6
674
R. J. Huntley, R. L. Funk / Tetrahedron Letters 52 (2011) 6671–6674
3
3. Catalytic asymmetric hydrogenation of enamides has been
2. Lewis, J. R. Nat. Prod. Rep. 1994, 11, 329.
3. (a± Gao, S.; Tu, Y. Q.; Song, Z.; Wang, A.; Fan, X.; Jiang, Y. J. Org. Chem. 2005,
523; (b± Yasuhara, T.; Osafune, E.; Nishimura, K.; Yamashita, M.; Yamada, K.)
extensively studied, however, there remains limited precedent
for the reduction of tetrasubstituted systems. We therefore entered
this investigation with some trepidation.
6
I.; Muraoka, O.; Tomioka, K. Tetrahedron Lett. 2004, 45, 3043; (c± Padwa, A.;
Brodney, M. A.; Lynch, S. M. J. Org. Chem. 2001, 66, 1716; (d± Shao, Z.; Chen, J.;
Huang, R.; Wang, C.; Li, L.; Zhang, H. Synlett 2003, 2228; (e± Cassayre, J.; Zard, S.
Z. Synlett 1999, 504; (f± Hoang)Cong, Z.; Quiclet)Sire, B.; Zard, S. Z. Tetrahedron
Lett. 1999, 40, 2125; (g± Cossy, J.; Tresnard, L.; Pardo, D. G. Eur. J. Org. Chem
1999, 1925; (h± Angle, S. R.; Boyce, J. P. Tetrahedron Lett. 1995, 36, 6185; (i±
Grotjahn, D. B.; Vollhardt, P. C. Synthesis 1993, 579; (j± Pearson, W. H.;
Schkeryantz, J. M. J. Org. Chem. 1992, 57, 6783; (k± Baeckvall, J. E.; Anderson, P.
G.; Stone, G. B.; Gogoll, A. J. Org. Chem. 1991, 56, 2988; (l± Hwang, H.; Magnus, P.
J. Chem. Soc., Perkin Trans. 1 1983, 693; (m± Iida, H.; Yuasa, Y.; Kibayashi, C. J.
Org. Chem. 1979, 44, 1074; (n± Umezawa, B.; Hoshino, O.; Sawaki, S.; Sato, S.;
Numao, N. J. Org. Chem. 1977, 42, 4272; (o± Iida, H.; Aoyagi, S.; Kibayashi, C. J.
Chem. Soc., Perkin Trans. 1 1975, 2502; (p± Hara, H.; Hoshino, O.; Umezawa, B.
Tetrahedron Lett. 1972, 13, 5031; (q± Ganem, B. Tetrahedron Lett. 1971, 12, 105;
We began with a brief screening of three Rh)ligand systems,
1
0
11
12 1
DuPhos, TangPhos, and BINAP.
H NMR analysis of the crude
mixtures revealed that in each of these cases 1,4)hydrogenation to
enecarbamate 39 was predominating. Unfortunately, chiral HPLC
analysis of the products revealed negligible enantioselectivity.
Use of a monodentate phosphoramide catalyst1 also proved
unrewarding, failing to give any identifiable hydrogenation prod)
ucts. Discouraged by the lack of even modest selectivity in this ini)
tial screening, we quickly turned our efforts to the synthesis of
3
(
r± Irie, H.; Nishutani, Y.; Sugita, M.; Uyeo, S. J. Chem. Soc., Chem. Commun. 1970,
racemic material.
To that end, deprotection14 of the carbamate was undertaken to
1313; (s± Ueda, N.; Tokuyam, T.; Sakan, T. Bull. Chem. Soc. Jpn. 1966, 39, 2012.
(a± Chapsal, B. D.; Ojima, I. Org. Lett. 2006, 8, 1395; (b± Fujioka, H.; Murai, K.;
Ohba, Y.; Hirose, H.; Kita, Y. Chem. Commun. 2006, 832; (c± Dong, L.; Xu, Y.)J.;
Cun, L.)F.; Cui, X.; Jiang, Y.)Z.; Gong, L.)Z. Org. Lett. 2005, 7, 4285; (d± Banwell,
M. G.; Harvey, J. E.; Hockless, D. C. R. J. Org. Chem. 2000, 65, 4241; (e± Ikeda, M.;
Ohtani, S.; Sato, T.; Ishibashi, H. Synthesis 1998, 1803; (f± Yoshizki, H.; Satoh, H.;
Sato, S.; Nukui, S.; Shibasaki, M.; Mori, M. J. Org. Chem. 1995, 60, 2016.
4.
give 40 (Scheme 8±, whose spectra correlated well with previously
3
j
published material. Pictet–Spengler ring closure under the condi)
tions reported by Umezawa3 gave
n
c)lycorane (1±.
In conclusion, we have completed a concise total synthesis of
c
)
lycorane in 9 steps from commercially available BOC)2)pyrrolidi)
none, demonstrating the utility of electrocyclic ring closures of
divinylpyrrolines for the synthesis of indolizidine ring systems.
Application of this methodology in the synthesis of other ring sys)
tems embodied in biologically active natural products is underway
in our laboratories.
5. Greshock, T. J.; Funk, R. L. J. Am. Chem. Soc. 2006, 128, 4946.
6
7
8
.
.
.
Greshock, T. J.; Funk, R. L. Org. Lett. 2006, 8, 2643.
Huntley, R. J.; Funk, R. L. Org. Lett. 2006, 8, 3403.
(a± Yuecel, B.; Arve, L.; de Meijere, A. Tetrahedron 2005, 61, 11355; (b± Pross, A.;
Sternhill, S. Aust. J. Chem. 1970, 23, 989.
9.
Overman, L. E.; Mendelson, L. T.; Jacobsen, E. J. J. Am. Chem. Soc. 1983, 105, 6629.
10. Burk, M. J.; Lee, J. R.; Martinez, J. P. J. Am. Chem. Soc. 1994, 116, 10847.
11. Tang, W.; Zhang, X. Angew. Chem. Int. Ed. 2002, 41, 1612.
12. Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. J.
Am. Chem. Soc. 1980, 102, 7932.
Acknowledgment
13. Van den Berg, M.; Haak, R. M.; Minnaard, A. J.; de Vries, A. H. M.; de Vries, J. G.;
Feringa, B. L. Adv. Synth Catal. 2002, 344, 1003.
14. Sakaitani, M.; Ohfune, Y. J. Org. Chem. 1990, 55, 870.
We appreciate the financial support provided by the National
Institutes of Health (GM28663±.
References and notes
1
.
Martin, S. F. In The Alkaloids; Brossi, A., Ed.; Academic Press: New York, 1987;
Vol. 30, pp 251–376.