Nucleophilic addition to 3-substituted pyridinium salts: Expedient syntheses of (-)-L-733,061 and (-)-CP-99,994

Organic Letters

Volumn 6, Issue 20, 2004, Pages 3517-3520

  Lemire, Alexandre ^a   Grenon, Michel ^a   Pourashraf, Mehrnaz ^a   Charette, André B ^a  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

3 (2 METHOXYBENZYLAMINO) 2 PHENYLPIPERIDINE; 3 [3,5 BIS(TRIFLUOROMETHYL)BENZYLOXY] 2 PHENYLPIPERIDINE; BENZAMIDE DERIVATIVE; PYRIDINE DERIVATIVE; PYRIDINIUM DERIVATIVE; SUBSTANCE P;

ADDITION REACTION; ARTICLE; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOSELECTIVITY; STRUCTURE ANALYSIS; SUBSTITUTION REACTION;

MOLECULAR STRUCTURE; PIPERIDINES; PYRIDINIUM COMPOUNDS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTANCE P;

EID: 6444238793     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol048624n     Document Type: Article

References (38)

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22. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
23. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
24. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
25. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
26. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
27. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
28. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
29. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
30. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
31. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
32. For examples of addition of organomagnesium reagents to N-acyl 3-substituted pyridinium salts, see: (a) Chia, W.-L.; Shen, S.-W.; Lin, H.-C. Tetrahedron Lett. 2001, 42, 2177-2179. (b) Comins, D. L.; Myoung, Y. C. J. Org. Chem. 1990, 55, 292-298. (c) Comins, D. L.; Mantlo, N. B. Tetrahedron Lett. 1987, 28, 759-762. (d) Krow, G. R.; Cannon, K. C.; Carey, J. T. J. Heterocycl. Chem. 1985, 22, 131-135. (e) Comins, D. L.; Mantlo, N. B. J. Heterocycl. Chem. 1983, 20, 1239-1243. (f) Comins, D. L.; Abdullah, A. H. J. Org. Chem. 1982, 47, 4315-4319. (g) Lyle, R. E.; Marshall, J. L.; Comins, D. L. Tetrahedron Lett. 1977, 18, 1015-1018. For examples of addition of organotin reagents leading to 1,2-dihydropyridines, see: (h) Itoh, T.; Hasegawa, H.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron 1994, 50, 13089-13100. (i) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1988, 53, 3507-3512. (j) Yamaguchi, R.; Hata, E.-I.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1785-1788. (k) Yamaguchi, R.; Moriyasu, M.; Yoshioka, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287-288.
33. For example, the addition of PhMgCl to N-acyl-3-picolinium salt (analogue to entry 2) gives a 16:66:15 mixture of C2:C6:C4 nucleophilic addition regioisomers (ref 17f).
34. For the preparation of amide 17 and its use in the stereoselective synthesis of 1,2-dihydropyridines, see ref 14.
35. See Supporting Information for details.
36. Use of 1.1 equiv of NaHMDS resulted in the exclusive formation of the bis-Boc-protected pyridine in 42% yield (50% max yield); see Supporting Information.
37. Demethylation of the aromatic methyl ether occurred during the amidine reduction step.
38. Basha, A.; Lipton, M.; Weinreb, S. M. Tetrahedron Lett. 1977, 18, 4171-4172.