From carbohydrates to polyoxygenated cyclooctenes via ring-closing metathesis

Full text of DOI:10.1021/jo0155761

4094
J . Org. Chem. 2001, 66, 4094-4096
capped cases where they displayed activity beyond that
F r om Ca r boh yd r a tes to P olyoxygen a ted
Cycloocten es via Rin g-Closin g Meta th esis
of the parent complex 1.7
Franc¸ois-Didier Boyer,† Issam Hanna,*,‡ and
Steven P. Nolan§
Unite´ de Phytopharmacie et Me´diateurs Chimiques,
I.N.R.A., Route de Saint-Cyr, F-78026 Versailles, France,
Laboratoire de Synthe`se Organique associe´ au CNRS, Ecole
Polytechnique, F-91128 Palaiseau, France, and Department
of Chemistry, University of New Orleans, Louisiana 70148
Carbohydrate to carbocycle transformations offer an
attractive route for the synthesis of optically active
natural products.8 Although a wide range of methods for
producing functionalized five-, six-, and seven-membered
rings from sugars are available,9,10 only two reports have
been published on the preparation of cyclooctenes using
Claisen rearrangement of 2-methylene-C-vinyl glyco-
sides.11 In an extension of our previous work on the
synthesis of medium-sized rings from carbohydrates,12
we report here studies dealing with substitution pattern
effects on the construction of polyoxygenated cyclooctenes
by RCM reaction and a comparative investigation of the
reactivity of catalysts 1 and 2.
The RCM precursors were prepared from methyl
6-deoxy-6-iodoglycosides 8a -c13 as illustrated in Scheme
1. Reductive ring-opening with zinc dust under sonication
converted 8 to aldehyde 9 in nearly quantitative yield.
Treatment of 9 with butenylmagnesium bromide at -60
°C in THF and subsequent protection of the resulting
alcohol 10 afforded acetate 11 in 63-77% overall yield
from 8. While addition of the Grignard reagent to 9b (R
) TBDMS) in ether gave a single alcohol, this reaction
has been found less stereoselective in THF and led, after
protection, to 11b as a mixture of diastereomers in 1.3:1
ratio. In the same manner 11a (R ) Bn) and 11c [R )
triethylsilyl (TES)] were obtained as a mixture of dia-
hanna@poly.polytechnique.fr
Received February 15, 2001
The construction of eight-membered rings, present in
many biologically active natural products, remains a
prominent synthetic challenge owing to the difficulties
associated with cyclooctane chemistry.1 Of all ring sizes,
the formation of these compounds by intramolecular ring
closure reactions is the most difficult. Despite the un-
favorable thermodynamic factors that impede the prepa-
ration of eight-membered rings, the olefin ring-closing
metathesis reaction (RCM)2 has been successfully applied
to the synthesis of carbocyclic rings of this size.3 The
presence in the substrates of conformational constraints,
such as preexisting rings, greatly facilitated the assembly
of cyclooctyl derivatives. In some cases the commercially
available Grubbs ruthenium catalyst 1 has been shown
to be of great efficiency.4 In contrast, previous attempts
to cyclize conformationaly flexible acyclic dienes to eight-
membered carbocycles using 1 have proven unsuccessful.
It has been shown that the replacement of one of the
phosphine ligands in 1 with a sterically demanding
nucleophilic carbene (e.g., N,N′-bis(mesityl)imidazol-2-
ylidene, IMes) to yield 25 leads to increased ring-closing
activity. This catalyst and its saturated imidazol-2-
ylidene analogue 36 have been applied to several handi-
(7) For recent examples on the use of catalysts 2 and 3, see: (a)
Efremov, I.; Paquette, L. A. J . Am. Chem. Soc. 2000, 122, 9324-9325.
(b) Lee, C. W.; Grubbs, R. H. Org. Lett. 2000, 2, 2145-2147 and
references therein. (c) Bourgeois, D.; Mahuteau, J .; Pancrazi, A.; Nolan,
S. P.; P.; Prunet, J . Synthesis 2000, 869-882. (d) Fu¨rstner, A.; Thiel,
O.; R.; Ackermann, L.; Schanz, H.-J .; Nolan, S. P. J . Org. Chem. 2000,
651, 2204-2207. (e) Briot, A.; Bujard, M.; Gouverneur, V.; Nolan, S.
P.; Mioskowski, C. Org. Lett. 2000, 2, 1517-1519.
† Unite´ de Phytopharmacie et Me´diateurs Chimiques, I.N.R.A.
‡ Ecole Polytechnique.
§ University of New Orleans.
(1) For reviews, see: (a) Petasis, N. A.; Patane, M. A. Tetrahedron
1992, 48, 5757-5821. (b) Mehta, G.; Singh, V. Chem. Rev. 1999, 99,
881-930.
(2) For recent reviews concernig ring-closure metathesis reactions,
see (a) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18-29.
(b) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012-3043. (c)
Armstrong, S. K. J . Chem. Soc., Perkin Trans. 1 1998, 371-388. (d)
Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413-4450.
(3) For a recent review see: Maeir, M. E. Angew. Chem., Int. Ed.
2000, 39, 2073-3077.
(4) For earlier examples of cyclooctene syntheses by RCM, see: ref
1. For more recent applications, see: (a) Paquette, L. A.; Schloss, J .
D.; Efremov, I.; Fabris, F.; Gallou, F.; Me´ndez-Andino, J .; Yang, J . Org.
Lett. 2000, 2, 1259-1261. (b) Paquette, L. A.; Tae, J . Arrington, M.
P.; Sadoun, A. H. J . Am. Chem. Soc. 2000, 122, 2742-2748 and
references therein. (c) Bourgeois, D.; Pancrazi, A.; Ricard, L.; P.;
Prunet, J . Angew. Chem., Int. Ed. 2000, 39, 725-728. For recent
reports on the synthesis of cyclic ethers of eight-membered ring, see:
Clark, J . S.; Hamelin, O. Angew. Chem., Int. Ed. 2000, 39, 372-374.
Crimmins, M. T.; Choy, A. L. J . Am. Chem. Soc. 1999, 121, 5653-
5660.
(8) For reviews, see: (a) Dalko, D. I.; Sinay¨, P. Angew. Chem., Int.
Ed. 1999, 38, 773-777. (b) Ferrier, R. J .; Middleton, S. Chem. Rev.
1993, 93, 2779-2831.
(9) For recent examples, see: (a) Ackermann, L.; El Tom, D.;
Fu¨rstner, A. Tetrahedron 2000, 56, 2195-2202. (b) Sollogoub, M.;
Mallet, J .-M.; Sinay¨, P. Angew. Chem., Int. Ed. 2000, 39, 362-364. (c)
Kan, T.; Nara, S.; Ozawa, T.; Shirahama, H.; Matsuda, F. Angew.
Chem., Int. Ed. 2000, 39, 355-357. (d) Collam, C. S.; Lowry, T. L. Org.
Lett. 2000, 2, 167-169. (e) Hyldtof, L.; Poulsen, C. S.; Madsen, R.
Chem. Commun. 1999, 122, 2101-2102. (f) Kornienko, A.; d’Alarcao,
M. Tetrahedron: Asymmetry 1999, 10, 827-829. (g) Ovaa, H.; Code´e,
J . D. C.; Lastrager, B.; Overkleeft, H. S.; van der Marel, G.; van Boom,
J . Tetrahedron Lett. 1999, 40, 5063-5066.
(10) For the synthesis of cycloheptane derivatives from carbohy-
drates, see: (a) Marco-contelles, J .; de Opazo, E. Tetrahedron Lett. 1999,
40, 4445-4448. (b) Marco-contelles, J .; de Opazo, E. J . Org. Chem.
2000, 65, 5416-5419. (c) Boyer, F.-D.; Lallemand, J .-Y. Tetrahedron
1994, 50, 10443 and Boyer, F.-D.; Lallemand, J .-Y. Synlett 1992, 969-
971. (d) Duclos, O.; Dure´ault, A.; Depezay, J . C. Tetrahedron Lett. 1992,
33, 1059-1062.
(5) This catalyst was originally and almost simultaneously described
by the groups of Nolan and Grubbs: Huang, J .; Stevens, E. D.; Nolan,
S. P.; Peterson, J . L.. J . Am. Chem. Soc. 1999, 121, 2674-2678. Scholl,
M.; Trnka, T. M.; Morgan, J . P.; Grubbs, R. H. Tetrahedron Lett. 1999,
40, 2247-2250.
(6) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953-956.
(11) For the synthesis of cyclooctane derivatives from sugars, see:
(a) Wang, W.; Zhang, Y.; Sollogoub, M.; Sinay¨, P. Angew. Chem., Int.
Ed. 2000, 39, 2466-2467. (b) Werschkum, B.; Thiem, J . Angew. Chem.,
Int. Ed. 1997, 36, 2793-2794.
(12) Hanna, I.; Ricard, L. Org. Lett. 2000, 2, 2651-2654.
10.1021/jo0155761 CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/25/2001

Notes
J . Org. Chem., Vol. 66, No. 11, 2001 4095
Sch em e 1
Ta ble 1. RCM for Cycloocten e Der iva tives Usin g Ca ta lysts 1 or 2
a
c
Isolated yield. bIn refluxing dichloromethane. In refluxing benzene. dReference 12.

4096 J . Org. Chem., Vol. 66, No. 11, 2001
Notes
stereomers in 2.1:1 and 3:1 ratios, respectively. The anti
configuration of the new asymmetric center in the major
isomer was assigned on the basis of the RCM reaction
product (vide infra). On the other hand, oxidation of the
crude alcohols 10 with the Dess-Martin periodinane
reagent16 furnished ketones 12 in 65-75% overall yield
from 8.
The dienes prepared above were submitted to RCM in
(3-6) × 10-3 M solution in dichloromethane or benzene.
For dienes 13-18 (Table 1), the reaction was carried out
either separately on each diastereomer or on the mixture.
In the latter case, the separation was undertaken at this
stage. It is worthy of note that, except for diene 16, both
diastereomers led to the cyclized products roughly in the
same yield.
As can be seen from the results compiled in Table 1,
dienes 13-15 bearing one or two acetonide groups gave
the corresponding cyclooctenes 23-25 in excellent yield
using Grubbs catalyst 1 in refluxing dichloromethane.12
The same catalyst has been found efficient for the
cyclization of the syn acetate 16a , affording 26a in 96%
yield. However, when the isomer anti 16b was treated
with catalyst 1 (10 mol %) either in refluxing dichloro-
methane or benzene for 18 h, the cyclized product 26b
was obtained in modest yield (49 and 40%, respectively).
In contrast, catalyst 2 in refluxing benzene converted 16b
into 26b in 95% yield (Table 1, entries 4-7). Hydrolysis
of this isomer (MeONa, MeOH, rt) led to the cyclooctenol
derivative 27b which is identical to the product described
by Sinay¨ et al.11a Thus the anti configuration of the
acetate group in this compound is established.
Treatment of diene 17, in which the allylic benzyloxy
group (OBn) was replaced by tert-butyldimethylsilyloxy
(OTBDMS), with catalyst 1 (10%) in refluxing CH2Cl2 for
24 h gave the corresponding dimer (mixture of Z and E
isomers) as the only isolated product in 64% yield. At
higher temperature (refluxing benzene), 17 led to a
mixture of the desired cyclooctene 28 and the dimeriza-
tion product together with unreacted starting material.
The same results were obtained with diene 18. A resolu-
tion of this problem was provided by the use of catalyst
2. In fact, treatment of 17 and 18 with 6% of 2 in
refluxing benzene for 2.5 h delivered 28 and 29, respec-
tively, in 95% and 94% yields (entries 8 and 9).
The RCM reactions of dienones 19-22 were next
investigated. Treatment of 19 with 1 in refluxing dichloro-
methane (13 mol %) for 21 h afforded cyclooctenone 30
in 68% yield (entry 10). Use of catalyst 2 (10 mol % in
refluxing CH2Cl2 for 1.5 h) increased the yield to 86%.
In the cases of dienones 20-22 only the use of catalyst 2
allowed the preparation of corresponding cyclooctenones
in synthetically useful yields (66-68%) (entries 12-14).
Obviously, the easier reaction with 19 is the result of the
presence of the acetonide group which acts as a confor-
mational constraint. The lower reactivity of ketodienes
20-22 compared to the corresponding acetates 16-18
suggested that carbonyl group might coordinate to the
ruthenium metal center, as does free hydoxyl group,17
changing catalyst properties.
(13) Compounds 8a -c were prepared by the known procedures
starting from methyl-R-D-glucopyranoside 4 as indicated in the fol-
lowing scheme. Compounds 7 and 8a were obtained by iodination with
PPh3-I2 reagent,14 8b and 8c from 7 by silylation with TBDMSOTf or
TESOTf in 2,6-lutidine-CH2Cl2.
In summary, we have developed a concise route to
polyoxygenated cyclooctenes from carbohydrates using
the ring-closing metathesis. In this reaction, 1,3-bis-
(mesityl)imidazol-2-ylidene ruthenium complex 2 shows
enhanced RCM activity compared to its parent 1. Even
in the absence of the acetonide group which acts as a
conformational contraint, catalyst 2 has been found
efficient for the eight-membered ring annulation.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure and characterization data for compounds 23-26b and
28-33. This material is available free of charge via Internet
at http://pubs.acs.org.
J O0155761
(14) Garegg, P. J .; J ohansson, R.; Ortega, C.; Samuelson, B. J . Chem.
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(15) Bernet, B.; Vasella A. Helv. Chim. Acta 1979, 62, 1990-2016.
(16) Dess, D. B.; Martin, J . C. J . Org. Chem. 1983, 48, 4155-4156.
Meyer, S. D.; Schreiber, S. L. J . Org. Chem. 1994, 59, 7549-7552.
(17) For the effect of hydroxyl group on RCM reaction, see Hoyes,
T. R.; Zhao, H. Org. Lett. 1999, 1, 1123-1125 and refs 7b and 10b.