Substituted diboron compounds

Details Substituted diboron compounds Substituted diboron compounds

2001-07-06

2004-09-21

Vollano, Jean F. (Department: 1621)

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

Organic compounds

Borate esters

C558S290000, C562S007000, C564S009000, C564S010000

Reexamination Certificate

active

06794529

ABSTRACT:

This invention relates to a process for the preparation of organic boronic acid derivatives. This invention also relates to a process for covalently coupling organic compounds, in particular to a process for covalently linking organic compounds via formation of an organic boronic acid derivative and coupling to other 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 reaction and Suzuki reactions (N. Migaura and A. Suzuki, Chem. Rev. 1995, 95, 2457-2483).
Catalysts of palladium, its complexes and its salts are well recognised for activation of C—H bonds towards coupling reactions. In this regard the Heck reaction of an aryl halide with an aryl or vinyl halide in the presence of palladium derivatives has been the subject of intensive study. However commercial development of the Heck reaction has not progressed as rapidly as could have been expected. Other Group VIII metal catalysts, such as platinum and nickel, have also been used to activate such carbon bonds.
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 are generally expensive, difficult to remove and/or toxic.
Other difficulties associated with the known coupling reactions are the high temperatures required and the lack of control of the functionality of the products, leading to complex mixtures which can be difficult to separate.
It has now been found that organic boronic acid derivatives can be prepared by reacting an organic compound having a halogen or halogen-like substituent with a penta- or hexa-substituted diboron derivative. The organic boronic acid derivatives are useful in the preparation of covalently coupled organic compounds.
Accordingly, one aspect of the present invention provides a process for the preparation of an organic boronic acid derivative comprising reacting a penta- or hexa-substituted diboron derivative with an organic compound having a halogen or halogen-like substituent at a coupling position in the presence of a Group VIII metal catalyst, such that direct carbon to boron bond is formed between said coupling position and a boron-containing residue of the penta- or hexa-substituted diboron derivative.
Another aspect of the present invention provides a process for the preparation of an organic boronic acid derivative comprising:
(A) reacting a tetra-substituted diboron derivative with a nucleophile to form a penta- or hexa-substituted diboron derivative; and
(B) reacting the penta- or hexa-substituted diboron derivative with an organic compound having a halogen or halogen-like substituent at a coupling position in the presence of a Group VIII metal catalyst such that a direct carbon to boron bond is formed between said coupling position and a boron-containing residue of the penta- or hexa-substituted diboron derivative.
It has also been surprisingly found that the two steps, i.e. formation of the penta or hexa substituted diboron derivatives and the reaction of these derivatives with the organic compound can be performed in a single pot without isolation of the penta or hexa derivatives.
Accordingly, in particularly preferred aspect the invention provides a process for the preparation of an organic boronic acid derivative comprising:
(A) reacting a tetra-substituted diboron derivative with a nucleophile to form a penta or as hexa substituted diboron derivative; and
(B) reacting the penta- or hexa-substituted diboron derivative in situ with an organic compound having a halogen or halogen-like substituent at a coupling position in the presence of a Group VIII metal catalyst such that a direct carbon to boron bond is formed between said coupling position and a boron-containing residue of the penta or hexa substituted diboron derivative.
The reaction of the penta- or hexa-substituted diboron derivative with an organic compound having a halogen or halogen-like substituent in a coupling position allows for the formation of organic boronic acid derivatives, with only minor amounts of carbon—carbon coupled product formed. This process conveniently allows for the controlled formation of organic boronic acid derivatives and is therefore useful in controlling the formation of carbon to carbon bonds.
In a further aspect, the present invention provides a process for coupling a first organic compound having at a coupling position a halogen or halogen-like substituent and a second organic compound having at a coupling position a halogen or halogen-like substituent comprising:
(A) preparing an organic boronic acid derivative by reacting a penta- or hexa-substituted diboron derivative with said first organic compound in the presence of a Group VIII metal catalyst such that a direct carbon to boron bond is formed between said coupling position and a boron-containing residue of the penta or hexa substituted diboron derivative; and
(B) reacting the organic boronic acid derivative with said second organic compound in the presence of a suitable base and a Group VIII metal catalyst, such that a carbon to carbon bond is formed between the respective coupling positions of the organic compounds.
In a particularly preferred embodiment the three steps, i.e. formation of the penta- or hexa-substituted diboron derivative, the reaction of the derivative with the organic compound to form the organic boronic acid derivative, and the coupling of that derivative with another organic compound are performed in the one pot without isolation of intermediates
According to this aspect the invention provides a process for coupling a first organic compound having at a coupling position a halogen or halogen-like substituent and a second organic compound having at a coupling position a halogen or halogen-like substituent comprising:
(A) reacting a tetra-substituted diboron derivative with a nucleophile to form a penta or hexa substituted diboron derivative;
(B) preparing a boronic acid derivative by reacting the penta- or hexa-substituted diboron derivative in situ with said first organic compound in the presence of a Group VIII metal catalyst such that a direct carbon to boron bond is formed between said coupling position and a boron-containing residue of the penta- or hexa-substituted diboron derivative; and
(C) reacting the boronic acid derivative in situ with said second organic compound in the presence of a Group VIII metal catalyst and a suitable base such that a carbon to carbon bond is formed between the respective coupling position of the organic compounds.
Prior to step (C) it is preferable to decompose any unreacted tetra-, penta- or hexa-substituted diboron derivative by adding water and a suitable base.
The base should be such that it is strong enough to break the boron to boron bond of the diboron compounds. Th

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