Triisobutylaluminium mediated carbocyclisation of sugar derived spiroketals and ketosides

Article abstract of DOI:10.1016/S0040-4039(00)02318-2

The carbocyclisation of sugar derived spiroketals and ketosides under the agency of triisobutylaluminium is presented. In addition, the synthetic usefulness of cyclooctenic product 21, derived from the corresponding exo-glycal 20, was shown by its transformation into conformationally locked L-idose analogues 22 and 23.

Full text of DOI:10.1016/S0040-4039(00)02318-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1769–1772
Triisobutylaluminium mediated carbocyclisation of sugar derived
spiroketals and ketosides
Peter A. V. van Hooft,a Gijsbert A. van der Marel,a Constant A. A. van Boeckelb and
Jacques H. van Booma,*
aLeiden Institute of Chemistry, PO Box 9502, 2300 RA Leiden, The Netherlands
bLead Discovery Unit, N.V. Organon, PO Box 20, 5340 BH Oss, The Netherlands
Received 13 December 2000; accepted 19 December 2000
Abstract—The carbocyclisation of sugar derived spiroketals and ketosides under the agency of triisobutylaluminium is presented.
In addition, the synthetic usefulness of cyclooctenic product 21, derived from the corresponding exo-glycal 20, was shown by its
transformation into conformationally locked L-idose analogues 22 and 23. © 2001 Elsevier Science Ltd. All rights reserved.
In 1997, Sinay¨ et al.1 reported for the first time that
fully benzylated a- or b-methyl 5-hexeno- -pyranosides
Two years ago, we revealed3 that perbenzylated
ketosides 4a (see Scheme 2), accessible by K-10 clay4
mediated stereoselective glycosidation of ketoses 3a
with allyl alcohol, were easily converted into the corre-
sponding spiroketals 5a by ring-closing metathesis5
(RCM). It was also established6 that the use of the
mono-silylated ketoses 3b–c led to the ketosides 4b–c
and spiroketals 5b–c. The ease of transforming the
latter orthogonally protected derivatives into the corre-
sponding exo-glycals urged us to explore whether these
compounds were amenable to TIBAL-mediated
carbocyclisation.7
D
1a (gluco, galacto and manno) undergo a triisobutylalu-
minium (TIBAL) promoted rearrangement (see Scheme
1) to give cyclohexane derivatives 2a with retention of
configuration at the anomeric centre. Later on, it was
shown2 that the same rearrangement also occurred in
the case of exo-glycals bearing other anomeric electron
donating groups. Thus, rearrangement of the exo-gly-
cals having 1-thio(seleno)phenyl (i.e. compounds 1b) or
C-aryl/furanyl groups (i.e. compounds 1c) resulted in
the corresponding carbocycles 2b–c.2
In order to substantiate this assumption, we initially
explored (see Scheme 3) the carbocyclisation of the
requisite dioxaspiro[4.5]decene 7, the synthesis of which
can be readily accomplished by the following three-step
sequence. Thus, desilylation of 5b, followed by
iodination8 gave iodide 6.9 Hydrogen iodide elimination
of 6 proved to be most effective using sodium hydride
Scheme 1. a: X=OMe; b: X=S(Se)phenyl; c: X=C-aryl/
furanyl.
Scheme 2. a: R=Bn, n=0, 1; b: R=TBDMS, n=0; c: R=TBDMS, n=1.
Keywords: carbocycles; triisobutylaluminium; spiroketals; cyclohexane; carbohydrates.
* Corresponding author. Tel.: +31 71 5274274; fax: +31 71 5274307; e-mail: j.boom@chem.leidenuniv.nl
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02318-2

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Scheme 3. Reagents and conditions: (i) (a) TBAF, THF, (b) I2, imidazole, PPh3, toluene, D (6, 10: 86%); (ii) NaH (60% disp.),
DMF, 20°C; (iii) TIBAL (4 equiv.), toluene, 20°C (8: 76% based on 6; 12: 81% based on 10); (iv) Ac2O, pyridine (9, 13: 99%).
Scheme 4. Reagents and conditions: (i) (a) TBAF, THF, (b) I2, imidazole, PPh3, toluene, D, (c) NaH (60% disp.), DMF, 20°C; (ii)
TIBAL (4 equiv.), toluene, 20°C (38% based on 4c); (iii) 16 (0.002 equiv.), CH2Cl2, D (92%); (iv) Ac2O, pyridine, 20°C (84%).
Scheme 5. Reagents and conditions: (i) (a) TBAF, THF, (b) I2, imidazole, PPh3, toluene, D, (c) NaH (60% disp.), DMF, 20°C (19:
,
82%; 20: 99%); (ii) MeOH (6 equiv.), K-10 clay (200 mass%), 3 A sieves, CH2Cl2, 20°C (74%); (iii) TIBAL (4 equiv.), toluene,
20°C (83%); (iv) p-TsOH, aq. THF, 20°C (86%); (v) m-CPBA, CH2Cl2, 20°C (51%).
resulting in the isolation of the spiroketal 7. Ensuing
rearrangement of crude 7 under the agency of excess
TIBAL proceeded smoothly to afford the 1-oxas-
high preference for hydrogen delivery from the b-face
of the newly formed cyclohexane ring to give an axial
orientated hydroxyl function (i.e. (R)-configuration).
piro[4.5]decene
8
in 65% overall yield as one
diastereoisomer, the identity of which was firmly
established by NOE experiments for the mono-acetyl-
ated spirocycle 9.9
On the basis of the above results it was of interest to
establish whether the stereochemical outcome of the
TIBAL-mediated rearrangement of allylketoside 14
would afford a cyclohexane derivative with the same
stereochemistry at C-8. However, carbocyclisation of
substrate 14 (see Scheme 4), easily prepared from 4c
by the earlier mentioned three-step sequence, led to
the exclusive isolation of product 15 having an axial
hydroxyl at C-8, as gauged by NMR spectroscopy.
The assignment of (R)-configuration of the latter
stereogenic centre was also fully ascertained by com-
parison of the NMR data of the mono-acetylated
spiroketal 13 with those of its epimer 18,9 resulting
from a high yielding RCM of 15 using 0.2 mol% of
the new Grubbs’ pre-catalyst 16,10 and subsequent
acetylation.
Similarly, TIBAL-mediated rearrangement of dioxa-
spiro[5.5]undecene 11, prepared by subjecting 5c to the
same sequence of reactions as mentioned for the con-
version of 5b into 7, resulted in the isolation of the
1-oxaspiro[5.5]undecene 12 in a 67% overall yield. The
assignment of the (S)-configuration to C-8 in 12 was
also in this case based on NOE measurements for the
mono-acetylated spirocycle 13.9 The observed stereo-
chemical outcome of both carbocyclisation reactions is
in sharp contrast with the previously reported1,2
TIBAL-mediated rearrangement of the 5-hexeno-
D-
glucopyranosides 1a–c, all of which proceeded with a

P. A. V. 6an Hooft et al. / Tetrahedron Letters 42 (2001) 1769–1772
1771
At this stage, the carbocyclisation of the vinylketoside
19 was undertaken (see Scheme 5). Unfortunately, reac-
tion of compound 19, prepared in the usual way start-
ing from 4b, with TIBAL led to a complex mixture of
products instead of the expected [3,3]-sigmatropic rear-
rangement.2a On the other hand, subjection of the
methyl vinylketoside 20, constructed by K-10 mediated
condensation of 3b with excess methanol and further
processing as mentioned before, gave the cyclooctenic
carbocycle 21,9 the identity of which was firmly estab-
lished by NMR spectroscopy.
5. Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1996, 118, 100.
6. Unpublished results.
7. Carbocyclisation of a glucose-derived enolic ortho ester
using TiCl4 has been reported previously: Bourke, D. G.;
Collins, D. J.; Hibberd, A. I.; McLeod, M. D. Aust. J.
Chem. 1996, 49, 425.
8. Garegg, P. J.; Samuelsson, B. Synthesis 1979, 813.
1
9. All new compounds were fully characterised by H (200
or 300 MHz) and 13C (50 or 75 MHz) NMR spec-
troscopy as well as mass spectrometry. Relevant spectro-
scopic data of the selected compounds 9, 13, 18, 21 and
1
The synthetic usefulness of this functionalised Claisen
rearrangement product11 was demonstrated by its con-
22 are as follows. 9: H NMR (300 MHz, CDCl3): l 5.99
(d, 1H, J 6.1 Hz, H-3), 5.49 (m, 1H, H-4), 5.18–5.27 (m,
1H, H-7), 4.67–4.89 (m, 5H, H-2a,2b and CH2 Bn), 4.58
(d, 1H, J 10.9 Hz, CH2 Bn), 3.96 (t, 1H, J 9.5 Hz, H-9),
3.53 (t, 1H, J 9.5 Hz, H-8), 3.40 (d, 1H, J 9.5 Hz, H-10),
2.03 (dd, 1H, J 5.1 and 13.1 Hz, H-6a), 1.93 (s, 3H, CH3
Ac), 1.51 (t, 1H, J 12.9 Hz, H-6b); 13C NMR (75 MHz,
CDCl3): l 105.4 (C-5), 91.0 (C-2), 72.5, 83.9, 84.6 and
84.8 (C-6,7,8,9), 76.0, 76.2 and 76.9 (CH2 Bn), 38.4
(C-10), 22.0 (CH3 Ac); MS (ESI): calcd for C32H34O6
514.2, found m/z 537.2 [M+Na]+. 13: 1H NMR (300
MHz, CDCl3): l 5.66 (m, 2H, H-3,4), 4.94–5.08 (m, 1H,
H-8), 4.65, 4.76, 4.87 and 4.98 (4d, each 1H, J 11.3 Hz,
CH2 Bn), 4.90 (s, 2H, CH2 Bn) 4.14–4.38 (m, 2H, H-
2a,2b), 4.16 (t, 1H, J 9.3 Hz, H-10), 3.61 (t, 1H, J 9.4 Hz,
H-9), 3.28 (d, 1H, J 9.6 Hz, H-11), 2.59–2.65 (m, 1H,
H-5a), 2.58 (dd, 1H, J 4.5 and 13.9 Hz, H-7a), 1.95 (s,
3H, CH3 Ac), 1.30 (m, 1H, H-5b), 1.03 (dd, 1H, J 12.1
and 13.9 Hz, H-7b); MS (ESI): calcd for C33H36O6 528.3,
found m/z 551.5 [M+Na]+. 18: 1H NMR (300 MHz,
CDCl3): l 5.67–5.80 (m, 2H, H-3,4), 5.57 (d, 1H, J 3.3
Hz, H-8), 4.66, 4.73, 4.83, 4.93, 5.04 and 5.12 (6d, each
1H, J 11.4, 11.3 and 10.7 Hz, CH2 Bn), 4.41 (t, 1H, J 9.6
Hz, H-10), 4.34 (m, 1H, H-2a), 4.09 (bd, 1H, J 17.7 Hz,
H-2b), 3.60 (dd, 1H, J 3.7 and 9.7 Hz, H-9), 3.28 (d, 1H,
J 9.6 Hz, H-11), 2.75 (bd, 1H, J 17 Hz, H-5a), 2.62 (dd,
1H, J 3.0 and 16.2 Hz, H-7a), 2.19 (s, 3H, CH3 Ac),
1.33–1.42 (m, 1H, H-5b), 1.19 (dd, 1H, J 3.0 and 16.2 Hz,
H-7b); 13C NMR (75 MHz, CDCl3): l 170.6 (CꢀO), 122.1
and 124.6 (C-3,4), 66.8, 79.6, 81.0 and 83.8 (C-7,8,9,10),
72.1, 73.4, 75.6 and 76.0 (C-6 and CH2 Bn), 60.9 (C-2),
30.1 and 30.6 (C-5,7), 22.4 (CH3 Ac); MS (ESI): calcd for
version into the conformationally restricted
L-idose
derivative 22. Thus, acid catalysed ring-closure of com-
pound 21 led to the exclusive formation of
L-idose
analogue 22.9 1H NMR spectroscopy of 22 clearly
4
indicated that the pyranose ring adopts a C1-confor-
mation, based on the trans configuration of H-2, 3 and
4. Moreover, treatment of 21 with m-CPBA led to the
isolation of the
L
-idose analogue 23 containing an
additional equatorial hydroxyl group, as gauged by
NMR spectroscopy. The stereochemical outcome of the
latter reaction results from a stereoselective epoxidation
followed by acid catalysed intramolecular ring-closure.
In conclusion, the results presented in this paper clearly
show that the TIBAL-mediated rearrangement of exo-
glycal derivatives 1a–c can be extended to sugar derived
spiroketals as well as ketosides to give the correspond-
ing carbacyclic derivatives in a highly diastereoselective
fashion. The synthetic usefulness of cyclooctenic deriva-
tive 21, obtained by a TIBAL-catalysed Claisen rear-
rangement of methyl vinylketoside 20, was illustrated
by its conversion into conformationally restricted ana-
logues of
L
-idose. Further exploitation of 21 is cur-
rently under investigation and will be reported in due
course.
Acknowledgements
The authors thank Fons Lefeber and Kees Erkelens for
recording the COSY and NOESY spectra and Hans
van den Elst for performing the mass spectrometric
analyses.
1
C33H36O6 528.3, found m/z 551.4 [M+Na]+. 21: H NMR
(200 MHz, CDCl3): l 4.80 (t, 1H, J 6.6 Hz, H-1), 4.78 (d,
1H, J 8.8 Hz, H-3), 4.28, 4.43, 4.55, 4.63, 4.66 and 4.90
(6d, each 1H, J 11.0 and 11.7 Hz, CH2 Bn), 4.19 (m, 1H,
H-6), 4.03 (dd, 1H, J 4.4 and 8.8 Hz, H-4), 3.73 (dd, 1H,
J 4.4 and 8.0 Hz, H-5), 3.44 (s, 3H, CH3), 3.35 (s, 1H,
OH), 2.34–2.41 (m, 1H, H-7a), 1.76–2.02 (m, 3H, H-
7b,8a,8b); 13C NMR (50 MHz, CDCl3): l 151.8 (C-2),
101.0 (C-1), 83.0 (C-4), 79.6 (C-5), 77.8 (C-3), 70.9, 72.8
and 74.7 (CH2 Bn), 71.2 (C-6), 54.3 (CH3), 33.8 (C-7),
18.7 (C-8); MS (ESI): calcd for C30H34O5 474.2, found
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1772
P. A. V. 6an Hooft et al. / Tetrahedron Letters 42 (2001) 1769–1772
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