A simple construction of chiral fused benzoxocine ring ethers from D-glucose by regioselective 8-endo-aryl radical cyclisation

Article abstract of DOI:10.1039/a706249d

A regioselective 8-endo-trig aryl radical cyclisation of the 5,6-deoxy-D-xylo-5-enofuranosides 3a and 3b with tri-n-butyltin hydride provides the chiral furo[3,2-c][2]benzoxocines 4a and 4b in good yields; the crystal structure of 4a is reported.

Full text of DOI:10.1039/a706249d

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A simple construction of chiral fused benzoxocine ring ethers from d-glucose
by regioselective 8-endo-aryl radical cyclisation
Partha Chattopadhyay,*a Monika Mukherjeeb and Soma Ghoshb
a Indian Institute of Chemical Biology, Calcutta-700 032, India
b Department of Solid State Physics, Indian Association for the Cultivation of Science, Jadavpur, Calcutta-700 032, India
A regioselective 8-endo-trig aryl radical cyclisation of the
O(2)
5,6-deoxy-D-xylo-5-enofuranosides 3a and 3b with tri-
n-butyltin hydride provides the chiral furo[3,2-c][2]benzox-
O(3)
ocines 4a and 4b in good yields; the crystal structure of 4a is
reported.
The synthesis of condensed cyclic ethers incorporating medium
size rings, a unique structural feature present in some highly
bioactive marine natural products,1 is
a
challenging
problem. The development of new and general methodology for
the synthesis of this class of compound,2,3 especially in chiral
form, has become an attractive area for investigation in recent
years. The syntheses of chiral 5-, 6- and 7-membered cyclic
ethers have been achieved from d-glucose by intramolecular
nitrone cycloaddition reactions.4 More recently, functionalised
9-membered chiral ethers have been prepared from d-glucose
through oxy-Cope rearrangement.5 We report herein a simple
and convenient conversion of d-glucose to highly function-
alised chiral condensed tricyclic benzoethers incorporating a cis
8-5 bicyclic system by regioselective 8-endo-trig aryl radical
cyclisation.6
The transformation of the easily accessible 5,6-deoxy-
O-isopropylidene-3-O-(o-bromobenzyl)-a-d-xylo-5-enofuran-
ose 3a and the corresponding 5A-methoxy derivative 3b to the
tricyclic furo[3,2-c][2]benzoxocines 4a and 4b is shown in
Scheme 1. d-Glucose was converted to the 3-O-(o-bro-
mobenzyl) ethers 1a† and 1b through O-benzylation of
O(4)
O(1)
Fig. 1 ORTEP diagram of 4a
aq. NaOH in a biphasic medium (CH2Cl2–H2O) using Bu4NBr
as phase transfer catalyst. Under mild acidic condition, the
5,6-O-isopropylidene group in 1a,b was selectively deprotected
to give 2a,b which on treatment with Ph3P, I2 and imidazole in
boiling toluene7 gave the desired dideoxy furanose derivatives
3a and 3b. Radical cyclisation of each of the alkenes 3a and 3b
in refluxing benzene (0.008 mol dm23) for 8–10 h with Bu3SnH
(1.5 equiv.) and a catalytic amount of AIBN furnished the
respective crystalline tricyclic ethers 4a and 4b in 50–60% yield
as the only isolable products in each case after separation of the
tin compounds8 followed by chromatography on silica gel. The
assigned structures of the products 4a and 4b resulting from
8-endo-trig aryl radical cyclisation were based upon spectro-
scopic data. Unequivocal confirmation of the structure of 4a
was obtained from an X-ray crystal structure‡ determination
(Fig. 1).
1,2:5,6-diisopropylidene-a-D-glucofuranose
with
50%
O
Me
Me
O
O
D-Glucose
O
O
H
Me
Me
HO
Br
In conclusion, the present investigation clearly shows the
potential of regioselective aryl radical cyclisation from car-
bohydrate derived substrates in the synthesis of chiral con-
densed cyclic ethers incorporating medium sized rings.
Grateful acknowledgement is due to Professor U. R. Ghatak,
INSA Senior Scientist, for his kind interest and valuable
suggestions. We also extend our thanks to the Regional
Sophisticated Instruments Center, Bose Institute, Calcutta,
India, for the use of its single crystal diffractometer facility.
i, 70.5%
Br
R
HO
O
O
Me
Me
ii
HO
Br
85–90%
O
Br
O
O
O
H
H
Me
Me
Me
R
O
R
O
O
O
Me
2
1a R = H
b R = OMe
Footnotes and References
iii 55%
10
11
H
9
6
* E-mail: iichbio@giasclo1.vsnl.net.in
iv
50–60%
H
O
† Satisfactory elemental analyses and spectroscopic data were obtained for
all new compounds. Selected data for 4a mp 151–152 °C; [a]2D7 220.6 (c
0.34, CHCl3); dH(CDCl3) 1.3 (s, 3 H), 1.46 (s, 3 H), 2.04–2.28 (m, 2 H),
2.44–2.68 (m, 1 H), 3.18–3.44 (m, 1 H), 4.04 (d, 1 H, J 4, H-3a), 4.28 (dt,
1 H, J 6 and 4, H-11a), 4.58 (d, 1 H, J 14), 4.62 (d, 1 H, J 4, H-3), 5.1 (d,
J 14, 1 H), 5.90 (d, 1 H, J 4, H-2), 7.02–7.34 (m, 4 H, Ar-H); dC(CDCl3)
26.2, 27.7, 28.6, 31.0, 75.0, 79.0, 84.5, 85.4, 104.0, 111.1, 126.1, 128.3,
128.8, 130.5, 135.7, 140.6; MS (EI) m/z 276 (M+). For 4b: mp 106–107 °C;
[a]2D4 + 2.6 (c 0.23, CHCl3); dH(CDCl3) 1.31 (s, 3 H), 1.46 (s, 3 H),
O
Br
O
3
2
O
R
H
O
Me
Me
Me
5
H
O
H
R
O
O
Me
3
4
Scheme 1 Reagents and conditions: Bu4NBr, 50% NaOH, CH2Cl2, 25 °C,
12 h; ii, 75% AcOH, 25 °C, 12 h; iii, PPh3, I2, imidazole, PhMe, reflux, 2
h; iv, Bu3SnH, AIBN, benzene, 200 W lamp, reflux, 10 h
Chem. Commun., 1997
2139

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Å3, Z = 4, Dc = 1.295 g cm23, m(Mo-Ka radiation, l = 0.71073 Å) = 0.86
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2
2
2
(SHELXL93). The function minimised was Sw(F0 2 Fc2) [w = 1/s (F0
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+ (0.06P)2 where P
=
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2
nonhydrogen atoms and isotropic refinement of hydrogen atoms, located
from difference Fourier maps, converged at R1 = 0.0415 (wR2 = 0.0881)
for 1069 reflections with, I > 2s(I). Goodness of fit = 1.146 maximum/
minimum residual electron densities +0.204/20.244
182/616.
e . CCDC
Å23
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Received in Cambridge, UK, 27th August 1997; 7/06249D
2140
Chem. Commun., 1997