Substituted 1,2,3,4-tetrahydro-1,1'-biphenyl compounds

Abstract

Provided herein are substituted 1,2,3,4-tetrahydro-1,1′-biphenyl compounds and methods of making same.

What is claimed is: 
     
         1 . A compound of formula (II), a racemate or a stereoisomer thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 5  are independently hydroxyl or a protected hydroxyl group; 
         R 2  and R 4  are independently hydrogen or C 1 -C 10  alkyl; 
         R 3  is C 1 -C 10  alkyl; and 
         R 6  and R 7  are independently hydrogen or C 1 -C 10  alkyl; 
         wherein R 2 , R 3 , R 4 , R 6 , and R 7  at each occurrence are independently optionally substituted with one or more substituents selected from the group consisting of alkenyl, alkynyl, alkoxycarbonyl, alkylcarbonyl, halogen, cyano, carboxyl, hydroxyl, protected hydroxyl, amino, oxo, aryl, arylcarbonyl, cycloalkyl, heteroaryl, and heterocycle. 
       
     
     
         2 . The compound of  claim 1 , wherein R 3  is —(CH 2 ) 2 —CH 3  or —(CH 2 ) 4 —CH 3 . 
     
     
         3 . A compound of formula (III), a racemate or a stereoisomer thereof, 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 5  are independently hydroxyl or a protected hydroxyl group; 
         R 2  and R 4  are independently hydrogen or C 1 -C 10  alkyl; 
         R 3  is C 1 -C 10  alkyl; 
         R 6  and R 7  are independently hydrogen or C 1 -C 10  alkyl; and 
         R 8  is hydroxyl, C 1 -C 10  alkyl, or C 1 -C 10  alkoxy; 
         wherein R 2 , R 3 , R 4 , R 6 , R 7 , and R 8  at each occurrence are independently optionally substituted with one or more substituents selected from the group consisting of alkenyl, alkynyl, alkoxycarbonyl, alkylcarbonyl, halogen, cyano, carboxyl, hydroxyl, protected hydroxyl, amino, oxo, aryl, arylcarbonyl, cycloalkyl, heteroaryl, and heterocycle. 
       
     
     
         4 . The compound of  claim 3 , wherein R 3  is —(CH 2 ) 2 —CH 3  or —(CH 2 ) 4 —CH 3 . 
     
     
         5 . A process for the preparation of a compound of formula (I), a racemate or a stereoisomer thereof, 
       
         
           
           
               
               
           
         
       
       the process comprising the steps of:
 (a) optionally converting a compound of formula (II) to a compound of formula (III), and 
 
       
         
           
           
               
               
           
         
         (b) converting the compound of formula (III) to the compound of formula (I), wherein 
         R 1  and R 5  at each occurrence are independently hydroxyl or a protected hydroxyl group; 
         R 2  and R 4  at each occurrence are independently hydrogen or C 1 -C 10  alkyl; 
         R 3  at each occurrence is independently C 1 -C 10  alkyl; 
         R 6  and R 7  at each occurrence are independently hydrogen or C 1 -C 10  alkyl; 
         R 8  at each occurrence is independently hydroxyl, C 1 -C 10  alkyl, or C 1 -C 10  alkoxy; 
         wherein R 2 , R 3 , R 4 , R 6 , R 7 , and R 8  at each occurrence are independently optionally substituted with one or more substituents selected from the group consisting of alkenyl, alkynyl, alkoxycarbonyl, alkylcarbonyl, halogen, cyano, carboxyl, hydroxyl, protected hydroxyl, amino, oxo, aryl, arylcarbonyl, cycloalkyl, heteroaryl, and heterocycle. 
       
     
     
         6 . The process of  claim 5 , wherein step (a) is present. 
     
     
         7 . The process of  claim 6 , further comprising the step of reacting a compound of formula (IV) with compound of formula (V) to produce the compound of formula (II) 
       
         
           
           
               
               
           
         
       
     
     
         8 . The process of  claim 7 , further comprising the step of converting a compound of formula (VI) to the compound of formula (IV) 
       
         
           
           
               
               
           
         
       
     
     
         9 . The process of  claim 8 , further comprising converting the steps of converting the compound of formula (VI) to a compound of formula (IV′), and reducing the compound of formula (IV′) to the compound of formula (IV) 
       
         
           
           
               
               
           
         
       
     
     
         10 . The process of  claim 6 , wherein step (a) comprises mixing potassium bis(trimethylsilyl)amide (KHMDS) with the compound of formula (II). 
     
     
         11 . The process of  claim 5 , wherein R 3  is —(CH 2 ) 4 —CH 3 . 
     
     
         12 . The process of  claim 5 , wherein R 1  and R 5  are —OCH 3 . 
     
     
         13 . The process of  claim 5 , wherein R 6  and R 7  are each —CH 3 . 
     
     
         14 . The process of  claim 5 , wherein R 8  is hydroxyl, —CH 3 , or —OCH 3 . 
     
     
         15 . The process of  claim 5 , wherein step (b) comprises mixing the compound of formula (III) with (1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium.