Ligands, their preparation and uses thereof in asymmetric reactions
Novel chemical agents are described herein. More a ligand of general Formula I: wherein R 1 , R 2 , R 3 and R 4 , are independently selected from the group consisting of hydrogen, halogen, hydroxy, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 alkoxy, C 1 -C 10 alkylthio, C(O)R 5 , C(O)OR 5 , C(O)NHR 5 , Si(R 5 ) 3 , benzyl and aryl; X is selected from the group consisting of Cl, Br, I, OR 6 , O-Prot, OPR 6 , P(R 6 ) 2 , NHR 6 , N(R 6 ) 2 , NHCSNHR 6 , NHCONHR 6 and SR 6 ; and R 5 and R 6 are independently selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, phenyl, and aryl. These ligands are useful in asymmetric reactions as well as in asymmetric synthesis of molecules of biological interest.
1. A ligand of Formula I:
wherein:
a) R 1 , R 2 , R 3 and R 4 , are independently selected from the group consisting of hydrogen, halogen, hydroxy, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 alkoxy, C 1 -C 10 alkylthio, C(O)R 5 , C(O)OR 5 , C(O)NHR 5 , Si(R 5 ) 3 , benzyl and aryl;
b) X is selected from the group consisting of Cl, Br, I, OR 6 , O-Prot, OPR 6 , P(R 6 ) 2 , NHR 6 , N(R 6 ) 2 , NHCSNHR 6 , NHCONHR 6 and SR 6 ; and
c) R 5 and R 6 are independently selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, phenyl, and aryl.
2. The ligand of claim 1 , wherein said ligand is selected from the group consisting of:
3. The ligand of claim 2 , wherein said ligand is selected from the group consisting of:
4. The ligand of claim 3 , wherein said ligand is a racemic mixture of enantiomers.
5. The ligand of claim 3 , wherein said ligand is a non-racemic mixture of enantiomers.
6. The ligand of claim 3 , wherein said ligand comprises the L-enantiomer.
7. The ligand of claim 3 , wherein said ligand comprises the R-enantiomer.
8. The ligand of claim 6 , wherein the optical purity of said ligand is at least 50% ee.
9. The ligand of claim 6 , wherein the optical purity of said ligand is at least 60% ee.
10. The ligand of claim 6 , wherein the optical purity of said ligand is at least 70% ee.
11. The ligand of claim 6 , wherein the optical purity of said ligand is at least 80% ee.
12. The ligand of claim 6 , wherein the optical purity of said ligand is at least 90% ee.
13. The ligand of claim 6 , wherein the optical purity of said ligand is at least 95% ee.
14. The ligand of claim 7 , wherein the optical purity of said ligand is at least 50% ee.
15. The ligand of claim 7 , wherein the optical purity of said ligand is at least 60% ee.
16. The ligand of claim 7 , wherein the optical purity of said ligand is at least 70% ee.
17. The ligand of claim 7 , wherein the optical purity of said ligand is at least 80% ee.
18. The ligand of claim 7 , wherein the optical purity of said ligand is at least 90% ee.
19. The ligand of claim 7 , wherein the optical purity of said ligand is at least 95% ee.
20. A process for the preparation of a ligand of Formula I as defined in claim 1 , the process comprising:
a) reacting a compound of general Formula Ia:
wherein:
i) R 1 , R 2 , R 3 and R 4 , are independently selected from the group consisting of hydrogen, halogen, hydroxy, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 1 -C 10 alkoxy, C 1 -C 10 alkylthio, C(O)R 5 , C(O)OR 5 , C(O)NHR 5 , Si(R 5 ) 3 , benzyl and aryl; and
ii) R 5 is selected from the group consisting of hydrogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkoxy, phenyl, and aryl;
with a triflating reagent to produce a compound of general Formula Ib:
ii) reacting the compound of general Formula Ib with an oxidant to produce a compound of general Formula Ic:
iii) converting the triflate to produce a ligand of general Formula I.
21. The process of claim 20 , further comprises isolating an optically pure form of a ligand of Formula I.