Claims
- 1. A process of stereoselective chemical synthesis, comprising: reacting a substoichiometric amount of a nucleophile with a racemic or diastereomeric mixture of a cyclic substrate, in the presence of a non-racemic, chiral catalyst, to effect a kinetic resolution of said cyclic substrate; said cyclic substrate comprises a carbocycle or heterocycle having an electrophilic center susceptible to attack by said nucleophile; and said chiral catalyst comprises an asymmetric tetradentate ligand complexed with a metal atom, which complex has a rectangular planar or rectangular pyramidal geometry.
- 2. The process of claim 1, wherein the metal atom is selected from Groups 3-12 of the periodic table, or from the lanthanide series.
- 3. The process of claim 1, wherein the metal atom is a transition metal from Groups 5-12.
- 4. The process of claim 1, wherein the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Co, Mo, W, Ru and Ni.
- 5. The process of claim 1, wherein the metal atom is Co.
- 6. The process of claim 1, wherein the tetradentate ligand is selected from the group consisting of: a chiral ligand represented by the formula 100; a chiral ligand represented by the formula 102; a chiral ligand represented by the formula 104; a chiral ligand represented by the formula 106; a chiral ligand represented by the formula 108; a chiral ligand represented by the formula 110; a chiral ligand represented by the formula 112; a chiral ligand represented by the formula 114; a chiral ligand represented by the formula 116; and a chiral crown ether.
- 7. The process of claim 1, wherein the tetradentate ligand comprises a Schiff base complexed with the metal atom.
- 8. The process of claim 1, wherein the chiral, non-racemic catalyst has a molecular weight of less than 5,000 a.m.u.
- 9. The process of claim 1, wherein the cyclic substrate is represented by the general formula 18:
- 10. The process of claim 9, wherein the substituents R30, R31, R32, and R33 each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m−R7;
or any two or more of the substituents R30, R31, R32, and R33 taken together 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 an integer in the range of 0 to 8 inclusive.
- 11. The process of claim 1 or 9, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones, and sultones.
- 12. The process of claim 1 or 9, wherein the cyclic substrate is a racemic or diastereomeric mixture of an epoxide, episulfide, or aziridine.
- 13. The process of claim 1, 2, 3, 4, or 5, wherein the cyclic substrate is a racemic terminal epoxide; and the nucleophile is water.
- 14. The process of claim 1, wherein the catalyst is immobilized on an insoluble matrix.
- 15. A process of stereoselective chemical synthesis, comprising: reacting a substoichiometric amount of a nucleophile with a racemic or diastereomeric mixture of a cyclic substrate, in the presence of a non-racemic, chiral catalyst, to effect a kinetic resolution of said cyclic substrate; said cyclic substrate comprises a carbocycle or heterocycle having an electrophilic center susceptible to attack by said nucleophile; and said chiral catalyst comprises an asymmetric tridentate ligand complexed with a metal atom, which complex has a trigonal planar or trigonal pyramidal geometry.
- 16. The process of claim 15, wherein the metal atom is selected from Groups 3-12 of the periodic table, or from the lanthanide series.
- 17. The process of claim 15, wherein the metal atom is a transition metal from Groups 5-12.
- 18. The process of claim 15, wherein the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Co, Mo, W, Ru and Ni.
- 19. The process of claim 15, wherein the metal atom is Co.
- 20. The process of claim 15, wherein the tridentate ligand comprises a Schiff base complexed with the metal atom.
- 21. The process of claim 15, wherein the chiral, non-racemic catalyst has a molecular weight of less than 5,000 a.m.u.
- 22. The process of claim 15, wherein the cyclic substrate is represented by the general formula 118:
- 23. The process of claim 22, wherein the substituents R30, R31, R32, and R33 each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7;
or any two or more of the substituents R30, R31, R32, and R33 taken together 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 an integer in the range of 0 to 8 inclusive.
- 24. The process of claim 15 or 22, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones, and sultones.
- 25. The process of claim 15 or 22, wherein the cyclic substrate is a racemic or diastereomeric mixture of an epoxide, episulfide, or aziridine.
- 26. The process of claim 15, 16, 17, 18, 19, or 22, wherein the cyclic substrate is a racemic terminal epoxide; and the nucleophile is water.
- 27. The process of claim 26, wherein the catalyst is immobilized on an insoluble matrix.
- 28. The process of claim 7, wherein the catalyst is represented by the general formula:
- 29. The process of claim 28, wherein the metal atom is selected from Groups 3-12 of the periodic table, or from the lanthanide series.
- 30. The process of claim 28, wherein the metal atom is a transition metal from Groups 5-12.
- 31. The process of claim 28, wherein the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Co, Mo, W, Ru and Ni.
- 32. The process of claim 28, wherein the metal atom is Co.
- 33. The process of claim 28, wherein the chiral, non-racemic catalyst has a molecular weight of less than 5,000 a.m.u.
- 34. The process of claim 28, wherein the cyclic substrate is represented by the general formula 118:
- 35. The process of claim 34, wherein the substituents R30, R31, R32, and R33 each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7;
or any two or more of the substituents R30, R31, R32, and R33 taken together 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 an integer in the range of 0 to 8 inclusive.
- 36. The process of claim 28 or 34, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones, and sultones.
- 37. The process of claim 28 or 34, wherein the cyclic substrate is a racemic or diastereomeric mixture of an epoxide, episulfide, or aziridine.
- 38. The process of claim 28, 29, 30, 31, 32, or 34, wherein the cyclic substrate is a racemic terminal epoxide; and the nucleophile is water.
- 39. The process of claim 38, wherein the catalyst is immobilized on an insoluble matrix.
- 40. The method of claim 6, wherein the chiral catalyst is represented by general formula 100:
- 41. The method of claim 40, wherein
R1, R2, R′1 and R′2, independently, represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7; each R40 and R41 occuring in 100 independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7; R7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; and m is an integer in the range of 0 to 8 inclusive.
- 42. The method of claim 41, wherein each Z1, Z2, Z3 and Z4 are independently selected from the group consisting of nitrogen, oxygen, phosphorus, arsenic, and sulfur.
- 43. The process of claim 42, wherein the metal atom is selected from Groups 3-12 of the periodic table, or from the lanthanide series.
- 44. The process of claim 42, wherein the metal atom is a transition metal from Groups 5-12.
- 45. The process of claim 42, wherein the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Co, Mo, W, Ru and Ni.
- 46. The process, of claim 42, wherein the metal atom is Co.
- 47. The process of claim 42, wherein the chiral, non-racemic catalyst has a molecular weight of less than 5,000 a.m.u.
- 48. The process of claim 42, wherein the cyclic substrate is represented by the general formula 118:
- 49. The process of claim 48, wherein the substituents R30, R31, R32, and R33 each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7;
or any two or more of the substituents R30, R31, R32, and R33 taken together 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 an integer in the range of 0 to 8 inclusive.
- 50. The process of claim 42 or 48, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones, and sultones.
- 51. The process of claim 42 or 48, wherein the cyclic substrate is a racemic or diastereomeric mixture of an epoxide, episulfide, or aziridine.
- 52. The process of claim 42, 43, 44, 45, 46, or 48, wherein the cyclic substrate is a racemic terminal epoxide; and the nucleophile is water.
- 53. The process of claim 52, wherein the catalyst is immobilized on an insoluble matrix.
- 54. The method of claim 15, wherein the chiral catalyst comprising a chiral tridentate ligand is represented by general formula 140:
- 55. The method of claim 54, wherein
R1, R2, R′1 and R′2, independently, represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7; each R40 and R41 occuring in 100 independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7; R7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; and m is an integer in the range of 0 to 8 inclusive.
- 56. The method of claim 55, wherein each Z1, Z2, Z3 and Z4 are independently selected from the group consisting of nitrogen, oxygen, phosphorus, arsenic, and sulfur.
- 57. The process of claim 56, wherein the metal atom is selected from Groups 3-12 of the periodic table, or from the lanthanide series.
- 58. The process of claim 56, wherein the metal atom is a transition metal from Groups 5-12.
- 59. The process of claim 56, wherein the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Co, Mo, W, Ru and Ni.
- 60. The process of claim 56, wherein the metal atom is Co.
- 61. The process of claim 56, wherein the chiral, non-racemic catalyst has a molecular weight of less than 5,000 a.m.u.
- 62. The process of claim 56, wherein the cyclic substrate is represented by the general formula 118:
- 63. The process of claim 62, wherein the substituents R30, R31, R32, and R33 each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7;
or any two or more of the substituents R30, R31, R32, and R33 taken together 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 an integer in the range of 0 to 8 inclusive.
- 64. The process of claim 56 or 62, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones, and sultones.
- 65. The process of claim 56 or 62, wherein the cyclic substrate is a racemic or diastereomeric mixture of an epoxide, episulfide, or aziridine.
- 66. The process of claim 56, 57, 58, 59, 60, or 62, wherein the cyclic substrate is a racemic terminal epoxide; and the nucleophile is water.
- 67. The process of claim 66, wherein the catalyst is immobilized on an insoluble matrix.
- 68. The method of claim 7, wherein the chiral catalyst comprising a chiral tetradentate ligand is represented by general formula 104:
- 69. The process of claim 68, wherein the metal atom is selected from Groups 3-12 of the periodic table, or from the lanthanide series.
- 70. The process of claim 68, wherein the metal atom is a transition metal from Groups 5-12.
- 71. The process of claim 68, wherein the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Co, Mo, W, Ru and Ni.
- 72. The process of claim 68, wherein the metal atom is Co.
- 73. The process of claim 68, wherein the chiral, non-racemic catalyst has a molecular weight of less than 5,000 a.m.u.
- 74. The process of claim 68, wherein the cyclic substrate is represented by the general formula 118:
- 75. The process of claim 74, wherein the substituents R30, R31, R32, and R33 each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7;
or any two or more of the substituents R30, R31, R32, and R33 taken together 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 an integer in the range of 0 to 8 inclusive.
- 76. The process of claim 68 or 74, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones, and sultones.
- 77. The process of claim 68 or 74, wherein the cyclic substrate is a racemic or diastereomeric mixture of an epoxide, episulfide, or aziridine.
- 78. The process of claim 68, 69, 70, 71, 72, or 74, wherein the cyclic substrate is a racemic terminal epoxide; and the nucleophile is water.
- 79. The process of claim 78, wherein the catalyst is immobilized on an insoluble matrix.
- 80. The method of claim 7, wherein the metallosalenate catalyst is represented by general formula 106:
- 81. The process of claim 80, wherein the metal atom is selected from Groups 3-12 of the periodic table, or from the lanthanide series.
- 82. The process of claim 80, wherein the metal atom is a transition metal from Groups 5-12.
- 83. The process of claim 80, wherein the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Co, Mo, W, Ru and Ni.
- 84. The process of claim 80, wherein the metal atom is Co.
- 85. The process of claim 80, wherein the chiral, non-racemic catalyst has a molecular weight of less than 5,000 a.m.u.
- 86. The process of claim 80, wherein the cyclic substrate is represented by the general formula 118:
- 87. The process of claim 86, wherein the substituents R30, R31, R32, and R33 each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —(CH2)m—R7;
or any two or more of the substituents R30, R31, R32, and R33 taken together 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 an integer in the range of 0 to 8 inclusive.
- 88. The process of claim 80 or 86, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones, and sultones.
- 89. The process of claim 80 or 86, wherein the cyclic substrate is a racemic or diastereomeric mixture of an epoxide, episulfide, or aziridine.
- 90. The process of claim 80, 81, 82, 83, 84, or 86, wherein the cyclic substrate is a racemic terminal epoxide; and the nucleophile is water.
- 91. The process of claim 90, wherein the catalyst is immobilized on an insoluble matrix.
- 92. The process of claim 1, 9, 15, 22, 28, 34, 42, 48, 56, 62, 68, 74, 80, or 86, wherein the nucleophile is water, an alcohol, or a thiol.
- 93. The process of claim 9, wherein the cyclic substrate is a racemic terminal epoxide; and the nucleophile is water.
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. Ser. No. 09/134,393, filed Aug. 14, 1998, now U.S. Pat. No. 6,262,278; which is a continuation-in-part of U.S. Ser. No. 08/622,549, filed on Mar. 25, 1996, now U.S. Pat. No. 5,929,232; which is a continuation-in-part of U.S. Ser. No. 08/403,374, filed Mar. 14, 1995, now U.S. Pat. No. 5,665,890.
GOVERNMENT FUNDING
[0002] Work described herein was supported in part with funding from the National Institutes of Health. The United States Government has certain rights in this invention.
Continuations (3)
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Continuation in Parts (2)
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