10.1002/chem.201704816
Chemistry - A European Journal
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cyclooctatetraenes, see: d) L. A. Paquette, Acc. Chem. Res. 1993, 26,
57–62 and references therein.
Finally, 7b was evaluated by a short catalytic asymmetric
synthesis of the key cyclization precursor 15 in Mulzer’s
synthesis of the dioxafenestrene natural product (–)-penifulvin A
(16) (Scheme 3). The prior asymmetric approach to this
compound has relied on auxiliary control.16 A 1,4-addition of o-
tolyl boronic acid to ester 12 afforded 13 in high yield and as a
single detected enantiomer. The reaction proceeded without
competing lactonization or interference from the free hydroxyl
group of the substrate. When conducting this reaction on a gram
scale, the catalyst could be recovered in 76% yield by
chromatography.27
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(o-tol)B(OH)2 (2.0 equiv)
1. TBSOTf, 2,6-lut., DMF
2. LiBH4, MeOH, THF
3. TsCl, DMAP, CH2Cl2
(S,S)-7b (5 mol%),
K3PO4 (1.0 equiv.)
O
O
Me
OH
OH
EtO
[6]
[7]
toluene/H2O (10:1)
89%, >99% ee
EtO
68% over three steps
12
13
O
H
O
O
O
HO
MgBr,
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CuI then
TBAF
Mulzer and Gaich
5 steps
H
Me
OTBS
Me
TsO
reference 16
54%
H
14
15
(–)-penifulvin A (16)
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of this complex. The synthesis of 15, and hence, the formal
synthesis of (–)-penifulvin A, was then completed in four
additional steps concluding with a Cu-mediated sp2-sp3 coupling
reaction. With small variations, this strategy should be applicable
to also to related natural products and their structural analogs.
In summary, this work introduces 5,11-disubstituted
dbCOTs as configurationally stable and readily accessible
planar chiral homologs to the parent dbCOT ligand. In particular,
5,11-di-methyl and di-phenyl substituted dbCOTs were shown to
form stable complexes with rhodium(I). When applied in 1,4- and
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achieved over a wide range of substrates, and in a synthesis of
a key intermediate in Mulzer’s synthesis of (–)-penifulvin A. More
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and types of catalytic reactions given the unique inertness and
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Acknowledgements
We thank the Swedish Research Council and the Royal
Physiographical Society in Lund for funding and L. Sirois and T.
J. Paxton (Wender Group) for discussions on penifulvin A.
Keywords: cyclooctatetraenes • planar chirality • asymmetric
catalysis • rhodium(I) complexes • fenestrenes
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