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We were able to further extend this method to the functionalization
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of optically enriched secondary alkyl iodides.[6b] For example, (R)-
3
(
i and (S)-3i were obtained in good yield and enantioselectivity
73% yield, 88% ee; 70% yield, 90% ee, see Scheme 2).
Furthermore, intermediates, which are present in the syntheses
of several natural products were prepared.[2,3,15]
Thus, (R)-3j,
occuring in the total synthesis of the above mentioned
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[
2]
aranorosin , was prepared in 71% yield and 88% ee. The
corresponding S-enantiomer (S)-3j, which was used for the total
synthesis of 6’epi-aranorosin, was also obtained in 70% yield, but
in lower optical purity (72% ee). Furthermore, (R)-3k (62% yield
and 82% ee) and (S)-3k (67% yield and 84% ee), were prepared
using this I/Li-exchange sequence.[15] Finally, we prepared the
corresponding S-enantiomer of a precursor, which was used in
the total synthesis of ent-stellettamide A.[3] Therefore, (S)-3l was
obtained in 63% yield with 81% ee.
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In summary, we have reported that γ–chiral Michael acceptors
were readily prepared from chiral secondary alkyl iodides via I/Li-
exchange reaction and subsequent transmetalation to copper
followed by addition to a broad range of 3-halogeno-α,β-
unsaturated carbonyl derivatives. This method afforded γ-methyl
unsaturated enones and enoates from relatively unfunctionalized
secondary alkyllithiums. Only a few functional groups are
tolerated by this method.[6b] Nevertheless, advanced precursors
for the preparation of natural products were prepared to underline
the synthetic value of this approach.
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anhydride was used instead of p-toluenesulfonyl chloride. (c) Same
procedure,but 2,3,4,5,6-pentafluorobenzoyl chloride was used instead of
p-toluenesulfonyl chloride.
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2
2
Acknowledgements
1
We thank the DFG for financial support. We also thank Albermarle
for the generous gift of chemicals. J.S thanks the FCI-foundation
for a fellowship.
1
[
[
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Keywords: lithium • copper • stereoselectivity • cross-coupling
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