Alkene borates and a process for covalently coupling organic compounds

Abstract

This invention describes a process for covalently coupling organic compounds which comprises reacting an olefinic compound having a halogen or halogen-like substituent at a coupling position with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base. The invention also describes a process for preparing alkene borate intermediates comprising reacting an olefinic compound having a halogen or halogen-like substituent with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base.

The claims:  
     
         1 . 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.  
     
     
         2 . A process according to  claim 1  wherein said diboron derivative is reacted with said olefinic compound to form a symmetrical covalently coupled product, said reaction proceeding via an alkene borate intermediate, this intermediate reacting with the remaining olefinic compound to form the coupled product, said covalent coupling comprising a covalent bond between the vinylic coupling positions of two molecules of said olefinic compound.  
     
     
         3 . A process according to  claim 2  wherein said suitable base catalyses both the formation of the alkene borate intermediate and the subsequent reaction with the remaining olefinic compound.  
     
     
         4 . A process according to  claim 2  wherein the suitable base only catalyses the formation of the alkene borate intermediate under the reaction conditions, a stronger base being added and/or the temperature being increased after the formation of the intermediate to catalyse reaction of the intermediate with the remaining olefinic compound.  
     
     
         5 . A process for covalently coupling organic compounds according to  claim 1  which comprises: 
 (i) 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, and  
 (ii) 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.  
 
     
     
         6  A process according to  claim 5  wherein the organic compound is different from the olefinic compound.  
     
     
         7 . A process according to  claim 5  wherein water or water and a suitable base are added after formation of the alkene borate intermediate to decompose unreacted diboron derivative.  
     
     
         8 . A process according to  claim 5  or  claim 7  conducted in a single pot.  
     
     
         9 . A process according to  claim 5  wherein the alkene borate intermediate is isolated prior to reaction with the organic compound.  
     
     
         10 . A process according to any one of  claims 5  to  8  wherein the organic compound is an aromatic or pseudoaromatic ring compound having a halogen or halogen-like substituent.  
     
     
         11 . A process according to any one of  claims 5  to  8  wherein the organic compound is an olefinic compound with a halogen or halogen-like substituent in a vinylic coupling position.  
     
     
         12 . A process according to any one of clams  5  to  8  wherein the organic compound is an aliphatic compound having a halogen or halogen-like substituent.  
     
     
         13 . A process according to any one of clams  5  to  8  wherein the organic compound is an allylic compound having a halogen or halogen-like substituent.  
     
     
         14 . A process according to any one of clams  5  to  8  wherein the organic compound is an acetylenic compound having a halogen or halogen-like substituent.  
     
     
         15 . A process according to  claim 2  or  claim 5  wherein the organic compound has more than one halogen or halogen-like substituents in vinylic coupling positions.  
     
     
         16 . A process according to  claim 5  wherein the olefinic compound has a substituent which is reactive with organometallic compounds.  
     
     
         17 . A process according to  claim 5  wherein the olefinic compound has an active hydrogen containing substituent.  
     
     
         18 . A process according to  claim 5  wherein at least one of the olefinic compound and the organic compound has more than one halogen or halogen-like substituent.  
     
     
         19 . A process according to any one of  claims 1  to  18  wherein the Group VIII metal catalyst comprises palladium, nickel or platinum.  
     
     
         20 . A process according to  claim 19  wherein the Group VIII metal catalyst is a palladium catalyst.  
     
     
         21 . A process according to  claim 20  wherein the palladium catalyst is a palladium complex.  
     
     
         22 . A process according to  claim 19  wherein the catalyst is a nickel complex.  
     
     
         23 . A process according to  claim 21  wherein the palladium complex is selected from PdCl 2 , Pd(OAc) 2 , PdCl 2 (dppf)CH 2 Cl 2 , Pd(PPh 3 ) 4 , or one containing trianisylphosphine, tritolylphosphine, Ph 2 P(CH 2 ) n PPh 2  where n is 2, 3 or 4, tricyclohexylphosphine, or benzonitrile.  
     
     
         24 . A process according to  claim 21  or  claim 23  wherein the palladium complex is tethered on a solid support.  
     
     
         25 . A process according to  claim 20  wherein the catalyst is selected from the group consisting of palladium black, palladium on carbon, palladium clusters and palladium in porous glass.  
     
     
         26 . A process according to  claim 22  wherein the catalyst is selected from the group consisting of nickel black, Raney nickel, nickel on carbon and nickel clusters or a nickel complex or a nickel complex tethered on a solid support.  
     
     
         27 . A process according to  claim 19  wherein the Group VIII metal catalyst is a platinum catalyst.  
     
     
         28 . A process according to  claim 27  wherein the platinum catalyst is selected from platinum black, platinum on carbon and platinum clusters or a platinum complex or a platinum complex tethered on a solid support.  
     
     
         29 . A process according to  claim 1  or  claim 5  wherein the olefinic compound is a compound of formula I:  
       
         
           
           
               
               
           
         
         where R 1 , R 2  and R 3  are each independently selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, acyl, arylalkyl and heteroarylalkyl (each of which may be optionally substituted); cyano, isocyano, formyl, carboxyl, nitro, halo, alkoxy, alkenoxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitroalkyl, nitroalkenyl, nitroalkynyl, arylamino, diarylamino, dibenzylamino, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy, alkylsulphonyloxy, arylsulphenyloxy, heterocycloxy, arylsulphenyl, carboalkoxy, carboaryloxy, alkylthio, benzylthio, acylthio, sulphonamide, sulfanyl, sulfo, carboxy, carbamoyl, carboximidyl, sulfinyl, sulfinimidyl, sulfinohydroximyl, sulfonimidyl, sulfondiimidyl, sulfonohydroximyl, sulfamyl, phosphorous containing groups, guanidinyl, duanidino, ureido and ureylene, and X is a halogen or halogen-like substituent.  
       
     
     
         30 . A process according to any one of  claims 1  to  29  wherein the diboron derivative is an ester or other stable derivative of diboronic acid.  
     
     
         31 . A process according to  claim 30  wherein the diboron derivative is a compound of the formula  
       (RO) 2 B—B(RO) 2    
       wherein R is optionally substituted alkyl or aryl or —B(OR) 2  represents a cyclic group of the formula  
       
         
           
           
               
               
           
         
       
       where R′ is optionally substituted alkylene, arylene or other divalent group comprising linked aromatic and aliphatic moieties.  
     
     
         32 . A process of  claim 31  wherein the diboron derivative is selected from the group consisting of bis(pinacolato)diboron, bis(ethanediolato)diboron, bis(n-propanediolato)diboron and bis(neopentyldiolato)diboron.  
     
     
         33 . A process of any one of  claims 1  to  32  conducted in the presence of a solvent.  
     
     
         34 . A process of  claim 33  wherein the solvent is a protic solvent.  
     
     
         35 . A process of  claim 34  wherein the protic solvent is water or an alcohol.  
     
     
         36 . A process of  claim 34  wherein the solvent is water, methanol, ethanol, isopropanol or a mixture thereof.  
     
     
         37 . A process of  claim 33  wherein the solvent is DMSO, DMF, dioxane, DME, diethyl ether, THF or a mixture thereof.  
     
     
         38 . A process of any one of  claims 1  to  36  conducted at a temperature between 0° and 120° C.  
     
     
         39 . A process of  claim 38  wherein the temperature is in the range of 15 to 40° C.  
     
     
         40 . A process of  claim 5  wherein the suitable base of step (i) is capable of catalysing reaction of the olefinic compound with the diboron derivative, but not strong enough under the conditions used in the reaction to catalyse the further reaction of the alkene borate intermediate with the organic compound.  
     
     
         41 . A process of  claim 40  wherein the suitable base is selected from the group consisting of aryl and alkyl carboxylates, carbonates, fluorides and phosphates of Li, Na, K, Rb, Cs, ammonium and alkylammonium.  
     
     
         42 . A process of  claim 1  or  claim 5  wherein the suitable base is selected from the group consisting of aryl and alkyl carboxylates, fluorides, hydroxides and carbonates of Li, Na, K, Rb, Cs, ammonium, alkylammonium, Mg, Ca and Ba; phosphates, and arylphosphates of Li, Na, K, Rb and Cs; phosphate esters of Li, Na, K, Rb and Cs, phenoxides of Li, Na, K, Rb and Cs; alkoxides of Li, Na, K, Rb and Cs; and thallium hydroxide.  
     
     
         43 . A process of  claim 5  wherein the suitable base of step (ii) is selected from cesium carbonate, potassium carbonate, potassium phosphate and alkali metal hydroxides.  
     
     
         44 . A process of  claim 5  wherein one of said olefinic compound and said organic compound is a polymer.  
     
     
         45 . A functionalised polymeric solid when prepared in accordance with the process of  claim 44 .  
     
     
         46 . A process of  claim 5  wherein either the olefinic compound or the organic compound is chemically linked to a solid polymer support.  
     
     
         47 . A process for preparing alkene borate intermediates comprising reacting an olefinic compound having a halogen or halogen-like substituent and an active hydrogen containing substituent with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base.  
     
     
         48 . A process for preparing alkene borate intermediates comprising reacting an olefinic compound having a halogen or halogen-like substituent with a diboron derivative in a protic solvent, DMSO, DMF, dioxane, DME, diethyl ether, THF or a mixture thereof in the presence of a Group VIII metal catalyst and a suitable base.  
     
     
         49 . A process according to  claim 47  or  claim 48  wherein water, water and suitable base, or a mild oxidising agent are added to decompose unreacted diboron derivative.  
     
     
         50 . An alkene borate intermediate prepared according to the process of any one of  claims 47  to  49 .  
     
     
         51 . A process for preparing an alkene boronic acid by hydrolysing an alkene borate intermediate of  claim 50 .  
     
     
         52 . A polymer prepared according to the process of  claim 1  wherein the olefinic compound has more than one halogen or halogen-like substituent.  
     
     
         53 . A dendrimer prepared according to the process of  claim 1  wherein the olefinic compound has more than two halogen or halogen-like substituents.  
     
     
         54 . A process according to  claim 5  wherein the olefinic compound and the organic compound are linked together such that the alkene borate intermediate formed after reaction of the olefinic compound with the diboron derivative reacts with the organic compound to provide an intramolecular ring closure.  
     
     
         55 . Novel alkene borates selected from the group consisting of 
 2-(1,2-dimethylprop-1-enyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane,    2-(1,2-dimethylprop-1-enyl)-5,5-dimethyl-1,3,2-dioxaborinane,    5,5-dimethyl-2-(1,2,2-triphenylvinyl)-1,3,2-dioxaborinane,    4,4,5,5-tetramethyl-2-(1,2,2-triphenylvinyl)-1,3,2-dioxaborolane,    ethyl (Z)-2(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethenyl ether,    4,4-dimethyl-2-4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclo-hex-2-en-1-one,    (E)-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-enenitrile,    ethyl (Z)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-2-enoate,    2-bicyclo[3.2.1]oct-2-en-3yl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, and 1,2,2-triphenylvinylboronic acid.    
     
     
         56 . 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 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; and    reacting the alkene 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.    
     
     
         57 . A process according to  claim 56  wherein the mild oxidizing agent is selected from N-chlorosuccinimide, dioxygen gas, chloramine-T, chloramine-B, 1-chlorotriazole, 1,3-dichloro-5,5-dimethylhydantoin, trichloroisocyanuric acid and dichloroisocyanuric acid potassium salt.