HETEROCYCLES

Communication | Special issue | Vol. 80, No. 2, 2010, pp. 773-778
Received, 24th July, 2009, Accepted, 15th September, 2009, Published online, 16th September, 2009.
DOI: 10.3987/COM-09-S(S)73

■ Facile Synthesis and Ring-Opening of 4-(Tributylstannyl)pyrrolidine-2-carboxylates

Makoto Shimizu,* Hiromi Ando, Hitoshi Shibuya, and Iwao Hachiya

Department of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Tsu, Mie 514-8507, Japan

Abstract

On treatment of ethyl 2-(4-methoxyphenylimino)acetate with (E)-1-tert-butyldimethylsiloxy-3-tributylstannylalkenes in the presence of methanesulfonic acid (MsOH) at -78 °C, a ring-closing reaction proceeded to give 4-(tributylstannyl)pyrrolidine-2-carboxylates, while their ring-opening reaction was observed to give homoallylic amines under the influence of MsOH at -20 °C to room temperature.

Pyrrolidine derivatives have received considerable attention as useful synthetic units for a variety of biologically intriguing materials1 as well as useful catalysts for asymmetric synthesis.2 We have been interested in the formation of pyrrole and pyrrolidine derivatives in a regiocontrolled manner.3 We previously carried out a stereocontrolled addition of 1-tert-butyldimethylsiloxy-3-tributylstannylalkenes4 to 2-(4-methoxyphenylimino)acetate, and this reaction was applied to the synthesis of erythro-sphingosine (eq 1).5 During these investigations we encountered an interesting observation that under certain reaction conditions a ring-closing reaction proceeded to give 4-(tributylstannyl)pyrrolidine- 2-carboxylates (3) as a major product (eq 2).6

This paper describes synthesis and ring-opening reaction of 4-(tributylstannyl)pyrrolidine-2-carboxylates (3), where allylstannanes were successfully used for the first time in the [3+2] cycloaddition with imines.7 The initial examination was carried out to find the best acid activator for the formation of pyrrolidine- 2-carboxylates (3), and Table 1 summarizes the results.

Under the influence of Lewis acids, the reaction gave the addition product (4) in moderate to good yields along with the pyrrolidines (3) in low yields (entries 1-8), in which TMSOTf was found to be the best promoter for the formation of the homoallyic amine (4) (entry 7). In particular, the reaction carried out in the presence of TMSOTf in relatively polar solvents or for a long time gave selectively the homoallylic amine (4) (entries 6-8). These observations suggested that the pyrrolidines (3) might undergo a ring-opening reaction to give the homoallylic amines. In contrast to the cases with Lewis acids, use of protic acids induced the formation of pyrrolidine derivatives (3) more effectively (entries 9-15). Among the protic acids examined methanesulfonic acid was found to be the most effective to promote the formation of the pyrrolidine (3) in 64% isolated yield (entry 15).8 However, the pyrrolidine formation was found to have a limited generality. As can be seen from Table 1, the allylstannanes (2) (R = Me, n-Pr) gave the pyrrolidines (3) in low yields (entries 16 and 17), whereas formation of the pyrrolidine (3) was not observed with 2 (R = Ph, H), and instead, only the homoallylic amines (4) were obtained (entries 18 and 19).

We also examined use of other siloxyallylstannanes (2b,c). Both the TIPS and TBDPS derivatives (2b,c) gave the pyrrolidines (3ab,ac) in moderate yields, in which the TBDPS derivative recorded a good diastereoselectivity.

An interesting ring-opening reaction was observed with the 4-(tributylstannyl)pyrrolidine-2-carboxylates (3a,b). When the pyrrolidine (3a, R = Me) was treated with MsOH at -78 to -20 oC, the ring-opened homoallylic amine ((Z)-anti-4) was obtained.

The best yield (82%) was recorded in the reaction conducted at -78 to 0 oC. The same reaction with the diastereomer (3b, R = Me) at -78 oC to rt gave (Z)-anti-4 in 84% yield. These results coupled with the NOE experiments9 established the relative stereochemistry of the 4-(tributylstannyl)pyrrolidine- 2-carboxylates (3a,b).

A possible reaction pathway is depicted below. First, protonation at the imino nitrogen induces the addition of the allylstannan (2) to form a cation intermediate (B), which in turn undergoes a migration of tributylstannyl group to give another cation intermediate (C). Cyclization gives the pyrrolidine (3a) as a major product.

In conclusion, we have found an interesting formation of 4-(tributylstannyl)pyrrolidine-2-carboxylates from γ-siloxyallylstannan and α-iminoacetate, where use of protic acids is crucial for this cyclization. Owing to the relatively reactive stannyl moiety, an interesting ring-opening reaction of the cyclized products was also observed at an elevated temperature to give homoallylic amines. This opening reaction may be used for the stereoselective preparation of (Z)- homoallylic amines. Thus, the present procedure offers a useful addition to the existing methodologies for the synthesis of highly substituted pyrrolidine-2-carboxylates in a stereocontrolled manner.

References

1. (a) C. Najera and J. M. Sansano, Angew. Chem. Int. Ed., 2005, 44, 6272; CrossRef (b) M. I. Calaza and C. Cativiela, Eur. J. Org. Chem., 2008, 3427; CrossRef (c) M. Limbach, Chem. Biodiversity, 2005, 2, 825; CrossRef (d) Z. Shao, J, Chen, Y. Tu, L. Li, and H. Zhang, Chem. Commun., 2003, 1918. CrossRef
2. (a) H. Kotsuki, H. Ikishima, and A. Okuyama, Heterocycles, 2008, 75, 757; CrossRef (b) G. Guillena, C. Nájera, and D. J. Ramón, Tetrahedron: Asymm., 2007, 18, 2249; CrossRef (c) R. O. Duthaler, Angew. Chem. Int. Ed., 2003, 42, 975; CrossRef (d) H. Groeger and J. Wilken, Angew. Chem. Int. Ed., 2001, 40, 529. CrossRef
3. (a) I. Mizota, Y. Matsuda, I. Hachiya, and M. Shimizu, Org. Lett., 2008, 10, 3977; CrossRef (b) I. Mizota, Y. Matsuda, I. Hachiya, and M. Shimizu, Eur. J. Org. Chem., 2009, 4073. CrossRef
4. (a) J. A. Marshall, Chem. Rev., 1996, 96, 31; CrossRef (b) J. A. Marshall and G. S. Welmaker, J. Org. Chem., 1992, 57, 7158; CrossRef (c) M. Koreeda and Y. Takeda, Tetrahedron Lett., 1987, 28 143; CrossRef (d) G. E. Keck, D. E. Abbott, and M. R. Wiley, Tetrahedron Lett., 1987, 28 139. CrossRef
5. M. Shimizu, H. Ando, and Y. Niwa, Lett. Org. Chem., 2005, 2, 512. CrossRef
6. Similar cyclizations using allylsilanes, see: (a) N. Shindoh, H. Tokuyama, Y. Takemoto, and K. Takasu, Heterocycles, 2009, 77, 187; CrossRef (b) T. Akiyama, M. Sugano, and H. Kagoshima, Tetrahedron Lett., 2001, 42, 3889; CrossRef (c) S. Kiyooka, Y. Shiomi, H. Kira, Y. Kaneko, and S. Tanimori, J. Org. Chem., 1994, 59, 1958; CrossRef (d) J. S. Panek and N. F. Jain, J. Org. Chem., 1994, 59, 2674. CrossRef
7. [3+2] Cycloaddition using allylstannanes and α,β-unsaturated acylirons, see: (a) J. W. Herndon, C. Wu, J. J. Harp, and K. A. Kreutzer, Synlett, 1991, 1; CrossRef (b) J. W. Herndon and C. Wu, Synlett, 1990, 411. CrossRef
8. The following is a typical experimental procedure: Under an argon atmosphere, to a solution of the imine (1) (143 mg, 0.69 mmol) in CH2Cl2 (0.5 mL) was added a solution of MsOH (88.4 mg, 0.92 mmol) in CH2Cl2 (0.5 mL) at -78 oC. After being stirred for 10 min at -78 oC, a solution of (E)-2 (R = Me) (276 mg, 0.58 mmol) in CH2Cl2 (1.0 mL) was added at -78 oC, and the mixture was stirred at that temperature for 30 min. Sat. aq. NaHCO3 was added to quench the reaction, and the whole mixture was extracted with Et2O (10 mL x 3). After a usual work-up, the reaction mixture was purified on preparative silica gel TLC (n-Hex:AcOEt = 20:1) to give 3a (Rf = 0.26, 158 mg, 40%), 3b (Rf = 0.35, 95 mg, 24%), and 4 (Rf = 0.21, 63.8 mg, 28% as a mixture of diastereomers in a ratio of 65:35). 3a: Colorless oil. 1H NMR (500 MHz, CDCl3): δ = 0.08 (s, 3H), 0.11 (s. 3H), 0.76-0.89 (m, 24H, including a singlet at 0.88 ppm), 1.20-1.28 (m, 9H), 1.40-1.46 (m. 9H), 1.87 (t, 1H, J = 4.8 Hz), 3.71 (s 3H), 3.80-3.93 (m, 1H), 3.98-4.13 (m, 1H), 4.11-4.22 (m, 2H), 4.60 (t, 1H, J = 5.5 Hz), 6.38-6.42 (m, 2H), 6.78-6.83 (m, 2H). 13C NMR (126 MHz, CDCl3): δ = -4.3, -4.6, 9.3, 13.7, 14.2, 17,9, 20.4, 25.8, 25.9, 27.5, 29.2, 40.0, 55.8, 59.3, 60.7, 72.1, 80.5, 114.8, 115.1, 139.9, 151.3, 172.4. 3b: Colorless oil. 1H NMR (500 MHz, CDCl3): δ = 0.08 (s, 3H), 0.11 (s, 3H), 0.75-0.89 (m, 24H, including a singlet at 0.86 ppm), 1.20-1.28 (m, 9H), 1.50-1.59 (m. 9H), 1.52-1.67 (m, 1H), 3.71 (s 3H), 4.13-4.28 (m, 4H), 4.60 (br, 1H), 6.46-6.49 (m, 2H), 6.79-6.82 (m, 2H). 13C NMR (126 MHz, CDCl3): δ = -4.1, 8.5, 13.6, 21.5, 21.7, 22.0, 25.9, 27.5, 29.2, 49.3, 55.9, 58.3, 68.3, 69.7, 112.9, 114.8, 140.3, 150.9, 171.7.
9. The following NOEs were observed.