Scheme 2a
Scheme 3a
a Legend: (i) (a) PhSeCl, EtOAc, 20 °C, 16 h, (b) m-CPBA,
NaHCO3, CH2Cl2, -78 to -20 °C, 1 h, then DMS, Et3N, 0 °C, 1
h (52%); (ii) NaBH4, CeCl3‚7H2O, MeOH, 0 °C, 4 h (56%); (iii)
CCl3CN, NaH (60% disp.), CH2Cl2, 0 °C, 6 h (57%); (iV) K2CO3,
1,2-dichlorobenzene, ∆, 2 h (80%).
a Legend: (i) TBSOTf (1.2 equiv), DiPEA (1.2 equiv), CH2Cl2,
-20 °C, 30 min (95%); (ii) p-TsOH, aqueous THF, 30 min (93%);
(iii) m-CPBA, CH2Cl2, 20 °C, 20 h (95%); (iV) m-CPBA (4 equiv),
NaHCO3 (3 equiv), CH2Cl2, 20 °C, 20 h (64%); (V) 1 M NaOH,
THF, 2 h (84%); (Vi) NaOMe, MeOH, 2 h (78%).
To this end, 6 was first converted into the R,â-unsaturated
ketone 11. Initial attempts to achieve this objective following
a standard protocol6 (i.e., LDA, benzeneselenyl chloride
(PhSeCl), then 30% H2O2) were unsatisfactory. On the other
hand, reaction of 6 with PhSeCl in ethyl acetate,7 followed
by oxidation of the resulting crude selenyl derivative with
m-CPBA and subsequent elimination,8 furnished the R,â-
unsaturated ketone 11 in 52% yield. Luche reduction9 of 11
with cerium(III) chloride and sodium borohydride in metha-
nol at 0 °C proceeded in a stereoselective fashion to give
(3R,4S,5R,6R,7S)-4,5,6-tri(benzyloxy)-7-tert-butyldimethyl-
silyloxy-3-hydroxycyclooct-1-ene (12), as evidenced by
NMR spectroscopy. Ensuing Overman rearrangement10 under
the improved conditions of Isobe et al.11 of the trichloro-
acetimidate 13, easily accessible by reaction of 12 with
trichloroacetonitrile in the presence of sodium hydride at 0
°C, gave the corresponding (3S,4R,5R,6S,8R)-3,4,5-tri(benz-
yloxy)-6-tert-butyldimethylsilyloxy-8-trichloroacetamidocy-
clooct-1-ene (14) in 46% yield over two steps. NOESY
experiments showed that the stereochemistry of 14 is in full
accordance with the proposed structure.
(see Scheme 2) resulted in the near quantitative isolation of
bicyclic compound 4, instead of the silylated carbocycle 5.
On the other hand, protection of 2 using tert-butyldimeth-
ylsilyl trifluoromethanesulfonate in the presence of N,N-
diisopropylethylamine in dichloromethane at -20 °C af-
forded 5 in an excellent yield. Subjection of 5 to a catalytic
amount of acid gave ketone 6 and a small amount of a
product with a higher Rf value. At this stage, it was of interest
to find out whether 6 would be compatible with a Baeyer-
Villiger oxidation under acidic conditions. It turned out that
reaction of 6 with m-chloroperoxybenzoic acid (m-CPBA, 2
equiv) in anhydrous dichloromethane led to the sole forma-
tion of the 1-O-silyl L-idose derivative 7, which was in every
aspect identical to the minor product observed in the
aforementioned acid-catalyzed reaction of 5. This result
indicates that the silyl protecting group in 5 does not inhibit
the highly favorable 6-exo-trig ring-closing reaction under
acidic conditions. Fortunately, oxidation of 6 under basic
conditions afforded the expected4 lactone 8. The regioselec-
tivity of the latter oxidation was corroborated independently
by ring opening of 8 with either NaOH or NaOMe to give
the respective open-chain derivatives 9 and 10, the structures
of which were fully ascertained by mass spectrometry as well
as NMR spectroscopy. The formation of the R,â-unsaturated
aldehydes 9 and 10 can be readily explained by base-assisted
elimination5 of benzyl alcohol from the initially formed
aldehyde.
The synthetic usefulness of allylic alcohol 12 was exem-
plified further by its transformation into the cis-oxazolidinone
derivative 16 (see Scheme 4) via a two-step sequence recently
devised by Nicolaou and co-workers.12 Accordingly, the
requisite urethane function in 15 was obtained by reaction
of 12 with p-methoxyphenyl isocyanate in the presence of
(6) For a review on the preparation of R,â-unsaturated ketones, see:
Reich, J.; Wollowitz, S. In Organic Reactions, Volume 44; Paquette, L.
A., Ed.; Wiley: New York, 1993.
The ketone function in 6 also offers a suitable handle for
the installation of different functionalities on the carbocyclic
framework. The latter possibility is demonstrated in the
synthesis of the allylic amine derivative 14 (see Scheme 3).
(7) Liotta, D.; Barnum, C.; Puleo, R.; Zima, G.; Bayer, C.; Kezar, H. S.
J. Org. Chem. 1981, 46, 2920. (b) Baker, R.; Gibson, C. L.; Swain, C. J.;
Tapolczay, D. J. J. Chem. Soc., Perkin Trans. 1 1985, 1509.
(8) Vedejs, E.; Wittenberger, S. J. J. Am. Chem. Soc. 1990, 112, 4357.
(9) Gemal, A. L.; Luche, J.-L. J. Am. Chem. Soc. 1981, 103, 5454.
(10) Overman, L. E. J. Am. Chem. Soc. 1976, 98, 2901.
(11) Nishikawa, T.; Asai, M.; Ohyabu, N.; Isobe, M. J. Org. Chem. 1998,
63, 188.
(4) For a review on the Baeyer-Villiger oxidation, see: Krow, G. R. In
Organic Reactions, Volume 43; Paquette, L. A., Ed.; Wiley: New York,
1993.
(5) Martin, O. R.; Szarek, W. A. Carbohydrate Res. 1984, 130, 195. (b)
Brimble, M.; Nairn, M. R.; Park, J. S. O. J. Chem. Soc., Perkin Trans. 1
2000, 5, 697.
(12) Nicolaou, K. C.; Zhong, Y.-L.; Baran, P. S. Angew. Chem., Int.
Ed. 2000, 39, 625. (b) Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Vega,
J. A. Angew. Chem., Int. Ed. 2000, 39, 2525.
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Org. Lett., Vol. 3, No. 5, 2001