Efficient 'dehomologation' of di-O-isopropylidenehexofuranose derivatives to give O-isopropylidenepentofuranoses by sequential treatment with periodic acid in ethyl acetate and sodium borohydride

Full text of DOI:10.1021/jo960355u

5178
J . Org. Chem. 1996, 61, 5178-5179
Ta ble 1. Sequ en tia l Hyd r olysis, Oxid a tion ,a a n d
Efficien t “Deh om ologa tion ” of
Di-O-isop r op ylid en eh exofu r a n ose
Der iva tives To Give
Red u ction of F u r a n ose Dia ceta l Der iva tives
O-Isop r op ylid en ep en tofu r a n oses by
Sequ en tia l Tr ea tm en t w ith P er iod ic Acid
in Eth yl Aceta te a n d Sod iu m Bor oh yd r id e
Meiqiang Xie, David A. Berges,* and Morris J . Robins*
Department of Chemistry and Biochemistry,
Brigham Young University, Provo, Utah 84602-5700
Received February 21, 1996
Cascade chemistry, “one-pot” sequential transforma-
tions in organic synthesis, provides convenient and
efficient methods for the preparation of a variety of
organic compounds,1,2 and carbohydrates are a readily
available source of chiral building blocks for the synthesis
of biologically relevant molecules. It was recently re-
ported that periodic acid in diethyl ether effected selective
hydrolysis of the terminal O-isopropylidene group from
acyclic carbohydrates that also contained internal acetals.3a
Sequential oxidative cleavage of the exposed glycol then
removed the terminal carbon with concomitant genera-
tion of an aldehyde.3 We now report parallel results
which extend the scope, provide improved reaction condi-
tions, and add the reduction step. This sequence results
in efficient “dehomologation” of di-O-isopropylidenehexo-
furanoses to give useful O-isopropylidenepentofuranoses
without purification of intermediates.
This methodology is readily applicable to furanose
diacetals. Ethyl acetate as solvent gives smoother con-
versions, and with a wider range of substrates, than
diethyl ether (dichloromethane and tetrahydrofuran gave
poor results). The mixture is filtered after selective
hydrolysis/oxidation is complete, and the filtrate is
evaporated. The syrupy residue is dissolved in ethanol
and treated with sodium borohydride to reduce the
terminal aldehyde and complete the overall dehomolo-
gation of hexofuranose diacetals to pentofuranose acetals.
Our results are summarized in Table 1. Sequential
treatment of 1,2:5,6-di-O-isopropylidene-R-D-glucofura-
nose (1, entry 1) gave 1,2-O-isopropylidene-R-D-xylofura-
nose (2, 95%). In entries 2 and 3, reduction to give 4
and 6 occurred stereoselectively from the â face (only the
selective acid catalyst for hydrolysis of a 6-membered
terminal isopropylidene acetal in the presence of a
5-membered anomeric acetal. Thus, treatment of 1,2:3,5-
di-O-isopropylidene-R-D-xylofuranose (11, Scheme 1) un-
der our usual conditions gave 1,2-O-isopropylidene-R-D-
xylofuranose (2, 96%). The products of the three-stage
sequential conversions have been reported previously,
except 6, and their 1H and 13C NMR spectra are in
agreement with literature values. The stereochemistry
at C3 of 6 was confirmed by its parallel preparation from
the known hexose derivative 127 (Scheme 1).
In summary, selective acid-catalyzed hydrolysis of
terminal O-isopropylidene acetals and oxidative cleavage
of the exposed glycol with periodic acid followed by
reduction of the resulting terminal aldehyde with sodium
borohydride provides an efficient three-stage dehomolo-
gation of readily available hexofuranose diacetals to
pentofuranose acetal derivatives. Ethyl acetate is an
advantageous solvent for periodic acid and a number of
carbohydrate derivatives.
1
noted isomer was observed in H and 13C NMR spectra).
Precedents exist for stereoselective reductions of ketones
and conjugated esters via participation of the hydroxy-
methyl group in delivery of borohydride species at the â
face.4-6 Entries 4 and 5 also have apparent selectivity
in harmony with participating delivery of the hydride and
opposite to that expected on steric grounds from a
bimolecular process. However, the anomeric structures
of those hemiacetals are mobile and could represent the
more thermodynamically stable diastereomers. The lac-
tones 7 and 9 have low solubility in diethyl ether, and
ethyl acetate as solvent was markedly advantageous. As
expected, periodic acid in ethyl acetate functioned as a
(1) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993, 32,
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Exp er im en ta l Section
1H (200 or 500 MHz) and 13C (50 MHz) NMR spectra were
recorded with solutions in TMS/CDCl3. Low-resolution electron-
impact mass spectra (MS) were determined at 20 eV. Com-
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S0022-3263(96)00355-6 CCC: $12.00 © 1996 American Chemical Society

Notes
J . Org. Chem., Vol. 61, No. 15, 1996 5179
were removed in vacuo (oil pump) overnight to give the product
with yields as noted.
Sch em e 1
1,2-O-Isop r op ylid en e-r-D-xylofu r a n ose (2). A solution of
11 (230 mg, 1.00 mmol) and H5IO6 (274 mg, 1.20 mmol) in EtOAc
(10 mL) was stirred for 2 h. The mixture was filtered, and the
filtrate was evaporated. The residue was dissolved (EtOAc),
washed (H2O), dried (Na2SO4), and evaporated to give 211 (171
mg, 96%): 1H NMR δ 5.97 (d, J ) 3.7 Hz, 1H), 4.51 (d, J ) 3.7
Hz, 1H), 4.31 (m, 1H), 4.25 (br, 1H), 4.15 (m, 1H), 4.04 (m, 2H),
3.26 (br, 1H), 1.47 (s, 3H), 1.31 (s, 3H); 13C NMR δ 112.2, 105.2,
85.8, 79.9, 76.4, 60.9, 27.1, 26.6.
3-Deoxy-3-C-[(eth oxyca r bon yl)m eth yl]-1,2-O-isop r op y-
lid en e-r-D-r ibofu r a n ose (6). NaBH4 (57 mg, 1.5 mmol) was
added portionwise to a solution of 59 (328 mg, 1.00 mmol) in
EtOH (abs, 15 mL), and the mixture was stirred overnight.
Excess HOAc was added, volatiles were evaporated, and the
residue was dissolved (EtOAc). The solution was filtered and
evaporated to give 3-deoxy-3-C-[(ethoxycarbonyl)methyl]-1,2:5,6-
di-O-isopropylidene-R-D-allofuranose7 (12, quantitative). Treat-
ment of 12 with H5IO6/EtOAc (dried) as described in the general
method gave 6 (oil; 234 mg, 90% from 5). “Diffusion” crystal-
lization15 (EtOAc/hexanes) gave 6: mp 37-39 °C; 1H NMR
(CDCl3) δ 5.80 (d, J ) 3.7 Hz, 1H), 4.77 (t, J ) 3.8 Hz, 1H), 4.15
(q, J ) 7.2 Hz, 2H), 3.81-3.91 (m, 2H), 3.70 (br s, 1H), 3.55 (dd,
J ) 13.2, 4.2 Hz, 1H), 2.60-2.74 (m, 1H), 2.30-2.50 (m, 2H),
1.47 (s, 3H), 1.30 (s, 3H), 1.25 (t, J ) 7.2 Hz, 3H); 1H NMR
(DMSO-d6/D2O) δ 5.77 (d, J ) 3.7 Hz, 1, H1), 4.70 (“t”, J ) 4.2
Hz, 1, H2), 4.07 (q, J ) 7.1 Hz, 2, OEt), 3.67 (dt, J ) 9.9, 3.7 Hz,
1, H4), 3.56 (dd, J ) 12.4, 3.0 Hz, 1, H5), 3.41 (dd, J ) 12.4, 4.4
Hz, 1, H5'), 2.49 (d, J ) 7.5 Hz, 2, CH2CO), 2.15-2.28 (m, 1,
H3), 1.40 (s, 3, Me), 1.25 (s, 3, Me), 1.21 (t, 3, OEt); irridiation
at δ 2.21 (H3) caused simplification of the signals at δ 4.70 (H2)
and 3.67 (H4); 13C NMR (CDCl3) δ 172.5, 111.7, 105.1, 81.7, 61.5,
60.9, 40.3, 30.0, 26.9, 26.6, 14.4; MS m/ z 260 (M+). Anal. Calcd
for C12H20O6: C, 55.37; H, 7.75. Found: C, 55.54; H, 7.76.
pounds 1 and 11 were obtained from Aldrich, and 3,8 5,9 7,10
and 910 were prepared as described. Products 2,11 4,12 8,13 10,14
and intermediate 127 were reported previously and have melting
points and 1H and 13C NMR data in harmony with literature
values.
Gen er a l Meth od for Sequ en tia l Selective Hyd r olysis,
Oxid a tive Clea va ge, a n d Red u ction . A solution of the dried
di-O-isopropylidene compound (1 mmol) and H5IO6 (1.2 mmol)
in dried EtOAc (10 mL) was stirred for 2 h. The reaction mixture
was filtered, and the filtrate was evaporated. The residue was
dissolved in EtOH (abs, 15 mL), and NaBH4 (Table 1) was added
in small portions with vigorous stirring. Stirring was continued
for 30 min, excess HOAc was added, and volatiles were evapo-
rated. The residue was dissolved (EtOAc), the solution was
washed (H2O), dried (Na2SO4), and evaporated, and volatiles
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Ack n ow led gm en t. We thank the American Cancer
Society (Grant DHP-34) and Brigham Young University
development funds for generous support. We thank Dr.
Stanislaw F. Wnuk for repetition of the 5 f 12 f 6
sequence and high-resolution NMR data.
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