Heck arylation of endocyclic enecarbamates with diazonium salts. Improvements and a concise enantioselective synthesis of (-)-codonopsinine

Organic Letters

Volumn 2, Issue 20, 2000, Pages 3039-3042

  Severino, Elias A ^a   Correia, Carlos Roque D ^a  

^a UNIVERSITY OF CAMPINAS   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

CODONOPSININE; DIAZONIUM COMPOUND; PYRROLIDINE DERIVATIVE;

ALKYLATION; ARTICLE; CHEMISTRY; GAS CHROMATOGRAPHY; STEREOISOMERISM; SYNTHESIS; THIN LAYER CHROMATOGRAPHY;

ALKYLATION; CHROMATOGRAPHY, GAS; CHROMATOGRAPHY, THIN LAYER; DIAZONIUM COMPOUNDS; PYRROLIDINES; STEREOISOMERISM;

EID: 0034609706     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol005762d     Document Type: Article

References (26)

1. 1H NMR coupling constants. The correct stereochemistry of codonopsinine was established by C. Kibayashi in 1986. For details, see: Iida, H.; Yamazaki, N.; Kibayashi, C. Tetrahedron Lett. 1986, 27, 5393.
2. For previous syntheses of codonopsinine and codonopsine, see: (a) Yoda, H.; Nakajima, T.; Takabe, K. Tetrahedron Lett. 1996, 37, 5531.
3. (b) Wang, C. L. J.; Calabrese, J. C. J. Org. Chem. 1991, 56, 4341.
4. (c) Iida, H.; Yamazaki, N.; Kibayashi, C. J. Org. Chem. 1987, 52, 1956.
5. (d) Iida, H.; Yamazaki, N.; Kibayashi, C. Tetrahedron Lett. 1985, 26, 3255. This last reference actually marks the first total synthesis of the unnatural (+)-codonopsinine. However, the stereochemical representation for (+)-codonopsinine made in this work was latter revised; see ref 1.
6. Reviews on the Heck reaction: (a) Shibasaki, M.; Vogl, E. M. J. Organomet. Chem. 1999, 576, 1.
7. (c) Crisp, G. T. Chem. Soc. Rev. 1998, 27, 427.
8. (c) Shibasaki, M.; Boden, D. J.; Kojima, A. Tetrahedron 1997, 53, 7371.
9. (d) Negishi, E.; Coperet, C.; Ma, S; Liou, S. Y.; Liu, F. Chem. Rev. 1996, 96, 365.
10. (e) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 36, 2379.
11. (f) Cabri, W.; Candiani, E. Acc. Chem. Res. 1995, 28, 8.
12. Oliveira, D. F.; Severino, E. A.; Correia, C. R. D. Tetrahedron Lett. 1999, 40, 2083.
13. Oliveira D. F.; Miranda, P. C. M. L.; Correia, C. R. D. J. Org. Chem. 1999, 64, 6646. In more recent experiments, the endocyclic enecarbamate 4 was obtained after three steps in 85% overall yield from the commercially available (S)-(+)-5-(trityloxymethyl)-2-pyrrolidinone using the protocol described therein.
14. Recently, Tietze and Ferraccioli reported on a Heck reaction of a five-membered endocyclic enecarbamate under Jeffrey conditions that afforded a 1.2:1 ratio of regioisomeric Heck products in 63% yield. See: Tietze, L. F.; Ferraccioli, R. Synlett 1998, 145.
15. (a) Ozawa, F.; Hayashi, T. J. Organomet. Chem. 1992, 428, 267.
16. (b) Nilsson, K.; Hallberg, A. J. Org. Chem. 1990, 55, 2464.
17. (c) Loiseleur, O.; Meier, P.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1996, 35, 200.
18. The Heck products are obtained as homogeneous material by TLC. Capillary gas chromatography and HPLC were ineffective to resolve the two diastereomers. Capillary GC led to significant decomposition, and HPLC (hexanes/EtOAc) provided only partial resolution of the two diastereomers.
19. 3·dba was obtained according to the procedure described in Takahashi, Y.; Ito, Ts.; Ishii, Y. J. Chem. Soc. Chem. Commun. 1970, 1065.
20. After much experimentation, these were conditions we have found optimum for the Heck arylation of endocyclic enecarbamates with diazonium salts. These were conditions almost identical to those previously reported by Matsuda to perform Heck arylation of cyclic olefins with diazonium salts (see: Kikukawa, K.; Nagira, K.; Matsuda, T. Tetrahedron 1981, 37, 31). However, they reported that these conditions gave poor results when applied to enamines and to some other cyclic olefins. Preliminary results from our laboratory indicate that these conditions could be applied to six- and seven-membered ring enecarbamates with good yields. Moreover, the nature of the functional group at C5 of the five-membered enecarbamates plays a critical role in the diastereoselectivity of the Heck arylation. These results should be reported in due course.
21. f = 0.22; hexane:EtOAc; 3:1).
22. This large difference in retention factors led us to a previous incorrect conclusion about the diastereoselectivity of the Heck arylation (see ref 4). The Heck arylation, although stereoselective (90:10), gives a mixture of two diastereomers. After deprotection, chromatography on silica gel furnishes the trans aryl-3-pyrroline 7a as a pure compound as analyzed by capillary GC and HPLC.
23. The synthesis of codonopsine 2 by Wang and Calabrese relied on a diastereomeric mixture (1.3:1 ratio) of 3-pyrrolines very similar to ours. See: Wang, C. L. J.; Calabrese, J. C. J. Org. Chem. 1991, 56, 4341.
24. Three epoxidizing agents were tested: m-CPBA, dimethyldioxirane (DMD), and magnesium monperoxyphthalate (MMPP). A period of 24 h was necessary for the epoxidation of 8 with 5 equiv of m-CPBA (90% conversion). DMD epoxidation was much faster (10 equiv of DMD, acetone, 0 °C, 3.5 h or at room temperature for 2.5 h), resulting in the same diastereomeric mixture (∼90:10), but in somewhat lower yields (55-61%). MMPP provided results very similar to those obtained with m-CPBA.
25. 1H NMR spectra complex. Nevertheless, we have noticed in several instances a good correlation between the vicinal coupling involving H4 and H5 and the stereochemistry of substituted pyrrolidines and proline systems. Large coupling constants are associated with eis H4-H5, whereas smaller coupling constants (between 0 and 4 Hertz) are associated with trans H4-H5. For a full analysis of related systems (3,4-epoxyprolines), see: Robinson, J. K.; Lee, V.; Claridge, T. D. W.; Baldwin, J. E.; Schofield, C. J. Tetrahedron 1998, 54, 981.
26. 4 concentrated in a ratio of 3/2/0.2 mL. Higher concentrations of the acid (3/2/0.5 mL) led to a diastereomeric diol whose structure was not determined yet. Basic hydrolysis of epoxide 9a (DMSO/KOH 10% solution, 90-100 °C, 15 h) provided trans diol 10 in ∼ 40% yield.