Quaternary heteroatom containing compounds

Abstract

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II):comprising treating a compound of Formula (I):with a transition metal catalyst and under alkylation conditions as valence and stability permit.

1 - 30 . (canceled) 
     
     
         31 . A compound represented by Formula A, Formula A(ii), Formula A(iv), Formula D or Formula D(i): 
       
         
           
           
               
               
           
         
       
       wherein
 a carbon atom carrying the R 3  and Y groups is a chiral center; 
 z is 0; 
 Q is a heteroatom; 
 R 2  and Y combine to form a ring in which a ring atom directly adjacent the Q atom and on a side of the Q atom opposite the ring atom bearing the R 8  and R 9  groups is not a chiral center, and R 2  and Y do not form an unsubstituted benzene ring or an ortho-substituted benzene ring; 
 each of R′, R″, R 1  and R 4  through R 7 , R 10  and R 11  is independently hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom containing hydrocarbyl group, or a functional group; 
 R 8  and R 9  is independently hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom containing hydrocarbyl group, or a functional group; or R 8  and R 9  optionally combine to form a carbonyl group; 
 R 3  is a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom containing hydrocarbyl group, or a functional group; 
 when R 8  and R 9  combine to form a carbonyl group, R 3  is not a substituted or unsubstituted phenyl group, an unsubstituted carbonyl group, or an unsubstituted ethyl group; 
 each of Ra through Rf is either:
 independently hydrogen, a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heteroatom containing hydrocarbyl group, or a functional group; or 
 combines with another of Ra through Rf to form a double bond or a carbonyl group; 
 
 each of d, e and f is independently an integer of 0 or greater; 
 each of A, B and D is independently a carbon atom or a heteroatom, and an A atom that is directly adjacent an OH group is not a chiral center; and 
 two or more groups selected from R′, R″, R 4  through R 11  and Ra through Rf optionally combine to form a ring, except that R 6  and R 10  do not form an unsubstituted benzene ring, and R 4  and R 6  do not form an unsubstituted benzene ring. 
 
     
     
         32 . The compound of  claim 31 , wherein R 8  and R 9  combine to form a carbonyl group. 
     
     
         33 . The compound of  claim 31 , wherein R 2  and Y combine to form a ring with Q, the ring including between 3 and 12 ring atoms. 
     
     
         34 . The compound of  claim 33 , wherein the ring includes between 4 and 7 ring atoms. 
     
     
         35 . The compound of  claim 31 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         36 . A compound represented by Formula (V) or Formula (VI): 
       
         
           
           
               
               
           
         
       
       or a tautomer and/or salt thereof, wherein:
 X is selected from —NR 6 — and —O—; 
 Z is selected from —C(O)— and —CR 7 R 7 —; 
 A is independently selected at each occurrence from —CR 8 R 8 — and —NR 9 —; 
 W is absent or selected from —O—, —NR 10 —, and —CR 11 R 11 —; 
 R 1  is selected from optionally substituted alkyl, alkenyl, alkynyl, carbocyclyl, heterocycle, aryl, heteroaryl, and halogen; 
 R 12 , R 13 , R 14 , R 15 , R 2 , R 3 , R 4  and R 5  are independently selected at each occurrence from hydrogen, halogen, nitro, alkyl, alkenyl, alkynyl, cyano, carboxyl, sulfate, amino, alkoxy, alkylamino, alkylthio, hydroxyalkyl, alkoxyalkyl, aminoalkyl, thioalkyl, ether, thioether, ester, amide, thioester, carbonate, carbamate, urea, sulfonate, sulfone, sulfoxide, sulfonamide, acyl, acyloxy, acylamino, aryl, heteroaryl, carbocyclyl, heterocyclyl, aralkyl, aralkyloxy, hetaralkyl, carbocyclylalkyl, and heterocyclylalkyl; 
 R 7 , R 8 , and R 11  are independently selected at each occurrence from hydrogen, halogen, nitro, alkyl, alkenyl, alkynyl, cyano, hydroxyl, thiol, carboxyl, sulfate, amino, alkoxy, alkylamino, alkylthio, hydroxyalkyl, alkoxyalkyl, aminoalkyl, thioalkyl, ether, thioether, ester, amide, thioester, carbonate, carbamate, urea, sulfonate, sulfone, sulfoxide, sulfonamide, acyl, acyloxy, acylamino, aryl, heteroaryl, carbocyclyl, heterocyclyl, aralkyl, aralkyloxy, hetaralkyl, carbocyclylalkyl, and heterocyclylalkyl;
 wherein R 7  and R 8  may combine with the carbons to which they are bound to form an optionally substituted 3-8-membered ring, R 8  and R 11  may combine with the carbons to which they are bound to form an optionally substituted 3-8-membered ring, and when n is 2 or 3, R 8  attached to one carbon may combine with R 8  attached to another carbon to combine with the carbons to which they are bound to form a 3-8-membered ring; 
 
 R 6 , R 9  and R 10  are independently selected at each occurrence from hydrogen, hydroxyl and optionally substituted alkyl, alkoxy, alkylthio, aryloxy, carbocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, aralkyloxy, heteroaryloxy, acyl, arylcarbonyl, aralkylcarbonyl, acyloxy, sulfone, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, and amide; and 
 n is 0-3. 
 
     
     
         37 . The compound of  claim 36 , wherein the compound comprises one of a (+) enantiomer of the compound or a (−) enantiomer of the compound in an enantiomeric excess of greater than 50%. 
     
     
         38 . The compound of  claim 36 , wherein:
 R 1  is selected from halogen, alkyl, optionally substituted aralkyl, optionally substituted alkoxycarbonylalkyl, optionally substituted cyanoalkyl, and optionally substituted hydroxyalkyl; and   R 6 , R 9 , and R 10  are independently selected at each occurrence from aralkyloxy, aralkoxycarbonyl, heteroaryloxy, acyl, arylcarbonyl, aralkylcarbonyl, arylsulfonyl, alkoxycarbonyl, and aryloxycarbonyl.   
     
     
         39 . The compound of  claim 38 , wherein:
 X is —NR 6 —;   Z is selected from —C(O)— and —CR 7 R 7 —;   A at each occurrence is —CR 8 R 8 —;   W is selected from —NR 10 — and —CR 11 R 11 —; and   n is 0-2.   
     
     
         40 . The compound of  claim 39 , wherein n is 1. 
     
     
         41 . The compound of  claim 36 , wherein:
 X is —O—;   Z is selected from —C(O)— and —CR 7 R 7 —;   A at each occurrence is —CR 8 R 8 —;   W is selected from —NR 10 —, and —CR 11 R 11 —; and   n is 0-2.