Organic Letters
Letter
3
,8
Scheme 5. Completion of the Total Synthesis of
Amphirionin-4 (1)
−5.8 (c 0.34, CHCl ). At present, we are unable to rationalize
3
these discrepancies, but the samples employed for the
measurement of specific rotation might have been contami-
nated with minute amounts of impurities with large optical
rotation values.
In conclusion, an enantioselective total synthesis of
amphirionin-4 (1) has been accomplished from (±)-1,4-
hexadien-3-ol [(±)-10] in eight operational steps. The new
expeditious synthesis of 1 featured the Sharpless kinetic
resolution as a chirality-inducing step [(±)-10 → 11],
exploitation of four one-pot transformations (8 → 16, 4 →
2
2, 23 → 24, and 24 → 2) to streamline the synthetic process,
highly efficient installation of the C8 asymmetric center by the
CBS reduction (24 → 2), and the Stille coupling reaction to
connect the two segments, 2 and 3, to complete the total
synthesis.
ASSOCIATED CONTENT
Supporting Information
■
*
S
Experimental procedures, characterization data, and
copies of NMR spectra for new compounds (PDF)
AUTHOR INFORMATION
■
*
*
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was financially supported by JSPS KAKENHI (No.
15K14718). We also thank Ms. Yuka Taguchi (Tohoku
University) for her help in NMR and MS measurements.
etherification of the β-keto ester 21 with TBSOTf and Et N to
3
give 22 as a single geometrical isomer (61% overall yield),
although the geometry of the newly formed double bond was
not assigned. It is worth mentioning that intermolecular
alkylation between the TBS-protected form of 4 and β-keto
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4
(
(
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21
3
(
494.
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which, upon SiO chromatographic purification, furnished 2 in
2
a pure state in 88% yield. Finally, the Stille coupling of 2 with
the right-hand stannane segment 3 completed our total
2
(
1
13
synthesis of amphirionin-4 (1), the H and C NMR spectra
of which showed good agreement with those reported in the
3
,8
23
literature. The specific rotation value of 1, [α] −13.8 (c
D
0
.16, CHCl ), was, however, significantly different from
previously reported data, [α] +6 (c 0.29, CHCl ) and [α]D
3
2
0
D
3
C
Org. Lett. XXXX, XXX, XXX−XXX