C O M M U N I C A T I O N S
Scheme 2. Total Synthesis of (-)-Plicatic Acid (1)a
a Conditions: (a) NaH, BnBr, quant. (b) (1) NMO, cat. OsO4; (2) NaIO4, quant. (c) N2CHCOOEt, cat. SnCl2, 92%. (d) 9, piperidine, PhCOOH, 80% (after
one cycle), E/Z ) 5:3. (e) (S,S)-TADOOH, cat. LiOH, 83%, 98% ee. (f) TfOH (0.04 equiv), 0 °C to r.t., 70% 2a, 17% 2b. (g) ClSi(Me)2CH2Br, imidazole,
75% (94% brsm). (h) SmI2, NiI2 (0.1 equiv), 0 °C, 58%. (i) H2O2, NaHCO3, 87% (90% brsm). (j) n-PrSNa, DMF, 97%. (k) H2, Pd/C, MeOH, then Dowex-
50, 72%.
addition with a metal reagent such as vinylmagnesium bromide,7a
vinyl-lithium,7b vinylcesium chloride,7c or benzyloxymethyl
magnesium chloride7d were unsuccessful. These basic metal
reagents only deprotonated the benzylic proton at C7 in 2a,
thereby leading to enolization, rather than nucleophilic addition
to the C8-carbonyl group. We then explored an alternative
strategy to execute a formal stereospecific addition of a
hydroxymethyl group to the ketone with the C-C bond formation
implemented under nearly neutral conditions (Scheme 2). Thus,
the C8′-OH in 2a was first silylated with ClSi(Me)2CH2Br to
form 10 in 75% isolated yield (94% yield brsm). To our delight,
10 underwent a SmI2-mediated, intramolecular Barbier reaction8
analyses for 2a, 4b-i (PDF). This material is available free of charge
References
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9
in the presence of 10 mol % of NiI2 to afford hydroxysilane
11, which was subjected to a Fleming-Tamao-Kumada oxida-
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However, triolester 12 decomposed rapidly when subjected to
hydrolysis by LiOH. On the other hand, upon treatment with
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carboxylate 13 in 97% yield.11 Global debenzylation of 13
followed by cationic exchange delivered synthetic (-)-plicatic
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ˇ
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Acknowledgment. We are grateful for financial support from
National Institute of Health (GM-61591). We thank Dr. C. R.
Daniels of Forintek Canada Corp. for kindly providing us with
an authentic sample of natural (-)-plicatic acid.
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(12) See the Supporting Information for details.
Supporting Information Available: Experimental procedures and
characterization data for all new compounds, chiral chromatographic
JA9039407
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