Tricyclic chiral compounds and their use in asymmetric catalysis
The present invention relates to a compound of general Formula (XX), its formation and its use in asymmetric catalysis. In Formula (XX) R and R 31 are independently —COOR 3 , —R 4 COOR 3 , —R 4 CHO, —R 4 COR 3 , —R 4 CONR 5 R 6 , —R 4 COX, —R 4 OP(═O)(OH) 2 , —R 4 P(═O)(OH) 2 ), —R 4 C(O)C(R 3 )CR 5 R 6 and —R 4 CO 2 COR 3 . In addition, R 31 may also be hydrogen. R 3 , R 5 and R 6 are independently hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group or an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si. R 4 an aliphatic bridge with a main chain having 1 to about 20 carbon atoms, an alicyclic bridge, an aromatic bridge, an arylaliphatic bridge or an arylalicyclic bridge, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si, and X is halogen. In Formula (XX) R 30 is —C(OH)R 1 R 2 or —COOR 14 , wherein R 1 , R 2 and R 14 are independently hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group or an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si.
1. A hexahydropyrrolo[2,3-b]indole compound of Formula (XX)
wherein R is —COOR 3 ,
wherein R 3 is selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si,
R 31 is hydrogen;
R 30 is one of —C(OH)R 1 R 2 and —COOH,
wherein R 1 and R 2 are independent from one another, and wherein
R 1 and R 2 are selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, and an aromatic group.
2. A hexahydropyrrolo[2,3-b]indole compound of Formula (VII)
wherein R is —COOR 3 ,
wherein R 3 is selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si, and
R 1 and R 2 are independent from one another, each selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, and an aromatic group.
3. The compound of claim 2 wherein R 1 and R 2 are identical.
4. A compound of Formula (VIA)
wherein R is —COOR 3 ,
wherein R 3 is selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si.
5. A method of forming a compound of Formula (VIA)
wherein R is —COOR 3 ,
wherein R 3 is selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si, and
the method comprising providing a compound of Formula (IVA)
wherein in Formula (IVA) R is —COOR 3 ,
wherein R 3 is selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si, and
Y is a nitrogen protecting group that is removable by hydrogenolysis, and
R 10 is a protecting group that is removable in the presence of R by hydrogenolysis; and
exposing the compound of Formula (IVA) to H 2 in the presence of a suitable catalyst, thereby (i) allowing the deprotection of the Nα group of compound (IVA) and (ii) allowing the cleavage of the ester bond to moiety R 10 of compound (IVA).
6. The method of claim 5 , wherein R 10 is aryl-methylenyl.
7. The method of claim 5 , wherein providing the compound of Formula (IVA) comprises contacting a compound of Formula (IIIA)
with an acyl halide RCOX in the presence of an alkali base,
wherein in Formula (IIIA) Y is a nitrogen protecting group that is removable by hydrogenolysis,
R 10 is a protecting group that is removable in the presence of R in a compound of Formula (IVA) by hydrogenolysis, and
X is halogen.
8. A method of preparing a compound of Formula (VII)
wherein R is —COOR 3 ,
wherein R 3 is selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si, and
R 1 and R 2 are independent from one another, each selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, and an aromatic group;
the method comprising reacting a compound of Formula (VI)
with a compound R 1 MgX, R 2 MgX or a mixture of R 1 MgX and R 2 MgX,
wherein R 1 and R 2 are independent from one another, each selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, and an aromatic group;
wherein in Formula VI, R is —COOR 3 ,
wherein R 3 is selected from one of hydrogen, an aliphatic group with a main chain having 1 to about 20 carbon atoms, an alicyclic group, an aromatic group, an arylaliphatic group and an arylalicyclic group, comprising 0 to about 3 heteroatoms independently selected from the group consisting of N, O, S, Se and Si,
and
R 9 is alkyl.
9. The method of claim 8 , wherein R 1 and R 2 are identical.
10. The method of claim 7 , wherein the compound of Formula (MA) is prepared by a process that comprises an acid catalyzed cyclization of an Nα-protected-tryptophan alkyl ester.