# Patent

## Title
Bipyridyl compound

## Abstract

There are provided a compound capable of being a novel ligand allowing regioselective borylation to be performed in the aromatic borylation reaction, and a catalyst using the same compound. There is provided a bipyridyl compound represented by a general formula (1): (wherein A represents a single bond, a vinylene group or an ethynylene group;

    
    
        X represents an oxygen atom or a sulfur atom;
        n pieces of R1 may be the same or different, and R1 represents a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon group, an optionally substituted alkoxy group, an optionally substituted aryloxy group, an optionally substituted amino group, a cyano group, a nitro group, or an alkoxycarbonyl group, or two adjacent R1 may form a saturated or unsaturated ring structure optionally containing a hetero atom together with the carbon atoms bonded to the two R1;
        R2 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted alkoxy group, or an optionally substituted aryloxy group; and
        n represents a number of 1 to 4).

## Background
FIELD OF THE INVENTION
The present invention relates to a bipyridyl compound useful as a ligand of a metal catalyst and a catalyst including the same bipyridyl compound as a ligand.
BACKGROUND OF THE INVENTION
The Suzuki-Miyaura reaction performing a cross coupling between an organic halogen compound and an organic boron compound is an important method for carbon-carbon bond formation reaction and is widely applied. The organic boron compound used in this reaction is stable against water or air, and the product of the reaction is a boric acid salt to be thereby low in toxicity and has an advantage of being easily separable from the target product by washing with water.
For the purpose of synthesizing a wide range of compounds by using the Suzuki-Miyaura reaction, it is important to produce compounds each having a boron atom bonded to a specific position in an aromatic compound. In this connection, catalysts such as rhodium catalysts, iridium catalysts and rhenium catalysts are known as the catalysts for the aromatic borylation reactions allowing boron atoms to be bonded to aromatic compounds. In these catalysts, bipyridyl compounds, ethylenediamine compounds, phenanthroline compounds, cyclopentadienyl compounds and the like are used as ligands (Non Patent Literature 1 to Non Patent Literature 9).
CITATION LIST
Non Patent Literature
[Non Patent Literature 1]


    J. Am. Chem. Soc. 1999, 121, 7696

[Non Patent Literature 2]

    Science 2002, 295, 305

[Non Patent Literature 3]

    J. Am. Chem. Soc. 2000, 122, 12868

[Non Patent Literature 4]

    Org. Lett. 2001, 3, 2831

[Non Patent Literature 5]

    Adv. Synth. Catal. 2003, 345, 1103

[Non Patent Literature 6]

    J. Am. Chem. Soc, 2002, 124, 390

[Non Patent Literature 7]

    Tetrahedron Lett. 2002, 43, 5649

[Non Patent Literature 8]

    Angew. Chem. Int. Ed. 2002, 41, 3056

[Non Patent Literature 9]

    J. Organomet. Chem. 2003, 660, 3


SUMMARY OF THE INVENTION
Problem to be Solved by the Invention
However, there has been a problem such that when an aromatic borylation reaction is performed by using an iridium catalyst including a hitherto reported bipyridyl compound as a ligand, the control of the substitution position of a boron in an aromatic compound is difficult, and a selective borylation at an intended position is not achievable.
Accordingly, the technical problem of the present invention is to provide a compound capable of being a novel ligand allowing regioselective borylation to be performed in the aromatic borylation reaction, and a catalyst, using the same compound.
Solution to Problem
Thus, the present inventors made various studies on the ligand enabling regioselective borylation in the aromatic borylation reaction, and consequently succeeded in the synthesis of a novel compound having a bipyridine skeleton and a benzeneureido skeleton. Moreover, when an aromatic borylation reaction was performed by using a catalyst having the aforementioned compound as a ligand, the borylation reaction proceeded selectively at the meta position of the aromatic compound, and thus, the present inventors found that the aforementioned catalyst is useful as a meta-selective borylation catalyst, and consequently accomplished, the present invention.
Specifically, the present invention provide the following [1] to [6].
[1] A bipyridyl compound represented by a general formula (1):




(wherein A represents a single bond, a vinylene group (—CH═CH—) of an ethynylene group (—C≡C—);

X represents an oxygen atom or a sulfur atom;
n pieces of R1 may be the same or different, and R1 represents a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon group, an optionally substituted alkoxy group, an optionally substituted aryloxy group, an optionally substituted amino group, a cyano group, a nitro group, or an alkoxycarbonyl group, or two adjacent R1 may form a saturated or unsaturated ring structure optionally containing a hetero atom together with the carbon atoms bonded to the two R1;
R2 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted alkoxy group, or an optionally substituted aryloxy group; and
n represents a number of 1 to 4).
[2] The bipyridyl compound according to [1], wherein A is a single bond.
[3] The bipyridyl compound according to [1] or [2], wherein R1 is a hydrogen atom, a halogen atom, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, an aryloxy group having 6 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a C1-6 alkylamino group, a di(C1-6 alkyl)amino group or a C1-10 alkoxycarbonyl group.

[4] The bipyridyl compound according to any one of [1] to [3], wherein R2 is a hydrogen atom, an optionally substituted alkyl group having 1 to 10 carbon atoms, an optionally substituted alkenyl group having 2 to 10 carbon atoms, an optionally substituted cycloalkyl group having 3 to 7 carbon atoms, an optionally substituted aryl group having 6 to 10 carbon atoms, an optionally substituted alkoxy group having 1 to 10 carbon atoms or an optionally substituted aryloxy group having 6 to 10 carbon atoms.

[5] An aromatic borylation catalyst including the bipyridyl compound according to any one of [1] to [4] as a ligand.

[6] The catalyst according to [5], wherein the bipyridyl compound according to any one of [1] to [4] is coordinated to iridium.

Effects of the Invention
The catalyst including the compound (1) of the present invention as a ligand is useful as a catalyst to selectively introduce a boron atom into the meta position of an aromatic compound. Accordingly, the use of the catalyst including the compound (1) of the present invention as a ligand enables the production of various regioselective aromatic boron compounds usable in the coupling reaction such as the Susuki-Miyaura reaction.
EMBODIMENTS TO CARRY OUT THE INVENTION
The bipyridyl compound of the general formula (1) is characterized by having both of a bipyridine skeleton and a benzeneureido skeleton.
In the general formula (1), A represents a single bond, a vinylene group or an ethynylene group. Among these, a single bond or an ethynylene group are preferable, and a single bond is more preferable.
The bonding position of A in the benzene ring may be any of the ortho position, meta position and para position in relation to the ureido group, and is more preferably the ortho position.
X represents an oxygen atom or a sulfur atom. Of these, an oxygen atom is preferable.
The n pieces of R1 may be the same or different, and R1 represents a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon group, an optionally substituted alkoxy group, an optionally substituted aryloxy group, an optionally substituted amino group, a cyano group, a nitro group, or an alkoxycarbonyl group, or two adjacent R1 may form a saturated or unsaturated ring structure optionally containing a hetero atom together with the carbon atoms bonded to the two, R1.
Examples of the halogen atom include a fluorine atom, a bromine atom, a chlorine atom and an iodine atom.
As a hydrocarbon group, a hydrocarbon group having 1 to 16 carbon atoms is preferable, an alkyl group having 1 to 16 carbon atoms, an alkenyl group having 2 to 16 carbon atoms, a cyoloalkyl group having 3 to 16 carbon atoms, an aryl group having 6 to 14 carbon atoms and an arylalkyl group having 7 to 16 carbon atoms are more preferable, and an alkyl group having 1 to 16 carbon atoms, an alkenyl group having 2 to 16 carbon atoms, a cyoloalkyl group having 3 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms and an arylalkyl group having 7 to 16 carbon atoms are furthermore preferable.
Examples of the alkyl group having 1 to 16 carbon atoms include: linear or branched alkyl groups such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, an n-hexyl group, an n-octyl group and an n-decyl group. Examples of the alkenyl group having 2 to 16 carbon atoms include: a vinyl group, an allyl group, a propenyl group, a butenyl group and a hexenyl group. Examples of the cyoloalkyl group having 3 to 7 carbon atoms include: a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and a cycloheptyl group. Examples of the aryl group having 6 to 10 carbon atoms include a phenyl group and a naphthyl group. Examples of the arylalkyl group having 7 to 16 carton atoms include a phenyl-C1-6 alkyl group and a naphthyl-C1-6 alkyl group.
As the an alkoxy group, an alkoxy group having 1 to 16 carbon atoms is preferable and an alkoxy group having 1 to 6 carbon atoms is more preferable. Specific examples of the alkoxy group include a methoxy group, an ethoxy group, an n-propyloxy group and an isopropyloxy group. Examples of the aryloxy group include a C6-10 aryloxy group, and as the aryloxy group, a phenoxy group, a naphthyloxy group and the like are more preferable.
Examples of the alkoxycarbonyl group include a alkoxycarbonyl group, and specific examples of the alkoxycarbonyl group include a methoxycarbonyl group and an ethoxycarbonyl group.
Here, examples of the group capable of being substituted in the hydrocarbon group represented by R1 include: 1 to 3 halogen atoms, a cyano group, a nitro group, a halogeno C1-6 alkyl group and a alkoxy group. Examples of the group capable of being substituted in the alkoxy group and the aryloxy group include 1 to 3 halogen atoms, a cyano group, a nitro group, a halogeno C1-6 alkyl group and a C1-6 alkoxy group. Examples of the group capable of being substituted in the amino group include a C1-6 alkyl group and a halogeno C1-6 alkyl group.
Here, n represents a number of 1 to 4, and is preferably a number of 1 or 2.
The substitution position, of R1 is not particularly limited, but is preferably a position not disturbing the coordination bonding of the nitrogen atom of the pyridine ring to a metal atom, namely, a position distant from the nitrogen atom, preferably a position at the meta position or the para position relative to the nitrogen atom, and particularly preferably the para position.
R2 represents a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted alkoxy group, or an optionally substituted aryloxy group.
As the hydrocarbon group, a hydrocarbon group having 1 to 16 carbon atoms is preferable, an alkyl group having 1 to 16 carbon atoms, an alkenyl group having 2 to 16 carbon atoms, a cycloalkyl group having 3 to 16 carbon atoms, an aryl group having 6 to 14 carbon atoms and an arylalkyl group having 7 to 16 carbon atoms are more preferable, and an alkyl group having 1 to 16 carbon atoms, an allkenyl group having 2 to 16 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms and an arylalkyl group having 7 to 16 carbon atoms are furthermore preferable.
Examples of the alkyl group having 1 to 16 carbon atoms include linear or branched alkyl groups such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, an n-hexyl group, an n-octyl group and an n-decyl group. Examples of the alkenyl group having 2 to 16 carbon atoms include: a vinyl group, an allyl group, a propenyl group, a butenyl group and a hexenyl group. Examples of the cycloalkyl group having 3 to 7 carbon atoms include: a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group and cycloheptyl group. Examples of the aryl group having 6 to 10 carbon atoms include: a phenyl group and a naphthyl group. Examples of the arylalkyl group having 7 to 16 carbon atoms include a phenyl C1-6 alkyl group and a naphthyl C1-6 alkyl group.
As the alkoxy group, an alkoxy group having 1 to 16 carbon atoms is preferable, and an alkoxy group having 1 to 6 carbon atoms is more preferable. Specific examples of the alkoxy group include: a methoxy group, an ethoxy group, an n-propyloxy group and an isopropyloxy group. Examples of the aryloxy group include a C6-10 aryloxy group, and a phenoxy group, a naphthyloxy group and the like are more preferable.
Examples of the group capable of being substituted in the hydrocarbon group represented by R2 include: 1 to 3 halogen atoms, a cyano group, a nitro group, a halogeno C1-6 alkyl group and a C1-6 alkoxy group. Examples of the group capable of being substituted in an alkoxy group and an aryloxy group include: 1 to 3 halogen atoms, a cyano group, a nitro group, a halogeno C1-6 alkyl group and a C1-6 alkoxy group.
As R1, a hydrogen atom, a halogen atom, an alkyl group having 1 to 10 carbon atoms, an alkenyl group having 2 to 10 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an aryl group having 6 to 10 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, an aryloxy group having 6 to 10 carbon atoms, a C1-6 alkylamino group, a di(C1-6 alkyl)amino group, a cyano group and a C1-16 alkoxycarbonyl group are more preferable.
As R2, a hydrogen atom, an optionally substituted alkyl group having 1 to 10 carbon atoms, an optionally substituted alkenyl group having 2 to 10 carbon atoms, an optionally substituted cycloalkyl group having 3 to 7 carbon atoms, an optionally substituted aryl group having 6 to 10 carbon atoms, an optionally substituted alkoxy group having 1 to 10 carbon atoms and an optionally substituted aryloxy group having 6 to 10 carbon atoms are preferable.
Particularly preferable as R2 are the C1-10 alkyl group optionally substituted with the substituent (such as a halogen atom or a C1-6 alkoxy group), the C3-7 cycloalkyl group optionally substituted with the substituent (such as a C1-6 alkyl group, a halogeno C1-6 alkyl group or a C1-6 alkoxy group), and the phenyl group optionally substituted with the substituent (such as a C1-6 alkyl group, a halogeno C1-6 alkyl group or a C1-6 alkoxy group).
The bipyridyl compound (1) can be produced according to, for example, the following reaction formula.




(wherein X1 represents a halogen atom, X2 represents a halogen atom, a vinylene group or an ethynylene group, and R1, A, X, R2 and n are the same as described above).

First Step
The first step is a step of obtaining a compound (4) by coupling a bipyridine compound (2) and an aniline compound (3) with each other.
In the case where in the compound (3), X2 is a halogen atom, preferable is the Suzuki-Miyaura coupling in which after the borylation of the compound (3), the compound (3) is coupled with the compound (2). The borylation reaction of the compound (3) can be performed by allowing a boron compound such as pinacolborane to react with the compound (3) in the presence of palladium-phosphine and a base. The subsequent coupling reaction can be performed by adding a base such as barium hydroxide.
As the boron compound, pinacolborane, bis(pinacolato)diborane and the like are used. As palladium-phosphine, for example, bis(diphenylphosphino)alkanes (such as DPPM, DPPE and DPPP), bis(diphosphino)ferrocene (DPPF), bis(diphenylphosphino) binaphthyl (BINAP) and xantphos are used. As the base, tertiary amines such as triethylamine are used.
Examples of the base used in the subsequent coupling reaction include: barium hydroxide, sodium carbonate, potassium carbonate and sodium hydrogen carbonate.
The coupling reaction can be performed in an inert solvent such as dioxane at 50 to 100° C. for 2 to 12 hours.
In the case where in the compound (3), X2 is an ethynylene group, the coupling reaction is preferably performed by the Sonogashira coupling using a palladium catalyst, a copper catalyst and a base.
Examples of the palladium catalyst include: tetrakis(triphenylphosphine) palladium (0) and dichlorobis(triphenylphosphine) palladium (II). As the copper catalyst, copper halides such as copper iodide are preferable. As the base, tertiary amines such as triethylamine are preferable.
The coupling reaction can be performed in an amine at 30 to 100° C. for 1 to 10 hours.
Second Step
The second step is a step of obtaining the bipyridyl compound (1) by allowing an isocyanate (5) or a thioisocyanate (5) to react with the compound (4).
This reaction can be performed by allowing; an isocyanate (5) or a thioisocyanate (5) to react with the compound (4), in an inert solvent such as dichloromethane, at a temperature from room temperature to 100° C., for 1 to 10 hours.
The bipyridyl compound (1) thus obtained is useful as a ligand of an aromatic borylation catalyst for borylation of an aromatic compound. More specifically, a metal catalyst including the bipyridyl compound (1) as a ligand is useful as a catalyst for selective borylation of the meta position of an aromatic compound, and hence the bipyridyl compound (1) is useful as a ligand of the aromatic borylation catalyst.
The aromatic borylation catalyst of the present invention is a transition metal catalyst in which the two nitrogen atoms in the bipyridine skeleton are coordination bonded to the transition metal (M).
Examples of such a transition metal include: iridium (Ir), rhenium (Re), rhodium (Rh), palladium (Pd) and ruthenium (Ru); among these, iridium is more preferable.
In the aromatic borylation catalyst, a compound other than the bipyridyl compound (1) can also be coordinated. Examples of such a ligand include cyclooctadiene (cod).
Such an aromatic borylation catalyst can be formed in a borylation reaction system by adding the bipyridyl compound (1) to, for example, M(OMe) (cod) or M(cod) (Cl).
The aromatic borylation reaction using the aromatic borylation catalyst is described.
An aromatic compound and a boron compound such as pinacolborane or bis(pinacolato)diboron are allowed to react with each other in the presence of the catalyst of the present invention, and thus a boron atom is introduced into the aromatic compound. In this case, the use of a monosubstituted aromatic compound as a raw material results in a selective introduction of a boron atom into the meta position of the monosubstituted aromatic compound. This reaction can be performed by using a boron compound in an amount 0.50 to 10 moles in relation to 1 mole of the aromatic compound, in an inert solvent such as p-xylene, cyclohexane or dioxane, at room temperature to 100° C. for 1 to 24 hours. The amount used of the catalyst can be 1.5 mol % in relation to 1 mole of the aromatic compound. Here, examples of the aromatic compound include an aromatic hydrocarbon having 6 to 50 carbon atoms and an aromatic heterocyclic compound having 5 to 45 carbon atoms. Examples of the substituted aromatic compound to be a substrate of the borylation reaction include: compounds: having 1 to 2 substituents in these aromatic hydrocarbons or these aromatic heterocyclic compounds. The substituents in such mono- or disubstituted aromatic compounds are not particularly limited; examples of the substituents include: a halogen atom, an alkyl group, a cyclic alkyl group, a hydroxyl group, an alkoxy group, an amino group, an alkylamino group, a dialkylamino group, an acyl group, a carboxyl group, a carbamoyl group, an N-substituted carbamoyl group, a phosphate group, a phosphine group, a carboxyalkyl group, an alkoxycarbonylalkyl group, a phosphinediamide group, an aromatic hydrocarbon group and an aromatic heterocyclic group.
The aromatic boron compound thus obtained are usable as the raw materials for the coupling reaction such as the Suzuki-Miyaura coupling.


EXAMPLES
Next, the present invention is described in detail with, reference to Examples, but the present invention is not limited by these Examples at all.
Example 1
(1) 2-([2,2′-Bipyridin]-5-yl) aniline




2-Bromaniline (0.566 mL, 5.00 mmol, 1 equiv) was dissolved, in 10 mL of dioxane 10 mL, and to the resulting solution, triethylamine (2.80 mL, 20.0 mmol, 4 equiv), PdCl2 (dppf) (183 mg, 0.250 mmol, 5 mol %) and pinacolborane (2.2 mL, 15.0 mmol, 3 equiv) were added and stirred at 100° C. for 4 hours. The reaction solution was cooled to room temperature, 2.2 mL of water, Ba(OH)2.8H2O (4.73 g, 15.0 mmol, 3 equiv) and 5′-bromo-2,2′-bipyridine (1.08 g, 4.60 mmol, 0.92 equiv) were added to the reaction solution, and then further stirred at 100° C. for 4 hours. The reaction solution was cooled to room temperature, then filtered with Celite, and washed with 120 mL of ethyl acetate. The filtrate was subjected to separatory washing with 120 mL of water, dried with anhydrous sodium sulfate, and then filtered; the solvent was removed under reduced pressure to yield a crude product. By using a silica gel pretreated with a 20% triethylamine-hexane solution (200 mL), the crude product was subjected to a column purification (hexane/ethyl acetate=3/1). Thus, 672 mg (yield: 59%) of a white solid was obtained.
59% yield; white solid; Rf=0.50 (hexane/ethyl acetate=1/1); 1H NMR (400 MHz, CDCl3) δ3.77 (s, 2H), 6.81 (d, J=7.8 Hz, 1H), 6.88 (d, J=7.5 Hz, 1H), 7.17 (d, J=7.5 Hz, 1H), 7.22 (d, J=7.8 Hz, 1H), 7.33 (d, J=7.8, 5.2 Hz, 1H), 7.84 (dd, J=7.8, 7.8 Hz, 1H), 7.96 (d, J=8.2 Hz, 1H), 8.43 (d, J=7.8 Hz, 1H), 8.47 (d, J=8.2 Hz, 1H), 8.71 (d, J=5.2 Hz, 1H), 8.80 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 116.0, 119.0, 121.0, 121.1, 123.6, 123.8, 129.5, 130.6, 135.3, 137.0, 137.5, 143.9, 149.3, 149.5, 154.9, 156.0; IR (KBr, ν/cm−1) 3346, 3219, 1459, 1357, 1240, 1094, 994, 858, 751, 644; HRMS (ESI+) Calcd for C16H13N3Na ([M+Na]+) 270.1002, Found 270.1007.
(2) 1-(2-[(2,2′-Bipyridin]-5-yl)phenyl)-3-cyclohexylurea




2-([2,2′-Bipyridin]-5-yl) aniline (371 mg, 1.5 mol, 1.0 equiv), isocyanatecyclohexane (0.29 mL, 2.3 mmol, 1.5 equiv) were dissolved in 5.0 mL of dichlororomethane, and stirred at room temperature for 24 hours. The solvent was removed under reduced pressure from the reaction solution to yield a crude product. By recrystallization (hexane/dichloromethane), 281 mg (yield: 50%) of a target product was obtained.
50% yield; white solid; Rf=0.53 (hexane/ethyl acetate=1/2); 1H NMR (400 MHz, CDCl3) δ0.94-1.10 (m, 3H), 1.27-1.34 (m, 3H), 1.52-1.67 (m, 2H), 1.86-1.89 (m, 2H), 3.51-3.59 (m, 1H), 4.86-4.97 (m, 1H), 6.26-6.35 (m, 1H), 7.21 (dd, J=7.2, 6.3 Hz, 1H), 7.30 (d, J=6.3 Hz, 1H), 7.35 (dd, J=7.2, 7.2 Hz, 1H), 7.42 (d, J=7.2 Hz, 1H), 7.84-7.87 (m, 2H), 7.92 (d, J=8.6 Hz, 1H), 8.39 (d, J=8.0 Hz, 1H), 8.44 (d, J=3.6 Hz, 1H), 8.69-8.71 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 25.0, 25.6, 33.7, 49.2, 121.1, 121.3, 122.5, 123.8, 124.1, 129.0, 129.6, 130.4, 134.8, 136.6, 137.2, 137.9, 149.4, 149.5, 154.8, 155.1, 155.5; IR (KBr, ν/cm−1) 3245, 3219, 1453, 1.367, 1240, 1094, 994, 858, 751, 644; HEMS (ESI+) Calcd for C23H24N4NaO ([M+Na]+) 395.1842, Found 395.1850.
Examples 2 to 8
The following compounds were synthesized in the same manner as Example 1.
Example 2
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-hexylurea




62% yield; white solid; Rf=0.32 (hexane/ethyl acetate=1/1); 1H NMR (500 MHz, CDCl3) δ 0.79 (t, J=6.9 Hz, 3H), 1.16-1.22 (m, 6H), 1.33-1.38 (m, 20), 3.14 (td, J=7.2, 7.2 Hz, 2H), 5.48 (brs, 1H), 6.70 (s, 1H), 7.12-7.20 (m, 2H), 7.32 (dd, J=6.3, 4.6, 1.2 Hz, 1H), 7.39 (ddd, J=6.3, 4.8, 1.1 Hz, 1H), 7.69 (ddd, J=8.5, 7.6, 2.2 Hz, 1H), 7.81 (ddd, J=7.7, 7.6, 1.6 Hz, 1H), 8.06 (d, J=8.1 Hz, 1H), 8.15 (d, J=8.5 Hz, 1H), 8.19 (d, J=8.1 Hz, 1H), 8.56 (d, J=2.2 Hz, 1H), 8.64 (dd, J=4.0, 1.1 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.0, 22.5, 26.6, 30.0, 31.5, 40.2, 120.9, 121.1, 122.3, 123.2, 124.0, 128.4, 129.4, 130.1, 135.1, 136.9, 137.1, 137.1, 149.1, 149.4, 154.3, 155.2, 156.1; IR (KBr, ν/cm31 1) 3292, 2922, 2855, 1626, 1457, 1371, 1266, 1090, 856, 649; HRMS (ESI+) Calcd for C23H26N4NaO ([M+Na]+) 397.1999, Found 397.1997.
Example 3
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(4-methoxyphenyl)urea




6.5% yield; white solid; Rf=0.50 (hexane/ethyl acetate=1/2); 1H NMR (400 MHz, CDCl3) δ 3.62 (s, 3H) 6.71 (d, J=8.6 Hz, 2H), 6.98 (d, J=8.6 Hz, 2H), 7.20-7.22 (m, 1H), 7.36-7.38 (m, 3H), 7.46-7.49 (m, 1H), 7.54 (s, 1H), 7.81 (dd, J=8.0, 2.0 Hz, 1H), 7.89 (ddd, J=8.0, 7.7, 1.7 Hz, 1H), 7.94-7.96 (m, 1H), 8.44 (d, J=3.0 Hz, 1H), 8.46 (d, J=8.0 Hz, 1H), 8.63 (d, J=1.7 Hz, 1H), 8.73 (d, J=4.6 Hz, 1H); 13C NMR (125 MHz, DMSO-d6) δ 55.6, 114.1, 120.4, 121.0, 124.7, 127.8, 129.2, 130.2, 130.6, 132.0, 135.5, 137.7, 137.1, 137.6, 137.9, 149.3, 149.8, 154.2, 155.3, 157.2, 181.4; IR (KBr, ν/cm−1) 3278, 1636, 1509, 1458, 1370, 1244, 1111, 855, 756, 649; HRMS (ESI+) Calcd for C24H20N4NaO2 ([M+Na]+) 419.1478, Found 419.1458.
Example 4
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(4-trifluoromethylphenyl)urea




50% yield; pale yellow solid; Rf=0.63 (hexane/ethyl acetate=1/2); 1H NMR (400 MHz, CDCl3) δ 7.10-7.16 (m, 2H), 7.35-7.53 (m, 7H), 7.64 (d, J=8.1 Hz, 1H), 7.84-7.85 (m, 2H), 8.22 (brs, 1H), 8.42 (d, J=8.3 Hz, 1H), 8.52 (d, J=1.3 Hz, 1H), 8.57 (d, J=3.1 Hz, 1H), 9.35 (brs, 1H); 13C HMR (125 MHz, CDCl3) δ 118.1, 118.7, 121.1, 121.3, 123.2, 123.6 (q, J=33.6 Hz), 124.3 (q, J=271 Hz), 124.5, 126.1 (q, J=3.6 Hz), 127.2, 120.9, 130.3, 135.8, 136.9, 137.7, 138.6, 143.0, 149.5, 150.1, 153.2, 153.5, 154.3; 19F NMR (368 MHz, CDCl3) δ −63.8 (s, 3F); IR (KBr, ν/cm−1) 3331, 3058, 1716, 1654, 1449, 1329, 1165, 1014, 842, 759; HRMS (ESI+) Calcd for C24H17F3N4NaO ([M+Na]+) 457.1247, Found 457.1252.
Example 5
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(4-butylphenyl)urea




27% yield; white solid; Rf=0.64 (hexane/ethyl acetate=1/2); 1H NMR (400 MHz, CDCl3) δ 0.85 (t, J=7.5 Hz, 3H), 1.20-1.28 (m, 2H), 1.38-1.46 (m, 2H), 2.38 (t, J=7.7 Hz, 2H), 6.94 (d, J=1.9 Hz, 2H), 7.05-7.15 (m, 4H), 7.34 (dd, J=7.2, 4.9 Hz, 1H), 7.41 (ddd, J=7.7, 7.7, 1.7 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.82 (dd, J=7.2, 7.2 Hz, 1H), 8.01-8.03 (m, 1H), 8.15-8.16 (m, 1H), 8.30 (d, J=8.6 Hz, 1H), 8.52 (s, 1H), 8.65 (d, J=4.6 Hz, 1H); 13C HMR (125 MHz, CDCl3) δ 14.0, 22.4, 33.7, 35.0, 120.6, 121.0, 121.3, 121.4, 123.2, 124.2, 127.8, 129.0, 129.6, 130.2, 133.1, 136.2, 136.8, 137.3, 138.1, 138.3, 149.4, 149.7, 153.6, 154.4, 1.55.0; IR (KBr, ν/cm−1) 3293, 1.637, 1546, 1509, 1458, 1372, 1246, 1122, 799, 757; HRMS (ESI+). Calcd for C27H26N4NaO ([M+Na]+) 445.1999, Found 445.1989.
Example 6
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(2,6-dimethylphenyl) urea




58% yield; white solid; Rf=0.30 (hexane/ethyl acetate=1/1); 1H NMR (400 MHz, CDCl3) δ 2.15 (s, 6H), 5.73 (s, 1H), 6.19 (s, 1H), 6.78-6.30 (m, 1H), 6.34 (d, J=6.7 Hz, 2H), 7.13-7.18 (m, 2H), 7.36-7.44 (m, 2H), 7.48 (d, J=7.6 Hz, 1H), 7.89 (ddd, J=7.6, 7.6, 1.8 Hz, 1H), 8.23 (d, J=8.1 Hz, 1H), 8.29 (d, J=8.5 Hz, 1H), 8.39 (s, 1H), 8.43 (d, J=8.1 Hz, 1H), 8.75 (d, J=4.9 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 18.3, 120.9, 121.1, 124.1, 128.4, 128.5, 129.0, 1.29.0, 130.0, 132.8, 133.3, 136.1, 137.0, 137.1, 137.3, 149.1, 149.5, 154.1, 155.3, 155.6, 155.7, 157.0; IR (KBr, ν/cm−1) 3265, 1632, 1550, 1457, 1371, 1240, 1002, 855, 797, 717; HRMS (ESI+) Calcd for C25H22N4NaO ([M+Na]+) 417.1686, Found 417.1679.
Example 7
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-cyclohexylthiourea




51% yield; white solid; Rf=0.36 (hexane/ethyl acetate=1/1); 1H NMR (400 MHz, CDCl3) δ 0.96-1.12 (m, 3H), 1.24-1.37 (m, 2H), 1.55-1.63 (m, 4H), 1.90-1.93 (m, 2H), 4.14 (s, 1H), 5.71 (s, 1H), 7.30-7.34 (m, 2H), 7.41-7.54 (m, 3H), 7.82 (d, J=8.1 Hz, 1H), 7.85 (ddd, J=8.1, 8.1, 2.2 Hz, 1H), 8.40 (d, J=0.1 Hz, 1H), 8.47 (d, J=9.0 Hz, 1H), 8.68-8.73 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 24.8, 25.5, 32.7, 54.1, 121.1, 121.4, 124.0, 127.9 (2C), 128.6, 130.0, 131.6, 133.6, 135.3, 137.0 (2C), 148.9, 149.4, 155.7, 155.8, 179.5; IR (KBr, ν/cm−1) 3293, 2931, 2857, 1637, 1458, 1373, 1229, 1001, 841, 656; HRMS (ESI+). Calcd for C23H24N4NaS ([M+Na]+) 411.1619, Found 411.1611.
Example 8
1-2-([2,2′-Bipyridin]-5-ylethynyl)aniline




A triethylamine (1.3 mL) solution of PdCl2(PPh3)2 (1.8 mg, 2.5 μmol, 0.5 mol %), CuI (1.0 mg, 5.0 μmol, 1.0 mol %) and 5-bromo-2,2′-bipyridine (118 mg, 0.50 mmol, 1 equiv) was stirred for 15 minutes at room temperature. To the resulting solution, 2-ethylaniline (93 μL, 0.6 mmol, 1.2 equiv) was added, and then stirred at 70° C. for 3.5 hours. The temperature of the solution was cooled to room temperature, then the solid substances were removed by filtration with Celite, and the obtained filtrate was washed with water (20 mL) and was subjected to extraction with diethyl ether (3×20 mL). The crude product was isolated and purified by silica gel column chromatography (hexane/ethyl acetate=3/1), and thus 106 mg (yield: 78%) of a target product was obtained as a white solid.
78% yield; white solid; Rf=0.15 (hexane/ethyl acetate=3/1); 1H mm (400 MHz, CDCl3) δ 4.32 (brs, 2H), 6.72-6.77 (m, 2H), 7.18 (dt, J=7.6, 1.3 Hz, 1H), 7.34 (dd, J=7.6, 4.9 Hz, 1H), 7.40 (dd, J=8.1, 1.8 Hz, 1H), 7.84 (dd, J=7.6, 7.6 Hz, 1H), 7.93 (dd, J=8.1, 2.2 Hz, 1H), 8.41-8.44 (m, 2H), 8.70 (d, J=4.0 Hz, 1H), 8.81 (dd, J=8.2, 1.8 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 90.4, 91.8, 107.3, 114.6, 118.2, 120.5 (2C), 121.5, 124.0, 130.4, 132.5, 137.1, 139.2, 148.1, 149.4, 151.5, 154.9, 155.6; IE (KBr, ν/cm−1). 3313, 2362, 2206, 1624, 1569, 1488, 1459, 1312, 1093, 739; HRMS (ESI+) Calcd for C18H13N3Na ([M+Na]+) 294.1007, Found 294.0999.
(2) 1-(2-([2,2′-Bipyridin]-5-ylethynyl)phenyl)-3-phenylurea




The target product was produced in the same manner as Example 1 (2).
46% yield; white solid; Rf=0.29 (ethyl acetate); 1H NMR (500 MHz, CDCl3) δ 6.49 (brs, 1H), 7.04-7.10 (m, 3H), 7.29-7.30 (m, 1H), 7.34-7.41 (m, 4H), 7.47-7.49 (m, 2H), 7.58 (d, J=6.3 Hz, 1H), 7.86 (dd, J=5.8, 5.8 Hz, 1H), 8.30 (d, J=6.7 Hz, 1H), 8.37 (d, J=10.2 Hz, 1H), 8.44 (d, J=6.3 Hz, 1H), 8.56 (s, 1H), 8.72 (d, J=3.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 88.8, 92.7, 111.4, 119.4, 134.4, 120.4, 121.6, 122.8, 123.4, 124.3, 125.7, 127.7, 129.8, 130.5, 132.2, 137.2, 139.5, 139.9, 149.5, 151.7, 153.0, 155.3; 153.4; IR (KBr, ν/cm−) 8299, 1844, 1576, 1552, 1458, 1296, 1091, 794, 743, 692; HRMS (ESI+) Calcd for C25H18N4NaO ([M+Na]+) 413.1378, Found 413.1388.
Example 9
(1) Meta-Selective Borylation of an Aromatic Compound with an Iridium Catalyst
In a dried test tube, to a p-xylene (1.5 mL) solution of N,N-dihexylbenzamide (72.4 mg, 0.250 mmol, 1.00 equiv), [Ir(OMe) (cod)]2 (1.2 mg, 1.9 μmol, 0.75 mol %), 1-(2-([2,2′-bipyridin]-5-yl)phenyl)-3-cyclohexylurea (1.2 mg, 3.8 μmol, 1.5 mol %) and bis(pinacolato)diboron (47.6 mg, 0.188 mmol, 0.750 equiv) were added and stirred at 25° C. for 24 hours. The solvent was removed under reduced pressure, and then the products were isolated and prepared by recycling preparative HPLC.




The obtained compounds were as follows.
N,N-Dihexyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




40% yield; colorless oil; 1H NMR (500 MHz, CDCl3) δ 0.82 (t, J=6.9 Hz, 3H), 0.89-0.92 (m, 3H), 1.10-1.21 (m, 6H), 130-141 (m, 18H), 1.46-1.50 (m, 2H), 1.65-1.66 (m, 2H), 3.15 (t, J=6.9 Hz, 2H), 3.46 (t, J=7.2 Hz, 2H), 7.38 (dd, J=8.0, 7.2 Hz, 1H), 7.43 (ddd, J=8.0, 1.7, 1.7 Hz, 1H), 7.78 (s, 1H), 7.80 (ddd, J=7.2, 1.7, 1.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.1, 14.2, 22.6, 22.8, 25.0, 26.3, 26.9, 27.6, 28.8, 31.4, 31.8, 45.0, 49.2, 84.1, 127.8, 129.3, 132.7, 135.4, 136.8, 171.8; 11B NMR. (130 MHz, CDCl3) δ 30.2; IR (neat, ν/cm−1) 2930, 2858, 1626, 1411, 1358, 1319, 1144, 861, 754, 666; HRMS (ESI+). Calcd for C25H42BNNaO3 ([M+Na]+) 438.3150, Found 438.3151.
N,N-Dihexyl-4-(4,4,5,5-tetrarmethyl-1,3,2-dioxaborolan-2-yl)benzamide




3.3% yield; colorless oil; 1H HMR (500 MHz, CDCl3) δ 0.82 (t, J=7.2 Hz, 3H), 0.89-0.92 (m, 3H), 1.06-1.11 (m, 4H), 1.18-1.25 (m, 2H), 1.35-1.36 (m, 18H), 1.46-1.47 (m, 2H), 1.63-1.66 (m, 2H), 3.13 (t, J=6.9 Hz, 2H), 3.46 (t, J=7.2 Hz, 2H), 7.32 (d, J=8.3 Hz, 2H), 7.81 (d, J=8.3 Hz, 2H); 13C NMR (125 MHz, CDCl3), δ 14.0, 14.1, 22.5, 22.7, 25.0, 26.3, 28.8, 27.6, 28.7, 31.4, 31.7, 44.8, 49.0, 84.1, 125.7, 134.8, 140.1, 171.6; 11B NMR (130 MHz, CDCl3) δ 29.9; IR (neat, ν/cm−1) 2929, 1636, 1511, 1396, 1360, 1322, 1144, 1108, 859, 659; HRMS (ESI+) Calcd for C25H42BNNaO3 ([M+Na]+) 438.3150, Found 438.3170.
N,N-Dihexyl-3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




3.0% yield; colorless oil; 1H NMR (500 MHz, CDCl3) δ 0.81 (t, J=7.2 Hz, 3H), 0.90-0.93 (m, 3H), 1.10-1.27 (m, 10H), 1.31-1.35 (m, 28H), 1.62-1.66 (m, 2H), 3.12 (t, J=6.9 Hz, 2H), 3.44 (t, J=7.2 Hz, 2H), 7.88 (s 2H), 8.26 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.1, 14.2, 22.5, 22.8, 25.0, 26.3, 27.0, 27.7, 28.9, 31.4, 31.8, 45.0, 49.3, 84.0, 135.5, 136.3, 141.7, 171.7; 11B: NMR (130 MHz, CDCl3) δ 32.9; IR (neat, ν/cm−1) 2929, 1628, 1329, 1265, 1142, 967, 889, 801, 755, 718; HRMS (ESI+) Calcd for C31H53B2NNaO5 ([M+Na]+) 564.4002, Found 564.4021.
By using the ligand used in (1), the following compounds ((2) to (27)) were obtained in the same manner as the method of (1).
(2) N,N-Dihexyl-2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl)benzamide and N,N-dihexyl-2methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




63% yield [meta/para=7.5]; colorless oil; 11B NMR (130 MHz, CDCl3) δ 31.9; IR (neat, ν/cm−1) 2930, 1627, 1410, 1355, 1140, 1027, 965, 851, 754, 683; HRMS (ESI+) Calcd for C25H44BNNaO4 ([M+Na]+) 468.3256, Found 468.3246.
N,N-Dihexyl-2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J=7.4 Hz, 3H), 0.91 (t, J=6.7 Hz, 3H), 1.06-1.08 (m, 4H), 1.16-1.50 (m, 22H), 1.62-1.64 (m, 2H), 3.01-3.04 (m, 2H), 3.48-3.49 (m, 2H), 3.82 (s, 3H), 6.87 (d, J=8.3 Hz, 1H), 7.63 (s, 1H), 7.76 (d, J=8.3 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 14.2, 22.5, 22.8, 24.7, 26.3, 26.7, 27.6, 28.4, 31.4, 31.8, 44.4, 48.5, 55.4, 83.7, 110.1, 126.6, 134.4, 137.0, 157.8, 169.2.
N,N-Dihexyl-2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J=7.4 Hz, 3H), 0.91 (t, J=6.7 Hz, 3H), 1.06-1.08 (m, 4H), 1.18-1.50 (m, 20H), 1.62-1.64 (m, 4H), 3.01-3.04 (m, 2H), 3.48-3.49 (m, 2H), 3.85 (s, 3H), 7.17 (d, J=7.2 Hz, 1H), 7.29 (s, 1H), 7.41 (d, J=7.2 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 14.2, 22.5, 22.8, 25.0, 26.3, 26.8, 27.5, 28.4, 31.4, 31.8, 44.3, 48.3, 55.6, 84.1, 116.4, 127.1, 127.4, 130.0, 154.6, 169.2.
3) N,N-Dihexyl-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide and N,N-dihexyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




39% yield [meta/para=15]; colorless oil; IR (neat, ν/cm−1) 2929, 1634, 1466, 1357, 1145, 1105, 965, 862, 754, 686; HRMS (ESI+) Calcd for C26H44BNNaO3 ([M+N]+) 452.3306, Found 452.3306.
N,N-Dihexyl-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (500 MHz, CDCl3) δ 0.82 (t, J=7.2 Hz, 3H), 0.91 (t, J=6.9 Hz, 3H), 1.07-1.11 (m, 4H), 1.14-1.21 (m, 2H), 1.25-1.39 (m, 18H), 1.41-1.47 (m, 2H), 1.62-1.70 (m, 2H), 2.29 (s, 3H), 3.01-3.05 (m, 2H), 3.39-3.56 (m, 2H), 7.19 (d, J=7.5 Hz, 1H), 7.59 (s, 1H), 7.67 (d, J=7.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 14.2, 19.4, 22.5, 22.8, 25.0, 26.3, 27.0, 27.7, 28.5, 31.3, 31.8, 44.6, 48.6, 83.9, 129.8, 132.3, 134.9, 136.8, 137.4, 171.3; 11B NMR (130 MHz, CDCl3) δ 30.5;
N,N-Dihexyl-2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (500 MHz, CDCl3) δ 0.81 (t, J=7.2 Hz, 3H), 0.90 (t, J=6.0 Hz, 3H), 1.04-1.11 (m, 4H), 1.14-1.26 (m, 2H), 1.28-1.47 (m, 20H), 1.62-1.67 (m, 2H), 2.27 (s, 3H), 2.85-3.15 (m, 2H), 3.20-3.75 (m, 2H), 7.14 (d, J=7.8 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.64 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 14.2, 18.9, 22.6, 22.8, 25.0, 26.4, 27.0, 27.6, 28.5, 31.4, 31.8, 44.4, 48.4, 84.1, 125.3, 132.2, 133.2, 136.7, 140.1, 171.2; 11B NMR (130 MHz, CDCl3) δ 31.3.
(4) 2-Bromo-N,N-dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide and 2-bromo-N,N-dihexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




91% yield [meta/para=8.6]; colorless oil; 11B NMR (130 MHz, CDCl3) δ 30.0; IR (neat, ν/cm−1) 2929, 1640, 1590, 1355, 1144, 1094, 964, 839, 754, 688; HRMS (ESI+) Calcd for C25H41BBrNNaO3 ([M+N]+) 516.2255, Found 516.2245. 2-Bromo-N,N-dibexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J=7.2 Hz, 3H), 0.91 (t, J=6.7 Hz, 3H), 1.07-1.10 (m, 4H), 1.16-1.20 (m, 2H), 1.32-1.34 (m, 16H), 1.45-1.59 (m, 4H), 1.66-1.68 (m, 2H), 3.01-3.08 (m, 2H), 3.22-3.29 (m, 1H), 3.66-3.73 (m, 1H), 7.55 (d, J=7.9 Hz, 1H), 7.61 (dd, J=7.9, 1.4 Hz, 1H), 7.67 (d, J=1.4 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.0, 14.2, 22.4, 22.7, 24.8 (br), 26.2, 26.9, 27.3, 28.3, 31.3, 31.7, 44.6, 48.3, 84.2, 122.8, 132.1, 134.2, 135.9, 138.4, 168.9.
2-Bromo-N,N-dibexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J=7.2 Hz, 3H), 0.91 (t, J=6.7 Hz, 3H), 1.07-1.10 (m, 4H), 1.16-1.20 (m, 2H), 1.32-1.34 (m, 16H), 1.45-1.59 (m, 4H), 1.66-1.68 (brs, 2H), 3.01-3.08 (m, 2H), 3.22-3.29 (m, 1H), 3.66-3.73 (m, 1H), 7.23 (d, J=7.4 Hz, 1H), 7.73 (dd, J=7.4, Hz, 1H), 7.98 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 14.0, 14.2, 22.5, 22.7, 24.9 (br), 26.3, 26.9, 27.2, 28.3, 31.2, 31.7, 44.7, 48.5, 84.4, 119.1, 127.3, 133.6, 138.7, 141.3, 168.8.
(5) 2-Chloro-N,N-dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide and 2-chloro-N,N-dihexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




84% yield [meta/para=12]; pale yellow oil; HRMS (ESI+). Calcd for C25H41BClNNaO3 ([M+N]+) 472.2760, Found 472.2764.
2-Chloro-N,N-dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J=7.2 Hz, 3H), 0.91 (t, J=6.7 Hz, 3H), 1.08-1.19 (m, 6H), 1.25-1.61 (m, 20H), 1.63-1.69 (m, 2H), 2.98-3.12 (m, 2H), 3.28-3.34 (m, 1H), 3.64-3.70 (m, 1H), 7.36 (d, J=8.5 Hz, 1H), 7.69 (s, 1H), 7.70 (d, J=8.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 14.2, 19.4, 22.5, 22.8, 24.8, 26.3, 26.9, 27.4, 28.4, 31.3, 31.8, 44.7, 48.5, 84.3, 129.0, 133.5, 134.3, 136.0, 136.4, 168.2; 11B NMR (130 MHz, CDCl3) δ 32.1; IR (neat, ν/cm−1) 2929, 2857, 1645, 1507, 1456, 1387, 1144, 1095, 963, 732.
2-Chloro-N,N-dihexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.81 (t, J=7.2 Hz, 3H), 0.90 (t, J=6.5 Hz, 3H), 1.07-1.20 (m, 6H), 1.25-1.51 (m, 20H), 1.65-1.67 (m, 2H), 2.98-3.12 (m, 2H), 3.19-3.26 (m, 1H), 3.71-3.79 (m, 1H), 7.25 (d, J=7.6 Hz, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.80 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 14.1, 14.2, 22.5, 22.8, 25.0, 26.4, 26.9, 27.3, 28.4, 31.4, 31.8, 44.6, 48.5, 84.3, 127.4, 132.2, 133.1, 135.7, 139.3, 168.1; 11B NMR (130 MHz, CDCl3) δ 30.2; IR (neat, ν/cm−1) 2929, 2857, 1644, 1498, 1456, 1355, 1143, 1096, 1047, 686.
(6N,N-Dihexyl-5-(4,4,5,5-tetrarmethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)benzamide




93.0% yield; colorless oil; 1H NMR (500 MHz, CDCl3) δ 0.80 (t, J=7.2 Hz, 3H), 0.91 (t, J=6.7 Hz, 3H), 1.07-1.22 (m, 6H), 1.33-1.49 (m, 20H), 1.64-1.65 (m, 2H), 2.88-3.04 (m, 2H), 3.13-3.23 (m, 1H), 3.69-3.79 (m, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.75 (s 1H), 7.88 (d, J=7.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.1, 22.4, 22.7, 24.9, 26.2, 26.8, 27.0, 28.0, 31.3, 31.7, 31.8, 44.5, 48.8, 84.5, 123.8 (q, J=275 Hz), 125.6, (q, J=4.8 Hz), 127.1, 128.7 (q, J=31.2 Hz), 133.8, 134.9, 168.6; 19F NMR (368 MHz, CDCl3) δ 62.0; 11B NMR (130 MHz, CDCl3) δ 30.5; IR (neat, ν/cm−1) 2930, 2859, 1644, 1505, 1467, 1312, 1102, 1041, 844, 690; HRMS (ESI+) Calcd for C26H41BF3NNaO3 ([M+Na]+) 506.3024, Found 506.3018.
(7) N,N-Dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl)-2-(trifluoromethoxy)benzamide and N,N-dihexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethoxy)benzamide




92% yield [meta/para=6.8]; colorless oil; 13F NMR (368 MHz, CDCl3) δ −58.6; 11B NMR (130 MHz, CDCl3) δ 30.2; IR (neat, ν/cm−1) 2931, 2859, 1644, 1468, 1359, 1255, 1003, 965, 850, 687; HRMS (ESI+) Calcd for C26H41BF3NNaO4 ([M+Na]+) 522.2973, Found 522.2996.
N,N-Dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethoxy)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J=7.2 Hz, 3H), 0.90 (t, J=6.7 Hz, 3H), 1.08-1.09 (m, 4H), 1.17-1.20 (m, 2H), 1.32-1.45 (m, 20H), 162-168 (m, 2H), 3.04 (t, J=7.6 Hz, 2H), 3.19-3.26 (m, 1H), 3.72-3.76 (m, 1H), 7.25 (d, J=8.3 Hz, 1H), 7.75 (s, 1H), 7.82 (d, J=8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 13.9, 14.1, 22.4, 22.6, 24.9, 26.2, 26.7, 27.2, 28.3, 31.2, 31.7, 44.4, 48.4, 84.3, 118.6 (q, J=1.9 Hz), 123.8 (q, J=258 Hz), 129.8, 135.2, 136.7, 147.1 (q, J=1.9 Hz), 166.8.
N,N-Dihexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethoxy)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.80 (t, J=7.2 Hz, 3H), 0.90 (t, J=6.7 Hz, 3H), 1.08-1.09 (m, 4H), 1.17-1.20 (m, 2H), 1.32-1.45 (m, 20H), 162-168 (m, 2H), 3.04 (t, J=7.6 Hz, 2H), 3.19-3.26 (m, 1H), 3.72-3.76 (m, 1H), 7.33 (d, J=7.4 Hz, 1H), 7.67 (s, 1H), 7.73 (d, J=7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 13.9, 14.1, 22.5, 22.6, 24.8, 26.2, 26.7, 27.2, 28.3, 31.3, 31.7, 44.4, 48.4, 84.4, 123.8 (q, J=258 Hz), 125.9, 127.9, 133.2, 133.3, 144.5 (q, J=1.9 Hz), 166.7.
(8)Methyl 2-(dihexylcarbamoyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate




96% yield; pale yellow oil; 1H NMR (400 MHz, CDCl3) δ 0.79 (t, J=7.2 Hz, 3H), 0.91 (t, J=7.0 Hz, 3H), 1.05-1.07 (m, 4H), 1.15-1.20 (m, 2H), 1.30-1.47 (m, 20H), 169-172 (m, 2H), 2.99 (t, J=7.8 Hz, 2H), 3.45-3.49 (m, 2H), 3.86 (s, 3H), 7.70 (d, J=1.0 Hz, 1H), 7.83 (dd, J=8.0, 1.0 Hz, H), 7.99 (d, J=8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 13.9, 14.1, 22.3, 22.7, 24.8, 26.2, 26.9, 27.1, 28.0, 31.2, 31.7, 44.8, 48.8, 52.2, 84.3, 129.1, 129.6, 133.4, 134.5, 138.3, 166.2, 170.6; 11B NMR (130 MHz, CDCl3) δ 29.6; IR (neat, ν/cm−1) 2930, 2858, 1730, 1639, 1494, 1359, 1143, 964, 855, 795; HRMS (ESI+). Calcd for C27H44BNNaO3 ([M+Na]+) 496.3205, Found 496.3186.
(9) N,N-Dihexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-carboxamide




26% yield; colorless oil; 1H NMR (400 MHz, CDCl3) δ 0.79 (t, J=7.2 Hz, 3H), 0.88 (t, J=7.0 Hz, 3H), 0.92-1.01 (m, 4H), 1.05-1.28 (m, 10H), 1.34 (s, 12H), 162-1.66 (m, 2H), 2.48-2.54 (m, 1H), 2.80-2.98 (m, 2H), 3.54-3.61 (m, 1H), 7.30-7.41 (m, 4H), 7.48-7.50 (m, 2H), 7.82 (s, 1H), 7.85 (dd, J=7.9, 1.1 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.1, 14.2, 22.5, 22.7, 24.8, 25.1, 26.2, 26.9, 27.9, 31.2, 31.8, 44.4, 48.3, 84.0, 127.8, 128.4, 128.7, 128.9, 134.1, 135.2, 136.0, 140.0, 141.0, 171.1; 11B NMR (130 MHz, CDCl3) δ 31.8; IR (neat, ν/cm−1) 2928, 2857, 1629, 1466, 1387, 1318, 1144, 965, 700, 611; HRMS (ESI+) Calcd for C31H46BNNaO3 ([M+Na]+) 514.3463, Found 514.3452.
(10) 2-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-isoindolin-1-one, and 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-isoindolin-1-one




39% yield [meta/para=3.3]; pale yellow solid; 11B NMR (130 MHz, CDCl3) δ 30.8; IR (neat, ν/cm−1) 2978, 2932, 1680, 1397, 1355, 1337, 1309, 1258, 1202, 1143, 1115, 967, 863, 849, 714, 655; HRMS (ESI+) Calcd for C15H20BNNaO3 ([M+Na]+) 296.1434, Found 296.1438.
2-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-isoindolin-1-one: 1H NMR (400 MHz, CDCl3) δ 1.35 (s, 12H), 3.18 (s, 3H), 4.36 (s, 2H), 7.41 (d, J=7.6 Hz, 1H), 7.93 (d, J=7.6 Hz, 1H), 8.29 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 24.8, 29.4, 52.1, 84.0, 121.9, 130.1, 132.3, 137.3, 143.8, 168.5.
2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-isoindolin-1-one: 1H NMR (400 MHz, CDCl3) δ 1.35 (s, 12H), 3.19 (s, 3H), 4.35 (s, 2H), 7.81 (d, J=7.6 Hz, 1H), 7.86 (s, 1H), 7.89 (d, J=7.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 24.9, 29.5, 52.9, 84.2, 122.7, 128.7, 134.3, 135.2, 140.1, 168.6.
(11) N,N-Dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




41% yield [meta/para=13]; white solid; 11B NMR (130 MHz, CDCl3) δ 30.6; IR (neat, ν/cm−1) 2978, 1634, 1482, 1356, 1267, 1213, 965, 812, 709, 671; HRMS (ESI+) Calcd for C15H22BNNaO3 ([M+Na]+) 298.1585, Found 298.1585.
N,N-Dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 12H), 2.96 (s, 3H), 3.10 (s, 3H), 7.40 (dd, J=8.0, 8.0 Hz, 1H), 7.49 (ddd, J=8.1, 1.1, 1.1 Hz, 1H), 7.82-7.84 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 25.0, 35.4, 39.7, 84.1, 127.9, 129.8, 133.2, 135.8, 135.9, 171.8.
N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 1.35 (s, 12H), 3.19 (s, 3H), 4.35 (s, 2H), 7.81 (d, J=7.6, Hz, 1H), 7.86 (s, 1H), 7.89 (d, J=7.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 24.9, 29.5, 51.9, 84.2, 122.7, 128.7, 134.3, 135.2, 140.1, 168.6.
N,N-Dimethyl-3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




11% yield; white solid; 1H NMR (400 MHz, CDCl3) δ 1.33 (s, 24H), 2.95 (s, 3H), 3.09 (s, 3H), 7.93 (d, J=1.3 Hz, 2H), 8.28 (t, J=1.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 25.0, 35.3, 39.8, 84.1, 135.5, 135.9, 142.1, 171.9; 11B NMR (130 MHz, CDCl3) δ 30.6; IR (neat, ν/cm−1) 2978, 1636, 1594, 1380, 1330, 1213, 1142, 889, 755, 689; HRMS (ESI+) Calcd for C21H33B2NNaO3 ([M+Na]+) 424.2437, Found 424.2455.
(12) 1-Piperidinyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanone




50% yield; white solid; 1H HMR (400 MHz, CDCl3) δ 1.34 (s, 1.2H), 1.48-1.51 (m, 2H), 1.63-1.70 (m, 4H), 3.29-3.37 (m, 2H), 3.67-3.73 (m, 2H), 7.38 (dd, J=7.6, 6.7 Hz, 1H), 7.46 (d, J=7.6 Hz, 1H), 7.81-7.82 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 24.7, 25.0, 25.7, 26.6, 43.1, 48.9, 84.1, 127.8, 129.5, 133.1, 135.7, 136.1, 170.4; 11B NMR (130 MHz, CDCl3) δ30.8; IR (neat, ν/cm−1) 2938, 1714, 1626, 1358, 1271, 1143, 1094, 964, 859, 754, 666; HRMS (ESI+) Calcd for C18H26BNNaO3 ([M+Na]+) 338.1898, Found 338.1897.
1-Piperidinyl(3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanone




11% yield; white solid; 1H NMR (400 MHz, CDCl3) δ 1.37 (s, 24H), 1.49-1.65 (m, 6H), 3.32-3.33 (m, 2H), 3.64-3.70 (m, 2H), 7.89 (s, 2H), 8.27 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 24.7, 25.0, 25.7, 26.6, 43.1, 48.9, 84.1, 135.6, 135.8, 142.1, 170.5; 11NMR (130 MHz, CDCl3) δ 30.8; IR (neat, ν/cm−1) 2979, 1624, 1329, 1267, 1142, 966, 889, 755, 716, 666; HRMS (ESI+) Calcd for C24H37B2NNaO5 ([M+Na]+) 464.2750, Found 464.2728.
(13) (2-Bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-morpholinylmethanone and (2-bromo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-morpholinylmethanone




88% yield [meta/para=3.2]; pale yellow solid; 11B NMR (130 MHz, CDCl3) δ 30.8; IR (KBr, ν/cm−1) 2977, 2927, 2857, 1645, 1592, 1434, 1386, 1356, 1280, 1248, 1143, 1114, 1094, 1016, 848, 689; HRMS (ESI+) Calcd for C17H23BBrNNaO4 ([M+Na]+) 418.0801, Found 418.0791
(2-Bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-morpholinylmethanone: 1H NMR (500 MHz, CDCl3) δ 1.30 (s, 12H), 3.10-3.29 (m, 2H), 3.50-3.61 (m, 1H), 3.64-3.80 (m, 4H), 3.80-3.89 (m, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.62 (dd, J=8.0, 1.8 Hz, 1H), 7.65 (d, J=1.8 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 24.9, 41.8, 47.0, 66.5, 66.6, 84.2, 122.4, 132.0, 133.8, 136.4, 138.7, 167.7.
(2-Bromo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-morpholinylmethanone: 1H NMR (500 MHz, CDCl3) δ 1.28 (s, 12H), 3.10-3.29 (m, 2H), 3.50-3.61 (m, 1H), 3.64-3.80 (m, 4H), 3.80-3.89 (m, 1H), 7.22 (d, J=7.5 Hz, 1H), 7.74 (d, J=7.5 Hz, 1H), 7.97 (s, 1H); 13C NMR (125 MHz, CDCl3) δ24.5, 41.8, 47.0, 66.5, 66.6, 84.3, 118.8, 127.0, 133.8, 136.9, 139.8, 167.5.
(14) Azepane-1-yl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl) methanone




36% yield; white solid; 1H NMR (400 MHz, CDCl3) δ 1.34 (s, 12H), 1.59-1.64 (m, 6H), 1.81-1.85 (m, 2H), 3.36 (t, J=5.4 Hz, 2H), 3.67 (t, J=5.8, Hz, 2H), 7.38 (dd, J=7.9, 7.6 Hz, 1H); 7.46 (d, J=7.9 Hz, 1H), 7.80-7.82 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 25.0, 26.6, 27.4, 28.0, 29.6, 46.3, 49.9, 84.1, 127.8, 129.2, 132.8, 135.4, 136.9, 171.7; 11B NMR (130 MHz, CDCl3) δ 30.6; IR (neat, ν/cm−1) 2977, 2928, 1631, 1409, 1356, 1319, 1216, 1099, 859, 708; HRMS (ESI+) Calcd for C13H28BNNaO3 ([M+H]+) 352.2054, Found 352.2049.
Azepane-1-yl(3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanone




12% yield; white solid; 1H NMR (400 MHz, CDCl3) δ 1.33 (s, 24H), 1.58-1.59 (m, 6H), 1.80-1.86 (m, 2H), 3.36 (t, J=5.4 Hz, 2H), 3.65 (t, J=5.4 Hz, 2H), 7.90 (s, 2H), 8.27 (s, 1H); 13C NMR (1.00 MHz, CDCl3) δ 25.0, 26.7, 27.5, 28.1, 29.6, 46.1, 50.0, 84.1, 135.5, 136.3, 141.8, 171.8; 11B NMR (130 MHz, CDCl3) δ 31.3; IR (neat, ν/cm−) 2930, 2927, 1628, 1429, 1389, 1270, 1142, 889, 754, 689; HRMS (ESI+) Calcd for C25H39B2NNaO5 ([M+Na]+) 478.2907, Found 478.2926.
N,N-Dihexyl-2-(trifluoromethyl)-5-(4,4,6-trimethyl-1,3,2-dioxaborolan-2-yl)benzamide and N,N-dihexyl-2-(trifluromethyl)-4-(4,4,6-trimethyl-1,3,2-dioxaborolan-2-yl)benzamide




62% yield, [meta/para=5.3]; colorless oil; 11B NMR (130 MHz, CDCl3) β 26.2; IR (neat, ν/cm−1) 2931, 1644, 1502, 1408, 1306, 1170, 1033, 844, 767, 687; HRMS (ESI+) Calcd for C25H41BF5NHaO3 ([M+Na]+) 506.3024, Found 506.3013.
N,N-Dihexyl-2-(trifluoromethyl)-5-(4,6-trimethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (500 MHz, CDCl3) δ 0.81, (t, J=7.2 Hz, 3H), 0.89-0.92 (m, 3H), 1.08-1.09 (m, 4H), 1.17-1.21 (m, 2H), 1.33-1.47 (m, 18H), 1.61-1.64 (m, 2H), 1.86-1.91 (m, 1H), 2.95-3.00 (m, 2H), 3.12-3.19 (m, 1), 3.77-3.84 (m, 1H), 4.13-4.37 (m, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.75 (s, 1H), 7.87 (d, J=7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.0, 14.1, 22.5, 22.7, 23.1, 26.2, 26.4, 26.9, 28.0, 28.2, 31.2, 31.4, 31.7, 44.4, 46.0, 48.7, 65.4, 71.6, 124.0 (q, J=274 Hz), 125.2 (q, J=3.6 Hz), 126.4, 127.6 (q, J=32.3 Hz), 132.9, 133.9, 169.2; 19F NMR (368 MHz, CDCl3) δ 61.9.
N,N-Dihexyl-2-(trifluoromethyl)-4-(4,4,6-trimethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (500 M Hz, CDCl3) δ 0.81 (t, J=7.2 Hz, 3H), 0.89-0.92 (m, 3H), 1.08-1.09 (m, 4H), 1.17-1.21 (m, 2H), 1.33-1.47 (m, 18H), 1.61-1.64 (m, 2H), 1.86-1.91 (m, 1H), 2.95-3.00 (m, 2H), 3.12-3.19 (m, 1H), 3.77-3.84 (m, 1H), 4.13-4.37 (m, 1H), 7.26 (d, J=6.7 Hz, 1H), 7.96 (d, J=6.7 Hz, 1H), 8.08 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.0, 14.1, 22.4, 22.7, 23.1, 26.2, 26.4, 26.9, 28.0, 28.2, 31.2, 31.3, 31.7, 44.4, 46.0, 48.7, 65.4, 71.6, 124.3 (q, J=296 Hz), 125.7, 127.6 (q, J=32.3 Hz), 131.8 (q, J=4.8 Hz), 134.6, 169.2; 19F NMR (368 MHz, CDCl3) δ −61.5.
(16) 3-Fluoro-N,N-dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide and 3-fluoro-N,N-dihexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




99% yield [meta/para=7.7]; colorless oil; 11B NMR (130 MHz, CDCl3) δ 30.0; IR, (neat, ν/cm−1) δ 2929, 1633, 1368, 1143, 1099, 968, 923, 854, 756, 676; HRMS (ESI−) Calcd for C25H41BFNNaO3 ([M+Na]+) 456.3056, Found 456.3035.
3-Fluoro-N,N-dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.82 (t, J=8.7 Hz, 3H), 0.89-0.91 (m, 3H), 1.12-1.17 (m, 4H), 1.21-1.49 (m, 22H), 1.61-1.62 (m, 2H), 3.14 (t, J=7.2 Hz, 2H), 3.44 (t, J=7.2 Hz, 2H), 7.13 (d, J=8.8 Hz, 1H), 7.48 (d, J=8.8 Hz, 1H), 7.55 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.0, 14.1, 22.5, 22.7, 24.9, 26.2, 26.8, 27.5, 28.7, 31.3, 31.7, 45.0, 49.1, 84.3, 116.5 (d, J=22.6 Hz) 121.6 (d, J=19.7 Hz), 128.2 (d, J=2.8 Hz), 138.9 (d, J=6.6 Hz), 162.2 (d, J=248 Hz), 170.1; 19F NMR (368 MHz, CDCl3) δ −115.3 (s, 1F).
3-Fluoro-N,N-dihexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide: 1H NMR (400 MHz, CDCl3) δ 0.82 (t, J=6.7 Hz, 3H), 0.89-0.91 (m, 3H), 1.12-1.18 (m, 4H), 1.21-1.49 (m, 22H), 1.61-1.62 (m, 2H), 3.14 (t, J=7.2 Hz, 2H), 3.44 (t, J=7.2 Hz, 2H), 7.01 (d, J=9.0 Hz, 1H), 7.11 (d, J=9.0 Hz, 1H), 7.73-7.77 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 14.0, 14.1, 22.5, 22.7, 24.9, 26.2, 26.8, 27.5, 28.7, 31.3, 31.7, 44.8, 49.0, 84.2, 113.6 (d, J=26.3 Hz), 132.0 (br), 137.1 (d, J=8.4 Hz), 142.4 (d, J=7.5 Hz), 165.4 (d, J=253 Hz), 169.9; 19F NMR (368 MHz, CDCl3) δ −103.7 (s, 1F).
(17) 3-Bromo-N,N-dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




86% yield; pale yellow oil; 1H NMR (400 MHz, CDCl3) δ 0.83 (t, J=7.2 Hz, 3H), 0.89-0.91 (m, 3H), 1.12-1.17 (m, 4H), 1.21-1.33 (m, 20H), 1.49-1.63 (m, 4H), 3.13 (t, J=7.6 Hz, 2H), 3.43 (t, J=7.6 Hz, 2H), 7.56 (s, 1H), 7.69 (s, 1H), 7.93 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.0, 14.1, 22.5, 22.7, 24.9, 26.2, 26.8, 27.5, 28.7, 31.3, 31.7, 45.0, 49.1, 84.4, 122.4, 131.0, 132.1, 138.0, 138.8, 169.9; 11B NMR (130 MHz, CDCl3) δ 30.7; IR (neat, ν/cm−1) 2929, 2857, 1635, 1435, 1348, 1143, 965, 964, 885, 704; HRMS (ESI+) Calcd for C25H41BBrNNaO3 ([M+N]+) 516.2255, Found 516.2255.
(18) N,N-Dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl)-[1,1′-biphenyl]-3-carboxamide




81% yield; pale yellow oil; 1H NMR (400 MHz, CDCl3) δ 0.79 (t, J=7.2 Hz, 3H), 0.90-0.92 (m, 3H), 1.11-1.19 (m, 6H), 1.23-1.35 (m, 18H), 1.51-1.53 (m, 2H), 1.63-1.66 (m, 2H), 3.20 (t, J=7.6 Hz, 2H), 3.48 (t, J=8.1 Hz, 2H), 7.34 (t, J=7.4 Hz, 1H), 7.43 (dd, J=8.1, 7.4 Hz, 2H), 7.62 (d, J=8.1 Hz, 2H), 7.66 (s, 1H), 7.76 (s, 1H), 8.05 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.1, 14.2, 22.5, 22.8, 25.0, 26.3, 27.0, 27.7, 28.9, 31.4, 31.8, 45.0, 49.3, 84.2, 127.3, 127.6, 128.0, 128.8, 131.6, 134.1, 137.5, 140.6, 140.8, 171.6; 11B NMR (130 MHz, CDCl3) δ 32.5; IR (neat, ν/cm−1) 2929, 2857, 1634, 1411, 1321, 1144, 966, 894, 756, 698; HRMS (ESI+) Calcd for C32H46BNNaO3 ([M+N]+) 514.3463, Found 514.3456.
(19) 3-Cyano-N,N-dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl)benzamide




87% yield; pale yellow oil; 1H HMR (400 MHz, CDCl3) δ 0.82 (t, J=7.2 Hz, 3H), 0.88-0.90 (m, 3H), 1.11-1.42 (m, 24H), 1.48-1.52 (m, 2H), 1.65-1.69 (m, 2H), 3.11 (t, J=7.6 Hz, 2H) 3.43 (t, J=7.6 Hz, 2H), 7.69 (dd, J=1.6, 1.6 Hz, 1H), 7.97 (dd, J=1.6, 1.4 Hz, 1H), 8.08 (dd, J=1.6, 1.4 Hz, 1H); 13C NRM (100 MHz, CDCl3) δ14.0, 14.1, 22.4, 22.6, 24.9, 26.2, 26.8, 27.5, 28.7, 31.2, 31.6, 45.1, 49.2, 84.8, 112.4, 118.2, 132.3, 136.6, 137.9, 138.7, 169.2; 11B NMR (130 MHz, CDCl3) δ 30.3; IR (neat, ν/cm−l) 2930, 2857, 2231, 1637, 1371, 1265, 1143, 966, 850, 704; HRMS (ESI+) Calcd for C26H41BN2NaO3 ([M+Na]+) 463.3102, Found 463.3124.
(20) 2,3-Dichloro-N,N-dihexyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide




94% yield; pale yellow oil; 1H HMR (500 MHz, CDCl3) δ 0.81 (t, J=7.5 Hz, 3H), 0.91 (t, J=6.7 Hz, 3H), 1.08-1.11 (m, 4H), 1.18-1.21 (m, 2H), 1.32-1.50 (m, 20H), 1.65-1.70 (m, 2H), 2.98-3.02 (m, 1H), 3.05-3.09 (m, 1H), 3.26-3.31 (m, 1H), 3.64-3.70 (m, 1H), 7.56 (d, J=1.2 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H); 13C NRM (100 MHz, CDCl3) δ 14.0, 14.1, 22.4, 22.7, 24.9 (br), 26.2, 26.8, 27.3, 28.3, 31.2, 31.7, 44.7, 48.5, 84.6, 131.6, 131.9, 133.1, 136.3, 138.4, 167.3; 11B NMR (130 MHz, CDCl3) δ 30.4; IR (neat, ν/cm−1) 2930, 2858, 1644, 1467, 1350, 1268, 1142, 965, 894, 755; HRMS (ESI+) Calcd for C25H40BCl2NNaO3 ([M+Na]+) 506.2371, Found 506.2394.
(21) 2-Fluoro-N,N-dihexyl-5-(4,4,5,5-tetraamethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)benzamide




89% yield; pale yellow oil; 1NMR (400 MHz, CDCl3) δ 0.80 (t, J=7.2 Hz, 3H), 0.90 (t, J=6.7 Hz, 3H), 1.08-1.11 (m, 4H), 1.17-1.22 (m, 2H), 1.33-1.49 (m, 20H), 1.65-1.67 (m, 2H), 3.14 (t, J=7.6 Hz, 2H), 3.40-3.64 (m, 2H), 7.94 (d, J=6.3 Hz, 1H), 8.05 (d, J=7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 13.9, 14.1, 22.4, 22.6, 24.9, 26.1, 26.7, 27.4, 28.4, 31.2, 31.7, 44.9, 48.8, 84.7, 118.4 (qd, J=33.6, 12.0 Hz), 122.5 (q, J=272 Hz), 126.6 (d, J=18.0 Hz), 134.1 (d, J=3.6 Hz), 139.2 (d, J=4.8 Hz), 157.3 (d, J=260 Hz), 165.0; 19F NMR (368 MHZ, CDCl3) δ −115.4 (s, 1F), −63.1 (s, 3F); 11B NMR (130 MHz, CDCl3) δ 30.1; IR (neat, ν/cm−1) 2931, 1644, 1468, 1385, 1302, 1239, 1197, 914, 756, 672; HRMS (ESI+) Calcd for C26H46BF4NNaO3 ([M+Na]+) 524.2930, Found 524.2939.
(22) N,N-Dihexyl-2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene) carboxamide




51% yield; pale yellow oil; 1H NMR (500 MHz, CDCl3) δ 0.80-0.92 (m, 6H), 1.16-1.38 (m, 12H), 1.33 (s, 12H), 1.53-1.70 (m, 4H), 3.38-3.44 (m, 4H), 7.30 (d, J=3.6 Hz, 1H), 7.50 (d, J=3.6 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 13.9 (2C), 22.5, 24.7 (2C), 26.4 (br, 2C), 27.5 (br), 28.8 (br), 31.4 (2C), 46.1 (br), 49.3 (br), 84.3, 129.1, 136.3, 144.2, 164.3; 11B NMR (130 MHz, CDCl3) δ 29.0; IR (neat, ν/cm−1) 2956, 2929, 2862, 1625, 1525, 1463, 1419, 1372, 1350, 1287, 1270, 1210, 1143, 1063, 1021, 997, 857, 853, 820, 739, 687, 667; HRMS (ESI+) Calcd for C23H40BNNaO3S ([M+Na]+) 444.2720, Found 444.2731.
N,N-Dihexyl-2-(3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene) carboxamide




14% yield; pale brown oil; 1H NMR (500 MHz, CDCl3) δ 0.75-0.96 (m, 6H), 1.03-1.53 (m, 40H), 3.05-3.22 (m, 2H), 3.35-3.55 (m, 2H), 7.83 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 13.97, 14.03, 22.4, 22.6, 24.7, 24.8, 26.2, 26.9, 27.0, 28.3, 31.3, 31.7, 45.2, 49.0, 83.6, 84.2, 143.1, 153.2, 165.5; 11B NMR (130 MHz, CDCl3) δ 28.6; 1H (neat, ν/cm−1) 3424, 2929, 2859, 1633, 1536, 1455, 1371, 1321, 1268, 1213, 1139, 1111, 1028, 1002, 967, 911, 882, 851, 829, 727, 688, 666; HRMS (ESI+) Calcd for C29H51B2NNaO5S ([M+Na]+) 570.3572, Found 570.3551.
(23) N,N-Dihexyl-5-(4,4,5,5-tetramethyl, 1,3,2-dioxaborolan-2-yl)-pyrrole-2-carboxamide




79% yield; colorless oil; 1H NMR (400 MHz, CDCl3) δ 0.81-0.93 (m, 6H), 1.23-1.36 (m, 24H), 1.53-1.78 (m, 4H), 3.25-3.70 (m, 4H), 6.43-6.70 (m, 1H), 6.74-6.78 (m, 1H), 9.85 (brs, 1H); 13C NMR (125 MHz, CDCl3) δ 14.0 (2C), 22.5, 24.7 (2C), 26.6 (2C), 27.6 (br), 28.8 (br), 31.5 (2C), 47.2 (br), 48.5 (br), 83.8, 111.6, 120.2, 129.2, 161.5; 11B NMR (130 MHz, CDCl3) δ 28.3; IR (neat, ν/cm−1) 3441, 3256, 2929, 2858, 1610, 1553, 1467, 1424, 1345, 1300, 1265, 1219, 1144, 973, 855, 790, 759, 704; HRMS (ESI+) Calcd for C23H41BN2NaO3 ([M+Na]+) 427.3108, Found 427.3114.
(24) N,N-Dihexyl-(1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole)-2-carboxamide and N,N-dihexyl-(1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole)-2-carboxamide




74% yield [5-/4-=6.7]; pale yellow oil; 11B NMR (130 MHz, CDCl3) δ 28.3; IR (neat, ν/cm−1) 2929, 2858, 1628, 1531, 1467, 1416, 1373, 1302, 1265, 1145, 1108, 1091, 965, 858, 754, 692; HRMS (ESI+) Calcd for C24H43BN2NaO3 ([M+Na]+) 441.3264, Found 441.3255.
N,N-Dihexyl-(1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole)-2-carboxamide: 1H NMR (500 MHz, CDCl3) δ 0.78-0.94 (m, 6H), 1.10-1.40 (m, 24H), 1.42-1.75 (m, 4H), 3.26-3.54 (m, 4H), 3.82 (s, 3H), 6.20 (d, J=4.0 Hz, 1H), 6.70 (d, J=4.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 13.9 (2C), 22.5 (2C), 24.7, 26.4 (br, 2C), 27.5 (br), 28.6 (br), 31.4 (2C), 34.6, 44.6 (br), 48.9 (br), 83.2, 109.7, 120.2, 132.5, 164.5.
N,N-Dihexyl-(1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole)-2-carboxamide: 1H NMR (500 MHz, CDCl3) δ 0.78-0.94 (m, 6H), 1.10-1.40 (m, 24H), 1.42-1.75 (m, 4H), 3.26-3.54 (m, 4H), 3.71 (s, 3H), 6.56-6.60 (m, 1H), 7.04-7.11 (m, 1H); 13C NMR, (125 MHz, CDCl3) δ13.9 (2C), 22.5 (2C), 24.7, 26.4 (2C), 27.5 (br), 28.6 (br), 31.4 (2C), 35.6, 44.6 (br), 48.9 (br), 82.9, 117.0, 127.6, 134.0, 164.0.
(25) N,N-Dihexyl-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole)-2-carboxamide




71% yield; pale yellow oil; 1H NMR (500 MHz, CDCl3) δ 0.87-0.96 (m, 6H), 1.30-1.41 (m, 12H), 1.39 (s, 12H), 1.60-1.85 (m, 4H), 3.30-3.90 (m, 4H), 6.75 (d, J=2.3 Hz, 1H), 7.15 (t, J=8.0 Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 9.94 (brs, 1H); 13C NMR (125 MHz, CDCl3) δ 14.0 (2C), 22.5 (2C), 24.9, 26.6 (br, 2C), 27.6 (br), 28.8 (br), 31.5 (2C), 47.4 (br), 49.0 (br), 83.9, 103.9, 119.9, 125.3, 126.9, 129.9, 131.7, 140.0, 162.5; 11B NMR (130 MHz, CDCl3) δ 31.2; IR (neat, ν/cm−1) 3438, 3056, 2927, 2857, 1615, 1595, 1529, 1463, 1443, 1369, 1288, 1200, 1146, 1130, 1110, 1045, 979, 849, 813, 748, 734, 678; HRMS (ESI+) Calcd for C27H43BN2NaO3 ([M+Na]+) 477.3264 Found 477.3264.
(26) N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) picolinamide and N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl) picolinamide




43% yield [4-/5=3.6]; white solid; 13C NMR (100 MHz, CDCl3) δ (4- and 5-position isomers) 25.0 (4- and 5-position isomers), 35.71, 35.76, 39.0, 39.1, 84.6, 84.8, 122.7, 128.5, 129.3, 143.4, 147.9, 154.07, 154.13, 156.5, 169.4 (4- and 5-position isomers); 11B NMR (130 MHz, CDCl3) δ 30.6; IR (neat, ν/cm−1) 2979, 1640, 1473, 1358, 1263, 1105, 965, 857, 752, 672; HRMS (ESI+) Calcd for C14H21BN2NaO3 ([M+Na]+) 299.1537, Found 299.1534.
N,N-Dimethyl-4-(4,4,5,5-tetraramethyl-1,3,2-dioxaborolan-2yl) picolinamide: 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 12H), 3.04 (s, 3H), 3.13 (s, 3H), 7.65 (d, J=5.8 Hz, 1H), 7.96 (s, 1H), 8.60 (d, J=5.8 Hz, 1H).
N,N-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaboralan-2-yl) picolinamide: 1H NMR (500 MHz, CDCl3) δ 1.36 (s, 12H), 3.04 (s, 3H), 3.13 (s, 3H), 7.58 (d, J=7.8 Hz, 1H), 8.15 (d, J=7.8 Hz, 1H), 8.91 (s, 1H).
As can be seen from the above-described results, the borylation of aromatic compounds by the catalyst of the present invention results in the meta-selective borylation.
(27) Table 1 shows the meta-para selectivity (m/p) in the case where the borylation reaction was performed in the same manner as Example 9(1) by using the ligands described in Examples 2 to 6.









TABLE 1





R2
X
m/p







n-Hex
◯
m/p = 7.4


 






◯
m/p = 14 


 






◯
m/p = 7.2


 






◯
m/p = 3.9


 






◯
m/p = 3.6









Example 10
(1) The borylation reaction was performed by using alkoxycarbonyl-substituted pyridines and alkoxycarbonylmethyl-substituted pyridines as the substituted aromatic compounds, the substrates of the borylation reaction, in the same manner as: Example 9 (1).
In a dried test tube, to a p-xylene (1.5 mL) solution of an alkoxycarbonyl-substituted pyridine (1.00 equiv), [Ir(OMe) (cod)]2 (1.5 mol %), 1-(2-([2,2′-bipyridin]-5-yl)phenyl)-3-(4-triflioromethylphenyl) urea (3.0 mol %) and bis(pinacolato)diboron (1.5 equiv) were added and stirred at 25° C. for 18 hours. The solvent was removed under reduced pressure, and then the products were isolated and prepared by recycling preparative HPLC.




The obtained compounds were as follows.
Ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate and ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate




70% yield [5-/4-=5.0]; white solid; 13C NMR (100 MHz, CDCl3) δ (4- and 5-position isomers) 25.0 (4- and 5-position isomers), 35.71, 35.76, 39.0, 39.1, 84.6, 84.8, 122.7, 128.5, 129.3, 143.4, 147.9, 154.07, 154.13, 156.5, 169.4 (4- and 5-position isomers); 11B NMR (130 MHz, CDCl3) δ 30.6; IR (neat, ν/cm−1) 2979, 1640, 1473, 1358, 1263, 1105, 965, 857, 752, 672; HRMS (ESI+) Calcd for C14H21BN2NaO3 ([M+Na]+) 299.1537, Found 299.1534.
Ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate: 1H NMR (500 MHz, CDCl3) δ 1.36 (s, 12H), 3.04 (s, 3H), 3.13 (s, 3H), 7.58 (d, J=7.8 Hz, 1H), 8.15 (d, J=7.6 Hz, 1H), 8.91 (s, 1H).
Ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxylate; 1H NMR (500 MHz, CDCl3) δ 1.34 (s, 12H), 3.04 (s, 3H), 3.13 (s, 3H), 7.65 (d, J=5.8 Hz, 1H), 7.96 (s, 1H), 8.60 (d, J=5.8 Hz, 1H).
By using the ligand used in (1), the following compounds were obtained in the same manner as the method of (1).
(2) 2-Ethoxycarbonylmethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine and 2-ethoxycarbonylmethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine




64% yield [5-/4-=1.7]; pale brown oil; 11B NMR (130 MHz, CDCl3) δ 30.9; IR (neat, ν/cm−1) 2980, 2934, 1739, 1600, 1557, 1480, 1403, 1371, 1258, 1166, 1145, 1099, 1028, 964, 856, 668; HRMS (ESI+) Calcd for C15H22BNNaO4 ([M+Na]+) 314.1540, Found 314.1539.
2-Ethoxycarbonylmethyl-5-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)pyridine: 1H NMR (500 MHz, CDCl3) δ 1.18-1.25 (m, 3H), 1.32 (s, 12H), 3.83 (s, 2H), 4.10-4.20 (m, 2H), 7.26 (d, J=8.0 Hz, 1H), 8.00 (d, J=8.0 Hz, 1H), 8.86 (s, 1H); NMR (100 MHz, CDCl3) δ 14.1, 24.7, 44.1, 61.0, 84.1, 123.1, 142.9, 155.2, 156.8, 170.4.
2-Ethoxycarbonylmethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine; 1H NMR (500 MHz, CDCl3) δ 1.18-1.25 (m, 3H), 1.32 (s, 12H), 3.82 (s, 2H), 4.10-4.20 (m, 2H), 7.50 (d, J=4.6 Hz, 1H), 7.60 (s, 1H), 8.56 (d, J=4.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.1, 24.8, 43.8, 60.9, 84.4, 127.0, 128.9, 148.9, 153.8, 170.7.
Example 11
(1) The borylation reaction was performed by using a phosphate-, phosphinediamide- or phosphine oxide-substituted benzene as the substituted aromatic compound, the substrate of the borylation reaction, in the same manner as Example 9.
In a dried test tube, to a p-xylene (1.5 mL) solution of a phosphate-, phosphinediamide- or phosphine oxide-substituted benzene (1.00 equiv), [Ir(OMe) (cod)]2 (1.5 mol %), 1-(2-([2,2′-bipyridin]-5-yl)phenyl)-3-cyclohexylurea (3.0 mol %) and bis(pinacolato)diboron (1.5 equiv) were added and stirred at 25° C. or 40° C. for 16 hours. The solvent was removed under reduced pressure, and then the products were isolated and prepared by recycling preparative HPLC.




(wherein R represents an ethoxy group, a diethylamino group or a cyclohexyl group (abbreviated as Cy), and Y represents H, Br, Cl, CF3, CMe or Me).

The obtained compounds were as follows.
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate




41% yield, [meta/para=17]; colorless solid; 11B NMR (130 MHz, CDCl3) δ 30.7; 31P NMR (158 MHz, CDCl3) δ 28.5, 28.1; IR (KBr, ν/cm−1) 2980, 1599, 1481, 1408, 1390, 1358, 1324, 1243, 1211, 1133, 1136, 1097, 1055, 1027, 965, 969, 843, 795, 767, 704, 669; HRMS (ESI+) Calcd for C16H26BO5P ([M+Na]+) 363.1509, Found 363.1498.
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate: 1H NMR (400 MHz, CDCl3) δ 1.30 (b, J=7.2 Hz, 6H), 1.32 (s, 12H), 3.98-4.18 (m, 4H), 7.44 (ddd, J=7.6, 7.6, 4.0 Hz, 1H), 7.88 (ddd, J=13.0, 7.6, 1.3 Hz, 1H), 7.95 (dd, J=7.6, 1.3 Hz, 1H), 8.24 (d, J=13.0 Hz, 1H), 13C NMR, (100 MHz, CDCl3) δ 16.3 (d, −JC-P=6.6 Hz), 24.8, 62.0 (d, JC-P=5.8 Hz), 84.0, 127.6 (d, JC-P=187 Hz), 127.7 (d, JC-P=15.0 Hz), 134.3 (d, JC-P=10.3 Hz), 133.0 (d, JC-P=9.4 Hz), 138.6 (d, JC-P=2.8 Hz).
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate; 1H NMR (400 MHz, CDCl3) δ 1.30 (t, J=7.2 Hz, 6H), 1.32 (s, 12H), 3.98-4.18 (m, 4H), 7.78 (dd, J=13.0, 8.0 Hz, 2H), 7.88 (dd, J=8.0, 4.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 16.3 (d, JC-P=6.6 Hz), 24.8, 62.0 (d, JC-P=5.8 Hz), 84.0, 130.9 (d, JC-P=185 Hz), 130.8 (d, JC-P=9.4 Hz), 134.5 (d, JC-P=15.0 Hz).
3,5-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl)phenyldiethylphosphonate




16% yield; colorless solid; 1H NMR (400 MHz, CDCl3) δ 1.31 (t, J=7.2 Hz, 6H), 1.33 (s, 24H), 3.99-4.20 (m, 4H), 8.32 (dd, J=13.0, 1.4 Hz, 1H), 8.40 (d, J=1.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 16.3 (d, JC-P=6.6 Hz), 24.8, 62.0 (d, JC-P=5.6 Hz), 84.0, 127.0 (d, JC-P=187 Hz), 140.7 (d, JC-P=10.3 Hz), 144.9 (d, JC-P=1.9 Hz); 11B NMR (130 MHz, CDCl3) δ 31.0; 31P NMR (153 MHz, CDCl3) δ 30.4; IR (KBr, ν/cm−1) 2977, 1597, 1389, 1331, 1318, 1272, 1248, 1214, 1168, 1141, 1048, 1019, 964, 952, 886, 848, 790, 718, 691, 662; HRMS (ESI+) Calcd for C22H37B2NaO7P ([M+Na]+) 489.2361, Found 489.2384.
By using the ligand used in (1), the following compounds ((2) to (9)) were obtained in the same manner as the method of (1).
(2) (2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate and (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate




59% yield [meta/para=0.54]; pale brown oil; 11B NMR (130 MHz, CDCl3) δ 30.7; 31P NMR (158 MHz, CDCl2) δ 28.1, 28.5; IR (neat, ν/cm−1) 2979, 2935, 2909, 1597, 1550, 1402, 1462, 1393, 1357, 1325, 1244, 1164, 1146, 1108, 1078, 1055, 1029, 965, 903, 851, 777, 760, 692, 675; HRMS (ESI+) Calcd for C17H26BNaO6P ([M+Na]+) 393.1614, Found 393.1599.
(2-Methoxy-5-(4,4,5,5-tetrarmethyl-1,3,5-dioxaborolan-2-yl)phenyldiethylphosphonate: 1H NMR (500 MHz, CDCl3) δ 1.15-1.45 (m, 18H), 3.88 (s, 3H), 4.00-4.25 (m, 4H), 6.85-6.92 (m, 1H), 7.91 (d, J=8.6 Hz, 1H), 8.24 (d, J=14.9 Hz, 1H), 13C NMR (125 MHz, CDCl3) δ 16.3, 24.8, 55.6, 62.0 (d, JC-P=4.8 Hz), 83.7, 110.3 (d, JC-P=8.4 Hz), 115.8 (d, JC-P=186 Hz), 141.1, 142.0 (d, JC-P=7.2 Hz), 163.5 (d, JC-P=2.4 Hz).
(2Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate: 1H NMR (500 MHz, CDCl3) δ 1.15-1.45 (m, 18H), 3.91 (s, 3H), 4.00-4.25 (m, 4H), 7.31 (d, J=6.3 Hz, 1H), 7.41 (dd, J=7.5, 3.4 Hz, 1H), 7.78 (dd, J=14.3, 7.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 16.2, 24.8, 55.8, 62.1 (d, JC-P=6.0 Hz), 84.1, 116.5 (d, JC-P=8.4 Hz), 119.0 (d, JC-P=185 Hz), 126.5 (d, JC-P=14.4 Hz), 134.2 (d, JC-P=7.2 Hz), 160.5 (d, JC-P=2.4 Hz).
(3) (2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate and (2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate




66% yield [meta/para=9.0]; pale yellow oil; 11B NMR (130 MHz, CDCl3) δ 30.9; 31P HMR (158 MHz, CDCl3) δ 30.7, 30.2; IR (neat, ν/cm−1) 2979, 2931, 2906, 1603, 1480, 1445, 1386, 1360, 1317, 1248, 1165, 1147, 1109, 1049, 1023, 963, 851, 795, 728, 674; HRMS (ESI+) Calcd for C17H28BNaO5P ([M+Na]+) 377.1665, Found 337.1666.
(2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyldiethylphosphonate: 1H NMR (500 MHz, CDCl3) δ 1.23-1.38 (m, 18H), 2.56 (s, 3H), 4.01-4.18 (m, 4H), 7.24 (dd, J=7.5, 5.2 Hz, 1H), 7.81 (d, J=7.5 Hz, 1H), 8.33 (d, J=14.4 Hz, 1H); 13C HMR (100 MHz, CDCl3) δ 16.2 (d, JC-P=6.1 Hz), 21.4 (d, JC-P=3.3 Hz), 24.8, 61.7 (d, JC-P=5.6 Hz), 83.8, 126.2 (d, JC-P=183 Hz), 130.5 (d, JC-P=14.1 Hz), 138.6 (d, JC-P=2.8 Hz), 140.4 (d, JC-P=10.3 Hz), 144.8 (d, JC-P=10.3 Hz).
(2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl)phenyldiethylphosphonate; 1H HMR (500 MHz, CDCl3) δ 1.23-1.38 (m, 1.8H), 2.56 (s, 3H), 4.00-4.17 (m, 4H), 7.65-7.70 (m, 2H), 7.88 (dd, J=14.3, 8.0 Hz, 1H); NMR (100 MHz, CDCl3) δ 16.2 (d, JC-P=6.6 Hz), 20.9 (d, JC-P=2.8 Hz), 24.8, 61.7 (d, JC-P=5.6 Hz), 84.0, 129.4 (d, JC-P=181 Hz), 131.5 (d, JC-P=14.4 Hz), 133.0 (d, JC-P=10.8 Hz), 137.2 (d, JC-P=14.4 Hz), 140.7 (d, JC-P=10.8 Hz).
(4) (2-Bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl) diethylphosphonate




65% yield; pale yellow oil; 1H HMR (400 MHz, CDCl3) δ 1.29 (s, 12H), 1.32 (t, J=7.2 Hz, 6H), 4.02-4.22 (m, 4H), 7.63 (dd, J=8.1, 4.9 Hz, 1H), 7.73 (dd, J=8.1, 1.3 Hz, 1H), 8.41 (d, J=13.9, 1.3 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 16.2 (d, JC-P=7.2 Hz), 24.8, 62.4 (d, JC-P=4.8 Hz), 84.2, 128.6 (d, JC-P=4.8 Hz), 128.7 (d, JC-P=191 Hz), 133.6 (d, JC-P=9.6 Hz), 139.5 (d, JC-P=2.4 Hz), 142.6 (d, JC-P=8.4 Hz); 11B NMR (130 MHz, CDCl3) δ 30.9; 31P NMR (158 MHz, CDCl3) δ 26.1; IR (neat, ν/cm−1) 2979, 2932, 2906, 1585, 1552, 1476, 1444, 1373, 1356, 1319, 1262, 1251, 1214, 1166, 1145, 1098, 1054, 1024, 964, 845, 796, 766, 726, 671; HRMS (ESI+) Calcd for C16H25BBrNaO5P ([M+Na]+) 441.0614, Found 441.0602.
(5) (5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-trifluoromethylphenyl) diethylphosphonate




30% yield; pale yellow solid; 1H NMR (500 MHz, CDCl3) δ 1.28-1.40 (m, 18H), 4.07-4.26 (m, 4H), 7.78 (dd, J=8.0, 5.7 Hz, 1H), 8.05 (d, J=8.0 Hz, 1H), 8.64 (d, J=14.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 16.1 (d, JC-P=6.6 Hz), 24.8, 62.6 (d, 6.1 Hz), 34.5, 121.9 (qd, JC-P, C-P=273, 4.7 Hz), 126.0 (d, JC-P=184 Hz), 127.4 (dq, JC-P, C-P=6.1, 10.8 Hz), 134.3 (qd, JC-P=32.4, 7.5 Hz), 138.6 (d, JC-P=2.8 Hz), 142.1 (d, JC-P=15.4 Hz); 11B NMR (130 MHz, CDCl3) δ 30.8; 19F NMR (368 MHz, CDCl3) δ −60.9 (s, 3F); 31P NMR (158 MHz, CDCl3) δ 26.1; IR (KBr, ν/cm−1) 2993, 1377, 1362, 1325, 1308, 1280, 1244, 1148, 1135, 1104, 1059, 1029, 977, 964, 951, 849, 768, 682; HRMS (ESI+) Calcd for C17H25BF3NaO5P ([M+Na]+) 431.1382, Found 431.1379.
(6) N,N,N′,N′-Tetraethyl-P-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphonic diamide




29% yield; pale brown oil; 1H NMR (500 MHz, CDCl3) δ 1.04 (t, J=7.5 Hz, 12H), 1.33 (s, 12H), 3.00-3.13 (m, 8H), 7.35-7.47 (m, 1H), 7.84 (dd, J=11.5, 7.5 Hz, 1H), 7.88 (d, J=6.9 Hz, 1H), 8.19 (d, J=11.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 13.6 (d, JC-P=2.4 Hz), 24.9, 38.4 (d, JC-P=4.8 Hz), 83.9, 127.5 (d, JC-P=12.0 Hz), 132.4 (d, JC-P=158 Hz), 134.5, (d, JC-P=8.4 Hz), 137.2, 138.3 (d, JC-P=8.4 Hz); 11B NMR (130 MHz, CDCl3) δ 31.5; 31P NMR (158 MHz, CDCl3) δ 39.4; IR (neat, ν/cm−1) 2973, 2932, 2871, 1594, 1470, 1383, 1357, 1317, 1262, 1216, 1187, 1015, 945, 866, 841, 791, 739, 711, 671, 656; HRMS (ESI+) Calcd for C20H37BN2O3P ([M+H]+) 395.2635, Found 395.2639.
N,N,N′,N′-Tetraethyl-P-(3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphonic diamide




9% yield; pale yellow solid; 1H NMR (500 MHz, CDCl3) δ 1.03 (t, J=6.9 Hz, 12H), 1.31 (s, 24H), 2.98-3.16 (m, 8H), 8.27 (d, J=12.1 Hz, 2H); 8.32 (s, 1H); 13C NMR (125 MHz, CDCl) δ 13.6 (d, JC-P=2.4 Hz), 24.8, 38.3 (d, JC-P=3.6 Hz), 83.8, 131.8 (d, JC-P=154 Hz), 141.1 (d, JC-P=9.6 Hz), 143.5 (d, JC-P=2.4 Hz); 11B NMR (130 MHz, CDCl3) δ 31.3; 31P NMR (158 MHz, CDCl3) δ 39.5 IR (KBr, ν/cm−1) 2978, 2932, 2873, 1594, 1458, 1383, 1327, 1313, 1272, 1220, 1189, 1163, 1144, 1020, 967, 945, 887, 847, 720, 659; HRMS (ESI+) Calcd for C26H47B2N2NaO5P ([M+Na]+) 543.3306, Found 543.3312.
(7) Dicyclohexyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2yl)phenyl)phosphine oxide




39% yield; pale brown solid; 1H NMR (500 MHz, CDCl3) δ 1.05-1.37 (m, 21H), 1.50-1.88 (m, 8H), 1.90-2.20 (m, 4H), 2.25-2.46 (m, 1H), 7.40-7.51 (m, 1H), 7.68-7.83 (m, 1H), 7.93 (d, J=6.9 Hz, 1H), 7.98-8.07 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 24.6, 24.9, 25.5, 25.8, 26.3-26.5 (m, 2C), 35.2 (d, JC-P=66.0 Hz), 84.0, 127.4-127.6 (m), 129.1 (d, JC-P=85.2 Hz), 134.1-134.4 (m), 137.2-137.5 (m), 137.6; 11B NMR (130 MHz, CDCl3) δ 30.9; 31P NMR (158 MHz, CDCl3) δ 56.7 IR (KBr, ν/cm−1) 2979, 29.30, 2853, 1594, 1449, 1404, 1359, 1316, 1278, 1211, 1166, 1145, 1130, 1115, 1077, 963, 891, 853, 840, 759, 731, 709, 671; HRMS (ESI+) Calcd for C24H38BNaO3P ([M+Na]+) 439.2549, Found 439.2567.
Dicyclohexyl(3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide




35% yield; pale brown solid; 1NMR (500 MHz, CDCl3) δ 1.08-1.36 (m, 33H), 1.51-1.86 (m, 8H), 1.94-2.13 (m, 4H), 2.23-2.45 (m, 1H), 8.11 (d, J=9.8 Hz, 1H), 8.37 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 24.7, 24.8, 25.5, 25.8, 26.2-26.5 (m, 2C), 35.3 (d, JC-P=67.2 Hz), 84.0, 128.5 (d, JC-P=85.2 Hz), 140.2 (d, JC-P=7.2 Hz), 144.0; 11B NMR (130 MHz, CDCl3) δ 31.2; 31P NMR (158 MHz, CDCl3) δ 56.4; IR (KBr, ν/cm−1) 2977, 2929, 2853, 1594, 1449, 1383, 1329, 1272, 1215, 1176, 1143, 966, 388, 849, 716; HRMS (ESI+) Calcd for C30H50B2O5P ([M+H]+) 543.3582, Found, 543.3588.
(8) Dicyclohexyl(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide




99% yield; pale yellow solid; NMR (400 MHz, CDCl3) δ 1.14-1.19 (m, 4H), 1.21-1.42 (m, 16H), 1.44-1.51 (m, 4B), 1.64-1.68 (m, 4H), 1.80-1.84 (m, 2H), 2.03-2.17 (m, 4H), 3.86 (s, 3H), 6.87 (dd, J=8.7, 4.7 Hz, 1H), 7.91 (d, J=8.7 Hz, 1H), 8.36 (d, J=11.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 24.9, 25.7 (d, 3.8 Hz), 25.9, 26.1 (d, JC-P=3.8 Hz), 26.6 (d, JC-P=12.3 Hz), 26.9 (d, JC-P=14.1 Hz), 36.9 (d, JC-P=67.7 Hz), 55.1, 83.7, 109.3 (d, JC-P=6.9 Hz), 118.3 (d, JC-P=83.8 Hz), 140.1 (d, JC-P=1.9 Hz), 142.8 (d, JC-P=3.8 Hz), 161.5 (d, JC-P=5.6 Hz); 11B NMR (130 MHz, CDCl3) δ 29.8; 31P NMR (158 MHz, CDCl3) δ 59.5; IR (KBr, ν/cm−1) 2978, 2931, 2852, 1594, 1448, 1407, 1385, 1357, 1317, 1279, 1266, 1250, 1212, 1147, 1104, 1077, 1014, 964, 887, 851, 824, 750, 673; HRMS (ESI+) Calcd for C25H40BNaO4P ([M+Na]+) 469.2655, Found 469.2668.
(9) Dicyclohexyl(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide




99% yield; pale yellow solid; 1H NMR (400 MHz, CDCl3) δ 1.16-1.21 (m, 4H) 1.24-1.36 (m, 18H), 1.59-1.70 (m, 6H), 1.83-1.86 (m, 2H), 2.07-2.10 (m, 2H), 2.27-2.36 (m, 2H), 7.36 (dd, J=7.9, 3.6 Hz, 1H), 7.81 (d, J=7.9 Hz, 1H), 8.49 (d, J=10.5 Hz, 1H); 13C NMR (100 MHz, CDCl3) β 24.9, 25.7 (d, JC-P=1.4 Hz), 26.2 (d, JC-P=3.3 Hz), 26.3 (d, JC-P=3.8 Hz), 26.5 (d, JC-P=12.7 Hz), 26.7 (d, JC-P=13.6 Hz), 37.4 (d, JC-P=13.6 Hz), 84.2, 129.3 (d, JC-P=6.1 Hz), 130.1, 137.3 (d, JC-P=6.1 Hz), 138.8 (d, JC-P=2.3 Hz), 143.1 (d, JC-P=4.7 Hz); 11B NMR (130 MHz, CDCl3) δ 30.5; 31P NMR (158 MHz, CDCl3) δ 59.4; IR (KBr, ν/cm−1) 2978, 29323, 2852, 1583, 1557, 1448, 1371, 1356, 1317, 1259, 1214, 1183, 1169, 1143, 1113, 1097, 1031, 964, 845, 755, 726, 671; HRMS (ESI+) Calcd for C24H38BClO3P ([M+H]+) 451.2340, Found 451.2341.

## Claims

1. A bipyridyl compound selected from the group consisting of
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-cyclohexylurea,
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-hexylurea,
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(4-trifluoromethylphenyl)urea,
1-(2-([2,2-Bipyridin]-5-yl)phenyl)-3-(4-butylphenyl)urea, and
1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(2,6-dimethylphenyl)urea.

2. The bipyridyl compound according to claim 1, which is 1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-cyclohexylurea.

3. The bipyridyl compound according to claim 1, which is 1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-hexylurea.

4. The bipyridyl compound according to claim 1, which is 1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(4-trifluoromethylphenyl)urea.

5. The bipyridyl compound according to claim 1, which is 1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(4-butylphenyl)urea.

6. The bipyridyl compound according to claim 1, which is 1-(2-([2,2′-Bipyridin]-5-yl)phenyl)-3-(2,6-dimethylphenyl)urea.