ORGANIC LETTERS
Synthesis of Spirocarbamate Oxindoles via Intramolecular Trapping of a β‑Silyl Carbocation by an N-Boc Group
2013 Vol. 15, No. 13 3218–3221
Benjamin H. Shupe, Emily E. Allen, Jacob P. MacDonald, Sean O. Wilson, and Annaliese K. Franz* Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, United States
[email protected] Received April 19, 2013
ABSTRACT
We report the Lewis acid catalyzed additions of allylsilanes to N-Boc-iminooxindoles and the formation of novel silicon-containing spirocarbamates via intramolecular trapping of a β-silyl carbocation by an N-Boc group. Several transformations display the synthetic utility of these spirocarbamate oxindoles, including a reductive cyclization to access new silylated furoindoline derivatives.
Synthetic interest in spirooxindoles has increased over the past decade due to the notable biological activity and occurrence of this class of heterocycles in natural products and pharmaceutical lead compounds.1 Recent synthetic methods to access spirocyclic 3-aminooxindoles have utilized preformed iminooxindoles2 and in situ generated iminium ions3 in various spirocyclization strategies; however, allylsilanes have not previously been investigated for annulations of iminooxindoles. Based on the steric and (1) For reviews, see: (a) Ball-Jones, N. R.; Badillo, J. J.; Franz, A. K. Org. Biomol. Chem. 2012, 10, 5165. (b) Trost, B. M.; Brennan, M. K. Synthesis 2009, 3003. (c) Galliford, C. V.; Scheidt, K. A. Angew. Chem., Int. Ed. 2007, 46, 8748. (d) Marti, C.; Carreira, E. M. Eur. J. Org. Chem. 2003, 2209. For selected examples of bioactive nitrogen-containing spirooxindoles, see: (a) Yong, S. R.; Ung, A. T.; Pyne, S. G.; Skelton, B. W.; White, A. H. Tetrahedron 2007, 63, 5579. (b) Vintonyak, V.; Warburg, K.; Kruse, H.; Grimme, S.; H€ ubel, K.; Rauh, D.; Waldmann, H. Angew. Chem., Int. Ed. 2010, 49, 5902. (c) Bhaskar, G.; Arun, Y.; Balachandran, C.; Saikumar, C.; Perumal, P. T. Eur. J. Med. Chem. 2012, 51, 79. (d) Ding, K.; Lu, Y.; Nikolovska-Coleska, Z.; Wang, G.; Qiu, S.; Shangary, S.; Gao, W.; Qin, D.; Stuckey, J.; Krajewski, K.; Roller, P. P.; Wang, S. J. Med. Chem. 2006, 49, 3432. (2) For selected recent examples, see: (a) Lv, H.; Tiwari, B.; Mo, J.; Xing, C.; Chi, Y. R. Org. Lett. 2012, 14, 5412. (b) Pei, C.; Jiang, Y.; Shi, M. Eur. J. Org. Chem. 2012, 12, 4206. (c) Zhang, B.; Feng, P.; Sun, L.; Cui, Y.; Ye, S.; Jiao, N. Chem.;Eur. J. 2012, 18, 9198. (3) For selected recent examples, see: (a) Badillo, J. J.; Silva-Garcı´ a, A.; Shupe, B. H.; Fettinger, J. C.; Franz, A. K. Tetrahedron Lett. 2011, 52, 5550. (b) Taghizadeh, M. J.; Arvinnezhad, H.; Samadi, S.; Jadidi, K.; Javidan, A.; Notash, B. Tetrahedron Lett. 2012, 53, 5148. (c) Shi, F.; Tao, Z.; Luo, S.; Tu, S.; Gong, L. Chem.;Eur. J. 2012, 18, 6885. 10.1021/ol4010867 r 2013 American Chemical Society Published on Web 06/12/2013
electronic effects of different silyl groups, allylsilane reagents can exhibit either an allylation (i.e., elimination) or annulation pathway.4 Both pathways proceed through a transient β-silyl stabilized carbocation intermediate,5 which can be directly intercepted (as a 1,2-dipole synthon),6 or a 1,2-silyl migration can occur with interception in a [3 þ 2] annulation (as a 1,3-dipole synthon).7 Herein we describe the discovery and development of a new Lewis acid catalyzed allylsilane annulation with N-Boc-iminooxindoles (1) to form spirocyclic carbamates such as 3 (Scheme 1). Previous work from our group has shown that chiral scandium(III)-indapybox complexes catalyze allylsilane additions to isatins to selectively afford (4) (a) Hosomi, A. Acc. Chem. Res. 1988, 21, 200. (b) Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004, 15, 3173. (c) Panek, J. S.; Yang, M. J. Am. Chem. Soc. 1991, 113, 9868. (d) Danheiser, R. L.; Dixon, B. R.; Gleason, R. W. J. Org. Chem. 1992, 57, 6094. (e) Kn€ olker, H.-J.; Foitzik, N.; Graf, R.; Pannek, J.-B. Tetrahedron 1993, 49, 9955. (5) (a) Lambert, J. B.; Zhao, Y. J. Am. Chem. Soc. 1996, 118, 7867. (b) Creary, X.; Kochly, E. D. J. Org. Chem. 2009, 74, 2134. (c) Lambert, J. B.; Zhao, Y.; Emblide, R. W.; Salvador, L. A.; Liu, X.; So, J.; Chelius, E. C. Acc. Chem. Res. 1999, 32, 183. (6) (a) Brocherieux-Lanoy, S.; Dhimane, H.; Poupon, J.-C.; Vanucci, C.; Lhommet, G. J. Chem. Soc. Perkin Trans. 1997, 1, 2163. (b) Angle, S. R.; El-Said, N. A. J. Am. Chem. Soc. 1999, 121, 10211. (c) Horino, Y.; Kimura, M.; Naito, M.; Tanaka, S.; Tamaru, Y. Tetrahedron Lett. 2000, 41, 3427. (d) Hirashita, T.; Kawai, D.; Araki, S. Tetrahedron Lett. 2007, 48, 5421. (e) Romero, A.; Woerpel, K. A. Org. Lett. 2006, 8, 2127. (f) Dressel, M.; Restorp, P.; Somfai, P. Chem.;Eur. J. 2008, 14, 3072.
Scheme 1. Annulation Pathways with N-Boc-iminooxindoles
either allylation8 or annulation9 products in high yields and enantioselectivities. The allylation of iminooxindoles represents a synthetic challenge, and limited examples have been reported.10,11 We also present methods to access 3-allyl-3-aminooxindoles and furoindolones upon transformation of the spirocarbamate. Our initial studies compared the reactivity of iminooxindoles 1 and 6 in Lewis acid catalyzed allylation reactions with methallyltrimethylsilane 7 (Scheme 2, eqs 1 and 2). Using the conditions we have previously optimized for isatins (i.e., Sc(OTf)3 with NaSbF6 and TMSCl),8 the allylation of ketimine 6 afforded the protected 3-aminooxindole 8 in 68% yield after 3 days.12 In comparison, the electron-deficient N-Boc protected ketimines 113 exhibit a significant increase in reactivity compared to N-aryl ketimines. The addition of methallyltrimethylsilane 7 to iminooxindoles 1 proceeds rapidly (
