Process for preparing organic boronic acid derivatives using...

Details Process for preparing organic boronic acid derivatives using... Process for preparing organic boronic acid derivatives using...

2000-05-10

2002-09-10

Vollano, Jean F. (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Boron acids or salts thereof

Reexamination Certificate

active

06448433

ABSTRACT:

This application is the national stage of PCT/AU98/00726, filed Sep. 8, 1998, now WO 99/12940.
The present invention relates to a method for preparing boron derivatives of organic compounds, in particular to boronic acid derivatives of organic compounds.
Boronic acid derivatives of organic compounds are of particular interest, not only as intermediary means for forming covalent carbon-carbon bonds between organic compounds, but as a starting point for further chemical manipulations and transformations or in conferring or increasing biological activity to otherwise biologically inactive compounds.
Whilst these boronic acid derivatives may be obtained by conventional hydrolysis or hydrogenolysis procedures applied to boronic ester compounds, many conventional conditions employed in the preparation of boronic ester compounds are incompatible with compounds bearing sensitive functionalities. Furthermore, there are practical and commercial advantages in reducing the number of chemical manipulations employed in a synthetic procedure and it is therefore desirable to obtain the boronic acid derivatives directly.
It has now surprisingly been found that diboronic acid can be reacted in the presence of a Group 8-11 metal catalyst with an organic compound under mild conditions to provide boronic acid derivatives directly, thereby circumventing the hydrolysis or hydrogenolysis step and allowing for the presence of sensitive functional groups.
Accordingly, the present invention provides the use of diboronic acid in the preparation of organic boronic acid derivatives containing at least one boronic acid residue.
The invention further provides a process for preparing organic boronic acid derivatives comprising reacting an organic compound having a boron reactive site with diboronic acid in the presence of a Group 8-11 metal catalyst.
The use of diboronic acid offers a convenient and advantageous means of introducing a boronic acid residue into an organic compound over conventional reagents. Its stability towards water and oxygen under ambient conditions provides for ease of use when compared with other reactive and sensitive reagents used to make boronic acids via the esters, which require a strictly controlled environment.
In the preparation of organic boronic acids, the use of diboronic acid affords a number of advantages over that of diboronic acid esters. Firstly, diboronic acid itself is readily prepared from tetra(dimethylamino)diboron. Secondly, the need for a hydrolysis or hydrogenolysis step is circumvented as the boronic acid is the primary reaction product. Thirdly, by avoiding a hydrolysis or hydrogenolysis step, the formation of alcoholic by-products in the reaction mixture is eliminated.
Diboronic acid can be dehydrated (T Wartik and E. F. Apple
J Am. Chem. Soc
. 1955 77 6400; 1958 80 6155).
nB
2
(OH)
4
→[(BO)
2
]
n
+2nH
2
O
It has now been found that the dehydrated form of diboronic acid can also be used to prepare boronic acid derivatives. The boron to boron bond of the dehydrated form is stable in refluxing methanol, ethanol, isopropyl alcohol or t-butyl alcohol and is not cleaved by cold water. The dehydrated form is soluble in methanol at room temperature, dissolves rapidly in ethanol or isopropanol on warning, and in t-butyl alcohol at 82° C. (A. L. McClosky, R. J. Brotherton & J. L. Boone,
J Am Chem. Soc
. 1961 83 4750)
As used herein, the term “diboronic acid or tetrahydroxydiboron” refers to (HO)
2
B—B(OH)
2
or its dehydration product; and the term “boronic acid residue” refers to the group —B(OH)
2
.
The term “organic boronic acid derivative” refers to an organic compound having a boronic acid residue at a substitution position.
The term “boron reactive site” as used herein refers to any carbon atom within a molecule capable of reacting with diboronic acid in the presence of a Group 8-11 metal catalyst to provide a boronic acid residue on that carbon atom. Examples of boron reactive sites include carbon atoms having halogen or halogen-like substituents, carbon atoms taking part in carbon to carbon double or triple bonds, and carbon atoms in an allylic position having a substituent leaving group.
It has been found, in particular, that when an organic compound having a halogen or halogen-like substituent is reacted with diboronic acid in the presence of a Group 8-11 metal catalyst and a suitable base, the halogen or halogen-like substituent on the organic compound can be replaced by a boronic acid residue.
Accordingly, in one embodiment of the invention, there is provided a process for preparing organic boronic acid derivatives which comprises reacting an organic compound having a halogen or halogen-like substituent at a substitution position with diboronic acid in the presence of a Group 8-11 metal catalyst and a suitable base such that the halogen or halogen-like substituent is substituted with a boronic acid residue.
As used herein, the term “organic compound having a halogen or halogen-like substituent at a substitution position” refers to any organic compound having a carbon to halogen or carbon to halogen-like substituent bond at a position at which substitution by a boronic acid residue is desired. The organic compound may be aliphatic, olefinic, acetylenic, aromatic, polymeric, dendritic, cyclic or any combination thereof. The compound may further comprise additional heteroatoms such as sulfur, oxygen, nitrogen, phosphorous, boron, silicon, arsenic, selenium, and tellurium.
The terms “aromatic” and “aromatic compound(s)” as used herein refer to any compound which includes or consists of one or more aromatic rings. The aromatic rings may be carbocyclic, or heterocyclic, and may be mono or polycyclic ring systems. Examples of suitable rings include but are not limited to benzene, biphenyl, terphenyl, quaterphenyl, naphthalene, tetradyronaphthalene, 1-benzylnaphthalene, anthracene, dihydroanthracene, benzanthracene, dibenzanthracene, phenanthracene, perylene, pyridine, 4-phenylpyridine, 3-phenylpyridine, thiophene, benzothiophene, naphthothiophene, thianthrene, furan, pyrene, isobenzofuram, chromene, xanthene, phenoxathiin, pyrrole, imidazole, pyrazole, pyrazine, pyrimidine, pyridazine, indole, indolizine, isoindole, purine, quinoline, isoquinoline, phthalazine, quinoxaline, quinazoline, quinoline, pteridine, carbazole, carboline, phenanthridine, acridine, phenanthroline, phenazine, isothiazole, isooxazole, phenoxazine and the like, each of which may be optionally substituted. The terms “aromatic” and “aromatic compound(s)” include molecules, and macromolecules, such as polymers, copolymers and dendrimers which include or consist of one or more aromatic rings. The term “pseudoaromatic” refers to a ring system which is not strictly aromatic, but which is stabilized by means of delocalization of &pgr; electrons and behaves in a similar manner to aromatic rings. Examples of pseudoaromatic rings include but are not limited to furan, thiophene, pyrrole and the like.
The term “olefinic compound” and “olefinic organic compound” as used herein refers to any organic compound having at least one carbon to carbon double bond which is not part of an aromatic or pseudo aromatic system. The olefinic compounds may be selected from optionally substituted straight chain, branched or cyclic alkenes; and molecules, monomers and macromolecules such as polymers and dendrimers, which include at least one carbon to carbon double bond. Examples of suitable olefinic compounds include but are not limited to ethylene, propylene, but-1-ene, but-2-ene, pent-1-ene, pent-2-ene, cyclopentene, 1-methylpent-2-ene, hex-1-ene, hex-2-ene, hex-3-ene, cyclohexene, hept-1-ene, hept-2-ene, hept-3-ene, oct-1-ene, oct-2-ene, cyclooctene, non-1-ene, non-4-ene, dec-1-ene, dec-3-ene, buta-1,3-diene, penta-1,4-diene, cyclopenta-1,4-diene, hex-1,4, diene, cyclohexa-1,3-diene, cyclohexa-1,4-diene, cyclohepta-1,3-diene, cyclohepta-1,3,5-triene and cycloocta-1,3,5,7-tetraene, each of which may be optionally substituted. Preferably the straight chain, branched or cyclic alkene contains between

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