20 carbon atoms, An optionally substituted alkenyl group having 2 to 20 carbon atoms, an optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, and an optionally substituted group. Good C4-C20 heteroaryl group, C5-C20 heteroaralkyl group which may be substituted, C1-C20 alkylene group which may be substituted, Carbon number which may be substituted Represents an arylene group having 6 to 20 or an optionally substituted arylene-alkylene group having 1 to 20 carbon atoms, R1 and R2 may form a ring, and R6 and R7 are each independently A silicon-containing group Good.)
2. The compound of 1 shown by following General formula (2).

(In formula (2), M and R3 to R7 are the same as in formula (1).)
3. 3. The compound according to 1 or 2, which is any compound of the compound group represented by the following formula (3).

  4). (A) a compound represented by the following general formula (4);

(In formula (4), R6 and R7 are each independently hydrogen, an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, or a substituted group. An optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, an optionally substituted heteroaryl group having 4 to 20 carbon atoms, and optionally substituted. Represents a heteroaralkyl group having 5 to 20 carbon atoms, and may independently be a silicon-containing group.
(B) a compound represented by the following general formula (5);

(In Formula (5), M represents a metal atom of any one of Sn, Si, and Ge. R3 to R5 and R8 each independently represent hydrogen or an optionally substituted alkyl having 1 to 20 carbon atoms. A group, an optionally substituted alkenyl group having 2 to 20 carbon atoms, an optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, and a substituted group. An optionally substituted heteroaryl group having 4 to 20 carbon atoms and an optionally substituted heteroaralkyl group having 5 to 20 carbon atoms, X represents oxygen, sulfur, or nitrogen.)
(C) a diboron compound having a boron-boron bond,
(D) a catalyst containing a copper complex having a ligand represented by a compound represented by the following general formula (6) or N-cyclic heterocarbene,
A method for producing a metal-boronated alkene compound comprising a step of reacting in the presence of

(In Formula (6), R11 to R13 are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, and substituted. An aryl group having 6 to 20 carbon atoms, an aralkyl group having 7 to 20 carbon atoms which may be substituted, a heteroaryl group having 4 to 20 carbon atoms which may be substituted, and an optionally substituted carbon number 5-20 heteroaralkyl group, C1-C20 alkylene group which may be substituted, C6-C20 arylene group which may be substituted, or C1-C20 which may be substituted Represents an arylene-alkylene group.
5. 5. The method for producing a compound according to 4, wherein the copper is a copper compound having a leaving group containing an oxygen atom.

  6). Said R11-R13 is a manufacturing method of the compound of 4 or 5 which is a cyclohexyl group, t-butyl group, or an octyl group.

  7). The said diboron compound is a manufacturing method of the compound in any one of 4-6 which is a compound shown by following General formula (7).

(In Formula (7), R21 to R24 are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, and substituted. An aryl group having 6 to 20 carbon atoms, an aralkyl group having 7 to 20 carbon atoms which may be substituted, a heteroaryl group having 4 to 20 carbon atoms which may be substituted, and an optionally substituted carbon number 5-20 heteroaralkyl group, C1-C20 alkylene group which may be substituted, C6-C20 arylene group which may be substituted, or C1-C20 which may be substituted R21 and R22, and R23 and R24 may form a ring.)
8). The diboron compounds include bis (pinacol) diboron, bis (neopentylglycolate) diboron, bis (hexyleneglycolate) diboron, bis (catechol) diboron, bis (N, N, N ′, N′-tetramethyl- L-tartalamide glycolate) diboron, bis (N, N, N ′, N′-tetramethyl-D-tartalamide glycolate) diboron, bis (diethyl-D-tartarate glycolate) diboron, bis (diisopropyl- D-tartarate glycolate) diboron, bis (diethyl-L-tartalate glycolate) diboron, bis [(+)-pinandiolate] diboron, bis [(−) pinandiolate] diboron, and bis (diisopropyl- L-tartarate glycolate) a compound selected from the group consisting of diboron The manufacturing method of the compound in any one of 4-7 which is these.

  9. The manufacturing method of a compound including the process of converting the boron site | part and metal site | part in the metal-boronated alkene compound in any one of said 1-3 to another functional group, respectively.

  Since the metal-boronated alkene compound according to the present invention has different reactivity between the metal site and the boron site, the compound having different functional groups introduced into each site can be produced. Therefore, it is useful for the production of compounds having various functions and activities.

  An embodiment of the present invention will be described in detail below. All academic and patent documents mentioned in this specification are hereby incorporated by reference. Unless otherwise specified in this specification, “A to B” indicating a numerical range means “A or more and B or less”. “%” Means “% by weight” and “parts” means “parts by weight”.

<1. Metal-Boronated Alkenes Compound>
The metal-borated alkene compound according to the present invention is a metal-borated alkene compound represented by the general formula (1).

  Here, in formula (1), M represents any metal atom of Sn (tin), Si (silicon), and Ge (germanium). Among these, Sn is particularly preferable because it is different in reactivity from the boron site and has high versatility because research is progressing on the reaction. Si is preferable in that raw materials can be obtained at low cost.

  In formula (1), R1 to R7 are each independently hydrogen, an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, or a substituted group. An optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, an optionally substituted heteroaryl group having 4 to 20 carbon atoms, and optionally substituted. Good C5-C20 heteroaralkyl group, C1-C20 alkylene group which may be substituted, C6-C20 arylene group which may be substituted, or Carbon number which may be substituted 1-20 arylene-alkylene groups are represented. R1 and R2 may form a ring.

  Examples of the “alkyl group” include a linear, branched or cyclic alkyl group. For example, a linear or branched alkyl group having 1 to 20 carbon atoms or a cyclic alkyl group may be mentioned. Among them, an alkyl group having 1 to 12 carbon atoms is preferable, and an alkyl group having 1 to 10 carbon atoms is more preferable. Groups are preferred. Specifically, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, s-butyl group, t-butyl group, pentyl group, cyclopentyl group, hexyl group, cyclohexyl group, heptyl group, A cycloheptyl group, an octyl group, a cyclooctyl group, etc. are mentioned.

  Examples of the “alkenyl group” include linear or branched alkenyl groups. For example, a linear or branched alkenyl group having 2 to 20 carbon atoms can be mentioned, among which an alkenyl group having 2 to 12 carbon atoms is preferable, and an alkenyl group having 2 to 10 carbon atoms is more preferable. Specific examples include a vinyl group, a propenyl group, an isopropenyl group, an allyl group, a butenyl group, a pentenyl group, a geranyl group, and a farnesyl group.

  Examples of the “aryl group” include an aryl group having 6 to 20 carbon atoms, and specific examples include a phenyl group, a naphthyl group, an anthracenyl group, a phenanthryl group, and the like. Of these, an aryl group having 6 to 12 carbon atoms is preferable, and an aryl group having 6 to 10 carbon atoms is more preferable.

  Examples of the “aralkyl group” include an aralkyl group having 7 to 20 carbon atoms, and specific examples include a benzyl group, a phenethyl group, a naphthylmethyl group, and a naphthylethyl group. Of these, an aralkyl group having 7 to 12 carbon atoms is preferable, and an aralkyl group having 7 to 10 carbon atoms is more preferable.

  Examples of the “heteroaryl group” include, for example, a heteroaryl group containing 1 to 5 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom in addition to a carbon atom as a ring constituent atom. For example, furyl group, thienyl group, pyrrolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, furazanyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, pyridyl group, pyrimidinyl group, Pyridazinyl group, pyrazinyl group, triazinyl group, benzofuranyl group, isobenzofuranyl group, benzo [b] thienyl group, indolyl group, isoindolyl group, 1H-indazolyl group, benzimidazolyl group, benzoxazolyl group, benzothiazolyl group, 1H − Nzotriazolyl, quinolyl, isoquinolyl, cinnolyl, quinazolyl, quinoxalinyl, phthalazinyl, naphthyridinyl, purinyl, pteridinyl, carbazolyl, acridinyl, phenoxazinyl, phenothiazinyl, phenazinyl Group, thiantenyl group, indolizinyl group and the like. Of these, furyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, quinolyl, isoquinolyl, quinazolyl, etc. are preferred. .

  Examples of the “heteroaralkyl group” include, but are not particularly limited to, a heteroaralkyl group containing 1 to 5 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom in addition to a carbon atom as a ring constituent atom.

  Examples of the “alkylene group” include a linear or branched alkylene group. For example, a linear or branched alkylene group having 1 to 20 carbon atoms can be mentioned, among which an alkylene group having 1 to 12 carbon atoms is preferable, and an alkylene group having 6 to 10 carbon atoms is more preferable. Specific examples include a methylene group, an ethylene group, a trimethylene group, a propylene group, a tetramethylene group, a pentamethylene group, and a hexamethylene group.

  Examples of the “arylene group” include an arylene group having 6 to 20 carbon atoms, and specific examples include a phenylene group, a naphthylene group, an anthracenylene group, and a phenanthrenylene group. Of these, an arylene group having 6 to 12 carbon atoms is preferable, and an arylene group having 6 to 10 carbon atoms is more preferable.

  Examples of the “arylene group” and the “alkylene group” in the “arylene-alkylene group” include the same groups as described above, and the same groups are preferable.

  Examples of the “optionally substituted” substituent include halogen atoms such as fluorine atom, chlorine atom, bromine atom and iodine atom; methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, s -Alkyl groups such as butyl group, t-butyl group, pentyl group, cyclopentyl group, hexyl group, cyclohexyl group, heptyl group, cycloheptyl group, octyl group, cyclooctyl group, trifluoromethyl group; vinyl group, propenyl group, Alkenyl groups such as isopropenyl group, allyl group, butenyl group, pentenyl group, geranyl group, farnesyl group; alkynyl groups such as ethynyl group, propynyl group, butynyl group; aryls such as phenyl group, naphthyl group, anthracenyl group, phenanthryl group Group: methylphenyl group, ethylphenyl group, s-butyl Alkylaryl groups such as ruphenyl group, t-butylphenyl group, 1-methylnaphthyl group, 2-methylnaphthyl group, 4-methylnaphthyl group, 1,6-dimethylnaphthyl group, 4-t-butylnaphthyl group; Hydroxyaryl groups such as hydroxyphenyl group; methoxyphenyl group, ethoxyphenyl group, s-butoxyphenyl group, t-butoxyphenyl group, 1-methoxynaphthyl group, 2-methoxynaphthyl group, 4-methoxynaphthyl group, 1,6 -Alkoxyaryl groups such as dimethoxynaphthyl group and 4-t-butoxynaphthyl group; pyridyl group, quinazolinyl group, quinolyl group, pyrimidinyl group, furyl group, thienyl group, pyrrolyl group, imidazolyl group, tetrazolyl group, indolyl group, phenanthate Heterocyclic groups such as rolinyl group; benzyl group, Aralkyl groups such as a netyl group; hydroxy groups; alkoxy groups such as methoxy groups, ethoxy groups, butoxy groups, and t-butoxy groups; aryloxy groups such as phenoxy groups; mercapto groups; alkylthio groups such as methylthio groups; Cyano group; nitro group; amino group; substituted amino group such as methylamino group, ethylamino group, cyclohexylamino group, dimethylamino group, diethylamino group, dibutylamino group, acetylamino group; t-butylcarbamate group, Carbamate groups such as methyl carbamate groups; Amido groups; Sulfonamide groups such as benzenesulfonamide groups and menthanesulfonamide groups; Imino groups; Imido groups such as phthalimide groups; Guanidino groups; Formyl groups; Carbonyl groups; Acetyl groups and propionyl groups And acyl groups such as benzoyl groups; carboxy groups; alkoxycarbonyl groups such as methoxycarbonyl groups, ethoxycarbonyl groups, and butoxycarbonyl groups; aryloxycarbonyl groups such as phenoxycarbonyl groups, alkylaryl groups, and alkoxyaryl groups. The number of substituents is, for example, 1 to the maximum number that can be substituted, and preferably 1 to 2.

Moreover, as R6 and R7, a silicon-containing group containing a silicon atom in addition to a carbon atom in a portion bonded to a carbon-carbon double bond is also included in the present invention. For example, - it can be given a "SiR _3". Here, the three R bonded to Si are each independently the same “alkyl group”, “alkenyl group”, “aryl group”, “aralkyl group”, “heteroaryl group” and “heteroaralkyl group” described above. And the like.

  The details will be described in the <2> column of the production method, but the boron moiety in the formula (1) is preferably derived from pinacol diboron. In particular, R1 and R2 are each independently more preferably an alkyl group having 1 to 6 carbon atoms, and it is preferable that R1 and R2 form a ring.

  For example, the compound shown by the said General formula (2) can be mentioned. In formula (2), M and R3 to R7 are the same as those in formula (1).

  R3 to R5 are each independently preferably an alkyl group having 1 to 6 carbon atoms. In particular, a butyl group is preferable from the viewpoint of easy availability of raw materials.

  In addition, the compound according to the present invention is preferably any compound represented by the above formula (3). These compounds can be obtained with high efficiency as shown in the Examples.

  Since the metal-boronated alkene compound according to the present invention has different reactivity at the boron site and the metal site, a compound having different functional groups introduced at each site can be produced. The above compounds are very useful because they can be used as intermediates for the production of various chemicals, functional molecules having Lewis acid catalytic ability and sugar recognition ability, and pharmaceuticals in neutron capture therapy for cancer. For example, by using the compound according to the present invention, it is possible to easily obtain tetra-substituted alkenes in which all four functional groups added to the carbon-carbon double bond are different. Therefore, it is useful for the production of compounds having various functions and activities (pharmacological activity and the like).

<2. Method for producing metal-borated alkene compound>
The method for producing a metal-borated alkene compound according to the present invention comprises:
(A) a compound represented by the above general formula (4);
(B) a compound represented by the above general formula (5);
(C) a diboron compound having a boron-boron bond,
(D) a catalyst containing a copper complex having a ligand represented by the compound represented by the general formula (6) or N-cyclic heterocarbene,
Other specific conditions, steps, materials, etc. are not particularly limited as long as they have a step of reacting in the presence of. Hereinafter, each element will be described.

<2-1. (A) Compound represented by general formula (4)>
The general formula (4) is a so-called alkyne compound, and is particularly preferably an internal alkyne compound having a carbon-carbon triple bond inside the main chain. For example, in the above formula (4), R6 and R7 are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, and substituted. An optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, an optionally substituted heteroaryl group having 6 to 20 carbon atoms, and optionally substituted. A C6-C20 heteroaralkyl group is represented. R6 and R7 may be a silicon-containing group.

  “Alkyl group”, “alkenyl group”, “aryl group”, “aralkyl group”, “heteroaryl group”, “heteroaralkyl group” and “silicon-containing group” are those described in the section <1> above. Since it is the same as that of FIG. R6 and R7 are particularly preferably an electronically neutral organic group or an electron-donating organic group.

<2-2. (B) Compound represented by general formula (5)>
The compound represented by the general formula (5) is a compound containing a metal atom M. Here, in Formula (5), M represents any metal atom of Sn, Si, and Ge. R3 to R5 and R8 are each independently hydrogen, an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, or an optionally substituted carbon. An aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, an optionally substituted heteroaryl group having 4 to 20 carbon atoms, and an optionally substituted carbon atom having 5 to 20 carbon atoms Represents a heteroaralkyl group. Since the “alkyl group”, “alkenyl group”, “aryl group”, “aralkyl group”, “heteroaryl group” and “heteroaralkyl group” are the same as those described in the section <1> above, Description is omitted. R3 to 5 are also preferably the organic groups described in the above <1> column.

  X represents a hetero element of oxygen, sulfur, or nitrogen. That is, “X—R8” can be said to function as a leaving group. Of these, X is preferably oxygen. When X is nitrogen, in addition to R8, another organic group R9 may be added to X. R9 in this case may include the same organic groups as exemplified for R3 to R5 and R8.

  As the compound represented by the general formula (5), R3 to R5 and R8 are each independently an organic group containing carbon and X is oxygen from the viewpoint of availability of raw materials. Is preferred. In particular, a tertiary tin alkoxide compound in which M is Sn is preferable.

<2-3. (C) Diboron compound having a boron-boron bond>
Moreover, the said diboron compound should just be a diboron compound which has a boron-boron single bond, and the specific structure is not specifically limited. For example, the diboron compound can be exemplified by the compound represented by the general formula (7).

  Here, in Formula (7), R21 to R24 are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, and substituted. An optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, an optionally substituted heteroaryl group having 4 to 20 carbon atoms, and optionally substituted. A heteroaralkyl group having 5 to 20 carbon atoms, an alkylene group having 1 to 20 carbon atoms which may be substituted, an arylene group having 6 to 20 carbon atoms which may be substituted, or 1 carbon atom which may be substituted Represents an arylene-alkylene group of ˜20. Since the “alkyl group”, “alkenyl group”, “aryl group”, “aralkyl group”, “heteroaryl group” and “heteroaralkyl group” are the same as those described in the section <1> above, Description is omitted.

  In particular, pinacol diboron in which R21 and R22 and R23 and R24 form a ring is preferable.

Specific examples include the following diboron compounds. In addition, these compounds may be used by 1 type and can also be used in combination of multiple.
・ Bis (pinacolato) diboron
・ Bis (neopentyl glycolato) diboron
・ Bis (hexylene glycolato) diboron
・ Bis (catecholato) diboron
Bis (N, N, N ′, N′-tetramethyl-L-tartaramide glycolato) diboron (Bis (N, N, N ′, N′-tetramethyl-L-tartaramide glycolato) diboron)
Bis (N, N, N ', N'-tetramethyl-D-tartaramide glycolate) diboron (Bis (N, N, N', N'-tetramethyl-D-tartaramide glycolato) diboron)
Bis (diethyl-D-tartrate glycolato) diboron
・ Bis (diisopropyl-D-tartrate glycolato) diboron
Bis (diethyl-L-tartrate glycolato) diboron
・ Bis [(+)-pinanediolate] diboron (Bis [(+)-pinanediolato] diboron)
・ Bis [(-) Pinandiolate] Diboron] (BIS [(-) PINANEDIOLATO] DIBORON)
・ Bis (diisopropyl-L-tartrate glycolato) diboron
In addition, since the said pinacol diboron is marketed, it is excellent also in terms of raw material procurement (such as bis (pinacolato) diboron manufactured by Aldrich or Wako Pure Chemical Industries).

<2-4. (D) Catalyst containing copper complex having ligand represented by compound represented by general formula (6) or N-cyclic heterocarbene>
This catalyst should just contain the copper complex which makes the compound shown by General formula (6) a ligand, or the copper complex which makes N-cyclic heterocarbene a ligand, and about other structures especially It is not limited.

  Here, in formula (6), R11 to R13 are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, and substituted. An optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, an optionally substituted heteroaryl group having 4 to 20 carbon atoms, and optionally substituted. A heteroaralkyl group having 5 to 20 carbon atoms, an alkylene group having 1 to 20 carbon atoms which may be substituted, an arylene group having 6 to 20 carbon atoms which may be substituted, or 1 carbon atom which may be substituted Represents an arylene-alkylene group of ˜20. Since the “alkyl group”, “alkenyl group”, “aryl group”, “aralkyl group”, “heteroaryl group” and “heteroaralkyl group” are the same as those described in the section <1> above, Description is omitted.

  Further, the atom directly bonded to phosphorus is preferably a carbon rather than a heteroatom.

  The compound represented by the general formula (6) is a so-called tertiary phosphine compound, but R11 to R13 are preferably organic groups having strong Lewis basicity (electron donating property). Moreover, it is preferable that R11-R13 is a bulky organic group as a three-dimensional structure. From the viewpoints of these points and availability, particularly preferred R11 to R13 include a cyclohexyl group, a t-butyl group or an octyl group, a phenyl group, and the like.

Further, the “N-cyclic heterocarbene” may be any cyclic structure in which nitrogen is bonded as a hetero atom to carbene (R ₂ C :) carbon. For example, what is shown by the following formula | equation (8) can be mentioned.

  Here, in formula (8), R31 and R32 are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, and substituted. An optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, an optionally substituted heteroaryl group having 4 to 20 carbon atoms, and optionally substituted. A heteroaralkyl group having 5 to 20 carbon atoms, an alkylene group having 1 to 20 carbon atoms which may be substituted, an arylene group having 6 to 20 carbon atoms which may be substituted, or 1 carbon atom which may be substituted Represents an arylene-alkylene group of ˜20. Since the “alkyl group”, “alkenyl group”, “aryl group”, “aralkyl group”, “heteroaryl group” and “heteroaralkyl group” are the same as those described in the section <1> above, Description is omitted.

  For example, IMes (1,3-bis (2,4,6-trimethylphenyl) imidazol-2-ylidene) used in Examples can be preferably used.

  Moreover, the said copper complex should just have copper as a metal compound, The structure is not specifically limited. For example, as the copper compound, a monovalent or divalent copper compound can be mentioned. Specifically, copper (I) trifluoromethanesulfonate, copper (II) trifluoromethanesulfonate, copper (I) acetate, copper acetate (II), copper bromide (I), copper bromide (II), copper chloride (I), copper (II) chloride, copper (II) acetylacetonate, tetrakis acetonitrile copper (I) hexafluorophosphate, etc. Is mentioned.

  In particular, the copper compound preferably has a leaving group containing an oxygen atom as a leaving group. Examples of the “leaving group containing an oxygen atom” include a hydroxy group, an acetoxy group, an alkoxy group, an aryloxy group, a carboxy group, and the like, which may be unsubstituted or substituted. Examples of the substituent include the same substituents as those described above in the <1> column. Examples of the alkoxy group include linear, branched or cyclic alkoxy groups, and specifically include methoxy group, ethoxy group, propoxy group, i-propoxy group, butoxy group, i-butoxy group, s -Butoxy group, t-butoxy group, pentyloxy group, hexyloxy group, cyclohexyloxy group and the like. Of these, a linear or molecular chain alkoxy group having 1 to 6 carbon atoms is preferable, and a linear or molecular chain alkoxy group having 1 to 4 carbon atoms is more preferable. Specific examples of the aryloxy group include a phenoxy group, a 1-naphthoxy group, and a 2-naphthoxy group. Of these, an aryloxy group having 6 to 12 carbon atoms is preferable, and an aryloxy group having 6 to 10 carbon atoms is more preferable. As the group containing an oxygen atom, among them, an acetoxy group, a hydroxy group, an alkoxy group and an aryloxy group are preferable, an acetoxy group, a hydroxy group, a methoxy group, an ethoxy group and a phenoxy group are preferable, and an acetoxy group is particularly preferable. These copper compounds may be used alone or in combination of two or more.

  A method for producing a copper complex will be described. The copper complex in which the tertiary phosphine compound is coordinated to a metal can be produced according to a method similar to the method for synthesizing a normal metal complex. For example, a method of newly coordinating a tertiary phosphine compound to a metal, a method of exchanging a previously coordinated ligand with a tertiary phosphine compound, and the like can be mentioned. Specifically, for example, by bringing a copper compound and a tertiary phosphine compound into contact with each other in a solvent, a copper complex in which the target tertiary phosphine compound is coordinated to copper can be produced. Those having N-cyclic heterocarbene as a ligand can be similarly produced.

  The amount of the tertiary phosphine compound or N-cyclic heterocarbene used varies depending on the coordination number of the compound with respect to the metal, but is usually appropriately selected from the range of about 0.8 to 10 equivalents with respect to the metal. it can. Among them, it is preferable to use 3.5 equivalents of a tertiary phosphine compound or 1 equivalent of an N-cyclic heterocarbene with respect to 1 equivalent of a metal compound, which is the amount used in the examples.

  Solvents include alcohols such as methanol and ethanol, hydrocarbon compounds such as hexane, heptane, benzene, toluene and xylene, esters such as ethyl acetate and butyl acetate, diethyl ether, t-butyl methyl ether, diisopropyl ether, Ethers such as tetrahydrofuran, aprotic polar solvents such as DMF, DMSO, and DMI, and halogenated hydrocarbons such as chloroform, dichloromethane, and dichlorobenzene can be preferably used.

  The reaction temperature can be appropriately selected from the range from about −78 ° C. to the boiling point of the solvent. Although there is no restriction | limiting in particular in contact time, Usually, it can select suitably from the range of 0.1 second-96 hours.

  The complex can also be obtained as a solid. Examples of the method for obtaining the complex as a solid include a method in which the reaction solvent and the tertiary phosphine compound or the N-cyclic heterocarbene are distilled off and then isolated as a solid by adding a solvent having low solubility of the complex. Can be mentioned. Moreover, a complex with higher purity can also be obtained by performing recrystallization as needed. It can also be isolated and purified by column chromatography.

  In addition, when using the catalyst containing this copper complex for a catalytic reaction, after preparing separately the metal compound and tertiary phosphine compound which are the precursors of a complex, it is made to contact in the reaction liquid used for a catalytic reaction. Alternatively, the asymmetric catalytic reaction can be carried out as it is. Such an embodiment may naturally be included in the present invention.

  In the method for producing a metal-borated alkene compound according to the present invention, a solvent is preferably used. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as pentane, hexane, heptane, cyclohexane, benzene, toluene, xylene, ethyl ether, tetrahydrofuran, etc. And halogenated hydrocarbons such as ethers, dichloromethane and 1,2-dichloroethane. These solvents are usually used in an amount of usually 1 to 1000 parts by weight, preferably 50 to 500 parts by weight, per 1 part by weight of the copper complex (including the case of a mixture of the above ligand and copper compound).

  Moreover, the usage-amount of a copper complex is about 0.1-20 mol% normally with respect to a raw material compound, Preferably it is about 0.5-10 mol%, More preferably, it is about 1-5 mol%. The copper complex may be used as a catalyst as it is, or a copper compound and a ligand which are precursors of a copper complex are separately charged into a reaction system and contacted in a reaction solution to be used as a catalyst. May be.

  The reaction temperature is generally about −100 ° C. to 150 ° C., preferably about 0 ° C. to 100 ° C., more preferably about 50 ° C. to 90 ° C. The reaction time can be appropriately set according to the reaction rate and is not particularly limited, but is usually about 1 to 200 hours. The reaction pressure is not particularly limited and may be normal pressure or increased pressure. Usually, the reaction is performed under 1 to 3 atmospheres, preferably under atmospheric pressure. Moreover, it is preferable to perform reaction in inert gas atmosphere, such as nitrogen and argon.

  The progress of the reaction can be determined, for example, by thin layer chromatography or column chromatography. After the reaction, water, methanol or the like is added to stop the reaction, and if necessary, extraction with an organic solvent is performed, and the target compound can be isolated by distilling off the solvent. If necessary, the target compound can be further purified by means such as distillation, recrystallization, column chromatography and the like. The purity of the obtained compound can be measured by high performance liquid chromatography (HPLC) or gas chromatography.

  A catalyst amount, a ligand amount, a substrate molar ratio (a molar ratio of raw material compounds), a solvent, and the like can be appropriately set and optimized by those skilled in the art based on the description in this specification.

  Moreover, as shown in the Example mentioned later, in the metal boronation reaction of alkyl (aryl) alkynes, regioselectivity is high and a metal containing group couple | bonds with the same carbon as an aryl group. For this reason, there also exists an advantage that reaction is easy to control.

  As described above, according to the method for producing a metal-borated alkene compound according to the present invention, a metal-borated alkene compound can be efficiently produced.

<3. Utilization Technology of the Present Invention>
The present invention includes a method for producing a compound, including a step of converting a boron site and a metal site in the metal-borated alkene compound described above into different functional groups. Specific steps, conditions, materials and the like are not particularly limited, and a known technique such as a cross coupling reaction can be suitably used.

  Moreover, arbitrary things can be mentioned as a functional group introduce | transduced into a metal- boronation alkene compound, It does not specifically limit. For example, each independently substituted alkyl group having 1 to 20 carbon atoms, optionally substituted alkenyl group having 2 to 20 carbon atoms, and optionally substituted aryl having 6 to 20 carbon atoms. Group, optionally substituted aralkyl group having 7 to 20 carbon atoms, optionally substituted heteroaryl group having 4 to 20 carbon atoms, optionally substituted heteroaralkyl group having 5 to 20 carbon atoms, substituted The C1-C20 alkylene group which may be substituted, the C6-C20 arylene group which may be substituted, or the C1-C20 arylene-alkylene group which may be substituted is represented. Since the “alkyl group”, “alkenyl group”, “aryl group”, “aralkyl group”, “heteroaryl group” and “heteroaralkyl group” are the same as those described in the section <1> above, Description is omitted.

  According to this method, compounds having various functions and activities such as pharmacological activity can be easily produced. In particular, tetra-substituted alkenes in which all four functional groups bonded to the carbon-carbon double bond are different can be easily obtained.

  The present invention is not limited to the configurations described above, and various modifications can be made within the scope described in the specification, and implementations obtained by appropriately combining technical means disclosed in different embodiments. The form is also included in the technical scope of the present invention. Moreover, all the literatures described in this specification are used as reference. EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited only to this Example.

  Hereinafter, the present invention will be described in more detail with reference to examples. The present invention is not limited to the following examples.

[Example 1]
Borylstannylated alkene was prepared according to the following procedure.

  First, a Schlenk fitted with a septum and a stir bar was flame-dried and then purged with argon. Next, copper (II) acetate (0.006 mmol, 2 mol%, manufactured by Kanto Chemical Co., Inc.), tricyclohexylphosphine (25% toluene solution, 0.021 mmol, 7 mol%, manufactured by Kanto Chemical Co., Ltd.), and methanol (1 ml) were schlenk. The septum was replaced with a greased ball plug to make a sealed system, and then immersed in an oil bath at 80 ° C. and stirred for 30 minutes.

  The Schlenk was cooled and then connected to a vacuum line, and the pressure was reduced with stirring to volatilize the methanol. Depressurization was continued for about 1 hour to prepare a copper complex. Next, the ball plug was removed while blowing argon, the grease adhering to Schlenk was wiped off, and a septum was attached.

  Tributyltin alkoxide (tributyltin methoxide, 0.39 mmol, 1.3 eq, manufactured by Aldrich), diphenylacetylene (0.3 mmol, 1 eq, manufactured by Tokyo Chemical Industry Co., Ltd.), bis (pinacolato) diboron (0.39 mmol, 1.3 eq, boron (Molecular Co., Ltd.) and toluene (1 ml) were added, and the septum was replaced with a greased ball plug to make a sealed system, followed by stirring at room temperature.

  After completion of the reaction, the reaction mixture was filtered using a Kiriyama funnel packed with celite while diluting with ethyl acetate. The filtrate was placed in a separatory funnel and washed with ethyl acetate and saturated brine, and the organic layer was collected by Meyer and dried using magnesium sulfate. Thereafter, the mixture was filtered using a Kiriyama funnel packed with Celite, and the filtrate was concentrated using an evaporator, and then connected to a vacuum line and dried. Finally, the target product was isolated using a silica gel column.

  The reaction scheme is as follows.

  With a reaction time of 6 h, the yield of the obtained borylstannyl compound was 72%.

  In addition to the above-described catalyst, copper (II) acetate (0.003 mmol) and tricyclohexylphosphine (25% toluene solution, 0.011 mmol) were used as the catalyst, and the resulting borylstannyl compound was obtained in a reaction time of 3 h. The yield of was 69%. Further, when copper (II) acetate (0.009 mmol) and tricyclohexylphosphine (25% toluene solution, 0.032 mmol) were used, the yield of the obtained borylstannyl compound was 69% in a reaction time of 13 h. .

  When tris (triphenylphosphine) copper acetate (I) (0.003 mmol) was used, the reaction time was 7 h, and the yield of the obtained borylstannyl compound was 58%. Moreover, when IMesCuCl (0.003 mmol) which is N-cyclic heterocarbene was used, the yield of the obtained borylstannyl compound was 55% in reaction time 12h.

[Example 2]
The procedure was the same as Example 1 except that instead of diphenylalkyne, a predetermined internal alkyne (0.3 mmol, 1 eq, manufactured by Tokyo Chemical Industry Co., Ltd.) was used. As the catalyst, copper (II) acetate (0.006 mmol, 2 mol%, manufactured by Kanto Chemical Co., Inc.) and tricyclohexylphosphine (25% toluene solution, 0.021 mmol, 7 mol%, manufactured by Kanto Chemical Co., Inc.) were used.

  The reaction scheme is shown below.

  The combinations of R and R 'of the internal alkyne are shown in the following table.

  The obtained borylstannylated alkene, yield, and reaction time are shown. If isomers are present, the ratio is also described.

  From the above results, it can be seen that in the borylstannylation reaction of alkyl (aryl) alkynes, the regioselectivity is high and the tin-containing group tends to bond to the same carbon as the aryl group. In addition, 4-octyne (both R and R ′ are n-Pr (propyl) groups) was less reactive to borylstannylation under standard conditions using tributyltin methoxide compared to aryl-substituted alkynes ( The yield was significantly improved when tributyltin tert-butoxide was used instead of tributyltin methoxide (yield 72%, 25h).

The present invention is not only used as an intermediate in organic synthesis, but also as a functional molecule having Lewis acid catalytic ability and sugar recognition ability, and a medicine in neutron capture therapy for cancer, as well as the medical industry, Can be widely used in various fields.

Claims (9)

A metal-borated alkene compound represented by the following general formula (1).

(In formula (1), M represents a metal atom of Sn, Si, or Ge. R1 to R7 are each independently hydrogen, an optionally substituted alkyl group having 1 to 20 carbon atoms, An optionally substituted alkenyl group having 2 to 20 carbon atoms, an optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, and an optionally substituted group. Good C4-C20 heteroaryl group, C5-C20 heteroaralkyl group which may be substituted, C1-C20 alkylene group which may be substituted, Carbon number which may be substituted Represents an arylene group having 6 to 20 or an optionally substituted arylene-alkylene group having 1 to 20 carbon atoms, R1 and R2 may form a ring, and R6 and R7 are each independently A silicon-containing group Good.) The compound of Claim 1 shown by following General formula (2).

(In formula (2), M and R3 to R7 are the same as in formula (1).) The compound of Claim 1 or 2 which is a compound in any one of the compound groups shown by following formula (3).

(A) a compound represented by the following general formula (4);

(In formula (4), R6 and R7 are each independently hydrogen, an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, or a substituted group. An optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, an optionally substituted heteroaryl group having 4 to 20 carbon atoms, and optionally substituted. This represents a heteroaralkyl group having 5 to 20 carbon atoms, and may be a silicon-containing group.
(B) a compound represented by the following general formula (5);

(In Formula (5), M represents a metal atom of any one of Sn, Si, and Ge. R3 to R5 and R8 each independently represent hydrogen or an optionally substituted alkyl having 1 to 20 carbon atoms. A group, an optionally substituted alkenyl group having 2 to 20 carbon atoms, an optionally substituted aryl group having 6 to 20 carbon atoms, an optionally substituted aralkyl group having 7 to 20 carbon atoms, and a substituted group. An optionally substituted heteroaryl group having 4 to 20 carbon atoms and an optionally substituted heteroaralkyl group having 5 to 20 carbon atoms, X represents oxygen, sulfur, or nitrogen.)
(C) a diboron compound having a boron-boron bond,
(D) a catalyst containing a copper complex having a ligand represented by a compound represented by the following general formula (6) or N-cyclic heterocarbene,
A method for producing a metal-boronated alkene compound comprising a step of reacting in the presence of

(In Formula (6), R11 to R13 are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, and substituted. An aryl group having 6 to 20 carbon atoms, an aralkyl group having 7 to 20 carbon atoms which may be substituted, a heteroaryl group having 4 to 20 carbon atoms which may be substituted, and an optionally substituted carbon number 5-20 heteroaralkyl group, C1-C20 alkylene group which may be substituted, C6-C20 arylene group which may be substituted, or C1-C20 which may be substituted Represents an arylene-alkylene group.   The said copper is a copper compound which has a leaving group containing an oxygen atom, The manufacturing method of the compound of Claim 4.   Said R11-R13 is a cyclohexyl group, t-butyl group, or an octyl group, The manufacturing method of the compound of Claim 4 or 5. The said diboron compound is a compound shown by following General formula (7), The manufacturing method of the compound of any one of Claims 4-6.

(In Formula (7), R21 to R24 are each independently an optionally substituted alkyl group having 1 to 20 carbon atoms, an optionally substituted alkenyl group having 2 to 20 carbon atoms, and substituted. An aryl group having 6 to 20 carbon atoms, an aralkyl group having 7 to 20 carbon atoms which may be substituted, a heteroaryl group having 4 to 20 carbon atoms which may be substituted, and an optionally substituted carbon number 5-20 heteroaralkyl group, C1-C20 alkylene group which may be substituted, C6-C20 arylene group which may be substituted, or C1-C20 which may be substituted R21 and R22, and R23 and R24 may form a ring.)   The diboron compounds include bis (pinacol) diboron, bis (neopentylglycolate) diboron, bis (hexyleneglycolate) diboron, bis (catechol) diboron, bis (N, N, N ′, N′-tetramethyl- L-tartalamide glycolate) diboron, bis (N, N, N ′, N′-tetramethyl-D-tartalamide glycolate) diboron, bis (diethyl-D-tartarate glycolate) diboron, bis (diisopropyl- D-tartarate glycolate) diboron, bis (diethyl-L-tartalate glycolate) diboron, bis [(+)-pinandiolate] diboron, bis [(−) pinandiolate] diboron, and bis (diisopropyl- L-tartarate glycolate) selected from the group consisting of diboron Process for the preparation of a compound according to any one of claims 4-7 is compound. The manufacturing method of a compound including the process of converting the boron site | part and metal site | part in the metal-boronated alkene compound of any one of Claims 1-3 into another functional group, respectively.