C O M M U N I C A T I O N S
under catalytic conditions due to a low concentration of the reactive
speciessthe enol form of the â-keto carboxylate 3 that may undergo
decarboxylation over time, in combination with the metal triflate-
or triflic acid-activated alkene. Indeed, when TMSOTf was used
in a stoichiometric amount, tricycle 2a was isolated in 70% yield,
and no trace of indanones 11a/11b was detected by analysis of the
crude reaction mixture.
triflic acid-activated alkene leads to 2c, providing tricycle 2a after
workup. The involvement of â-keto trimethylsilyl carboxylate enol
3a, in lieu of enolized 11a or its TMS enol ether, is supported by
the failure of the indanone mixture 11a/11b to produce 2a under
the optimized reaction conditions.
The synthesis of 1 was completed by selective deprotection of
the methoxy group adjacent to the carbonyl group in 90% yield.13
Installation of the phenoxy group was realized by treatment of 2a
with CAN to provide a quinone, which was reduced using H2,
culminating in taiwaniaquinol B (1) in 52% for the two steps.
In conclusion, the first synthesis of taiwaniaquinol B was
accomplished in 15 steps and 6% overall yield. The crux of the
approach is a TMSOTf-mediated intramolecular Friedel-Crafts
acylation/carbonyl R-tert-alkylation domino reaction that exploits
the unique reactivity of Meldrum’s acid. The facile precursor
synthesis makes this a powerful methodology for the modification
and assembly of sterically congested indanone-containing ring
systems.
Figure 1. Byproducts of the domino reactions.
The location and substitution of the tethered alkene had no impact
on the efficiency of the tandem process, as shown by the cyclization
of trisubstituted alkene 4b to 2a in 73% yield (Scheme 3). The
methodology was further applied to the synthesis of the analogous
fused 6-5-5 tricyclic carbon skeleton. Substrate 4c provided a
53% yield of two tricyclic products, in a 2:1 ratio (Scheme 3).
Tricycle 2b was the major product and tricycle 12 the minor
component (Figure 1). The latter arose from a competing Friedel-
Crafts alkylation reaction at the highly congested 4-position of the
1-indanone intermediate, installing two contiguous all-carbon
quaternary centers on the aromatic moiety.12 This mode of
cyclization was not observed for 4a and 4b, likely due to the
relatively slow formation of seven-membered ring carbocycles.
Acknowledgment. This work was funded by Boehringer
Ingelheim (Canada) Ltd. (Young Investigator Award for Organic
Chemistry to E.F.), the Natural Sciences and Engineering Research
Council of Canada (NSERC-CRD grant), the Canadian Foundation
for Innovation, the Ontario Innovation Trust, and the University
of Waterloo.
Supporting Information Available: Experimental procedures and
NMR spectra. This material is available free of charge via the Internet
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Scheme 3
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Scheme 4
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