Boronic compounds

Details Boronic compounds Boronic compounds

2001-10-22

2003-02-04

Vollano, Jean F. (Department: 1621)

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

Organic compounds

Borate esters

C558S286000, C558S292000

Reexamination Certificate

active

06515160

ABSTRACT:

The invention relates to boronic compounds, in particular to novel diboron derivatives and organic boronic acid derivatives prepared therefrom. The invention also relates to processes for the preparation of these derivatives. These diboron derivatives and organic boronic acid derivatives are useful intermediates in processes for covalently linking organic compounds.
Processes for forming covalent bonds between organic compounds, both inter- and intra-molecular, are of particular importance to the synthetic organic chemist. Many such reactions are known, each requiring its own special reaction conditions, solvents, catalysts, ring activating groups etc. Some known types of coupling reactions include the Grignard reaction, Heck reactions and Suzuki reactions (N. Migaura and A. Suzuki, Chem. Rev. 1995, 95, 2457-2483).
Substituted bi- and tri-aryl compounds are of great interest to the pharmaceutical and agrochemical industries. A great number of these compounds have been found to possess pharmaceutical activity, while others have been found to be useful herbicides. There is also interest from the polymer industry in polymers prepared by the linking together of organic compounds.
Conventional methods for covalently linking aromatic rings, such as by reaction of an appropriate Grignard reagent, involve harsh conditions and are not suitable for aromatic rings with active hydrogen containing substituents. Substituents with active hydrogen atoms also can become involved in unwanted side reactions leading to undesirable products. Such substituents need to be protected prior to reaction. Boronic acid derivatives required for the Suzuki reaction are traditionally synthesized through highly reactive organo metallic intermediates.
In view of the severity of the reaction conditions the range of substituents which could be present during the linking reaction was considerably limited, and the range of useful reaction media (solvents) was restricted to those which can be expensive, difficult to remove and/or toxic.
A difficulty associated with the known coupling reactions is the limited control of the functionality of the products, leading to complex mixtures which can be difficult to separate.
Some known diboron derivatives are relatively unstable compounds, which decompose readily in aqueous solution or on exposure to air. For this reason, and a perceived difficulty in making the compounds, their use in chemical reaction is relatively unexplored.
It has now been found that diboron derivatives can be quite stable and useful in the preparation of organic boronic acid derivatives, and that properties of the diboron derivatives can be adjusted to suit particular reaction conditions or to provide particular products by selection of appropriate substituents.
Accordingly in a first aspect of the present invention there is provided a diboron derivative of formula (I)
where
R
1
, R
1
, R
3
and R
4
are each independently selected from the group consisting of optionally substituted allyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, and a group of the formula —(R
5
Q)
m
R
6
where Q is selected from O, S, NR
7
, optionally substituted arylene and optionally substituted cycloalkylene, m is an integer from 1 to 3, the or each R
5
is independently an optionally substituted C
1
-C
3
alkylene, R
6
is C
1
-C
3
alkyl or hydrogen and
R
7
is hydrogen or C
1
-C
12
alkyl; and
each X is independently selected from O, S(O)
n
and NR
7
, where n is an integer of 0 to 3 and R
7
is hydrogen or C
1
-C
12
alkyl, or one or more of —NR
1
R
7
, —NR
2
R
7
, —NR
3
R
7
and —NR
4
R
7
represent an optionally substituted 5 or 6 membered heterocyclyl group,
provided that when each X is O and R
1
to R
4
are identical, R
1
to R
4
are not unsubstituted straight chain akyl, phenyl or naphthyl, isopropyl, or phenyl substituted with alkyl; when each X is N(C
1
-C
6
alkyl), R
1
to R
4
are not C
1-C
6
alkyl and —NR
1
R
7
, —NR
2
R
7
, —NR
3
R
7
and —NR
4
R
7
are not unsubstituted piperidyl or unsubstituted pyrolidinyl; when each X is NH, R
1
to R
4
are not C
1
-C
6
alkyl or unsubstituted phenyl; and when —XR
1
is —OCH
3
, —XR
2
is —N(CH
3
)
2
and —XR
4
is —N(CH
3
)
2
, —XR
3
is not OCH
3
.
In a second aspect of the invention there is provided a diboron derivative of formula (II)
where X is independently selected from O, S(O)
n
and NR
7
where n is an integer from 0 to 2, R
7
is hydrogen or C
1
-C
12
alkyl, and A
1
and A
2
are divalent groups which may be the same or different, provided that when each X is O, A
1
and A
2
are not unsubstituted C
1
-C
3
alkylene, 1,1,2,2-tetramethylethylene, 2,2-dimethylpropylene, 1,2-dialkoxycarbonylethylene, 1,2 diphenylethylene, 1 phenylethylene, unsubstituted phenylene or phenylene mono- or di-substituted with C
1
-C
4
alkyl; and when each X is S or NMe, both of A
1
and A
2
are not ethylene.
Preferably A
1
and A
2
are independently selected from optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted arylene, optionally substituted alkylarylene, optionally substituted cycloalkylene, optionally substituted cycloalkenylene, or a group of the formula —(R
5
Q)
m
R
6
where Q is selected from O, S, NR
7
, optionally substituted arylene and optionally substituted cycloalkylene, m is an integer of 1 to 3, R
5
and R
6
are independently an optionally substituted C
1
-C
3
alkylene, and R
7
is hydrogen or C
1
-C
12
alkyl. The divalent groups, A
1
and A
2
, may include a fused 5 or 6 membered aliphatic or aromatic ring.
In a third aspect of the present invention there is provided a diboron derivative of formula
where
R
1
and R
2
are each independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, a group of the formula —(R
5
Q)
m
R
6
where Q is selected from O, S, NR
7
, optionally substituted arylene and optionally substituted cycloalkylene, m is an integer of 1 to 3, the or each R
5
is independently an optionally substituted C
1
-C
3
alkylene, R
6
is hydrogen or C
1
-C
3
alky, and R
7
is hydrogen or C
1
-C
12
alkyl;
each X is independently selected from O, S(O)
n
and NR
7
, where n is an integer of 0 to 3 and R
7
is hydrogen or C
1
-C
12
alky, or one or both of —NR
1
R
7
and —NR
2
R
7
represent an optionally substituted 5 or 6 membered heterocyclyl group; and
A is a divalent group;
provided that when R
1
and R
2
are Me and each X is NMe then A is not unsubstituted ethylene.
Preferably A is independently selected from optionally substituted alkylene, optionally substituted alkenylene, optionally substituted arylene, optionally substituted cycloalkylene, optionally substituted cycloalkenylene, or a group of the formula —(R
5
Q)
m
R
6
— where Q is selected from O, S, NR
7
, optionally substituted arylene and optionally substituted cycloalkylene, m is an integer of 1 to 3, R
5
and R
6
are independently an optionally substituted C
1
-C
3
alkylene, and R
7
is hydrogen or C
1
-C
12
alkyl. The divalent group A, may include a fused aliphatic or aromatic ring or ring system.
The invention also provides a diboron derivative of formula (I)
or a diboron derivative of formula (II)
or a diboron derivative of formula (III)
where
R
1
, R
2
, R
3
and R
4
are each independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, a group of the formula —(R
5
Q)
m
R
6
where Q is selected from O, S, NR
7
, optionally substituted arylene and optionally substituted cycloalkylene, m is an integer of 1 to 3, the or and each R
5
is independently an optionally substituted C
1
-C
3
alkylene, R
6
is C
1
-C
3
alkyl or hydrogen, and R
7
is hydrogen or C
1
-C
12
alkyl;
each X

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