A facile synthesis of a chiral furan diol from glycals catalyzed by indium trichloride

Full text of DOI:10.1021/jo000074t

4198
J . Org. Chem. 2000, 65, 4198-4199
Sch em e 1
A F a cile Syn th esis of a Ch ir a l F u r a n Diol
fr om Glyca ls Ca ta lyzed by In d iu m
Tr ich lor id e†
B. Sobhana Babu and K. K. Balasubramanian*
Indian Institute of Technology, Madras,
Chennai - 600 036, India
Sch em e 2
Received J anuary 19, 2000
The furan ring system constitutes the basic framework
of many natural products. Monosaccharides under acidic
conditions lead to furans.1 2-(D-glycero-1,2-dihydroxy-
ethyl)furan 3, an optically active furan diol, is a potential
chiral building block in organic synthesis. The transfor-
mation of D-glucal to 3 was first reported by Gonzalez et
al.2 using the toxic metal salt HgSO4 in concentrated H2-
SO4. A recent report by Hayashi et al.3 on the use of
relatively less toxic Sm(OTf)3 or RuCl2(PPh3)3 for the
same transformation prompts us to communicate our own
findings in this regard.
Sch em e 3
Of late, indium trichloride, which is a relatively strong
Lewis acid, has been used as a catalyst for a wide variety
of organic reactions, viz. Mukaiyama aldol reaction,4
imino Diels-Alder reaction,5 and Barbier reactions in-
volving diastereoselective addition of allyltin to aldehydes
or aldoses.6
As part of our ongoing program on the use of various
Lewis acids in carbohydrate chemistry,7 we have found
InCl3‚3H2O to be a less expensive and equally efficient
catalyst for the synthesis of 3 from unprotected D-glucal
1 and D-galactal 2 under mild conditions.
When 1 equiv of D-glucal 1 was treated with 0.1 equiv
(10 mol %) of InCl3‚3H2O in acetonitrile for 2.5 h at
ambient temperature, chiral furan diol 3 was obtained
in 82% yield. As expected, D-galactal 2 also underwent
facile transformation to afford the same product, viz. 3
(Scheme 1).
absence of signals due to H-2 at δ 4.73 (t) and C-2 at δ
68.22, characteristic of 3.9 Instead, it displayed signals
1
at δ 1.53, 3.9-4.2, 5.8-6.01, 6.28, 7.31 in the H NMR
spectrum and at δ 18.05, 33.12, 104.86, 105.35, 110.06,
141.14, 155.28, 155.38, 156.73 in the 13C NMR spectrum.
1
The multiplet at δ 3.9-4.2 in the H NMR spectrum and
the signal at δ 33.12 in the 13C NMR spectrum10 clearly
reveals that this carbon is not attached to oxygen.11
(Scheme 2).
It is likely that under the reaction conditions the
carbinol 5, if it all initially formed, would be unstable
leading to spontaneous dehydration, followed by inter-
molecular alkylation and ultimately cyclization leading
to complex mixture of products.
Surprisingly, extension of the same reaction to L-
rhamnal 4 did not provide the expected chiral furyl-
methyl carbinol 5, but led to a more complex mixture as
1
revealed by HPLC analysis. The H NMR spectrum and
13C NMR spectrum of this mixture clearly showed
Indeed, when rac-5, prepared from the borohydride
reduction of 2-acetylfuran, was treated with InCl3‚3H2O
in CH3CN, it afforded the same complex mixture as
obtained from the direct reaction of 4.12
In summary, we have found that InCl3‚3H2O is an
efficient catalyst for the synthesis of 2-(D-glycero-1,2-
* To whom correspondence should be addressed. Fax: 91 44
2350509.
† Dedicated to Prof. K. Nagarajan, Director, R&D, Recon Ltd.
Bangalore, India, on the occasion of his 70th birthday.
(1) (a) Bosshard, P.; Eugster, C. H. In Advances in Heterocyclic
chemistry; Katritzky, R., Boulton, A. J ., Eds.; Academic Press: New
York, 1966; Vol. 7, p 377 and references cited therein. (b) Harris, J .
M.; O’Doherty, G. A. Tetrhedron Lett. 2000, 41, 183.
(2) Gonzalez, F.; Lesage, S.; Perlin, A. S. Carbohydr. Res. 1975, 42,
267.
(8) Lit. [R]D +36.4 (c 1.2, CHCl3); see ref 3.
(9) Da ta for 2-(D-glycer o-1,2-d ih yd r oxyeth yl)fu r a n (3): [R]D
)
(3) Hayashi, M.; Kawabata, H.; Yamada, K. Chem. Comm. 1999,
965.
(4) (a) Mukaiyama, T.; Banno, T.; Narasaka, K. J . Am. Chem. Soc.
1974, 96, 7503. (b) Mukaiyama, T.; Han, J .-S.; Kobayashi, S. Chem.
Lett. 1991, 949. (c) Loh, T. P.; Pei, J .; Cao, G. Q. J . Chem. Soc., Chem.
Commun. 1996, 1819.
+34.5° (c 2.4, CHCl3); IR (CHCl3 cm-1) 3600, 3424, 2928, 1600, 1494,
1468, 1376, 1145, 1088, 1068, 998, 937, 873, 825, 652, 595; 1H NMR
(200 MHz, CDCl3, δ) 3.76 (d, 2H, J ) 5.7 Hz), 4.73 (t, 1H, J ) 5.54
Hz), 6.23-6.30 (m, 2H), 7.32-7.33 (m, 1H); 13C NMR (50 MHz, CDCl3,
δ) 64.83, 68.22, 106.78, 110.17, 142.07, 153.58; HRMS m/z calcd for
C6H8O3 128.047 345, found 128.050 232 t2.
(5) Babu, G.; Perumal, P. T. Tetrahedron Lett. 1997, 38, 5025.
(6) Li, X. R.; Loh, T.-P. Tetrahedron: Asymmetry 1996, 7, 1535.
(7) (a) Sobhana Babu, B.; Balasubramanian, K. K. Tetrahedron Lett.
1999, 40, 5777. (b) Sobhana Babu, B.; Balasubramanian, K. K.
Synthesis of alkyl and aryl 2,3-unsaturated glycopyranosides-Catalysed
by Indium trichloride; 218th American Chemical Society meeting, New
Orleans, LA, Aug 22-26, 1999. (c) Sobhana Babu, B.; Balasubrama-
nian, K. K. Tetrahedron Lett. 2000, 41, 1271.
(10) The DEPT spectrum indicated CH at δ 33.12 and CH3 at δ
18.05.
(11) We believe that one of the products could be the anhydro
tetramer or the quaterene 6 based on literature reports,12 or an
oligomer (see Scheme 3).
(12) (a) Ackman, R. G.; Brown, W. H.; Wright, G. F. J . Org. Chem.
1955, 20, 1147. (b) Beals, R. E.; Brown, W. H. J . Org. Chem. 1956, 21,
447. (c) Brown, W. H.; French, W. N. Can. J . Chem. 1958, 36, 537.
10.1021/jo000074t CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/02/2000

Notes
J . Org. Chem., Vol. 65, No. 13, 2000 4199
concentrated. The residue was purified by flash column chro-
matography on silica gel to obtain 3.
dihydroxyethyl)furan 3, an optically active furandiol. The
reaction proceeds at ambient temperature unlike the Sm-
(OTf)3- or RuCl2(PPh3)3-catalyzed reaction, which re-
quires relatively higher temperature (80 °C). Besides, the
workup is simple and amenable for scale-up, thereby
providing an useful alternative to the reported methods.
Ack n ow led gm en t. The authors thank the Depart-
ment of Science and Technology, India, for financial
support and RSIC, IIT, Chennai, SPIC Science Founda-
tion, Chennai and Sun Pharmaceutical Advanced Re-
search Centre, Baroda for spectral data. One of us
(B.S.B.) also thanks Dr. K. Vijayakumaran, Director,
R&D, Chimique Laboratories, Chennai.
Exp er im en ta l Section
Typically, to D-glucal 1 (1 mmol) was added InCl3‚3H2O (0.1
mmol; 10 mol %) in CH3CN (1-3 mL) at ambient temperature
and magnetically stirred. After completion (2.5 h, TLC), the
reaction mixture was quenched with aqueous sodium hydrogen
carbonate (10%, 25 mL), extracted with dichloromethane (3 ×
25 mL), dried over anhydrous sodium sulfate, filtered, and
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra for compounds 3 and 6. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O000074T