E. B. Arévalo-García, J. C. Colmenares / Tetrahedron Letters 49 (2008) 6972–6973
6973
Boc
Bn
Boc
Bn
N
N
.
MsCl,Et3N,CH2Cl2,
90%
BH3 THF then
TBSO
TBSO
H2O2/NaOH, THF
68% in two steps
OH
OTBS
Bn
6
7
OTBS
OTBS
Boc
N
1) sec-BuLi,TMEDA
H2/Pd-C
96%
2) DMF
OTBS
TBSO
N
83% in two steps
OMs
Boc
4
5
OTBS
OTBS
P+Ph3I-
1) H2/Pd-C
OTBS
OH
n-C10H21
2) Bu4NF/THF
n-BuLi 91%
3) HCl/CH3OH
OH
OTBS
OTBS
N
N
Boc
N
H
Boc
C
11H23
O
3
2
1
C10H21
Scheme 1.
OH
Boc
Bn
N
OH
TBSO
N
H
C11H23
OTBS
1'
7'
Scheme 2.
1169; (d) Jourdant, A.; Zhu, J. Tetrahedron Lett. 2001, 42, 3431; (e) Koulocheri, S.
D.; Haroutounian, S. A. Tetrahedron Lett. 1999, 40, 6869; (f) Yang, C.; Liao, L.; Xu,
Y.; Zhang, H.; Xia, P.; Zhou, W. Tetrahedron: Asymmetry 1999, 10, 2311; (g) Yang,
C.-F.; Xu, Y.-M.; Liao, L.-X.; Zhou, W.-S. Tetrahedron Lett. 1998, 39, 9227; (h)
Dransfield, P. J.; Gore, P. M.; Shipman, M.; Slawin, A. M. Z. Chem. Commun. 2002,
150; (i) Luker, T.; Hiemstra, H.; Speckamp, W. N. J. Org. Chem. 1997, 62, 3592; (j)
Herdeis, C.; Telser, J. Eur. J. Org. Chem. 1999, 1407; (k) Jourdant, A.; Zhu, J.
Heterocycles 2004, 64, 249; (l) Ma, N.; Ma, D. Tetrahedron: Asymmetry 2003, 14,
1403.
Acknowledgements
The authors are grateful to C.W. Post Long Island University
Chemistry Department and to Loker Hydrocarbon Research Insti-
tute for partial support of this work.
References and notes
4. Ginesta, X.; Pericas, M. A.; Riera, A. Synth. Commun. 2005, 35, 289.
5. Wilkinson, T.; Stehle, N. W.; Beak, P. J. C. Org. Lett. 2000, 2, 155.
6. The derivative is obtained via (L)-serine methyl ester hydrochloride was reacted
1. For reviews see: (a) Weintraub, P. M.; Sabd, J. S.; Kane, J. M.; Borcherding, D. R.
Tetrahedron 2003, 59, 2953; (b) Strunz, G. M.; Findlay, J. A. In The Alkaloids;
Brossi, A., Ed.; Academic Press: New York, 1985; Vol. 26, pp 89–183; (c) Laschat,
S.; Dickner, T. Synthesis 2000, 1781; (d) Foder, G. B.; Colasanti, B. The Pyridine
and Piperidine Alkaloids: Chemistry and Pharmacology. In Alkaloids: Chemical
and Biological Perspectives; Pelletier, S. W., Ed.; Wiley: New York, 1985; 3, p 1; (e)
Schneider, M. J. In Alkaloids: Chemical and Biological Perspectives; Pelletier, S. W.,
Ed.; Pergamon: Oxford, 1996; pp 155–299; (f) Wang, C. J.; Wuonola, M. A. Org.
Prep. Proced. Int. 1992, 24, 585.
2. Previous synthesis of deoxoprosopinine: (a) Pandey, S. K.; Kumar, P. Synlett
2007, 2894; (b) Fuhshuku, K.; Mori, K. Tetrahedron: Asymmetry 2007, 18, 2104;
(c) Wang, Q.; Sasaki, A. J. Org. Chem. 2004, 69, 4767; (d) Comins, D.; Sandelier, M.
J.; Grillo, T. A. J. Org. Chem. 2001, 66, 6829; (e) Agami, C.; Couty, F.; Mathieu, H.
Tetrahedron Lett. 1998, 39, 3505; (f) Yuasa, Y.; Ando, J.; Shibuya, S. J. Chem. Soc.,
Perkin Trans. 1 1996, 793; (g) Kadota, I.; Kawada, M.; Muramatsu, Y.; Yamamoto,
Y. Tetrahedron Lett. 1997, 38, 7469; (h) Tadano, K.; Takao, K.; Nigawara, Y.;
Nishino, E.; Takagi, I.; Maeda, K.; Ogawa, S. Synlett 1993, 565; (i) Saitoh, Y.;
Moriyama, Y.; Takahashi, T. Tetrahedron Lett. 1980, 21, 75; (j) Saitoh, Y.;
Moriyama, Y.; Hirota, H.; Takahashi, T.; Khuong-Huu, Q. Bull. Chem. Soc. Jpn.
1981, 54, 488.
with 1 equiv of benzaldehyde and 1 equiv of Et3N/CH3OH, followed by reduction
of the resulting imine with NaBH4. The resulting N-monoprotected methyl ester
is reacted with (Boc)2O/Et3N/THF and then with TBSCl/Imidazole obtaining an
N-diprotected, OTBS serine derivative. This product is then treated with DIBAL-
H at ꢀ40 °C obtaining the desired amino aldehyde. To a suspension of this
aldehyde/zinc powder/aqueous solution of NH4Cl in THF is added allyl bromide
at ꢀ10 °C; after stirring at room temperature, until the substrate disappeared,
the reaction mixture was extracted with Et2O; then the combined extracts were
dried and evaporated in vacuo. The final product is obtained as a mixture of
syn(minor) and anti(major) adducts that can be separated by column
chromatography after protection of the hydroxyl moiety with the TBS group.
7. (a) Saitoh, Y.; Moriyama, Y.; Takahashi, T.; Khuong-Huu, Q. Tetrahedron Lett.
1980, 21, 75; (b) Fuhshuku, K.; Mori, K. Tetrahedron: Asymmetry 2007, 18, 2104;
(c) Takao, K.; Nigawara, Y.; Nishino, E.; Takagi, I.; Maeda, K.; Tadano, K.; Ogawa,
S. Tetrahedron 1994, 50, 5681; (d) Daniel, L.; Comins, D.; SandelierGrillo, M. J.;
Grillo, T. A. J. Org. Chem. 2001, 66, 6829.
8. It is noteworthy that isomerization on silica gel5 of the aldehyde 3 (and also 30),
generates the corresponding diastereomeric products with great
regioselectivity. This fact leads to the synthesis of the alkaloids (ꢀ)-
3. Previous synthesis of deoxoprosophylline: (a) Andre´s, J. M.; Pedrosa, R.; Pe´rez-
Encabo, A. Eur. J. Org. Chem. 2007, 1803; (b) Chavan, S. P.; Praveen, C. Tetrahedron
Lett. 2004, 45, 421; (c) Datta, A.; Kumar, J. S. R.; Roy, S. Tetrahedron 2001, 57,
deoxoprosopinine and (+)-deoxoprosphyline in
presented in Schemes 1 and 2.
a similar straight way as