A new catalytic cross-coupling approach for the synthesis of protected aryl and heteroaryl amidines

Organic Letters

Volumn 4, Issue 6, 2002, Pages 983-985

  Kusturin, Carrie L ^a   Liebeskind, Lanny S ^b   Neumann, William L ^a  

^a PFIZER INC   (United States)

^b EMORY UNIVERSITY   (United States)

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ARTICLE;

EID: 0012215670     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol025547s     Document Type: Article

References (14)

1. Patai, S.; Rappoport, Z. The Chemistry of Amidines and Imidates, Wiley: New York, 1991; Vol. 27.
2. Zablocki, J. A.; Miyano, M.; Garland, R.; Pireh, D.; Schretzman, L.; Rao, S. N.; Lindmark, R. J.; Panzer-Knodle, S. G.; Nicholson, N. S.; Taite, B. B.; Salyers, A. K.; King, L. W.; Campion, J. G.; Feigen, L. P. J. Med. Chem. 1993, 36, 1811. Greenhill, J. V.; Lue, P. In Amidines and Guanidines in Medicinal Chemistry, Progress in Medicinal Chemistry; Ellis, G. P., Luscombe, D. K., Eds.; Elsevier: New York, 1993; Vol. 30, Chapter 5, pp 203-326.
3. Zablocki, J. A.; Miyano, M.; Garland, R.; Pireh, D.; Schretzman, L.; Rao, S. N.; Lindmark, R. J.; Panzer-Knodle, S. G.; Nicholson, N. S.; Taite, B. B.; Salyers, A. K.; King, L. W.; Campion, J. G.; Feigen, L. P. J. Med. Chem. 1993, 36, 1811. Greenhill, J. V.; Lue, P. In Amidines and Guanidines in Medicinal Chemistry, Progress in Medicinal Chemistry; Ellis, G. P., Luscombe, D. K., Eds.; Elsevier: New York, 1993; Vol. 30, Chapter 5, pp 203-326.
4. For an excellent review, see: Yet, L. A Survey of Amidine Synthesis. Technical Report No. 3, Vol. 4, 2000; Albany Molecular Research, Inc., New York.
5. (a) Liebeskind, L. S.; Srogl, J. Org. Lett. 2002, 4, 979.
6. (b) Savarin, C.; Srogl, J. Liebeskind, L. S. Org. Lett. 2001, 3, 91.
7. (c) Liebeskind, L. S.; Sroel, J. J. Am. Chem. Soc. 2000, 122, 11260.
8. Bergeron, R. J.; McManis, J. S. J. Org. Chem. 1987, 52, 1700.
9. Low yields of cross-coupling products have been detected in the palladium-catalyzed copper carboxylate-mediated reactions of reagent 1 with 3-methoxyphenylboronic acid, but the reaction mixtures have proven difficult to optimize. β-Hydride elimination may divert the reaction manifold away from the desired cross-coupling chemistry. (equation presented)
10. 3 was purchased from Aldrich Chemical Co. and used as received.
11. It is possible that the solution aggregation hinders the transmetalation of heterocyclic boronic acids to the oxidative addition product of the Pd catalyst and thiomethyl reagent 2.
12. Vieweg, H.; Wagner, G. Pharm. 1983, 38, 170. Kent, D. R.; Cody, W. L.; Doherty, A. M. J. Pept. Res. 1998, 52, 201.
13. Vieweg, H.; Wagner, G. Pharm. 1983, 38, 170. Kent, D. R.; Cody, W. L.; Doherty, A. M. J. Pept. Res. 1998, 52, 201.
14. 3 (27 mg, 5 mol %, 10 mol % Pd), and TFP (43 mg, 7 × 5 mol %). Additional dioxane (10 mL) was added, and the reaction was heated at 65°C for 16 h; after radial chromatography (10/1 hexanes-ethyl acetate), 13 (200 mg, 80% yield) was obtained. Full details are contained in the Supporting Information.