8462
M. S. Bodas, P. Kumar / Tetrahedron Letters 45 (2004) 8461–8463
jar for his support and encouragement. P.K. is thankful
to DST, New Delhi for generous funding of the project.
This is NCL Communication No. 6669.
a
b
PMBO
c
HO
OH
OH
5
4
OH
O
O
O
O
d
PMBO
PMBO
PMBO
OEt
OEt
OH
7
6
ee 88%
References and notes
O
OH
e
1. (a) Wang, C. J.; Wuonota, M. A. Org. Prep. Proced. Int.
1992, 24, 585–621; (b) Bailey, P. D.; Millwood, P. A.;
Smith, P. D. Chem. Commun. 1998, 633–640.
2. Hanessian, S.; M-Smith, G.; Lombart, H.-G.; Lubell, W.
D. Tetrahedron 1997, 53, 12789–12854.
3. Scott, J. D.; Tippie, T. N.; Williams, R. M. Tetrahedron
Lett. 1998, 39, 3659–3662.
4. Ferreira, F.; Greck, C.; Genet, J. P. Bull. Soc. Chim. Fr.
1997, 134, 615–621.
PMBO
g
OEt
OH
OEt
S
O
O
8
N3
O
9
OH
O
f
HO
OEt
OEt
NHBoc
N
10
O
11
Boc
OH
O
5. Jourdant, A.; Zhu, J. Tetrahedron Lett. 2000, 41, 7033–
7036, and references cited therein.
h
OH
N
H
1
6. (a) Battistini, L.; Zanardi, F.; Rassu, G.; Spanu, P.; Pelosi,
G.; Fava, G. G.; Ferrari, M. B.; Casiraghi, G. Tetra-
hedron: Asymmetry 1997, 8, 2975–2987; (b) Roemmele, R.
C.; Rapoport, H. J. Org. Chem. 1989, 54, 1866–1875; (c)
Agami, C.; Couty, F.; Mathieu, H. Tetrahedron Lett.
1996, 37, 4001–4002; (d) Horikawa, M.; Busch-Petersen,
J.; Corey, E. J. Tetrahedron Lett. 1999, 40, 3843–3846; (e)
Haddad, M.; Larcheveque, M. Tetrahedron Lett. 2001, 42,
5223–5225.
7. (a) Knight, E. W.; Lewis, N.; Share, A. Tetrahedron:
Asymmetry 1993, 4, 625–628; (b) Scott, J. D.; Williams, R.
M. Tetrahedron Lett. 2000, 41, 8413–8416.
8. Greck, C.; Ferreira, F.; Genet, J. P. Tetrahedron Lett.
1996, 37, 2031–2034.
Scheme 1. Reagents and conditions: (a) DMF, NaH, p-
MeOC6H4CH2Br, 80%. (b) (i) PCC, NaOAc, Celite, CH2Cl2, 0ꢁC;
(ii) Ph3P@CHCO2Et, benzene, reflux 4h, 80%. (c) K2CO3, K3FeCN6,
CH3SO2NH2, (DHQ)2PHAL (1mol%), 0.1M OsO4 (0.4mol%), t-
BuOH/H2O (1:1), 85%. (d) (i) SOCl2, Et3N, CH2Cl2, 0ꢁC, 20min; (ii)
RuCl3ÆH2O, NaIO4, CCl4/CH3CN/H2O (1:1:1.5), 0ꢁC, 2h, 92%. (e)
NaN3, DMF, 80ꢁC, 94%. (f) (i) DDQ, CH2Cl2, H2O; (ii) H2/Pd–C,
Boc2O, EtOAc, 70%. (g) MsCl, Et3N, CH2Cl2, ꢀ78ꢁC, 95%. (h) (i)
LiOHÆH2O, THF, MeOH, H2O, 6h; (ii) TFA/CH2Cl2 (1:1), 1.5h; then
Dowex 50, 90%.
group must be responsible for the increased reactivity of
the a-position.13
9. (a) Fernandes, R. A.; Kumar, P. Tetrahedron: Asymmetry
1999, 10, 4797–4802; (b) Fernandes, R. A.; Kumar, P. Eur.
J. Org. Chem. 2000, 3447–3449; (c) Fernandes, R. A.;
Kumar, P. Tetrahedron Lett. 2000, 41, 10309–10312; (d)
Pandey, R. K.; Fernandes, R. A.; Kumar, P. Tetrahedron
Lett. 2002, 43, 4425–4426; (e) Naidu, S. V.; Kumar, P.
Tetrahedron Lett. 2003, 44, 1035–1037; (f) Kandula, S. V.;
Kumar, P. Tetrahedron Lett. 2003, 44, 1957–1958; (g)
Pandey, R. K.; Upadhyay, P. K.; Kumar, P. Tetrahedron
Lett. 2003, 44, 6245–6246; (h) Gupta, P.; Fernandes, R.
A.; Kumar, P. Tetrahedron Lett. 2003, 44, 4231–4232; (i)
Bodas, M. S.; Upadhyay, P. K.; Kumar, P. Tetrahedron
Lett. 2004, 45, 987–988; (j) Pandey, S. K.; Kandula, S. V.;
Kumar, P. Tetrahedron Lett. 2004, 45, 5877–
5879.
Deprotection of the p-methoxybenzyl group with DDQ
followed by reduction of the azide 9 under hydrogena-
tion conditions in the presence of Boc2O gave the amino
diol 10.14 Compound 10 was subjected to cyclization using
methanesulfonyl chloride and triethylamine at ꢀ78ꢁC to
afford 11 in 95% yield. The subsequent ester hydro-
lysis with lithium hydroxide in THF/H2O followed by
deprotection of the Boc group with trifluoroacetic acid
furnished (2S,3S)-3-hydroxypipecolic acid 1 as a white
20
D
solid [mp ꢀ232–236ꢁC (lit.5 230–238ꢁC)] {½aꢁ +13.5
20
(c 0.2, 10% aq. HCl) [lit.5 ½aꢁ +12.90 (c 0.23, 10% aq.
D
HCl)]} in 90% yield. The physical and spectroscopic
10. (a) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev. 1994, 94, 2483–2547; (b) Torri, S.; Liu, P.;
Bhuvaneswari, N.; Amatore, C.; Jutand, A. J. Org. Chem.
1996, 61, 3055–3060.
data of 1 are in full agreement with the literature data.6a
20
In conclusion, a practical and enantioselective syn-
thesis of 3-hydroxypipecolic acid 1 has been achieved
using Sharpless asymmetric dihydroxylation with regio-
selective opening of a cyclic sulfate. To the best of our
knowledge, this is the first asymmetric synthesis of
3-hydroxypipecolic acid using Sharpless asymmetric
dihydroxylation as the source of chirality. The synthetic
strategy described has significant potential for further
extension to other isomers and related analogues. Cur-
rently studies are in progress in this direction.
11. The spectral data for 7: ½aꢁD +2.87 (c 1.08, CHCl3) IR
(CHCl3, cmꢀ1): mmax 1032, 1130, 1248, 1513, 1612, 1736,
1
2864, 2938, 3440; H NMR (500MHz, CDCl3): d 1.30 (t,
3H, J = 6Hz), 1.73 (m, 4H), 2.82 (br s, 2H), 3.49 (t, 2H,
J = 6Hz), 3.80 (s, 3H), 3.91 (d, 1H, J = 5Hz), 4.06 (m,
1H), 4.26 (q, 2H, J = 5Hz), 4.44 (s, 2H), 6.87 (d, 2H,
J = 10Hz), 7.25 (d, 2H, J = 10Hz); 13C NMR (125MHz,
CDCl3): d 13.77, 25.69, 30.03, 42.58, 54.83, 61.21, 69.51,
72.12, 73.41, 113.48, 128.97, 130.14, 158.87, 173.21; Mass
(ESI): 312 (M+); Anal. Calcd for C16H24O6: C, 61.52; H,
7.74. Found: C, 61.66; H, 7.70.
12. For the measurement of the enantiomeric excess, the diol 7
was converted into its dibenzoate. The enantiomeric purity
of the dibenzoate was estimated to be 97% by chiral HPLC
analysis using Lichocart 250-4 (4mm ID · 25cm) HPLC-
Cartridge (R.R.-Whelk-01), 10% i-PrOH in hexane,
0.8mL/min.
Acknowledgements
M.S.B. thanks CSIR, New Delhi for the award of Senior
Research Fellowship. We are grateful to Dr. M. K. Gur-