Aryl borates

Details Aryl borates Aryl borates

1998-12-18

2002-06-04

Vollano, Jean F. (Department: 1621)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C549S456000, C549S469000, C562S045000, C558S288000

Reexamination Certificate

active

06399779

ABSTRACT:

This invention relates to a process for covalently coupling organic compounds, in particular to a process for covalently linking aromatic ring compounds via an organoboron intermediate to other organic compounds. The invention also relates to a process for the preparation of the organoboron intermediates.
Processes for forming covalent bonds between aromatic ring compounds and 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 which can involve aromatic ring compounds include the Grignard reaction, Heck reactions and Suzuki reactions (N. Miyaura 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, 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 aromatic ring 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 coupling of aromatic ring compounds to other organic compounds can be achieved via an arylboron intermediate in the presence of a Group VIII metal catalyst and a suitable base.
Accordingly the invention provides a process for covalently coupling organic compounds which comprises reacting an aromatic ring compound having a halogen or halogen-like substituent at a ring coupling position with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base.
In one embodiment this process may be used to prepare a symmetrical product by reacting the diboron derivative with about two equivalents of aromatic ring compound. In this embodiment the coupling proceeds in two steps. In the first step the diboron derivative reacts with about one equivalent of aromatic ring compound in the presence of the Group VIII metal catalyst and suitable base to form an arylboron intermediate, which intermediate reacts in the presence of base with the remaining equivalent of aromatic ring compound. According to this embodiment the covalent coupling comprises a covalent bond between ring coupling positions of two molecules of aromatic ring compound.
Preferably the suitable base used to catalyse the reaction with the boron derivative is also able to catalyse the coupling of the arylboron intermediate to the remaining aromatic compound. However, if necessary, a stronger base can be added after the formation of the arylboron intermediate to catalyse the coupling reaction.
The process according to the invention also allows the preparation of unsymmetrical products. Accordingly in another embodiment of the invention there is provided a process for covalently coupling organic compounds which comprises:
reacting an aromatic ring compound having a halogen or halogen-like substituent at a ring coupling position with a diboron derivative in the presence of a Group VIII catalyst and a suitable base to form an arylboron intermediate, and
reacting the arylboron intermediate with an organic compound having a halogen or halogen-like substituent at a coupling position in the presence of a Group VIII metal catalyst and a suitable base, whereby the aromatic ring compound is coupled to the organic compound via a direct bond between the respective coupling positions.
The process according to this embodiment allows the preparation of unsymmetrical compounds when the organic compound is different from the aromatic ring compound, although symmetrical products will be obtained if the organic compound is the same as the aromatic ring compound.
It is especially convenient to conduct the process in a single pot without isolation of the arylboron intermediate, however it has been found that the presence of unreacted diboron derivative can interfere with the coupling step, resulting in the formation of unwanted by-products.
Accordingly in another embodiment of the present invention there is provided a process for covalently coupling organic compounds which comprises:
reacting an aromatic ring compound having a halogen or halogen-like substituent at a ring coupling position with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base to form an arylboron intermediate,
adding water and a suitable base to decompose excess diboron derivative,
reacting the arylboron intermediate with an organic compound having a halogen or halogen-like substituent at a coupling position in the presence of a Group VIII metal catalyst and a suitable base, whereby the aromatic ring compound is coupled to the organic compound via a direct bond between respective coupling positions.
Preferably the reaction is conducted in a single pot, although it is possible to isolate the arylboron intermediate prior to the final coupling step. If the reaction is conducted in a single pot it is preferred that the base added to decompose the diboron derivative is suitable for catalysing the coupling reaction. In this case there is no need to add further base with the organic compound in the coupling reaction.
In cases where there is a need to remove excess diboron derivative but the use of water and/or base is deleterious because of the sensitivity of substituents, etc, or other factors the excess diboron derivative may be decomposed by addition of mild oxidising agents following the formation of the arylboron intermediate.
Accordingly in a further embodiment there is provided a process for covalently coupling organic compounds which comprises:
reacting an aromatic ring compound having a halogen or halogen-like substituent at a ring coupling position with a diboron derivative in the presence of a Group VIII
metal catalyst and a suitable base to form an arylboron intermediate;
adding a mild oxidising agent to decompose excess diboron derivative;
reacting the arylboron intermediate with an organic compound having a halogen or halogen-like substituent at a coupling position in the presence of a Group VIII metal catalyst and a suitable base whereby the aromatic ring compound is coupled to the organic compound via a direct bond between respective coupling positions.
The mild oxidising agent may be any compound which will break the B—B bond of the diboron derivative but which is not strong enough to break boron-carbon bonds of the arylboron intermediate. Suitable mild

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