| LICENSEE | This data is not available for free |
| LICENSOR | This data is not available for free |
| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | July 27, 1999 |
| PATENT TITLE |
Stereoselective ring opening reactions |
| PATENT ABSTRACT |
The present invention relates to a process for stereoselective or regioselective chemical synthesis which generally comprises reacting a nucleophile and a chiral or prochiral cyclic substrate in the presence of a non-racemic chiral catalyst to produce a stereoisomerically or regioselectively enriched product. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | March 25, 1996 |
| PATENT REFERENCES CITED |
Adam, W. et al. (1994) "Tridentate .beta.-Hydroperoxy Alcohols As Novel Oxygen Donors For The Titanium-Catalyzed Epoxidation of .nu.,.delta.-Unsaturated .alpha., .beta.-Diols: A Direct Diastereoselective Synthesis Of Epoxy Diols" Angew Chem Int Ed Engl 33(10):1170-1108. Agarwal, D. et al. (1992) "Olefin Epoxidation Using Iron (III) Schiff Base Complexes As Catalyst" Indian Journal of Chemistry 31A:785-787. Barili, P et al. (1993) "Regio- and Stereochemistry Of The Acid Catalyzed And Of A Highly Enantioselective Enzymatic Hydrolysis of some Epoxyterahydrofurans" Tetrahedron 49(28):6263-6276. Brandes, B. and E. Jacobsen (1994) "Highly Enantioselective, Catalytic Epoxidation Of Trisubstituted Olefins" J. of Am. Chem. Soc. 59:4378-80. Chang, S. et al. (1994) "Effect of Chiral Quaternary Ammonium Salts On (Salen) Mn-Catalyzed Epoxidation Of Cis-Olefins. A Highly Enantioselective, Catalytic Route to Trans-Epoxides" J. Am. Chem. Soc. 116:(15):6937-8. Chen, X. et al. (1993) "Microbiological Transformations. 27. The First Examples for Preparative-Scale Enantioselective or Diastereoselective Epoxide Hydrolyses Using Microorganisms. An Unequivocal Access to All Four Bisabolol Stereoisomers" J. Am. Chem. Soc. 58(20):5528-32. Collman, J. et al. (1993) "Regioselective and Enantioselective Epoxidation Catalyzed By Metalloporphyrins" Science 261:1404-1411. Collman, J. et al. (1993) "Enantioselective Epoxidation Of Unfunctionalized Olefins Catalyzed By Threitol-Strapped Manganese Porphyrins" J. Am. Chem. Soc. 115:3834-3835. Corey, E. and F. Hannon (1987) "Chiral Catalysts For The Enantioselective Addition Of Organometallic Reagents To Aldehydes" Tetrahedron Letters 28(44)5233-5236. Desimoni, G. et al. (1992) "Copper(II) In Organic Synthesis. X (*). The Importance of Steric Hindrance In The Design of Chiral Tridentate Ligand Copper (II) Catalysts For Enantiosective Michael Reactions(**)" Gazzetta Chimica Italiana 122:268-273. Emziane, M. et al. ( 1988) "Asymmetric Ring-Opening Of Cyclohexene Oxide With Trimethylsilyl Azide In The Presence Of Titanium Isopropoxide/Chiral Ligand" J. of Organometallic Chemistry 346:C7-C10. Groves, J. and R. Neumann (1989) "Regioselective Oxidation Catalysis In Synthetic Phospholipid Vesicles. Membrane-Spanning Steroidal Metalloporphyrins" J. Am. Chem. Soc. 111:2900-2909. Groves, J. and R. Neumann (1987) "Membrane-Spanning Steroidal Metalloporphyrins as Site-Selective Catalysts in Synthetic Vesicles" J. Am. Chem. Soc. 109:5045-5047. Jameson, D. (1990) "2,6-Bis(N-pyrazolyl)pyridines: The Convenient Synthesis of a Famity of Planar Tridentate N3 Ligands that are Terpyridine Analogues" J. Org. Chem. 55:4992-4994. Jacobsen, E. et al. (1991) "Highly Enantioselective Epoxidation Catalysts Derived From 1,2-Diaminocyclohexane" J. Am. Chem. Soc. 113:7063-7064. Knebel, W. and R. Angelici (1974) "Kinetic and Equilibrium Studies of Bi-and Tridentate Chelate Ring-Opening Reactions of Metal Carbonyl Complexes" Inorganic Chemistry 13(3):632-637. Kruper, W. and Dellar, D. (1995) "Catalytic Formation of Cyclic Carbonates From Epoxides and CO2 With Chromium Metalloporphyrinates" J. Org. Chem. 60:725-727. Larrow, J. and E. Jacobsen (1994) "Kinetic Resolution Of 1,2-Dihydronaphthalene Oxide And Related Epoxides Via Asymmetric C-H Hydroxylation" J. Am. Chem. Soc. 116:12129-30. Larrow, J. and E. Jacobsen (1994) "A Practical Method For The Large-Scale Preparation Of ›N, N'-Bis(3,5-di-tert-butylsalicylidene)-1,2-Cyclohexanediaminato (2-)!manganese (III) Chloride, A Highly Enantioselective Epoxidation Catalyst" J. Org. Chem. 59:1939-42. Li, Z. et al. (1993) "Asymmetric Alkene Aziridination with Readily Available Chiral Diimine-Based Catalysts" J. Am. Chem Soc. 115(12):5326-5327. Marangoni, G. and B. Pitteri (1993) "Crystal Structure of Cationic Square Planar Platinum(II) Complexes Containing The Tridentate Chelate Ligand 2,6-Bis(methylthiomethyl)pyridine" Polyhdron 12(13):1669-1673. Maruoka, K et al. (1989) "An Efficient Catalytic Procedure For Epoxide Rearrangement" Tetrahedron Letters 30(41):5607-5610. Narasaka, K. (1991) "Chiral Lewis Acids In Catalytic Asymmertric Reactions" Synthesis Jan.:1-11. Nugent, W. et al. (1993) "Beyond Nature's Chiral Pool: Enantioselective Catalysis In Industry" Science 259:479-483. Nugent, W. (1992) "Chiral Lewis Acid Catalysis. Enantioselective Addition of Azide to Meso Epoxides" J. Am. Chem. Soc. 114:2768-2769. Oppolzer, W. and R. Radinov (1988) "Enantioselective Synthesis of Sec-Allylalcohols by Catalytic Asymmetric Addition Of Divinylzinc To Aldehydes" Tetrahedron Letters 29(44):5645-5648. Ozaki, S. et al. (1990) "Synthesis Of Chiral Square Planar Cobalt(III) Complexes and Catalytic Asymmetric Epoxidations With There Complexes" J. Chem. Soc. Perkin Trans. 2 Issue 1:353-359. Palucki, M. et al. (1994) "Highly Enantioselective, Low-Temperature Epoxidation of Styrene" J. Am. Chem. Soc. 116:9333-9334. Palucki, A. et al. (1992) "Asymmetric Oxidation Of Sulfides With H202 Catalyzed By (Salen) Mn (III) Complexes" Tetrahedron Letters, 33(47):7111-7114. Sasaki, H. et al. (1994) "Rational Design Of Mn-Salen Catalyst (2): Highly Enantioselective Epoxidation of Conjugated cis-Olefins" Tetrahedron 50(41):11827-11838. Schurig, V. and F. Betschinger (1992) "Metal-Mediated Enantioselective Access to Un-functionalized Allphatic Oxiranes: Prochiral and Chiral Recognition" Chem. Rev. 92:873-888. Srinivasan, K. et al. (1986) "Epoxidation of Olefins With Cationic (Salen) Mn III Complexes. The Modulation of Catalytic Activity By Substituents" J. Am. Chem. Soc. 108:2309-2320. Stinson, S. (1992) "Chiral Drugs" Chemical and Chemical Engineering News Sep. 28 pp. 46-79. Ward, R. (1990) "Non-Enzymatic Asymmetric Transformations Involving Symmetrical Bifunctional Compounds" Chem. Soc. Rev. 19:1-19. Woolley, P. (1975) "Models For Metal Ion Function In Carbonic Anhydrase" Nature 258:677682. Yamashita, H. (1988) "Metal(II) d-Tartrates Catalyzed Asymmetric Ring Opening Of Oxiranes With Various Nucleophiles" The Chemical Society of Japan 61:1213-1220. Zhang, W. et al. (1990) "Enantioselective Epoxidation Of Unfunctionalized Olefins Catalyzed By (Selen)manganese Complexes" J. Am. Chem. Soc. 112:2801-2803. Zhang, W. and E. Jacobsen (1991) "Asymmetric Olefin Epoxidation With Sodium Hypochlorite Catalyzed By Easily Preparted Chiral Mn (III) Salen Complexes" J. Org. Chem. 56:2296-2298. Martinez, L.E. et al. (1995) "Highly enantioselective ring opening of epoxides catalized by (salen)Cr(III)complexes" J. Am. Chem Soc. 117:5897-5898. Leighton, J.L. et al. (1996) "Efficient synthesis of (R)-4-((trimethylsilyl)oxy)-2-cyclopentenone by enantioselective catalytic epoxide ring opening" J. Org. Chem. 61:389-390. Hayashi, M. et al. (1994) "Novel asymmetric ring-opening of symmetrical N-acylaziridines with arenethiols catalysed by chiral dialkyl tartrate-diethylzinc complexes" J. Chem. Soc., Chem Commun. 23:2699-2700. Hayashi, M. et al. (1991) "Asymmetric ring opening of symmetrical epoxides with trimethylsilyl azide using chiral titanium complexes" Synlett 11:774-776. Maruyama, M. et al. (1991) "Cobalt Schiff base complex catalysed solvolytic ring opening of epoxy compounds" Reaction Kinetics and Catalysis Letters 45:165-171. Adolfsson, H. et al. (1995) "Chiral Lewis acid catalysed asymmetric nucleophilic ring opening of cyclohexene oxide" Tetrahedron: Asymmetry 6:2023-2031. |
| PATENT GOVERNMENT INTERESTS | This invention was supported by NIH Grant No. GM43214, and the U.S. government has certain rights to the invention |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
We claim: 1. A kinetic resolution process which comprises reacting a nucleophile and a racemic mixture of a chiral cyclic substrate in the presence of a non-racemic chiral catalyst to produce a stereoisomerically enriched cyclic substrate by kinetic resolution, wherein said cyclic substrate comprises a carbocycle or heterocycle having a reactive center susceptible to nucleophilic 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 pyrimidal geometry. 2. The process of claim 1, wherein the metal atom is a transition metal from Groups 3-12 or from the lanthanide series. 3. The process of claim 1, wherein the metal atom is a late transition metal which is not in its highest state of oxidation. 4. The process of claim 2, wherein the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Mo, W, Ru and Ni. 5. The process of claim 1, wherein the tetradentate ligand is selected from the group consisting of ##STR91## a chiral ligand represented by the formula 102 ##STR92## a chiral ligand represented by the formula 102 ##STR93## a chiral ligand represented by the formula 112 ##STR94## a chiral ligand represented by the formula 114 ##STR95## a chiral ligand represented by the formula 116 a chiral crown ether. 6. The process of claim 1, wherein the tetradentate ligand has at least one schiff base complexes with the metal atom. 7. The process of claim 1, wherein the chiral catalyst has a molecular weight of less than 10,000 a.m.u. 8. The process of claim 1, wherein the substrate is represented by the general formula 118: ##STR96## in which Y represents O, S, N(R.sub.50), C(R.sub.52)(R.sub.54), or has the formula A--B--C; wherein R.sub.50 represents a hydrogen, an alkyl, a carbonyl-substituted alkyl, a carbonyl-substituted aryl, or a sulfonate, R.sub.52 and R.sub.54 each independently represent an electron-withdrawing group; A and C are independently absent, or represent a C.sub.1 -C.sub.5 alkyl, O, S, carbonyl, or N(R.sub.50); and B is a carbonyl, a thiocarbonyl, a phosphoryl, or a sulfonyl; and R.sub.30, R.sub.31, R.sub.32, and R.sub.33 represent organic or inorganic substituent which form a covalent bond with the C1 or C2 carbon atoms of 118, and which permit formation of a stable ring structure including Y. 9. The process of claim 8, wherein the substituents R.sub.30, R.sub.31, R.sub.32, and R.sub.33 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 --(CH.sub.2).sub.m --R.sub.7 ; or any two or more of the substituents R.sub.30, R.sub.31, R.sub.32, and R.sub.33 taken together form a carbocylic or heterocyclic ring having from 4 to 8 atoms in the ring structure; R.sub.7 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 R.sub.30, R.sub.31, R.sub.32, and R.sub.33 are chosen such that the substrate has a plane of symmetry. 11. The process of claim 1, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydridcs, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones and sultones. 12. The process of claim 1, wherein the catalyst is immobilized on an insoluble matrix. 13. A kinetic resolution process which comprises reacting a nucleophile and a racemic mixture of a chiral cyclic substrate in the presence of a non-racemic chiral catalyst to produce a stereoisomerically enriched cyclic substrate by kinetic resolution, wherein said cyclic substrate comprises a carbocycle or heterocycle having a reactive center susceptible to nucleophilic attack by said nucleophile, and said chiral catalyst comprises an asymmetric tridentate ligand complexed with a metal atom, which complex has a planar geometry. 14. The process of claim 13, wherein the metal atom is a transition metal from Groups 3-12 or from the lanthanide series. 15. The process of claim 13, wherein the metal is selected from the group consisting of Cr, Mn, V, Fe, Mo, W, Ru and Ni. 16. The process of claim 1 or 13, wherein the tridentate or tetradentate ligand has at least one Schiff base which complexes with the metal atom. 17. The process of claim 13, wherein the catalyst is immobilized on an insoluble matrix. 18. The process of claim 1 or 13, wherein the cyclic substrate is immobilized on an insoluble matrix. 19. The process of claim 1 or 13, wherein the nucleophile is immobilized on an insoluble matrix. 20. The process of claim 13, wherein the cyclic substrate is selected from the group consisting of epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphaces, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones and sultones. 21. The process of claim 13, wherein the cyclic substrate is represented by general formula 118: ##STR97## wherein Y represents O, S, N(R.sub.50), C(R.sub.52)(R.sub.54), or has the formula A--B--C; wherein R.sub.50 represents a hydrogen, an alkyl, a carbonyl-substltuced alkyl, a carbonyl-substituted aryl, or a sulfonate, R.sub.52 and R.sub.54 each independently represent an electron-withdrawing group; A and C are independently absent, or represent a C.sub.1 -C.sub.5 alkyl, O, S, carbonyl, or N(R.sub.50); and B is a carbonyl, a thiocarbonyl, a phosphoryl, or a sulfonyl; and R.sub.30, R.sub.31, R.sub.32, and R.sub.33 represent organic or inorganic substituent which form a covalent bond with the C1 or C2 carbon atoms of formula 118, and which permit formation of a stable ring structure with Y. 22. The process of claim 21, wherein the substituents R.sub.30, R.sub.31, R.sub.32, and R.sub.33 each independently represent hydrogen, halogens, alkyls alkenyls, atlynyls, hydroxyl, amino, nitro, thiol, arnines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or --(CH.sub.2).sub.m --R.sub.7 ; or any two or more of the substituents R.sub.30, R.sub.31, R.sub.32, and R.sub.33 taken together form a carbocylic or heterocyclic ring having from 4 to 8 atoms in the ring structure; R.sub.7 represents an aryl, a cycloallyl, a cycloalkenyl, a heterocycle or a polycycle; and m is zero or an integer in the range of 1 to 8. 23. The process of claim 21, wherein R.sub.30, R.sub.31, R.sub.32, and R.sub.33 are chosen such that the cyclic substrate has a plane of symmetry. 24. The process of claim 13, wherein the catalyst has a molecular weight of less than 10,000 a.m.u. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
BACKGROUND OF THE INVENTION The demand for enantiomerically pure compounds has grown rapidly in recent years. One important use for such chiral, non-racemic compounds is as intermediates for synthesis in the pharmaceutical industry. For instance, it has become increasingly clear that advantages (reviewed in, e.g. , Stinson, S. C. , Chem Eng News, Sep. 28, 1992, pp. 46-79) include fewer side effects and greater potency of enantiomerically pure compounds. Traditional methods of organic synthesis have often been optimized for the production of racemic materials. The production of enantiomerically pure material has historically been achieved in one of two ways: use of enantiomerically pure starting materials derived from natural sources (the so-called "chiral pool"), or resolution of racemic mixtures by classical techniques. Each of these methods has serious drawbacks, however. The chiral pool is limited to compounds found in nature, so only certain structures and configurations are readily available. Resolution of racemates often requires the use of resolving agents, which may be inconvenient and time-consuming. Furthermore, resolution often means that the undesired enantiomer is discarded, thus wasting half of the material. Epoxides are valuable intermediates for the stereocontrolled synthesis of complex organic compounds due to the variety of compounds which can be obtained by epoxide-opening reactions. For example, .alpha.-amino alcohols can be obtained simply by opening of an epoxide with azide ion, and reduction of the resulting .alpha.-azido alcohol (for example, by hydrogenation). Reaction of other nucleophiles similarly yields functionalized compounds which can be converted to useful materials. A Lewis acid may be added to act as an epoxide-activating reagent. The utility of epoxides has expanded dramatically with the advent of practical asymmetric catalytic methods for their synthesis (Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis. Ojima, I., Ed.: VCH: New York, 1993; Chapter 4.1. Jacobsen, E. N. Ibid. Chapter 4.2). In addition to epoxidation of prochiral and chiral olefins, approaches to the use of epoxides in the synthesis of enantiomerically enriched compounds include kinetic resolutions of racemic epoxides (Maruoka, K.; Nagahara, S.; Ooi, T.; Yamamoto, H. Tetrahedron Lett 1989, 30, 5607. Chen, X.-J.; Archelas, A.; Rurstoss, R. J Org Chem 1993, 58, 5528. Barili, P. L.; Berti, G.; Mastrorilli, E. Tetrahedron 1993, 49, 6263.) A particularly desirable reaction is the asymmetric ring-opening of symmetrical epoxides, a technique which utilizes easily made achiral starting materials and can simultaneously set two stereogenic centers in the functionalized product. Although the asymmetric ring-opening of epoxides with a chiral reagent has been reported, in most previously known cases the enantiomeric purity of the products has been poor. Furthermore, many previously reported methods have required stoichiometric amounts of the chiral reagent, which is likely to be expensive on a large scale. A catalytic asymmetric ring-opening of epoxides has been reported (Nugent, W. A., J Am Chem Soc 1992, 114, 2768); however, the catalyst is expensive to make. Furthermore, good asymmetric induction (>90% e.e.) was observed only for a few substrates and required the use of a Lewis-acid additive. Moreover, the catalytic species is not well characterized, making rational mechanism-based modifications to the catalyst difficult. SUMMARY OF THE INVENTION In one aspect of the present invention, there is provided a process for stereoselective chemical synthesis which generally comprises reacting a nucleophile and a chiral or prochiral cyclic substrate in the presence of a non-racemic chiral catalyst to produce a stereoisomerically enriched product. The cyclic substrate comprises a carbocycle or heterocycle having a reactive center susceptible to nucleophilic attack by the nucleophile, and the chiral catalyst comprises an asymmetric tetradentate or tridentate ligand complexed with a metal atom. In the instance of the tetradentate ligand, the catalyst complex has a rectangular planar or rectangular pyrimidal geometry. The tridentate ligand-metal complex assumes a planar geometry. In a preferred embodiment, the ligand has at least one schiff base nitrogen complexed with the metal core of the catalyst. In another preferred embodiment, the ligand provides at least one stereogenic center within two bonds of an ligand atom which coordinates the metal. In general, the metal atom is a transition metal from Groups 3-12 or from the lanthanide series, and is preferably not in its highest state of oxidation. For example, the metal can be a late transition metal, such as selected from Group 5-12 transition metals. In preferred embodiments, the metal atom is selected from the group consisting of Cr, Mn, V, Fe, Mo, W, Ru and Ni. In preferred embodiments, the substrate is represented which is acted on by the nucleophile is represented by the general formula 118: ##STR1## in which Y represents O, S, N(R.sub.50), C(R.sub.52)(R.sub.54), or has the formula A-B-C; wherein R.sub.50 represents a hydrogen, an alkyl, a carbonyl-substituted alkyl, a carbonyl-substituted aryl, or a sulfonate, R.sub.52 and R.sub.54 each independently represent an electron-withdrawing group; A and C are independently absent, or represent a C.sub.1 -C.sub.5 alkyl, O, S, carbonyl, or N(R.sub.50); and B is a carbonyl, a thiocarbonyl, a phosphoryl, or a sulfonyl; and R.sub.30, R.sub.31, R.sub.32, and R.sub.33 represent organic or inorganic substituent which form a covalent bond with the C1 or C2 carbon atoms of 118, and which permit formation of a stable ring structure including Y. For instance, the substituents R.sub.30, R.sub.31, R.sub.32, and R.sub.33 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 --(CH.sub.2).sub.m --R.sub.7 ; or any two or more of the substituents R.sub.30, R.sub.31, R.sub.32, and R.sub.33 taken together form a carbocylic or heterocyclic ring having from 4 to 8 atoms in the ring structure. In this formula, R.sub.7 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. In certain embodiments, R.sub.30, R.sub.31, R.sub.32, and R.sub.33 are chosen such that the substrate has a plane of symmetry. Exemplary cyclic substrate for the subject reaction include epoxides, aziridines, episulfides, cyclopropanes, cyclic carbonates, cyclic thiocarbonates, cyclic sulfates, cyclic anhydrides, cyclic phosphates, cyclic ureas, cyclic thioureas, lactams, thiolactams, lactones, thiolactones and sultones. In a preferred embodiment, the method includes combining a nucleophilic reactant, a prochiral or chiral cyclic substrate, and a non-racemic chiral catalyst as described herein, and maintaining the combination under conditions appropriate for the chiral catalyst to catalyze stereoselective opening of the cyclic substrate at the electrophilic atom by reaction with the nucleophilic reactant. In preferred embodiments, the chiral catalyst which is employed in the subject reaction is represented by the general formula: ##STR2## in which Z.sub.1, Z.sub.2, Z.sub.3 and Z.sub.4 each represent a Lewis base; the C.sub.1 moiety, taken with Z.sub.1, Z.sub.3 and M, and the C.sub.2 moiety, taken with Z.sub.2, Z.sub.4 and M, each, independently, form a heterocycle; R.sub.1, R.sub.2, R'.sub.1 and R'.sub.2 each, independently, are absent or represent a covalent substitution with an organic or inorganic substituent permitted by valence requirements of the electron donor atom to which it is attached, R.sub.40 and R.sub.41 each independently are absent, or represent one or more covalent substitutions of C.sub.1 and C.sub.2 with an organic or inorganic substituent permitted by valence requirements of the ring atom to which it is attached, or any two or more of the R.sub.1, R.sub.2, R'.sub.1, R'.sub.2 R.sub.40 and R.sub.41 taken together form a bridging substituent; with the proviso that C.sub.1 is substituted at at least one site by R.sub.1, R'.sub.1 or R.sub.41, and C.sub.2 is substituted at at least one site by R.sub.2, R'.sub.2 or R.sub.40, and at least one of R.sub.1, R'.sub.1 and R.sub.41 is taken together with at least one of R.sub.2, R'.sub.2 and R.sub.40 to form a bridging substituent so as to provide Z.sub.1, Z.sub.2, Z.sub.3 and Z.sub.4 as a tetradentate; M represents the late transition metal; and A represents a counterion or a nucleophile, wherein each R.sub.1, R.sub.2, R'.sub.1, R'.sub.2 R.sub.40 and R.sub.41 are selected to provide at least one stereogenic center in the tetradentate ligand. In exemplary embodiments, R.sub.1, R.sub.2, R'.sub.1 and R'.sub.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 --(CH.sub.2).sub.m --R.sub.7 ; each R.sub.40 and R.sub.41 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 --(CH.sub.2).sub.m --R.sub.7 ; R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; Z.sub.1, Z.sub.2, Z.sub.3 and Z.sub.4 are independently selected from the group consisting of nitrogen, oxygen, phosphorus, arsenic, and sulfur; and m is zero or an integer in the range of 1 to 8. For example, the catalyst can be represented by the general formula: ##STR3## in which the substituents R.sub.1, R.sub.2, Y.sub.1, Y.sub.2, X.sub.1, X.sub.2, X.sub.3 and X.sub.4 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 --(CH.sub.2).sub.m --R.sub.7, or any two or more of the substituents taken together form a carbocyle or heterocycle ring having from 4 to 8 atoms in the ring structure, with the proviso that at least one of R.sub.1, Y.sub.1, X.sub.1 and X.sub.2 is covalently bonded to at least one of R.sub.2, Y.sub.2, X.sub.3 and X.sub.4 to provide the .beta.-iminocarbonyls to which they are attached as a tetradentate ligand, and at least one of Y.sub.1 and Y.sub.2 is a hydrogen; R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle , or a polycycle; m is zero or an integer in the range of 1 to 8; M represents the late transition metal; and A represents a counterion or a nucleophile, wherein each of of the substituents R.sub.1, R.sub.2, Y.sub.1, Y.sub.2, X.sub.1, X.sub.2, X.sub.3 and X.sub.4, are selected such that the catalyst is asymmetric. For example, a preferred class of catalysts are represented by the general formula: ##STR4## in which the B.sub.1 moiety represents a diimine bridging substituent represented by --R.sub.15 --R.sub.16 --R.sub.17 --, wherein R.sub.15 and R.sub.17 each independently are absent or represent an alkyl, an alkenyl, or an alkynyl, and R.sub.16 is absent or represents an amine, an imine, an amide, a phosphoryl, a carbonyl, a silyl, an oxygen, a sulfur, a sufonyl, a selenium, a carbonyl, or an ester; each of B.sub.2 and B.sub.3 independently represent rings selected from a group consisting of cycloalkyls, cycloakenyls, aryls, and heterocyclic rings, which rings comprising from 4 to 8 atoms in a ring structure; Y.sub.1 and Y.sub.2 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 --(CH.sub.2).sub.m --R.sub.7, R.sub.12, R.sub.13, and R.sub.14 each independently are absent, or represent one or more covalent substitutions of B.sub.1, B.sub.2 and B.sub.3 with 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 --(CH.sub.2).sub.m --R.sub.7, wherein R.sub.12 can occur on one or more positions of --R.sub.15 --R.sub.16 --R.sub.17 --, or any two or more of the R.sub.12, R.sub.13, R.sub.14, Y.sub.1 and Y.sub.2 taken together form a bridging substituent; R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle , or a polycycle; m is zero or an integer in the range of 1 to 8; M represents a transition metal; and A represents a counterion or a nucleophile, wherein R.sub.12, R.sub.13, R.sub.14, Y.sub.1 and Y.sub.2 are selected such that the catalyst is asymmetric. In yet further preferred embodiments, the catalyst is a metallosalenate catalyst represented by the general formula: ##STR5## in which each of the substituents R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, Y.sub.1, Y.sub.2, X.sub.1, X.sub.2, X.sub.3, X.sub.4, X.sub.5, X.sub.6, X.sub.7, and X.sub.8, 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 --(CH.sub.2).sub.m --R.sub.7 ; or any two or more of the substituents taken together form a carbocycle or heterocycle having from 4 to 10 atoms in the ring structure; R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; m is zero or an integer in the range of 1 to 8; M represents a transition metal; and A represents a counterion or a nucleophile; wherein if R.sub.5 is absent, at least one of R.sub.1 and R.sub.2 is taken together with at least one of R.sub.3 and R.sub.4 to form a bridging substituent, and each of of the substituents of 106 are selected such that the salenate is asymmetric. Alternatively, the catalyst can have a tridentate ligand, such as the ligand represented by the general formula: ##STR6## in which Z.sub.1, Z.sub.2, and Z.sub.3 each represent a Lewis base; the E.sub.1 moiety, taken with Z.sub.1, Z.sub.2 and M, and the E.sub.2 moiety, taken with Z.sub.2, Z.sub.3 and M, each, independently, form a heterocycle; R.sub.80 and R.sub.81 each independently are absent, hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or --(CH.sub.2).sub.m --R.sub.7, or any two or more of the R.sub.80 and R.sub.81 substituents taken together form a bridging substituent; R.sub.7 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; m is zero or an integer in the range of 1 to 8; M represents a transition metal; and A represents a counteranion or a nucleophile, wherein the tridentate ligand is asymmetric. As described herein, the subject method can be used for carrying out enantioselective ring opening, diastereoselective ring opening (including kinetic resolution) as well as expanding a ring of a cyclic compound. |
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