Computer-aided design of chiral ligands. Part 2. Functionality mapping as a method to identify stereocontrol elements for asymmetric reactions

Journal of Organic Chemistry

Volumn 68, Issue 6, 2003, Pages 2061-2076

  Kozlowski, Marisa C ^a   Panda, Manoranjan ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHIRAL LIGANDS;

CATALYSTS; COMPUTER AIDED DESIGN; MAPPING;

ORGANIC COMPOUNDS;

ALLYL COMPOUND; AMINE; BORONIC ACID DERIVATIVE; FUNCTIONAL GROUP; LIGAND; TARTARIC ACID DERIVATIVE;

ARTICLE; CATALYST; CHEMICAL REACTION; CHEMICAL STRUCTURE; CHIRALITY; COMPUTER AIDED DESIGN; DIELS ALDER REACTION; ENERGY; MOLECULAR INTERACTION; MOLECULAR STABILITY; STEREOCHEMISTRY; TECHNIQUE;

BORANES; CATALYSIS; COMPUTER-AIDED DESIGN; DRUG DESIGN; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; STEREOISOMERISM;

EID: 0037459732     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo020401s     Document Type: Article

References (93)

1. (a) Miranker, A.; Karplus, M. Proteins: Struct. Funct. Genet. 1991, 11, 29.
2. (b) For a related study see: Hart, T. N.; Read, R. J. Proteins: Struct. Funct. Genet. 1992, 13, 206.
3. (a) Caflisch, A.; Miranker, A.; Karplus, M. J. Med. Chem. 1993, 36, 2142.
4. (b) Zheng, Q.; Kyle, D. J. Proteins: Struct. Funct. Genet. 1994, 19, 29324.
5. (c) Ringe, D. Curr. Opin. Struct. Biol. 1995, 5, 825.
6. (d) Ringe, D. Protein Eng. 1995, 8, 111.
7. (e) Mattos C.; Ringe D. Nat. Biotechnol. 1996, 14, 595.
8. (f) Sezerman, U.; Vajda, S.; DeLisi, C. Protein Sci. 1996, 5, 1272.
9. (g) Laskowski, R. A.; Thornton, J. M.; Humblet, C.; Singh, J. J. Mol. Biol. 1996, 259, 175.
10. (h) Allen, K. N.; Bellamacina, C. R.; Ding, X. C.; Jeffery, C. J.; Mattos, C.; Petsko, G. A.; Ringe, D. J. Phy. Chem. 1996, 100, 2605.
11. (i) Caflisch A. J. Comput.-Aided Mol. Des. 1996, 10, 372.
12. (j) Grootenhuis, P. D. J.; Karplus, M. J. Comput-Aided Mol. Des. 1996, 10, 1.
13. (k) Joseph-McCarthy, D.; Fedorov, A. A.; Almo, S. C. Protein Eng. 1996, 9, 773.
14. (l) Joseph-McCarthy, D.; Hogle, J. M.; Karplus, M. Proteins 1997, 29, 32.
15. (m) Caflisch, A.; Walchli, R.; Ehrhardt, C. News Phys. Sci. 1998, 13, 182.
16. (n) Leclerc, F.; Karplus, M. Theor. Chem. Acc. 1999, 101,131.
17. (o) Castro, A.; Richards, W. G.; Lyne P. D. Med. Chem. Res. 1999, 9, 98.
18. (p) Stultz, C. M.; Karplus, M. Proteins 1999, 37, 512.
19. (q) English, A. C.; Groom, C. R.; Hubbard R. E. Protein Eng. 2001, 14, 47.
20. (r) Ahmed, S.; Majeux, N.; Caflisch A. J. Mol. Graphics Modell. 2001, 19, 307.
21. (s) Joseph-McCarthy, D.; Tsang, S. K.; Filman, D. J.; Hogle, J. M.; Karplus, M. J. Am. Chem. Soc. 2001, 123, 12758.
22. Papers in this series: (a) Kozlowski, M. C.; Panda, M. Computer-Aided Design of Chiral Ligands. Part I. Database Search Methods to Identify Chiral Ligand Types for Asymmetric Reactions. In J. Mol. Graphics Modell. 2002, 20, 399-409.
23. (b) Kozlowski, M. C.; Evans, Catherine A. Computer-Aided Design of Chiral Ligands. Part III. Novel Auxiliaries for Selective Boron Aldol and Allylation Reactions. In preparation.
24. For recent work on transition state placement in antibody binding sites, see: Tantillo, D. J.; Houk, K. N. J. Comput. Chem. 2002, 23, 84.
25. For cases in which the relative energies of the diastereomeric transition states incorporating the chiral ligands correlate to the experimentally measured product selectivity.
26. FUNMAP; G. Lauri, developed in the laboratory of Paul A. Bartlett, U. C. Berkeley. This program uses the same prinicples as the MCSS method of Miranker and Karplus (ref 1). FUNMAP was benchmarked by using the cases studied in ref la and was found to perform similarly.
27. (a) MacroModel V4.0, V5.0, V6.0, V6.5; Still, W. C.; Columbia University.
28. (b) Mohamdi, F.; Richards, N. G.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J. Comput. Chem. 1990, 11, 440.
29. Lauri, G.; Bartlett, P. A. J. Comput.-Aided Mol. Des. 1993, 8, 51.
30. CAVEAT V2.2; Bartlett, P. A.; U. C. Berkeley.
31. Aldol force field: (a) Bernardi, A.; Capelli, A. M.; Gennari, C. J. Org. Chem. 1990, 55, 3576.
32. (b) Bernardi, A.; Capelli, A. M.; Comotti, A.; Gennari, C.; Gardner, M.; Goodman, J. M.; Paterson, I. Tetrahedron 1991, 47, 3471.
33. (c) Bernardi, A.; Cassinari, A.; Comotti, A.; Gardner, M.; Gennari, C.; Goodman, J. M.; Paterson, I. Tetrahedron 1992, 48, 4183.
34. (d) Gennari, C.; Vieth, S.; Comotti, A.; Vulpetti, A.; Goodman, J. M.; Paterson, I. Tetrahedron 1992, 48, 4439.
35. (e) Vulpetti, A.; Bernardi, A.; Gennari, C.; Goodman, J. M.; Paterson, I. Tetrahedron 1993, 49, 685.
36. Allylation force field: (f) Vulpetti, A.; Gardner, M.; Gennari, C.; Bernardi, A.; Goodman, J. M.; Paterson, I. J. Org. Chem. 1993, 58, 1711.
37. For a further description of these transition states and for a discussion of stereodiscriminating groups, see ref 3a.
38. The Diels-Alder transition state parameters included in MacroModel 6.5 were used to obtain the MM2* transition states. See Supporting Information.
39. Panda, M.; Kozlowski, M. C. Unpublished results. HF/3-21G transition states were located with Gaussian98: Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, J. V.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.6; Gaussian, Inc.: Pittsburgh, PA, 1998.
40. Panda, M.; Kozlowski, M. C. Unpublished results. HF/3-21G transition states were located with Gaussian98: Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, J. V.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.6; Gaussian, Inc.: Pittsburgh, PA, 1998.
41. Charges for the HF/3-21G transitions states were obtained by single point calculations in MacroModel. The charge distribution was not found to significantly alter the results for the cases in this paper, but more accurate charges may be needed with other probes and targets.
42. Surface points were generated with the MS program of Connolly: (a) Connolly, M. L. J. Mol. Graphics 1993, 11, 139.
43. (b) The molecular surface program (MS) was obtained separately from the Quantum Chemistry Program Exchange (QCPE No. 429; http://qcpe.chem.indiana.edu).
44. Parameters need to be specified for FUNMAP to determine which portions of the target are used for the minimization and/or allowed to move during the minimization of the probes. In this case, the entire target structure was utilized in generating the nonbonded interactions with the probes and the target structure was held fixed.
45. The CPU time required to run the FUNMAP program on an SGI Octane (R10,000) with 100 probes and the transition states described in the text ranged from 1 min to 2 h. See Supporting Information.
46. (a) Nogradi, M. Stereoselective Synthesis: A Practical Approach, 2nd ed.; VCH: Weinheim, Germany, 1995.
47. (b) Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-Verlag: Berlin, Germany, 1999; Vols. I-III.
48. For lead references: Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, UK, 1991; Vol. 2 (Heathcock, C. H., Volume Ed.).
49. (a) Li, Y.; Paddon-Row, M. N.; Houk, K. N. J. Am. Chem. Soc. 1988, 110, 3684.
50. (b) Li, Y.; Paddon-Row, M. N.; Houk, K. N. J. Org. Chem. 1990, 55, 481 and references therein.
51. (c) Bernardi, F.; Robb, M. A.; Suzi-Valli, G.; Tagliavini, E.; Tromboni, C.; Umani-Ronchi, A. J. Org. Chem. 1991, 56, 6472.
52. For the design of the dimenthylborane aldol chiral auxiliary see: (a) Gennari, C.; Hewkin, C. T.; Molinari, F.; Bernardi, A.; Comotti, A.; Goodman, J. M.; Paterson, I. J. Org. Chem. 1992, 57, 5173.
53. (b) Paterson, I. Pure Appl. Chem. 1992, 64, 1821.
54. (c) Gennari, C.; Moresca, D.; Vieth, S.; Vulpetti, A. Angew. Chem., Int. Ed. Engl. 1993, 32, 1618.
55. (d) Bernardi, A.; Comotti, A.; Gennari, C.; Hwekin, C. T.; Goodman, J. M.; Schlapbach, A.; Paterson, I. Tetrahedron 1994, 50, 1227.
56. (e) Bernardi, A.; Gennari, C.; Goodman, J. M.; Paterson, I. Tetrahedron: Asymmetry 1995, 6, 2613.
57. (f) Gennari, C. Pure Appl. Chem. 1997, 69, 507.
58. (g) Gennari, C.; Ceccarelli, S.; Piarulli, U.; Aboutayab, K. J. Braz. Chem. Soc. 1998, 9, 319.
59. For examples in other systems see: Transition State Modeling for Catalysis; ACS Symp. Ser. No. 721: Truhlar, D. G., Morokuma, K., Eds.; American Chemical Society: Washington, DC, 1999; and references contained therein.
60. (a) Masamune, S.; Sata, T.; Kim, B. M.; Wollmann, T. A. J. Am. Chem. Soc. 1986, 108, 8279.
61. (b) For the related diphenylborolane in aldol reactions see: Reetz, M. T.; Heitmann, P. Tetrahedron Lett. 1986, 27, 4721.
62. For an example of the correlation of the reaction selectivity with calculated transition state energies for the Masamune dimethylborolane see ref 9c.
63. Very little change in the geometry of the core portion of the transition state occurred upon minimization, indicating that the ligand induces very little strain into this structure.
64. In contrast, the OSVM, FMNR, and SD gradients effect a more thorough search of the potential energy surface environment and identify shallower minima. This trend is confirmed by the wider range of interaction energies exhibited by the clusters when these gradients were employed (see Supporting Information). Similar trends were also observed for other functional group probes such as benzene, methyl acetate, and methyl formate. In terms of utility, the TNCG and PRCG gradients were found to provide the best compromise between identification of all sites of interaction and identification of the most favorable interaction sites.
65. Corey, E. J.; Imwinkelried, R.; Pikul, S.; Xiang, Y. B. J. Am. Chem. Soc. 1989, 111, 5493.
66. 2CHO) and diethyl ketone examined experimentally by Corey where a 99:1 ratio was observed (see ref 26).
67. For a review see ref 17a; pp 162-167.
68. A number of highly selective reagents for aymmetric allylboration of achiral aldehydes have been reported. (a) Hoffmann, R. W.; Herold, T. Chem. Ber. 1981, 114, 375.
69. (b) Hoffmann, R. W.; Helbig, W. Chem. Ber. 1981, 114, 2802.
70. (c) Hoffmann, R. W.; Zeiss, H. J.; Ladner, W.; Tabche, S. Chem. Ber. 1982, 115, 2357.
71. (d) Reetz, M. T.; Zierke, T. Chem. Ind. (Britain) 1988, 20, 663.
72. (e) Corey, E. J.; Yu, C. M.; Kim, S. S. J. Am. Chem. Soc. 1989, 111, 5495.
73. (f) Jadhav, P. K.; Bhat, K. S.; Perumal, P. T.; Brown, H. C. J. Org. Chem. 1986, 51, 432.
74. (g) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919.
75. (h) Brown, H. C.; Jadhav, P. K.; Bhat, K. S. J. Am. Chem. Soc. 1988, 110, 1538.
76. (i) Brown, H. C.; Jadhav, P. K.; Bhat, K. S. J. Am. Chem. Soc. 1988, 110, 1535.
77. (j) Brown, H. C.; Ramachandran, P. V. Pure Appl. Chem. 1991, 63, 307.
78. (k) Garcia, J.; Kim, B. M.; Masamune, S. J. Org. Chem. 1987, 52, 4831.
79. (l) Short, R. P.; Masamune, S. J. Am. Chem. Soc. 1989, 111, 1892. See also ref 18.
80. (a) Roush, W. R.; Walts, A. E.; Hoong, L. K. J. Am. Chem. Soc. 1985, 107, 8186.
81. (b) Roush, W. R.; Banfi, L. J. Am. Chem. Soc. 1988, 110, 3979.
82. (c) Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.; Park, J. C. J. Org. Chem. 1990, 55, 4109.
83. (d) Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.; Straub, J. A.; Palkowitz, A. D. J. Org. Chem. 1990, 55, 4117.
84. (e) Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A.; Halterman, R. L. J. Am. Chem. Soc. 1990, 112, 6339.
85. Roush, W. R.; Ratz, A. M.; Jablonowski, J. A. J. Org. Chem. 1992, 57, 2047.
86. Using these models, Roush et al. have designed improved chiral auxiliaries: (a) Roush, W. R.; Banfi, L. J. Am. Chem. Soc. 1988, 110, 3979.
87. (b) Roush, W. R.; Grover, P. T. J. Org. Chem. 1995, 60, 3806.
88. 3CHO and PhCHO, as well as for the addition of the (-)-2,3-butanediol allylboronate to PhCHO. The product ratios calculated from the transition state energies qualitatively agree with the experimentally measured selectivities: Kozlowski, M. C.; Ganguly, B.; Panda, M.; Skudlarek, J. W. Tetrahedron. Submitted for publication.
89. If the methyl substituents destabilize one of the transition states (disfavorable interactions), then there should be no methanes from the functionality mapping matching the ligand methyl substituents in that transition state. This is not the case for (-)-2,3-butanediol since there is a similar level of matching for 5(si) and the map of E(si) compared to 5(re) and the map of E(re).
90. Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243.
91. For a further discussion as well as listings of transition state energies and structures, see the Supporting Information.
92. The α,β-unsaturated iminium portion of the most stable transition structure is very similar to the most stable ground-state iminium structure identified by MacMillan et al. As a result, the rationale to explain the selectivity by using the transition structures is analogous to that invoked for the ground states (ref 35).
93. Lii, J.-H.; Allinger, N. L. J. Am. Chem. Soc. 1989, 111 8576.