HETEROCYCLES

Communication | Special issue | Vol. 77, No. 1, 2009, pp. 187-192
Received, 13th May, 2008, Accepted, 27th June, 2008, Published online, 30th June, 2008.
DOI: 10.3987/COM-08-S(F)17

■ Triflic Imide Catalyzed [3+2] Cycloaddition of Aldimines with α,α-Dimethylallylsilane

Naoya Shindoh, Hidetoshi Tokuyama, Yoshiji Takemoto,* and Kiyosei Takasu*

Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-machi, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Tf₂NH-catalyzed [3 + 2] cycloaddition of N-aryl imines with α,α-dimethylallylsilane to give substituted pyrrolidines is described. We have found the mode of cycloaddition depends upon α-substituents of allylsilanes.

Triflic imide (Tf2NH), which is recognized as a super Brønsted acid,1 catalyzes several classes of C-C bond formation reactions.2 We have shown Tf2NH efficiently activates imines in hetero Diels-Alder reaction of imines with 2-siloxydienes.3,4 Moreover, we have recently reported Tf2NH-catalyzed cascade hetero Diels-Alder and hydrogen transfer reaction.5 Namely, treatment of N-aryl imine (1) with allylsilane (2) in the presence of a catalytic amount of Tf2NH afforded substituted quinoline (4) in a single operation along with amine (5). Notably, in the cascade reaction Tf2NH activates two mechanistically distinct reactions, such as hetero Diels-Alder reaction of 1 with 2 and hydrogen transfer between produced tetrahydroquinoline (3) and imine (1) (Scheme 1). During the course of our study, we observed that reaction of 1 with α,α-dimethylallylsilane in the presence of Tf2NH furnished, unexpectedly, not

quinolines but substituted pyrrolidines. In this communication, we wish to describe the Tf2NH catalyzed [3+2] cycloaddition of imines with α,α-dimethylallylsilane.
α,α-Dimethylallylsilane (8) bearing tert-butyldimethylsilyl (TBS) moiety was prepared by Wittig reaction of α-silylisobutyraldehyde (7), which was synthesized from acetaldehyde tert-butylimine (6) in 3 steps,6 in 83% yield (Scheme 2). Imines (1a-1h) were prepared from the corresponding aldehydes and anilines according to a reported procedure.7

First of all, reaction of 1a (3 equiv) with 8 (1 equiv) was attempted for the purpose of preparation of quinoline (9) under the reported conditions.5 As the result, neither 9 nor tetrahydroquinoline was observed, but formation of substituted pyrrolidine (10a), which corresponds to a [3+2] cycloadduct, was obtained in 77% yield (Scheme 3). When a mixture of 1a and 8 (molar ratio = 1 : 1.2) was treated with a catalytic amount of Tf2NH (10 mol%) in toluene at 60 oC for 24 h, 10a was obtained in 84% yield as a 3 : 2 mixture of diastereomers (Table 1, entry 1). In 1,2-dichloroethane, which has been reported to be an appropriate solvent for the Tf2NH-catalyzed hetero Diels-Alder reaction,5 [3+2] cycloaddition also promoted to furnish 10a in 76% yield (entry 2). 1H NMR spectra of each diastereomer of 10a,8 in which two sets of doublet peaks derived from p-trifluoromethylaniline moiety were observed, ruled out production of [4+2] cycloadducts, such as tetrahydroquinoline or quinoline (9). Careful recrystalization of a diastereomeric mixture of 10a from MeOH gave single crystals of cis-10a, which corresponds to the major diastereomer. The structure of cis-10a was confirmed unambiguously by an X-ray analysis (Figure 1).9 As shown in Table 1, benzylidene and heteroarylidene imines except for 2-pyridylidene imine (1e) underwent [3+2] cycloaddition to give substituted pyrrolidines (10) in 44―94% yield. All products were obtained as a diastereomeric mixture (cis : trans = 1 : 1 ― 3 : 2). In the reaction of 1b, homoallylamine (11b) was obtained in 27% yield along with 10b (entry 3). Since almost no formation of 11b was observed at the early stage of the reaction, not Hosomi-Sakurai type allylation to 1b10 but decomposition of 10b via β-silyl carbocation intermediate would cause formation of 11b. Actually, treatment of isolated 10b with Tf2NH (10 mol%) in refluxing toluene afforded 11b exclusively. Reaction of α,β-unsaturated imine (1h) was unsuccessful only to give a mixture of unidentified compounds (entry 10). We have assessed the multicomponent variant starting from three materials: an allylsilane, an aldehyde and an aniline (Scheme 4). Treatment of a mixture of 8, p-tolylaldehyde (12) and p-trifluoromethylaniline (13) (molar ratio = 1.2 : 1 : 1) with 10 mol% of Tf2NH in toluene furnished the desired pyrrolidine (10a) in 78% yield as a 3 : 2 mixture of diastereomers.

In sharp contrast to our previous results,5 the mode of cycloaddition depends upon α-substitution of the allylsilane. A plausible mechanism for reactions of imines with allylsilanes is outlined in Figure 2. With α-nonsubstituted allylsilane (2), [4+2] cycloaddition took place to give tetrahydroquinolines 3 through a stepwise manner. Namely, SE2’ reaction of 2 to imine (1) in the presence of Tf2NH would afford β-silyl cation intermediate (14), and then intramolecular addition of the aromatic carbon of 14 would promote to furnish [4+2] cycloadduct (3) (mode a). If intramolecular addition of the nitrogen atom of 14 takes place, azetidine (15) would be produced (mode b). In contrast, in the reaction with α,α-disubstituted allylsilane (8), intermediate (14) would transform into more stable β-silyl cation (16) or siliranium cation (17) by 1,2-silyl shift or silacyclopronation, respectively.11 Then, intramolecular addition of the nitrogen atom of 16 or 17 would afford [3+2] cycloadduct (10) (mode c).

Although several studies on cycloaddition reactions of imines with allylsilanes have been reported,12—15 studies to control modes of the cyloadditions are quite limited. Akiyama and his co-workers described [3+2] cycloaddition of N-sulfonyl imines with triisipropylsilylpropene in the presence of a stoichiometric amount of BF3-OEt2,13d whereas N-acyl and N-aryl imines took place [2+2]14 and [4+2] cycloadditions,15 respectively. They concluded N-substituent of imines would be a control factor in the selective formation of [2+2], [3+2], or [4+2] cycloadducts. Our abovementioned study indicates α-substitution of allylsilane is one of factors to control the mode of cycloaddition of N-aryl imines with allylsilanes.
In conclusion, reaction of imines with α,α-dimethylallylsilane in the presence of Tf2NH provides substituted pyrrolidines by [3+2] cycloaddition. We found the mode of cycloaddition depends upon α-substituents of allylsilanes. It is noteworthy that, to the best of our knowledge, it is the first example to achieve the catalytic [3+2] cycloaddition of imines with allylsilanes.

ACKNOWLEDGEMENTS
This work was financially supported by a Grant-in-Aid for Scientific Research and Targeted Proteins Research Program from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

This paper is dedicated to Professor Emeritus Keiichiro Fukumoto on the occasion of his 75th birthday.

References

1. H. Yamamoto and M. B. Boxer, Chimia, 2007, 61, 279. CrossRef
2. Recent representative examples, see: (a) K. Ishihara, Y. Hiraiwa, and H. Yamamoto, Synlett, 2001, 1851; CrossRef (b) J. Cossy, F. Lutz, V. Alauze, and C. Meyer, Synlett, 2002, 45; CrossRef (c) L. Zhang and S. A. Kozmin, J. Am. Chem. Soc., 2004, 126, 10204; CrossRef (d) K. Inanaga, K. Takasu, and M. Ihara, J. Am. Chem. Soc., 2005, 127, 3668; CrossRef (e) K. Takasu, S. Nagao, and M. Ihara, Adv. Synth. Catal., 2006, 348, 2376; CrossRef (f) K. Takasu, N. Hosokawa, K. Inanaga, and M. Ihara, Tetrahedron Lett., 2006, 47, 6053; CrossRef (g) M. B. Boxer and H. Yamamoto, J. Am. Chem. Soc., 2006, 128, 48; CrossRef (h) M. E. Jung and D. G. Ho, Org. Lett., 2007, 9, 375; CrossRef (i) K. Takasu, J. Syn. Org. Chem., Jpn., 2008, 66, 554.
3. A review of C-C bond formation reactions in the presence of a catalytic amount of Brønsted acids, see: T. Akiyama, Chem. Rev., 2007, 107, 5744. CrossRef
4. K. Takasu, N. Shindoh, H. Tokuyama, and M. Ihara, Tetrahedron, 2006, 62, 11900. CrossRef
5. N. Shindoh, H. Tokuyama, and K. Takasu, Tetrahedron Lett., 2007, 48, 4749. CrossRef
6. L. F. Tietze, T. Neumann, M. Kajino, and M. Pretor, Synthesis, 1995, 1003. CrossRef
7. A. Simion, C. Simion, T. Kanda, S. Nagashima, Y. Mitoma, T. Yamada, K. Mimura, and M. Tashiro, J. Chem. Soc., Perkin Trans. 1, 2001, 2071. CrossRef
8. Spectral data for cis-10a; Mp 169-170 °C (colorless pillars from MeOH); IR (KBr) 2953, 2854, 1613, 1523, 1324 cm^-1; ¹H NMR (400 MHz, CDCl₃) δ 7.23 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.67 (d, J = 8.0 Hz, 2H), 4.74 (dd, J = 10.3, 6.3 Hz, 1H), 2.41 (ddd, J = 12.3, 6.3, 5.5 Hz, 1H), 2.40 (s, 3H), 1.78 (ddd, J = 14.9, 12.3, 10.3 Hz, 1H), 1.64 (s, 3H), 1.54 (dd, J = 14.9, 5.5 Hz, 1H), 0.92 (s, 9H), 0.19 (s, 3H), 0.02 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 147.8, 140.9, 136.4, 129.4, 125.9, 125.2 (q, ³J_(C,F) = 3.6 Hz), 124.0, 123.0 (q, ¹J(_(C,F) = 269.9 Hz), 117.7 (q, ²J(_(C,F) = 32.4 Hz), 116.3, 66.7, 65.6, 39.7, 38.5, 27.5, 27.1, 26.8, 21.1, 17.2, -4.7, -6.0; LRMS (FAB) m/z 447 (M⁺), for trans-10b; ¹H NMR (400 MHz, CDCl₃) δ 7.29 (d, J = 8.8 Hz, 2H), 7.09 (m, 4H), 6.63 (d, J = 8.8 Hz, 2H), 4.74 (m, 1H), 2.42 (m, 1H), 2.31 (s, 3H), 1.88 (dd, J = 12.4, 5.1 Hz, 1H), 1.81 (s, 3H), 1.66 (m, 1H), 1.49 (s, 3H), 0.75 (s, 9H), 0.18 (s, 3H), 0.03 (s, 3H).
9. Crystal data for cis-10a. C₂₆H₃₆F₃NSi, monoclinic, space group P2₁/n, a = 13.8584(3) Å, b = 9.9621(2) Å, c = 17.7342 Å, β = 91.7284(9)°, V= 2447.25(8) ų, Z = 4, Dcalc = 1.215 g/cm³, R = 0.050, R_w = 0.064, GOF = 1.416.
10. Y. Yamamoto and N. Asao, Chem. Rev., 1993, 93, 2207. CrossRef
11. We have reported [3 + 2] cycloaddition of acrylates with allylsilanes through formation of similar intermediates, see: ref 2f.
12. For reviews of cycloaddition of allylsilanes, see: (a) C. E. Masse and J. S. Panek, Chem. Rev., 1995, 95, 1293; CrossRef (b) H.-J. Knölker, J. Prakt. Chem., 1997, 339, 304. CrossRef
13. (a) J. S. Panek and F. Jain, J. Org. Chem., 1994, 59, 2674 ; CrossRef (b) A. Stahl, E. Steckhan, and M. Nieger, Tetrahedron Lett., 1994, 35, 7371; CrossRef (c) J. V. Schaus, N. Jain, and J. S. Panek, Tetrahedron, 2000, 56, 10263; CrossRef (d) T. Akiyama, M. Sugano, and H. Kagoshima, Tetrahedron Lett., 2001, 42, 3889. CrossRef
14. T. Uyehara, M. Yuuki, H. Masaki, M. Matsumoto, M. Ueno, and T. Sato, Chem. Lett., 1995, 24, 789. CrossRef
15. T. Akiyama, M. Suzuki, and H. Kagoshima, Heterocycles, 2000, 52, 529. CrossRef