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Y. H. Jin, C. K. Chu / Tetrahedron Letters 43 (2002) 4141–4143
Scheme 1. Reagents and conditions: (a) 2,2-dimethoxypropane, p-toluenesulfonic acid, acetone, 0°C to rt, 1 h; (b) TBDMSCl,
imidazole, CH2Cl2, rt, 1 h; (c) vinylmagnesium bromide, anhydrous THF, −78°C to rt, 1 h; (d) TBAF, THF, rt, 1 h; (e) NaIO4,
H2O, rt, 1 h; (f) NaH, DMSO, methyltriphenylphosphonium bromide, THF, 0°C to reflux, 3 h; (g) Grubbs catalyst, anhydrous
,
CH2Cl2, 24°C, 4 h; (h) pyridinium chlorochromate, 4 A molecular sieve, AcOH, CH2Cl2, rt, 12 h.
In this communication, we wish to report a significantly
improved and practical method for the synthesis of
13: To a 500 mL round bottom flask filled with the
Grubbs catalyst (446 mg, 1 mol%, flushed with N2 three
times), a solution of the diene 13 (10.0 g, 0.054 mol) in
anhydrous CH2Cl2 (300 mL) was added. After stirring
optically pure
D
-cyclopent-2-enone 15 from
D-ribose in
eight steps with overall yield of 56% in a large scale (10
g scale).
,
at 24°C for 4 h, 4 A molecular sieve (20.0 g), pyri-
dinium chlorochromate (23.5 g, 0.108 mol) and acetic
acid (0.15 mL, 5 mol%) were added to the resulting
dark brown mixture. The reaction mixture was stirred
at the same temperature for 12 h and filtered over a
silica-gel pad with EtOAc. The filtrate was concentrated
in vacuo and the residue was purified by column chro-
matography on a silica-gel column with 10% hexane in
EtOAc to give cyclopetenone 15 (7.6 g, 93% yield) as
white crystals.
The isopropylidene protected derivative 8 (Scheme 1)
was obtained from D-ribose with 2,2-dimethoxypropane
in the presence of catalytic amount of p-toluenesulfonic
acid in 90% yield, followed by t-butyldimethylsilane
chloride with imidazole to afford the silylated lactol 9
in 85% yield. To introduce an olefin moiety, Grignard
reaction was carried out with vinylmagnesium bromide
to provide alcohol 10 in 100% yield. The deprotection
of the silyl group using 1 M solution of tetra-
butylammonium fluoride in THF followed by an oxida-
tive cleavage with sodium periodate afforded lactol 12.
Wittig reaction16 was carried out using NaH and
DMSO in THF to give diene 13 in 86% yield which
underwent a RCM16,17 reaction. Several RCM reaction
conditions using the Grubbs catalyst from diene 13 to
cyclopentenol 14 were investigated, among which 1%
Grubbs catalyst at 24°C in anhydrous CH2Cl2 provided
the best result to obtain cyclopentenol 14. As the
obtained cyclopentenol 14 was volatile, the desired
cyclopentenone 1518 was directly obtained in two steps
93% yield from diene 13 by PCC oxidation of cyclopen-
tenol 14 without purification.
Acknowledgements
This research was supported by grants of National
Institute of Allergy and Infectious Diseases (U01
AI48495 and AI 32351).
References
1. Kusaka, T.; Yamamoto, H.; Muroi, M.; Kishi, T.;
Mizuno, K. J. Antibiot. 1968, 21, 255.
In summary, we have developed
improved synthetic method for -cyclopent-2-enone 15
in a preparative scale, which is a versatile intermediate
for the synthesis of carbocyclic nucleosides in overall
a
significantly
2. Yaginuma, S.; Muto, N.; Tsujino, M.; Sudate, Y.;
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D
56% yield from
D-ribose.
Experimental
Procedure for the preparation of compound 15 from