Diisobutylaluminium hydride (DIBAL-H) as a molecular scalpel: A new mechanistic proposal for a spiroketal rearrangement

Article abstract of DOI:10.1016/j.tetlet.2004.09.030

Taking advantage of our knowledge of the capacity of DIBAL-H to de-O-alkylate, we propose an alternative mechanism for a spiroketal rearrangement described by E. Suàrez. We also show that this proposal can account for the formation of the secondary product, whose original structure we propose to correct.

Full text of DOI:10.1016/j.tetlet.2004.09.030

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8165–8168
Diisobutylaluminium hydride (DIBAL-H) as a molecular scalpel:
a new mechanistic proposal for a spiroketal rearrangement
*
Xiangbao Meng, Yongmin Zhang, Matthieu Sollogoub and Pierre Sinay
€
´ ´ ´
Ecole Normale Superieure, Departement de Chimie, UMR 8642: CNRS-ENS-Universite Pierre et Marie Curie Paris 6,
24, rue Lhomond, 75231 Paris Cedex 05, France
Received 11 June 2004; revised 6 September 2004; accepted 6 September 2004
Available online 21 September 2004
Abstract—Taking advantage of our knowledge of the capacity of DIBAL-H to de-O-alkylate, we propose an alternative mechanism
`
for a spiroketal rearrangement described by E. Suarez. We also show that this proposal can account for the formation of the sec-
ondary product, whose original structure we propose to correct.
Ó 2004 Elsevier Ltd. All rights reserved.
In our ongoing interest in de-O-benzylation reactions
mediated by aluminium reagents,1–4 we were stimulated
mesyl and a reduction of the formed primary methane-
sulfonyl group, as shown in Scheme 3. A distinctive
feature of both proposed mechanisms is that the meth-
anesulfonate is not chosen as the leaving group in the
presence of an alcoholate on the molecule.
`
by a rearrangement described by Suarez and co-work-
ers.5 This reaction, depicted in Scheme 1, is a DIBAL-
H mediated transformation of the spiroketal 1 into a
major bicyclic product 2. It is, overall, a reductive ring
opening and a nucleophilic substitution to form a dioxa-
decalin, and is interestingly accompanied by a de-O-ben-
zylation reaction. A secondary product is formed; its
supposed structure 3 is shown in Scheme 1.
We have recently demonstrated1 that perbenzylated
methyl a-D-mannopyranoside is de-O-benzylated on
positions 2 and 3 with TIBAL (Scheme 4). DIBAL-H
having similar de-O-benzylating properties, we won-
dered whether the formation of compound 2, having a
manno-type configuration, could be explained in this
way.
The mechanism proposed by the Spanish group for the
formation of 2 is depicted in Scheme 2, the opening
and reduction of the spiroketal being followed by a
reductive debenzylation, which is promoted by a hydride
ion and assisted by the neighbouring methanesulfonyl
group. The alkoxy anion would finally attack the cyclic
adduct to form 2.
In the present paper, we would like to propose an alter-
native mechanism accounting for the formation of the
two products, based on our experience on de-O-benzyla-
tion reactions mediated by DIBAL-H.
`
To explain the formation of the minor product 3, Suarez
et al. proposed that the spiroketal opening and reduc-
tion would be followed by a trans-esterification of the
To this purpose we synthesised the bicyclic compound 8,
that we anticipated to be the precursor of 2. Indeed, it
seemed reasonable to think that the first step of the
`
Scheme 1. E. Suarezꢀs rearrangement of spiroketal 1. Reagents and conditions: (i) DIBAL-H (10equiv), CH2Cl2, reflux, 72h, 72%, 2:3, 3:1.
Keywords: Aluminium; Diisobutylaluminium hydride (DIBAL-H); Carbohydrates; Spiroketal.
*
Corresponding author. Tel.: +33 1 4432 3335; fax: +33 1 4432 3397; e-mail: matthieu.sollogoub@ens.fr
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.030

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X. Meng et al. / Tetrahedron Letters 45 (2004) 8165–8168
`
Scheme 2. E. Suarezꢀs mechanism proposal for the formation of 2.
Scheme 3. E. Sua`rezꢀs mechanism proposal for the formation of 3.
Scheme 4. De-O-benzylation of perbenzylated methyl a-D-mannopyranoside. Reagents and conditions: (i) TIBAL (5equiv), toluene, 50°C, 3h, 89%,
1:1.
Scheme 5. Synthesis of bicyclic compound 8. Reagents and conditions: (i) (a) BH3ÆTHF (2.8equiv), THF, 0°C, 2h; (b) H2O2, NaOH (3N), rt, 30min,
63%. (ii) (a) TBDMSCl (1.2equiv), imidazole (1.5equiv), DMF, rt, 6h; (b) MsCl (12equiv), pyridine, rt, 12h, 73%. (iii) TBAF (1.5equiv), THF, rt,
4h, 96%. (iv) NaH (10equiv), DMF, 60°C, 20h, 67%.
sodium hydride in DMF at 60°C gave the desired bicyc-
lic benzylated compound 8 in 67% yield.
Bicyclic compound 8 was now submitted to the action of
DIBAL-H for 72h at 50°C and the product of the reac-
Scheme 6. Action of DIBAL-H on compound 8. Reagents and
tion showed the same spectral and analytical data as the
conditions: (i) DIBAL-H (10equiv), CH2Cl2, reflux, 72h, 72%.
`
major compound 2 obtained by Suarezꢀs (Scheme 6). No
other product being observed in the reaction, we then
supposed that minor product 3 of the rearrangement
reaction might be formed through a different intermedi-
ate than 8.
rearrangement consisted in the reductive spiroketal ring
opening followed by an intramolecular nucleophilic sub-
stitution of the mesylate to form the bicyclic compound
8. The synthesis of this compound is shown in Scheme 5.
The known C-allyl glucoside 46 is transformed into the
diol 57 thanks to a hydroboration, subsequent selective
silylation of the primary alcohol on 5 followed by mesyl-
ation of the remaining hydroxyl group afforded 6. Desi-
lylation of 6 and treatment of the resulting alcohol 7 by
On careful analysis of NMR data, it appeared to us that
the proposed structure 3 could hardly be a pyranose
ring. To confirm our thought, we reduced the double
bond of 46 into the saturated C-propyl-glucoside 3 and
showed that the NMR8 was clearly different from the
`
one given by Suarez (Scheme 7).

X. Meng et al. / Tetrahedron Letters 45 (2004) 8165–8168
8167
the furanose (path b) rings, next followed by recyclisa-
tion through SN2 type displacement of the mesylate by
`
the formed alcoholate. E. Suarez himself already re-
ported about this possibility elsewhere.11 The second
step would therefore be a de-O-alkylation reaction pro-
moted by excess of DIBAL-H. As recently proposed by
us,4 this de-O-alkylation would start with the formation
of a penta-coordinated complex between the aluminium
reagent and the 1,2-cis oxygen pattern of the sugar. A
second aluminium atom selects the less hindered oxygen
and directs the dealkylation. In the case of product 2,
the benzyl on position 3 is cleaved, in the case of 3 re-
vised the less substituted tetrahydrofuranic ring is
opened (Scheme 9).
Scheme 7. Synthesis of C-propyl-glucoside 3. Reagents and condi-
tions: (i) H2, PtO2, AcOEt, rt, 30min, 75%.
In fact, we also reproduced the rearrangement reaction
`
as described by Suarez et al. and isolated the two same
products that we analysed by NMR. Hence, we propose
another structure for the minor product,9 whose NMR
compares very well to closely related furanosidic com-
pound.10 (Scheme 8 and supporting information).
In conclusion, we propose that the mechanisms account-
ing for the formation of 2 and 3 revised are both com-
posed, as shown in Scheme 9, of two independent
reactions. The first step would consist in the spiroketal
reductive opening of either the pyranose (path a) or
In summary, it is worth noting that DIBAL-H is a pow-
erful agent of de-O-alkylation, provided that a suitable
1,2-cis deoxygenated pattern is available on the mole-
cule. This work offers two more examples of DIBAL-
H acting so-to-say as molecular scalpel.12
`
Scheme 8. E. Suarezꢀs rearrangement of spiroketal 1 with the revised structure for the minor product. Reagents and conditions: (i) DIBAL-H
(10equiv), CH2Cl2, reflux, 72h, 72%, 2:3 revised, 3:1.
Scheme 9. New proposal for the formation of 2 and 3 revised from 1.

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X. Meng et al. / Tetrahedron Letters 45 (2004) 8165–8168
6. Cipolla, L.; Lay, L.; Nicotra, F. J. Org. Chem. 1997, 62,
6678–6681.
Acknowledgements
7. Shuto, S.; Terauchi, M.; Yahiro, Y.; Abe, H.; Ichikawa,
S.; Matsuda, A. Tetrahedron Lett. 2000, 41, 4151–4155.
8. 1H NMR (400MHz, CDCl3): d 7.40–7.20 (m, 15H, H-
arom.), 5.02 (d, 1H, J = 11.5Hz, CH2Ph), 4.85 (d, 1H,
J = 10.8Hz, CH2Ph), 4.77 (d, 1H, J = 11.5Hz, CH2Ph),
4.69 (d, 1H, J = 12.3Hz, CH2Ph), 4.64 (d, 1H, J = 10.5Hz,
CH2Ph), 4.61 (d, 1H, J = 12.1Hz, CH2Ph), 3.78 (dd, 1H,
The authors would like to thank the French Ministry of
Research and Technology for post-doctoral fellowship
to XM (No. 2003-375).
Supplementary data
0
0
J5,6 = 2.3, J6,6 = 11Hz, H-6), 3.74 (dd, 1H, J5,6 = 4Hz, H-
60), 3.66 (t, 1H, J4,3 = J4,5 = 9.3Hz, H-4), 3.52 (t, 1H,
J3,2 = 9Hz, H-3), 3.46 (ddd, 1H, H-5), 3.35 (t, 1H,
J2,1 = 9.1Hz, H-2), 3.22 (dt, 1H, J1,2 = J1,7 = 9.1,
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/
j.tetlet.2004.09.030.
0
J1,7 = 2.5Hz, H-1), 2.11 (br s, 1H, OH), 1.82 (dddd, 1H,
J = 2.5, J = 4.4, J = 10.3Hz, H-7), 1.68–1.37 (m, 3H, H-70,
H-8), 0.97 (t, 3H, J9,8 = 7.3Hz, H-9); 13C NMR (100MHz,
CDCl3): d 138.6, 138.2, 138.0 (3C arom. quat.), 128.7–
127.5 (C arom.), 86.9 (C-3), 79.2 (C-1), 79.0 (C-5), 78.6 (C-
4), 75.1, 74.7, 73.4 (3CH2Ph), 73.9 (C-2), 69.0 (C-6), 33.8
(C-7), 18.5 (C-8), 14.1 (C-9).
References and notes
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´
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2. Chevalier-du Roizel, B.; Cabianca, E.; Rollin, P.; Sinay, P.
€
Tetrahedron 2002, 58, 9579–9583.
€
9. The absolute configuration of the exocyclic stereocenter
has not been determined in this work.
10. Persky, R.; Albeck, A. J. Org. Chem. 2000, 65, 5632–5638.
3. Pearce, A. J.; Sinay, P. Angew. Chem. 2000, 112, 3756–
3758; Angew. Chem., Int. Ed. 2000, 39, 3610–3612.
´
´
4. Lecourt, T.; Herault, A.; Pearce, A. J.; Sollogoub, M.;
Sina, P. Chem. Eur. J. 2004, 12, 2960–2971.
´ `
5. Betancor, C.; Dorta, R. L.; Freire, R.; Prange, T.; Suarez,
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T.; Sua`rez, E. J. Org. Chem. 1998, 63, 6355–6362.
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