Claims
- 1. A process of stereoselective chemical synthesis, comprising the step of reacting a chiral or prochiral dienophile and a chiral or prochiral 1,3-diene in the presence of a non-racemic chiral catalyst to produce a stereoisomerically enriched product; wherein said dienophile contains at least one carbon-heteroatom π-bond, said 1,3-diene contains at least one pair of conjugated π-bonds, and said chiral catalyst comprises an asymmetric tridentate ligand complexed with a metal atom, and said catalyst has a trigonal planar or trigonal pyrimidal geometry.
- 2. The process of claim 1, wherein the metal atom is a transition metal or lanthanide metal.
- 3. The process of claim 1, wherein the metal atom is a main group metal.
- 4. The process of claim 1, wherein the metal atom is selected from the group consisting of Na, K, Rb, Mg, Ca, Sr, B, Al, Ga, In, Si, Ge, and Sn.
- 5. The process of claim 1, wherein the metal atom is selected from the group consisting of Co, Cr, Mn, V, Fe, Mo, W, Ru and Ni.
- 6. The process of claim 1, 2, 3, 4, or 5, wherein the tridentate ligand has at least one Schiff base nitrogen atom which complexes with the metal atom.
- 7. The process of claim 1, 2, 3, 4, or 5, wherein the chiral catalyst has a molecular weight of less than 5,000 a.m.u.
- 8. The process of claim 1, 2, 3, 4, or 5, wherein the substrate 1,3-diene is represented by the general formula 118 and the substrate dienophile is represented by the general formula 119:
- 9. The process of claim 8, wherein the substituents R1, R2, R3, and R4 each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7;
any two of the substituents R1, R2, and R50, or R3, and R4 taken together may form a carbocylic or heterocyclic ring having from 4 to 8 atoms in the ring structure; R7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; and m is zero or an integer in the range of 1 to 8.
- 10. The process of claim 8, wherein either the 1,3-diene substrate, the dienophile substrate, or both have a plane of symmetry.
- 11. The process of claim 1, 2, 3, 4, or 5, wherein the dienophile substrate is selected from the group consisting of aldehydes, thioaldehydes, esters, thionoesters, thioesters, dithioesters, amides, thioamides, lactones, thionolactones, thiolactones, dithiolactones, lactams, thiolactams, phosphorus ylides, ketones, thioketones, acid halides, anhydrides, imines, iminium ions, imines, oximes, oximes, hydrazones, nitroso-containing compounds, nitro-containing compounds, compounds containing a phosphorus-oxygen π-bond, and compounds containing a phosphorus-sulfur π-bond; and the 1,3-diene substrate is selected from the group comprising substituted 1,3-butadienes, 1-aza-1,3-butadienes, 2-aza-1,3′-butadienes, 1,2-diaza-1,3-butadienes, 1,3-diaza-1,3-butadienes, 1,4-diaza-1,3-butadienes, 2,3-diaza-1,3-butadienes, 1-phosphorous-1,3-butadienes, and 2-phosphorous-1,3′-butadienes.
- 12. The process of claim 1, 2, 3, 4, or 5, wherein the catalyst is immobilized on an insoluble matrix.
- 13. The process of claim 1, 2, 3, 4, or 5, wherein said process is an enantioselective reaction.
- 14. The process of claim 1, 2, 3, 4, or 5, wherein said process is a diastereoselective reaction.
- 15. The process of claim 14, wherein said diastereoselective reaction is a kinetic resolution reaction.
- 16. A method for catalyzing a stereoselective cycloaddition reaction, comprising the steps of:
combining a prochiral or chiral dienophile, a prochiral or chiral 1,3-diene, and a non-racemic chiral catalyst, wherein said dienophile contains at least one carbon-heteroatom α-bond, said 1,3-diene contains at least one pair of conjugated π-bonds, and said chiral catalyst comprises a chiral tridentate ligand complexed with a metal; and maintaining the combination under conditions appropriate for said chiral catalyst to catalyze a stereoselective cycloaddition reaction between said dienophile substrate and said 1,3-diene substrate.
- 17. The process of claim 16, wherein the metal is a transition metal or lanthanide metal.
- 18. The process of claim 16, wherein the metal is a main group metal.
- 19. The process of claim 16, wherein the metal atom is selected from the group consisting of Na, K, Rb, Mg, Ca, Sr, B, Al, Ga, In, Si, Ge and Sn.
- 20. The process of claim 16, wherein the metal atom is selected from the group consisting of Co, Cr, Mn, V, Fe, Mo, W, Ru and Ni.
- 21. The method of claim 16, 17, 18, 19, or 20, wherein the chiral catalyst is represented by the general formula:
- 22. The method of claim 21, wherein each Z1, Z2, and Z3 are independently selected from the group consisting of nitrogen, oxygen, phosphorus, arsenic, and sulfur.
- 23. The method of claim 21, wherein the 1,3-diene and dienophile substrates are represented by general formulas 118 and 119, respectively:
- 24. The method of claim 23, wherein either the 1,3-diene substrate, the dienophile substrate, or both have a plane of symmetry.
- 25. The process of claim 23, wherein the dienophile substrate is selected from the group consisting of aldehydes, thioaldehydes, esters, thionoesters, thioesters, dithioesters, amides, thioamides, lactones, thionolactones, thiolactones, dithiolactones, lactams, thiolactams, phosphorus ylides, ketones, thioketones, acid halides, anhydrides, imines, iminium ions, imines, oximes, oximes, hydrazones, nitroso-containing compounds, nitro-containing compounds, compounds containing a phosphorus-oxygen π-bond, and compounds containing a phosphorus-sulfur π-bond; and the 1,3-diene substrate is selected from the group consisting of substituted 1,3-butadienes, 1-aza-1,3-butadienes, 2-aza-1,3-butadienes, 1,2-diaza-1,3-butadienes, 1,3-diaza-1,3-butadienes, 1,4-diaza-1,3-butadienes, 2,3-diaza-1,3-butadienes, 1-phosphorous-1,3-butadienes, and 2-phosphorous-1,3-butadienes.
- 26. The method of claim 23, wherein said process is an enantioselective cycloaddition.
- 27. The method of claim 23, wherein said process is a diastereoselective cycloaddition.
- 28. The method of claim 27, wherein said diastereoselective cycloaddition produces a kinetic resolution.
- 29. A method of providing a non-racemic chiral dihydropyran, comprising the step of reacting a prochiral aldehyde with a prochiral 1,3-diene in the presence of a chiral, non-racemic catalyst such that a non-racemic chiral dihydropyran is formed, wherein the chiral catalyst comprises an asymmetric tridentate ligand complexed with a metal atom, said complex having a trigonal planar or trigonal pyrimidal geometry.
- 30. The process of claim 29, wherein the metal is a transition metal or lanthanide metal.
- 31. The process of claim 29, wherein the metal is a main group metal.
- 32. The process of claim 29, wherein the metal atom is selected from the group consisting of Na, K, Rb, Mg, Ca, Sr, B, Al, Ga, In, Si, Ge and Sn.
- 33. The process of claim 29, wherein the metal atom is selected from the group consisting of Co, Cr, Mn, V, Fe, Mo, W, Ru and Ni.
- 34. The method of claim 1, 2, 3, 4, 5, 16, 17, 18, 19, 20, 29, 30, 31, 32, or 33, wherein the chiral tridentate ligand of the chiral catalyst is represented by general formula 150:
- 35. The method of claim 34, wherein the metal is Cr.
- 36. The method of claim 1, 16, or 29, wherein the chiral catalyst is represented by general structure 160:
- 37. The method of claim 36, wherein M represents Cr(III).
- 38. The method of claim 36, wherein X represents O.
- 39. The method of claim 36, wherein Z represents N.
- 40. The method of claim 36, wherein X represents O; and Z represents N.
- 41. The method of claim 36, wherein both of the carbons bearing an instance of R′ are asymmetric.
- 42. The method of claim 36, wherein X represents O; and both of the carbons bearing an instance of R′ are asymmetric.
- 43. The method of claim 36, wherein Z represents N; and both of the carbons bearing an instance of R′ are asymmetric.
- 44. The method of claim 36, wherein M represents Cr(III); X represents O; Z represents N; and both of the carbons bearing an instance of R′ are asymmetric.
- 45. The method of claim 1, 16, or 29, wherein the chiral catalyst is represented by general structure 162:
- 46. The method of claim 45, wherein M represents Cr(III).
- 47. The method of claim 45, wherein Z represents N.
- 48. The method of claim 45, wherein X represents O.
- 49. The method of claim 45, wherein X represents O; and Z represents N.
- 50. The method of claim 45, wherein both carbons bearing R2 are asymmetric.
- 51. The method of claim 45, wherein X represents O; Z represents N; and both carbons bearing R2 are asymmetric.
- 52. The method of claim 45, wherein R1 represents hydrogen.
- 53. The method of claim 45, wherein X represents O; Z represents N; both carbons bearing R2 are asymmetric; and R1 represents hydrogen.
- 54. The method of claim 45, wherein M represents Cr(III); X represents O; Z represents N; both carbons bearing R2 are asymmetric; R1 represents hydrogen; and R3 is present once or twice and represents alkyl.
- 55. The catalyst complex represented by general structure 160:
- 56. The catalyst complex of claim 55, wherein M represents Cr(III).
- 57. The catalyst complex of claim 55, wherein X represents O.
- 58. The catalyst complex of claim 55, wherein Z represents N.
- 59. The catalyst complex of claim 55, wherein X represents O; and Z represents N.
- 60. The catalyst complex of claim 55, wherein both of the carbons bearing an instance of R′ are asymmetric.
- 61. The catalyst complex of claim 55, wherein X represents O; and both of the carbons bearing an instance of R′ are asymmetric.
- 62. The catalyst complex of claim 55, wherein Z represents N; and both of the carbons bearing an instance of R′ are asymmetric.
- 63. The catalyst complex of claim 55, wherein M represents Cr(III); X represents O; Z represents N; and both of the carbons bearing an instance of R′ are asymmetric.
- 64. The catalyst complex represented by general structure 162:
- 65. The catalyst complex of claim 64, wherein M represents Cr(III).
- 66. The catalyst complex of claim 64, wherein Z represents N.
- 67. The catalyst complex of claim 64, wherein X represents O.
- 68. The catalyst complex of claim 64, wherein X represents O; and Z represents N.
- 69. The catalyst complex of claim 64, wherein both carbons bearing R2 are asymmetric.
- 70. The catalyst complex of claim 64, wherein X represents O; Z represents N; and both carbons bearing R2 are asymmetric.
- 71. The catalyst complex of claim 64, wherein R1 represents hydrogen.
- 72. The catalyst complex of claim 64, wherein X represents O; Z represents N; both carbons bearing R2 are asymmetric; and R1 represents hydrogen.
- 73. The catalyst complex of claim 64, wherein M represents Cr(III); X represents O; Z represents N; both carbons bearing R2 are asymmetric; R1 represents hydrogen; and R3 is present once or twice and represents alkyl.
- 74. The catalyst complex represented by 164:
- 75. The catalyst complex of claim 74, wherein X represents Cl or SbF6.
- 76. The catalyst complex of claim 74, wherein R1 and R2 are independently selected from the group consisting of hydrogen and alkyl.
- 77. The catalyst complex of claim 74, wherein X represents Cl or SbF6; and R1 and R2 are independently selected from the group consisting of hydrogen and alkyl.
- 78. The catalyst complex of claim 74, wherein X represents Cl or SbF6; R1 represents hydrogen, methyl or tert-butyl; and R2 represents tert-butyl, —CEt2Me or 1-adamantyl.
- 79. The catalyst complex of claim 74, 75, 76, 77, or 78, wherein the catalyst complex is not a racemic mixture.
- 80. The catalyst complex of claim 79, wherein the catalyst complex has an enantiomeric excess greater than about 80%.
- 81. The catalyst complex of claim 79, wherein the catalyst complex has an enantiomeric excess greater than about 90%.
- 82. The catalyst complex of claim 79, wherein the catalyst complex has an enantiomeric excess greater than about 95%.
RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No. 09/006,104, filed Jan. 13, 1998.
GOVERNMENT FUNDING
[0002] The present invention was made with support from the National Institutes of Health; the government, therefore, has certain rights in the invention.
Continuations (1)
|
Number |
Date |
Country |
Parent |
09255480 |
Feb 1999 |
US |
Child |
09755612 |
Jan 2001 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
09006104 |
Jan 1998 |
US |
Child |
09255480 |
Feb 1999 |
US |