Method of using rhodium quinonoid catalysts

Abstract

In accordance with aspects of the invention methods of using rhodium hydroquinone catalysts for the conjugate addition of boronic acids are disclosed.

1 . A method of making an acyclic or cyclic compound comprising combining in a reaction mixture an aryl or vinylic boronic compound, a conjugate acceptor and a rhodium hydroquinone catalyst under suitable reaction conditions, allowing the reaction to proceed to its end, and isolating the desired acylic or cyclic compound from the reaction mixture. 
   
   
       2 . The method of  claim 1  comprising using the rhodium hydroquinone catalyst for conjugate addition of a boronic substrate of the boronic compound comprising transferring a carbon group from the boronic compound to the conjugate acceptor via the rhodium hydroquinone catalyst; and forming a product of conjugate addition. 
   
   
       3 . The method of  claim 2  comprising:
 combining the boronic compound, rhodium hydroquinone catalyst, conjugate acceptor and a solvent, wherein the boronic compound is an aryl boronic acid, the conjugate acceoptor is enone and the solvent is dimethoxyethane;   adding an aqueous solution of LiOH base followed by deoxygenated H 2 O to obtain a mixture;   stirring the mixture at about 50° C. for about 1 hour;   then diluting the mixture with a solution of NH 4 Cl, extracted with EtOAc/hexanes and dried Na 2 S0 4 ; followed by filtering to obtain the desired compound.   
   
   
       4 . The method of  claim 2  wherein the carbon group is a sp2 carbon group. 
   
   
       5 . The method of  claim 2  wherein the catalyst comprises the formula formula (I) 
     
       
         
         
             
             
         
       
     
     wherein X −  is selected from the group consisting of BF 4   − , SbF 6   − , PO 2 F 2   − , PF 6   − , OTf − ,  − OTs, SO 4   2− , B(C 6 F 5 ) 4   − , B(C 6 H 5 ) 4   − , ClO 4   − , NO 3   − , NO 2   − , HOSO 3   − , CO 3   2− , O 3 SCF 2 CF 2 CF 2 CF 3   − ; wherein OTf=O 3 SCF 3   − ; OTs=O 3 SC 6 H 4 CH 3   − ; R′CO 2   − ; 
     wherein R′ is selected from the group consisting of hydrogen or an alkyl, aryl or carbon atom bearing three identical or non-identical substituents; 
     wherein L 1  and L 2  are each a ligand that donates electron density to rhodium to stabilize it; 
     wherein 
     
       
         
         
             
             
         
       
     
     is either chiral or achiral and M 1  and M 2  comprise hydroxo (OH) groups in the ortho-, meta-, and para-positions and R is selected from the group consisting of H, C, O, N and S, with or without substituents, said substituents being identical or non-identical. 
   
   
       6 . The method of  claim 5  wherein L 1  and L 2  are identical or non-identical ligands that are either chiral or achiral and selected from the group consisting of alkenes, dialkenes, alkyene, phosphines, water, phosphites, sulfides, sulfoxides, sulfonates, sulfonamides, sulfones, ethers, amines, imines, amides, aldehydes, ketones, esters, nitriles, and combinations thereof. 
   
   
       7 . The method of  claim 2  wherein the catalyst comprises the formula (II) 
     
       
         
         
             
             
         
       
     
     wherein X −  is selected from the group consisting of BF 4   − , SbF 6   − , PO 2 F 2   − , PF 6   − , OTf − ,  − OTs, SO 4   2− , B(C 6 F 5 ) 4   − , B(C 6 H 5 ) 4   − , ClO 4   − , NO 3   − , NO 2   − , HOSO 3   − , CO 3   2− , O 3 SCF 2 CF 2 CF 2 CF 3   −  wherein OTf=O 3 SCF 3   − ; OTs=O 3 SC 6 H 4 CH 3   − ; R′CO 2   − ; 
     wherein R′ is selected from the group consisting of hydrogen or an alkyl, aryl or carbon bearing three identical or non-identical substituents; 
     wherein L 1  and L 2  are each a ligand that donates electron density to rhodium to stabilize it;
 wherein R is selected from the group consisting of H, C, O, N and S, with or without substituents, said substituents being identical or non-identical. 
 
   
   
       8 . The method of  claim 7  wherein L 1  and L 2  are identical or non-identical ligands that are either chiral or achiral and selected from the group consisting of alkenes, dialkenes, alkyene, phosphines, water, phosphites, sulfides, sulfoxides, sulfonates, sulfonamides, sulfones, ethers, amines, imines, amides, aldehydes, ketones, esters, nitriles, and combinations thereof. 
   
   
       9 . (canceled) 
   
   
       10 . (canceled) 
   
   
       11 . The method of  claim 2  wherein the catalyst comprises 1,4-hydroquinone π-bonded to rhodium. 
   
   
       12 . The method of  claim 11  wherein the catalyst comprises [1,4-(hydroquine)Rh(COD)] +  cation, wherein COD is cyclooctadiene. 
   
   
       13 . The method of  claim 2  wherein the catalyst comprises 1,3-hydroquinone π-bonded to rhodium. 
   
   
       14 . The method of  claim 13  wherein the catalyst comprises [1,3-(hydroquine)Rh(COD)] +  cation, wherein COD is cyclooctadiene. 
   
   
       15 . The method of  claim 2  wherein the catalyst comprises 1,2-hydroquinone π-bonded to rhodium. 
   
   
       16 . The method of  claim 2  comprising 1,2-hydroquinone, 1,3-hydroquinone or 1,4-hydroquinone α-bonded to Rh(P(OPh) 3 ) 2   +  cation. 
   
   
       17 .- 18 . (canceled) 
   
   
       19 . The method of  claim 2  wherein the complex comprises η 6 -hydroquinone complex 1 + BF 4   −  synthesized by reaction of [Rh(COD)Cl) 2  with AgBF 4  and hydroquinone. 
   
   
       20 . The method of  claim 2  wherein the rhodium complex comprises two independent complexes of rhodium with hydroquinone and COD ligands, a BF 4  counterion and a diethyl ether molecule. 
   
   
       21 .- 22 . (canceled) 
   
   
       23 . The method of  claim 2  comprising about 0.1 to 1.0 mol % Rh 1  catalyst. 
   
   
       24 . The method of  claim 1  wherein the conjugate acceptor is selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
     wherein X═H, O, N, C or S. 
   
   
       25 . The method of  claim 2  comprising a reaction: 
     
       
         
         
             
             
         
       
       wherein the reaction comprises providing an active rhodium hydroquinone catalyst, Rh 1 , and reacting the catalyst with the boronic compound comprising a sp2 hybridized carbon-center bearing a boron to transfer the sp2 hybridized carbon to rhodium and subsequently to the conjugate acceptor, which is an electron deficient olefin, an olefin bearing one or more electron withdrawing groups (EWG), through carbo-metallation followed by proto-demetallation in a presence of a base; 
       wherein EWG is selected from the group consisting of a ketone, aldehyde, imide, amide, ester, thioester, acid anhydride, nitro, sulfone, nitrile, sulfoxide, phosphinate, electron deficient aromatic ring or other suitable electron withdrawing substituent that withdraws electron density either through inductive or resonance effects from olefins, and combinations thereof; and R is selected from the group consisting of hydrogen, carbon, halide, oxygen, sulfur, nitrogen, silicon, phosphorus, sulfur, selenium, and combinations thereof. 
     
   
   
       26 . The method of  claim 2  comprising a reaction: 
     
       
         
         
             
             
         
       
       wherein the reaction comprises providing the boronic compound and the catalyst and reacting the compound and catalyst under conditions sufficient to cause the reaction, 
       X is selected from the group consisting of hydrogen, carbon, halide, oxygen, sulfur, nitrogen, silicon, phosphorus, sulfur, selenium, and combinations thereof. 
       M +  is a positively charged ion including any metal ion having an oxidation state at or higher than +1, and is selected from the group consisting of cationic L 1 , K, Cs, Be, Sr, Ba, Al, Ti, Zr, B, Si, Cd, Ag, Ph 3 PNPPh 3 , Rb, Mg 2+ , Ca 2+ , Na, R4N + , Zn 2+ , ammonium salts including tetraalkylammonium cations, tetraalkylarsonium cations, guanidinium salts, amidinium salts, and combinations thereof; 
       Y is selected from the group consisting of hydrogen, carbon, halide, oxygen, sulfur, nitrogen, silicon, phosphorus, sulfur, selenium, and combinations thereof; 
       L is a ligand that donates electron density to the rhodium to stabilize it and each L is an identical or non-identical ligand that is either chiral or achiral and selected from the group consisting of alkenes, dialkenes, alkyene, phosphines, water, phosphites, sulfides, sulfoxides, sulfonates, sulfonamides, sulfones, ethers, amines, imines, amides, aldehydes, ketones, esters, nitriles, and combinations thereof; 
       wherein EWG is selected from the group consisting of a ketone, aldehyde, imide, amide, ester, thioester, acid anhydride, nitro, sulfone, nitrile, sulfoxide, phosphinate, electron deficient aromatic ring or other suitable electron withdrawing substituent that withdraws electron density either through inductive or resonance effects from olefins, and combinations thereof; R is selected from the group consisting of hydrogen, carbon, halide, oxygen, sulfur, nitrogen, silicon, phosphorus, sulfur, selenium, and combinations thereof; and 
       —BR 2  is any boronic containing species neutral or anionically charged where boron is bound to a transfer group. 
     
   
   
       27 . A reagent for the conjugate addition of aryl or vinylic boronic acids wherein the reagent comprises a rhodium hydroquinone catalyst. 
   
   
       28 . The method of  claim 2  comprising using the rhodium hydroquinone catalyst for the conjugate addition of boronic acid comprising a reaction: 
     
       
         
         
             
             
         
       
     
     wherein the reaction comprises mixing reagents (a) and (b) and reacting the reagents and the rhodium hydroquinone catalyst under conditions sufficient to cause the reaction in the presence of a base and a solvent, wherein:
 X is selected from the group consisting of p-Me, m-NO 2 , H, o-Me, 4NH-Boc, p-OMe, p-Cl, p-F, 3Cl, 4F, m-NO 2 , 3,4,5 triF, 2,3,4-triF; 
 the solvent is selected from the group consisting of DME/H 2 0, H 2 O and THF; and 
 the base is LiOH or KOH. 
 
   
   
       29 . The method of  claim 28  comprising using the catalyst for the conjugate addition of aryl boronic acid to 2-cyclohexen-1-one comprising a reaction 
     
       
         
         
             
             
         
       
     
     wherein:
 Rh+ is the catalyst; and 
 X is selected from the group consisting of p-Me and m-NO 2 . 
 
   
   
       30 . (canceled) 
   
   
       31 . A method for double deprotonation of a rhodium hydroquinone catalyst to active quinone complex 3•K comprising a reaction: 
     
       
         
         
             
             
         
       
     
     wherein the reaction comprises mixing reagents (a) and (b) and reacting the reagents and the catalyst in the presence of water and DME under conditions sufficient to cause the reaction. 
   
   
       32 . The method of  claim 2  comprising a reaction 
     
       
         
         
             
             
         
       
     
     wherein:
 Rh+ is a rhodium hydroquinone catalyst; and 
 X is selected from the group consisting of: H, p-Me, o-Me, 4NH-Boc, p-OMe, p-Cl, p-F, 3Cl, 4F, m-NO 2 , 3,4,5 triF, 2,3,4-triF. 
 
   
   
       33 . The method of  claim 32  further comprising an additive, wherein the additive is selected from the group consisting of hydroquinone, LiBF 4 , LiCl, pyridine, Cs 2 CO3, Cs 2 CO 3  and Na 2 CO 3 . 
   
   
       34 . A method of using a catalyst for the conjugate addition of aryl or vinyl boronic substrates comprising the steps of:
 a) providing a rhodium hydroquinone catalyst;   b) transferring a sp2 hybridized carbon group from boron to a conjugate acceptor via the catalyst; and   c) forming a product of conjugate addition.   
   
   
       35 . The method of  claim 2  comprising using the hydroquinone rhodium catalyst for the conjugate addition to tri-substituted olefins comprising at least one of the following reactions: 
     
       
         
         
             
             
         
       
     
   
   
       36 . The method of  claim 35  wherein the reaction is carried out at about 55° C. 
   
   
       37 . The method of  claim 35  wherein the reaction is carried out at about 75° C.