S. K. Pandey, P. Kumar / Tetrahedron Letters 46 (2005) 4091–4093
4093
Further, in order to achieve the synthesis of target com-
pounds 1 and 2 from 8, we required a suitable amino
protecting group for further synthetic manipulation
1999, 121, 2651–2652; (c) Kuethe, J. T.; Comins, D. L.
Org. Lett. 1999, 1, 1031–1033.
. (a) Ratovelomanana, V.; Royer, J.; Husson, H. P.
Tetrahedron Lett. 1985, 26, 3803–3806; (b) Masaki, Y.;
Imaeda, T.; Nagata, K.; Oda, H.; Ito, A. Tetrahedron Lett.
4
(
to debenzylation by hydrogenation using Pd(OH)2 fol-
Scheme 3). To this end, compound 8a was subjected
3
1
1
989, 30, 6395–6396; (c) Comins, D. L.; Williams, A. L.
lowed by protection of the amino group with (Boc) O to
2
Tetrahedron Lett. 2000, 41, 2839–2842; (d) Guerreiro, P.;
Ratevelomanana-Vidal, V.; Genet, J. P. Chirality 2000, 12,
1
4
afford compound 9a in 83% yield. The successive pro-
tection as the acetonide using 2,2-dimethoxypropane in
the presence of a catalytic amount of p-TSA and concom-
itant deprotection of the TBS group afforded 10a in 87%
yield. Compound 10a was oxidized to the aldehyde
4
08–410; (e) Agami, C.; Couty, F.; Rabasso, N. Tetrahe-
dron Lett. 2000, 41, 4113–4116; (f) Agami, C.; Couty, F.;
Rabasso, N. Tetrahedron 2001, 57, 5393–5401; (g) Enders,
D.; Nolte, B.; Raabe, G.; Runsink, J. Tetrahedron:
Asymmetry 2002, 13, 285–291.
1
5
by a Swern oxidation, and subsequently treated with
ethoxycarbonylmethylene)triphenylphosphorane in
dry THF at room temperature to furnish the Wittig
5
. Kandula, S. V.; Kumar, P. Tetrahedron Lett. 2003, 44,
(
1
957–1958.
6. (a) Fernandes, R. A.; Kumar, P. Eur. J. Org. Chem. 2000,
447–3449; (b) Pandey, R. K.; Fernandes, R. A.; Kumar,
1
6
product 11a in 96% yield with an E:Z ratio of 95:5.
The olefin and ester reduction of 11a were carried out
3
P. Tetrahedron Lett. 2002, 43, 4425–4426; (c) Fernandes,
R. A.; Kumar, P. Tetrahedron Lett. 2000, 41, 10309–
in a single step with LiAlH to give the corresponding
4
alcohol 12a in excellent yield which was subjected to
cyclization using methanesulfonyl chloride and triethyl-
amine followed by deprotection of the Boc group to
1
0312; (d) Naidu, S. V.; Kumar, P. Tetrahedron Lett. 2003,
44, 1035–1037; (e) Gupta, P.; Fernandes, R. A.; Kumar, P.
Tetrahedron Lett. 2003, 44, 4231–4232; (f) Kondekar, N.
B.; Kandula, S. V.; Kumar, P. Tetrahedron Lett. 2004, 45,
20
furnish (+)-a-conhydrine 1, ½aꢁ +8.9 (c 0.85, EtOH),
D
4
c
20
D
5
477–5479; (g) Pandey, S. K.; Kandula, S. V.; Kumar, P.
{
lit. ½aꢁ +9.0 (c 0.85, EtOH)}.
Tetrahedron Lett. 2004, 45, 5877–5879; (h) Kumar, P.;
Bodas, M. S. J. Org. Chem. 2005, 70, 360–363.
(
an analogous series of reactions as shown in Scheme 3,
ꢀ)-b-Conhydrine 2 was synthesized from 8b following
7
. (a) Fernandes, R. A.; Kumar, P. Tetrahedron: Asymmetry
1999, 10, 4797–4802; (b) Fernandes, R. A.; Kumar, P. Eur.
J. Org. Chem. 2002, 2921–2923; (c) Kandula, S. V.;
Kumar, P. Tetrahedron Lett. 2003, 44, 6149–6151; (d)
Gupta, P.; Naidu, S. V.; Kumar, P. Tetrahedron Lett.
2
0
4f
20
½
aꢁ ꢀ34.8 (c 0.4, CHCl ), {lit. ½aꢁ ꢀ34.1( c 0.4,
D
3
D
CHCl )}. The physical and spectroscopic data of 1
3
4
c,f
and 2 were in full agreement with the literature data.
2
004, 45, 849–851.
In conclusion, practical and stereocontrolled syntheses
of (+)-a-conhydrine and (ꢀ)-b-conhydrine has been
achieved from L-aspartic acid. The synthetic strategy de-
scribed has significant potential for further extension
of the 2-(1-hydroxyalkyl)piperidine unit and to the other
isomers, (ꢀ)-a-conhydrine and (+)-b-conhydrine. Cur-
rently, studies are in progress in this direction.
8. (a) Gmieir, P.; Junge, D.; Kartner, A. J. Org. Chem. 1994,
59, 6766–6776; (b) Oestreich, M.; Frohlich, R.; Hoppe, D.
Tetrahedron Lett. 1998, 39, 1745–1748.
9
. The diastereoselectivities of non-chelated 8a and chelated
product 8b were determined by H NMR spectroscopy
1
and also by comparison with the literature data.
0. Andres, J. M.; Munoz, E. M.; Pedrosa, R.; Perez-Encabo,
A. Eur. J. Org. Chem. 2003, 3387–3397.
1
1
1. (a) Reetz, M. T. Chem. Rev. 1999, 99, 1121–1162; (b)
Reetz, M. T. Angew. Chem., Int. Ed. Engl. 1991, 30, 1531–
1546.
Acknowledgements
1
1
1
2. Andres, J. M.; deElena, N.; Pedrosa, R. Tetrahedron 2000,
56, 1523–1531.
S.K.P. thanks CSIR, New Delhi, for a research fellow-
ship. We are grateful to Dr. M. K. Gurjar for his sup-
port and encouragement. Financial support from the
DST, New Delhi (Project Grant No. SR/S1/OC-40/
2003) is gratefully acknowledged. This is NCL commu-
nication No. 6679.
3. Yoshida, K.; Nakajima, S.; Wakamatsu, T.; Ban, Y.;
Shibasaki, M. Heterocycles 1988, 27, 1167–1168.
2
0
4. Spectral data of compound 9a: ½aꢁ +12.98 (c 1.0, CHCl3),
D
IR (neat): mmax 3443, 3412, 2931, 1694, 1673, 1394,
ꢀ1
1
1
6
1
174 cm
H), 0.91(s, 9H), 0.98 (t, J = 7.3, 3H), 1.44 (s, 9H), 1.48–
.
3
H NMR (300 MHz, CDCl ): d = 0.08 (s,
.55 (m, 2H), 1.70 (br s, 1H) 1.73–1.81 (m, 2H), 3.46–3.57
C
1
3
(
m, 2H), 3.73 (t, J = 5.9, 2H), 5.34 (d, J = 7.3, 1H).
References and notes
. Casiraghi, G.; Zanardi, F.; Rassu, G.; Spanu, P. Chem.
Rev. 1995, 95, 1677–1716.
NMR (75 MHz, CDCl ): d = ꢀ5.7, 10.3, 18.0, 25.7, 26.5,
3
2
8.2, 31.4, 53.2, 59.9, 75.3, 79.0, 155.9. Anal. Calcd for
C H NO Si (347.57): C, 58.75; H, 10.73; N, 4.03.
1
1
7
37
4
Found: C, 58.80; H, 10.71; N, 4.00.
2
3
. Wertheim, T. Liebigs Ann. Chem. 1856, 100, 328–330.
. (a) Elbein, A. D.; Molyneux, R. J. In Alkaloids: Chemical
and Biological Perspective; Pelletier, S. W., Ed.; Wiley:
New York, 1986; Vol. 5, pp 1–54; (b) Comins, D. L.;
Kuethe, J. T.; Hong, H.; Lakner, F. J. J. Am. Chem. Soc.
15. For reviews on the Swern oxidation, see: (a) Tidwell, T. T.
Synthesis 1990, 857; (b) Tidwell, T. T. Org. React. 1990,
39, 297.
16. The E:Z ratio of compound 11a was determined from the
H NMR spectrum.
1