J. CHEM. RESEARCH (S), 1998 497
J. Chem. Research (S),
1998, 497$
Synthesis of (3R,4R)-Hexane-3,4-diol from
D-Mannitol$
P. Saravanan and Vinod K. Singh*
Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India
(3R,4R)-Hexane-3,4-diol was synthesized from D-mannitol by using a strategy of protection and deprotection of
hydroxyl groups.
7.35 (d, J 8, 8 H), 7.80 (d, J 8 Hz, 8 H). (Found: C, 52.78;
Enantiomerically pure vicinal diols are very useful chiral
synthons in organic synthesis. Recently we reported a short
H, 5.10, O, 26.82. Calc. for C37H42O14S4: C, 52.98; H, 5.01,
O, 26.73%).
and convenient synthesis of (2R,5R)-hexane-2,5-diol from
Tetratosylate Diol 4.ÐA solution of acetonide 3 (3.5 g, 4.2 mmol)
D-mannitol.1 While working in this area, we realized that
in MeCN (50 mL) was treated with CuCl2 Á 2H2O (2.1 g, 12.6 mmol)
(3R,4R)-hexane-3,4-diol2 1 can also be synthesized from
at r.t. and the reaction mixture stirred under re¯ux for 24 h. The
D-mannitol only by changing the strategy of protection and
deprotection of hydroxyl groups. Thus, a tetraol 23 was
treated with Et3N and p-tosyl chloride in pyridine at 0 8C
and further stirred at room temperature (r.t.) for 48 h to
provide a tetratosylate 3 in 79% yield. The acetonide group
of the tetratosylate 3 was deprotected using CuCl2 Á 2H2O4
in MeCN at re¯ux temperature for 24 h to give a diol tosy-
late 4 in 96% yield. The diol tosylate 4 was treated with
LiAlH4 in THF±diethyl ether at r.t. for 24 h to provide the
®nal diol 12a in 49% yield.
¯ask was cooled and the solvent removed on a rotary evaporator.
The crude mixture was chromatographed over silica gel to aord
the tetratosylate diol 4 (3.2 g, 96% yield) as a white crystalline
solid; mp 107±108 8C; Rf 0.80 (2:3, EtOAc in light petroleum);
38.98 (c 1.0, CHCl3); IR (KBr) 3500 cm ;
1H NMR (CCl4,
25
1
[ꢀ]D
60 MHz) ꢁ 2.5 (s, 12 H), 3.6±4.85 (m, 8 H), 7.35 (d, J 8, 8 H),
7.80 (d, J 8 Hz, 8 H). (Found: C, 51.08; H, 4.78, O, 28.22. Calc.
for C34H38O14S4: C, 51.13; H, 4.76, O, 28.07%).
(3R,4R)-Hexane-3,4-diol 1.ÐA solution of tetratosylate 4 (2.5 g,
3.1 mmol) in THF (10 mL) was added slowly to a stirred suspension
of LiAlH4 (1.2 g, 31.5 mmol) in ether (50 mL) at r.t. The reaction
mixture was stirred at the same temperature for 24 h. The excess of
LiAlH4 was destroyed by adding a few drops of EtOAc and the
mixture treated with water (500 ꢂL), 4 M NaOH (aq) (400 ꢂL), and
then water (1 mL) and stirred for 15 min. The white precipitate was
®ltered o, the ®ltrate was dried over anhydrous Na2SO4 and
the solvent removed on a rotary evaporator. The crude mixture was
puri®ed over silica gel to aord the diol 1 (180 mg, 49% yield)
In conclusion, (3R,4R)-hexane-3,4-diol was synthesized in
three steps from an easily available precursor in an ecient
manner.
25
as an oil; Rf 0.50 (1:1, EtOAc in light petroleum); [ꢀ]D25 16.68
(c 1.2, CHCl3) {lit.2a (95% e.e. for its enantiomer) [ꢀ]D
(c 2.0, CHCl3)}.
12.48
We thank Council for Scienti®c and Industrial research
for ®nancial support to the project and a senior research
fellowship (to P.S.).
Experimental
Received, 16th April 1998; Accepted, 26th May 1998
Paper E/8/02866D
Acetonide Tetratosylate 3.ÐSolid p-toluenesulfonyl chloride (7 g,
36 mmol) was added in portions to a stirred solution of tetraol 23
(1 g, 4.5 mmol) in pyridine (15 mL) and Et3N (2.5 mL, 18 mmol) at
0 8C. The reaction mixture was stirred for 48 h (0 8C to r.t.). It was
diluted with CH2Cl2 (50 mL) and the organic layer washed with 1 M
HCl, water, brine, and dried over anhydrous Na2SO4. The solvent
was removed on a rotary evaporator, and the crude compound
chromatographed over silica gel to aord tetratosylate 3 (3.8 g,
79% yield) as a white crystalline solid; mp 118±119 8C; Rf 0.60 (2:3,
References
1 P. Saravanan, S. Raina, T. Sambamurthy and V. K. Singh,
J. Org. Chem., 1997, 62, 2669.
2 For some other synthesis of such diols, see (a) O. Bortolini,
G. Fantin, M. Fogagnolo, P. P. Giovannini, A. Guerrini and
A. Medici, J. Org. Chem., 1997, 62, 1854 and refs. therein;
(b) P. N. Devine and T. Oh, Tetrahedron Lett., 1991, 32, 883 and
refs. therein.
3 D. A. Nugiel, K. Jacobs, T. Worley, M. Patel, R. F. Kaltenbach
III, D. T. Meyer, P. K. Jadhav, G. V. De Lucca, T. E. Smyser,
R. M. Klabe, L. T. Bachelor, M. M. Rayner and S. P. Seitz,
J. Med. Chem., 1996, 39, 2156; B. B. Lohray, M. Chatterjee and
Y. Jayamma, Synth. Commun., 1997, 27, 1711.
25
EtOAc in light petroleum); [ꢀ]D 12.08 (c 1.0, CHCl3); 1H NMR
(CCl4, 60 MHz) ꢁ 1.26 (s, 6 H), 2.50 (s, 12 H), 3.9±4.8 (m, 8 H),
*To receive any correspondence
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
4 P. Saravanan, M. Chandrasekhar, R. V. Anand and V. K. Singh,
Tetrahedron Lett., 1998, 39, 3091.
Saravanan
