Organic compounds -- part of the class 532-570 series – Organic compounds – Borate esters
Reexamination Certificate
2001-07-24
2003-01-14
Vollano, Jean F. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Borate esters
C558S286000, C558S298000
Reexamination Certificate
active
06506925
ABSTRACT:
This invention relates to a process for covalently coupling organic compounds, in particular to a process for covalently linking an olefinic moiety via an organoboron intermediate to other organic compounds. The invention also relates to a process for the preparation of the organoboron intermediates.
Process for forming covalent bonds between olefinic 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, activating groups etc. Some known types of coupling reactions involving olefinic moieties include the Michael reaction and reactions described in the following references: Transition Metals in the Synthesis of Complex Organic Molecules (L. S. Hegedus, University Science Books, 1994, ISBN 0-935702-28-8); Handbook of Palladium Catalysed Organic Reactions (J. Malleron, J. Fiaud and J. Legros, Academic Press, 1997, ISBN 0-12-466615-9); Palladium Reagents and Catalysts (Innovations in Organic Synthesis by J. Tsuji, John Wiley & Sons, 1995, ISBN 0-471-95483-7); and N. Miyuara 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 alkene 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.
The success of the Heck reaction depends to a large extent on the substrates and the reaction conditions. When two &bgr;-hydrogens are present in the alkene the reaction generally leads to the formation of the (E)-alkenes which are often contaminated with the corresponding (Z)-alkenes.
Although alkene borates (alkenylborates) can be reacted with a variety of organic molecules to give coupled products via the formation of new carbon-carbon bonds (See for example the references above) the process for the preparation of the alkenylborates by the commonly used hydroboration reaction of alkynes is limited because of the difficulties that are encountered through the lack of regiochemistry and/or chemoselectivity (such as the reduction of a number of different functional groups) (See N. Miyuara and A. Suzuki, Chem Rev. 1995, 95, 2457-2483).
Improved methodologies are thus required for the synthesis of alkene borates.
It has now been found that alkene borates can be synthesised from haloalkenes or pseudo-haloalkenes under mild conditions and in the presence of a range of substituents. This process overcomes or at least alleviates one or more of the limitations encountered in the use of the hydroboration methodology and is fundamentally different in that the starting material is an alkene and not an alkyne. Coupling of the alkenylborates with an organic compound may be achieved in the presence of Group VIII metal catalyst and a suitable base.
Accordingly the invention provides a process for covalently coupling organic compounds which comprises reacting an olefinic compound having a halogen or halogen-like substituent in a vinylic 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. In this embodiment the coupling proceeds in two steps. In the first step the diboron derivative reacts with an olefinic compound in the presence of the Group VIII metal catalyst and suitable base to form an alkene borate intermediate, this intermediate reacts in the presence of base with remaining olefinic compound. According to this embodiment the covalent coupling comprises a covalent bond between coupling positions of two molecules of olefinic compound.
Preferably the suitable base used to catalyse the reaction with the diboron derivative is also able to catalyse the coupling of the alkene borate intermediate to the remaining olefinic compound. However, if necessary, a stronger base can be added or the reaction mixture can be heated after the formation of the alkene borate intermediate to catalyse or promote 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 olefinic compound having a halogen or halogen-like substituent at a vinylic coupling position with a diboron derivative in the presence of a Group VIII catalyst and a suitable base to form an alkene borate intermediate, and
reacting the alkene borate 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 olefinic 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 olefinic compound, although symmetrical products will be obtained if the organic compound is the same as the olefinic compound.
It is especially convenient to conduct the process in a single pot without isolation of the alkene borate 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 olefinic compound having a halogen or halogen-like substituent at a vinylic coupling position with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base to form an alkene borate intermediate,
adding water or water and a suitable base to decompose excess diboron derivative,
reacting the alkene borate 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 olefinic 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 alkene borate 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 another embodiment, after formation of the alkene borate intermediate, the coupling of the alkene borate intermediate with the organic compound is achieved by increasing the temperature of the reaction mixture to a temperature sufficient for said coupling reacting to occur. In this embodiment it may not be necessary to add a stronger base to catalyse the coupling reaction.
In cases where there is a need to remove excess diboron derivative but the use of water or water and 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 alkene borate intermediate.
Accordingly in a further embodiment there is provided a process for covalently coupling organic compounds which comprises:
reacting an olefinic compound having a halogen or halogen-like substituent at a vinylic coupling position with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base to form an alkene borate intermediate;
adding a mild oxidising agent to decompose excess diboron derivative;
reacting the alkene borate intermedi
Marcuccio Sebastian Mario
Rodopoulos Mary
Weigold Helmut
Bacon & Thomas
Commonwealth Scientific and Industrial Research Organisation
Vollano Jean F.
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