Chiral phosphines, transition metal complexes thereof and uses thereof in asymmetric reactions

Abstract

Chiral ligands and transition metal complexes based on such chiral ligands useful in asymmetric catalysis are disclosed. The chiral ligands include (R,S,S,R)-DIOP*. The ruthenium complex reduces enamide to the corresponding amine with up to 99% enantioselectivity. The transition metal complexes of the chiral ligands are useful in asymmetric reactions such as asymmetric hydrogenation, hydride transfer, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, isomerization, allylic alkylation, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition and epoxidation reactions.

What is claimed is:  
     
         1 . A ligand selected from the group consisting of compounds represented by I through XI:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein X′ is selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, hydroxy, alkoxy, aryloxy, siloxy, thioalkoxy, arylthio, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, amido, ester, reverse ester, keto, halo, silyl and SH;  
         wherein R′ is selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino and amido;  
         wherein each X, Z and Z′ is independently selected from the group consisting of: O, NH, NR, CH 2 , CHR, CR 2 , C═O, S, SO 2 , and SO;  
         wherein each Z″ is independently selected from the group consisting of: N, P, CH, and CR;  
         wherein each R 1 , R 2 , R 3  and R 4  is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl and OR;  
         wherein each Y and Y′ is independently selected from the group consisting of: a diol protecting group residue, O, CO, C(OR) 2 , CH(OR), CH 2 , CHR, CR 2 , CR 2 , NR, SO 2 , —(CH 2 ) n — wherein n is 0 or an integer from 1 to 8, —(CH 2 ) n Q(CH 2 ) m — wherein each n and m is independently an integer from 1 to 8, divalent phenyl, substituted divalent phenyl, 2,2′-divalent-1,1′-biphenyl, substituted 2,2′-divalent-1,1′-biphenyl, 2,2′-divalent-1,1′-binaphthyl, substituted 2,2′-divalent-1,1′-binaphthyl, 1,1′-ferrocene, substituted 1,1′-ferrocene, wherein the substituent in each of said substituted divalent phenyl, biphenyl, binaphthyl and ferrocene is one or more moiety each independently selected from the group consisting of: alkyl, aryl, aralkyl, alkaryl, alkenyl, akkynyl, F, Cl, Br, I, OH, OR, SH, SR, COOH, COOR, SO 3 H, SO 3 R, PO 3 H 2 , PO 3 HR, PO 3 R 2 , NH 2 , NHR, NR 2 , PR 2 , AsR 2 , SbR 2  and nitro; and  
         wherein each R is independently selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, fluoroalkyl, perfluoroalkyl and —CR′ 2 (CR′ 2 ) q Q(CR′ 2 ) p R′ wherein each q and p is independently an integer from 1 to 8, Q is selected from the group consisting of: O, S, NR, PR, AsR, SbR, divalent aryl, divalent fused aryl, divalent 5-membered ring heterocycle and divalent fused heterocycle.  
       
     
     
         2 . The ligand of  claim 1 , wherein said ligand is a racemic mixture of enantiomers.  
     
     
         3 . The ligand of  claim 1 , wherein said ligand is a non-racemic mixture of enantiomers.  
     
     
         4 . The ligand of  claim 1 , wherein said ligand is one of the enantiomers.  
     
     
         5 . The ligand of  claim 1 , having an optical purity of at least 85% ee.  
     
     
         6 . The ligand of  claim 1 , having an optical purity of at least 95% ee.  
     
     
         7 . The ligand of  claim 1 , wherein said ligand is supported on a support material.  
     
     
         8 . The ligand of  claim 7 , wherein said support is selected from the group consisting of: a polymer support and an inorganic support.  
     
     
         9 . The ligand of  claim 8 , wherein said polymer support is selected from the group consisting of polystyrene, polyacrylate, resin, polyethylene glycol, methoxy polyethylene glycol, dendritic polyester and dendritic polyenamide.  
     
     
         10 . The ligand of  claim 8 , wherein said inorganic support is selected from the group consisting of: silica, alumina, zeolite and molecular sieve.  
     
     
         11 . The ligand of  claim 8 , wherein said ligand is linked to a support material by a linker group selected from the group consisting of: NH(CH 2 ) n Si(OEt) 3 , CO(CH 2 ) n Si(OEt) 3 , (CH 2 ) n Si(OEt) 3 , C—O, C—N and and NCF 2  linker, wherein n=1 to 8.  
     
     
         12 . The ligand of  claim 1 , including at least one water soluble functional group selected from the group consisting of: sulfonic, phosphoric and carboxylic.  
     
     
         13 . A ligand selected from the group consisting of:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         14 . A ligand represented by the formula:  
       
         
           
           
               
               
           
         
       
     
     
         15 . A catalyst prepared by a process comprising: contacting a transition metal salt, or a complex thereof, and a ligand selected from the group consisting of compounds represented by I through XI:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein X′ is selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, hydroxy, alkoxy, aryloxy, siloxy, thioalkoxy, arylthio, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, amido, ester, reverse ester, keto, halo, silyl and SH;  
         wherein R′ is selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino and amido;  
         wherein each X, Z and Z′ is independently selected from the group consisting of: O, NH, NR, CH 2 , CHR, CR 2 , C═O, S, SO 2 , and SO;  
         wherein each Z″ is independently selected from the group consisting of: N, P, CH, and CR;  
         wherein each R 1 , R 2 , R 3  and R 4  is independently selected from the group consisting of H, alkyl, aryl, substituted alkyl, substituted aryl and OR;  
         wherein each Y and Y′ is independently selected from the group consisting of: a diol protecting group residue, O, CO, C(OR) 2 , CH(OR), CH 2 , CHR, CR 2 , CR 2 , NR, SO 2 , —(CH 2 ) n — wherein n is 0 or an integer from 1 to 8, —(CH 2 ) n Q(CH 2 ) m — wherein each n and m is independently an integer from 1 to 8, divalent phenyl, substituted divalent phenyl, 2,2′-divalent-1,1′-biphenyl, substituted 2,2′-divalent-1,1′-biphenyl, 2,2′-divalent-1,1′-binaphthyl, substituted 2,2′-divalent-1,1′-binaphthyl, 1,1′-ferrocene, substituted 1,1′-ferrocene, wherein the substituent in each of said substituted divalent phenyl, biphenyl, binaphthyl and ferrocene is one or more moiety each independently selected from the group consisting of: alkyl, aryl, aralkyl, alkaryl, alkenyl, akkynyl, F, Cl, Br, I, OH, OR, SH, SR, COOH, COOR, SO 3 H, SO 3 R, PO 3 H 2 , PO 3 HR, PO 3 R 2 , NH 2 , NHR, NR 2 , PR 2 , AsR 2 , SbR 2  and nitro; and  
         wherein each R is independently selected from the group consisting of: alkyl, aryl, substituted alkyl substituted aryl, fluoroalkyl, perfluoroalkyl and —CR′ 2 (CR′ 2 ) q Q(CR′ 2 ) p R′ wherein each q and p is independently an integer from 1 to 8, Q is selected from the group consisting of: O, S, NR, PR, AsR, SbR, divalent aryl, divalent fused aryl, divalent 5-membered ring heterocycle and divalent fused heterocycle.  
       
     
     
         16 . The catalyst of  claim 15 , wherein said catalyst is a racemic mixture of enantiomers.  
     
     
         17 . The catalyst of  claim 15 , wherein said catalyst is a non-racemic mixture of enantiomers.  
     
     
         18 . The catalyst of  claim 15 , wherein said catalyst is one of the enantiomers.  
     
     
         19 . The catalyst of  claim 15 , having an optical purity of at least 95% ee.  
     
     
         20 . The catalyst of  claim 15 , wherein said transition metal is selected from the group consisting of: Pt, Pd, Rh, Ru, Ir, Cu, Ni, Mo, Ti, V, Re and Mn.  
     
     
         21 . The catalyst of  claim 15 , wherein said transition metal is selected from the group consisting of: Pd, Rh, Ru and Ir.  
     
     
         22 . The catalyst of  claim 20 , wherein said transition metal salt, or complex thereof, is selected from the group consisting of: PtCl 2 ; Pd 2 (DBA) 3 ; Pd(OAc) 2 ; PdCl 2 (RCN) 2 ; (Pd(allyl)Cl) 2 ; (Rh(COD)Cl) 2 ; (Rh(COD) 2 )X; Rh(acac)(CO) 2 ; Rh(ethylene) 2 (acac); Rh(CO) 2 Cl 2 ; Ru(RCOO) 2 (diphosphine); Ru(methylallyl)2(diphosphine); Ru(aryl group)X 2 (diphosphine); RuCl 2 (COD); (Rh(COD) 2 )X; RuX 2 (diphosphine); RuCl 2 (═CHR)(PR′ 3 ) 2 ; Ru(ArH)Cl 2 ; Ru(COD)(methylallyl) 2 ; (Ir(COD) 2 Cl) 2 ; (Ir(COD) 2 )X; Cu(OTf); Cu(OTf) 2 ; Cu(Ar)X; CuX; NiX 2 ; Ni(COD) 2 ; MoO 2 (acac) 2 ; Ti(OiPr) 4 ; VO(acac) 2 ; MeReO 3 ; MnX 2  and Mn(acac) 2 ; wherein each R and R′ is independently selected from the group consisting of: alkyl or aryl; Ar is an aryl group; and X is a counteranion.  
     
     
         23 . The catalyst of  claim 22 , wherein said counteranion X is selected from the group consisting of: halogen, BF 4 , B(Ar) 4  wherein Ar is 3,5-di-trifluoromethyl-1-phenyl, ClO 4 , SbF 6 , CF 3 SO 3,  RCOO and a mixture thereof.  
     
     
         24 . The catalyst of  claim 15 , prepared in situ or as an isolated compound.  
     
     
         25 . A catalyst prepared by a process comprising: contacting a ruthenium salt, or a complex thereof, and a ligand represented by the formula:  
       
         
           
           
               
               
           
         
       
     
     
         26 . A process for preparation of an asymmetric compound comprising: 
 contacting a substrate capable of forming an asymmetric product by an asymmetric reaction and a catalyst prepared by a process comprising: contacting a transition metal salt, or a complex thereof, and a ligand selected from the group consisting of compounds represented by I through XI:                                            wherein X′ is selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, hydroxy, alkoxy, aryloxy, siloxy, thioalkoxy, arylthio, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino, amido, ester, reverse ester, keto, halo, silyl and SH;    wherein R′ is selected from the group consisting of: alkyl, aryl, substituted alkyl, substituted aryl, hydroxy, alkoxy, aryloxy, amino, alkylamino, dialkylamino, arylamino, diarylamino, alkylarylamino and amido;    wherein each X, Z and Z′ is independently selected from the group consisting of: O, NH, NR, CH 2 , CHR, CR 2 , C═O, S, SO 2 , and SO;    wherein each Z″ is independently selected from the group consisting of: N, P, CH, and CR;    wherein each R 1 , R 2 , R 3  and R 4  is independently selected from the group consisting of: H, alkyl, aryl, substituted alkyl, substituted aryl and OR;    wherein each Y and Y′ is independently selected from the group consisting of: a diol protecting group residue, O, CO, C(OR) 2 , CH(OR), CH 2 , CHR, CR 2 , CR 2 , NR, SO 2 , —(CH 2 )n— wherein n is 0 or an integer from 1 to 8, —(CH 2 ) n Q(CH 2 ) m — wherein each n and m is independently an integer from 1 to 8, divalent phenyl, substituted divalent phenyl, 2,2′-divalent-1,1′-biphenyl, substituted 2,2′-divalent-1,1′-biphenyl, 2,2′-divalent-1,1′-binaphthyl, substituted 2,2′-divalent-1,1′-binaphthyl, 1,1′-ferrocene, substituted 1,1′-ferrocene, wherein the substituent in each of said substituted divalent phenyl, biphenyl, binaphthyl and ferrocene is one or more moiety each independently selected from the group consisting of: alkyl, aryl, aralkyl, alkaryl, alkenyl, akkynyl, F, Cl, Br, I, OH, OR, SH, SR, COOH, COOR, SO 3 H, SO 3 R, PO 3 H 2 , PO 3 HR, PO 3 R 2 , NH 2 , NHR, NR 2 , PR 2 , AsR 2 , SbR 2  and nitro; and    wherein each R is independently selected from the group consisting of: alkyl aryl, substituted alkyl, substituted aryl, fluoroalkyl, perfluoroalkyl and —CR′ 2 (CR′ 2 ) q Q(CR′ 2 ) p R′ wherein each q and p is independently an integer from 1 to 8, Q is selected from the group consisting of: O, S, NR, PR, AsR, SbR, divalent aryl, divalent fused aryl, divalent 5-membered ring heterocycle and divalent fused heterocycle.    
     
     
         27 . The process of  claim 26 , wherein said asymmetric reaction is selected from the group consisting of: hydrogenation, hydride transfer, allylic alkylation, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, isomerization, cyclopropanation, Diels-Alder reaction, Heck reaction, isomerization, Aldol reaction, Michael addition and epoxidation.  
     
     
         28 . The process of  claim 27 , wherein said asymmetric reaction is hydrogenation and said substrate is selected from the group consisting of: imine, ketone, ethylenically unsaturated compound, enamine, enamide and vinyl ester.  
     
     
         29 . The process of  claim 27 , wherein said substrate is an electron-rich substrate.  
     
     
         30 . The process of  claim 26 , wherein said catalyst is an Rh complex of (R,S,S,R)-DIOP*.  
     
     
         31 . The process of  claim 26 , wherein said catalyst is an Rh complex of  
       ligand 18.  
     
     
         32 . A process for preparing a ligand enantiomer comprising the steps of: 
 contacting an enantiomer of tartaric acid diester and a diol protecting group in the presence of an acid catalyst to produce a bis-protected tartrate diester;    contacting said bis-protected tartrate diester and a reducing agent to convert the ester functional groups in said tartaric acid diester to a diol;    converting said diol to a sulfonate ester; and    displacing the sulfonate group in said sulfonate ester with lithium diphenylphosphinide to produce ligand enantiomer.