C O M M U N I C A T I O N S
Scheme 4. Esterification of Alcohol 13
Acknowledgment. This work is supported by the National
Institutes of Health (Grants GM38907 and GM38436). We thank
Dr. Troy Ryba for assistance with HPLC purification of amphidi-
nolide E and Prof. Jun-ichi Kobayashi for providing comparative
spectroscopic data for the natural product.
Note Added after ASAP Publication. After this paper was
published ASAP on November 30, 2006, Scheme 4 was revised to
show the correct stereochemistry of 15a,b. The Supporting Infor-
mation has also been updated with corrected structures. The
corrected version was published ASAP on December 6, 2006.
Scheme 5. Completion of Amphidinolide E Total Synthesis
Supporting Information Available: Experimental procedures and
spectroscopic data for all new compounds. This material is available
References
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(2) References to total syntheses of amphidinolides A, J, K, P, T, W, X, and
Y are provided in the Supporting Information.
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Mohapatra, S.; Phalgune, U. D.; Puranik, V. G.; Mohapatra, D. K.
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S. K.; Jung, S. K.; Lee, E. Angew. Chem. Int. Ed. 2006, 45, DOI:
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we reasoned that use of a “diene protected” analog of acid 14 might
be effective. Gratifyingly, esterification of alcohol 13a using
(CO)3Fe-complexed dienoic acid 15a18 (1.6 equiv) provided the
targeted ester via the modified Yamaguchi method.19 Oxidative
decomplexation of the (CO)3Fe-unit then provided polyene 16 in
94% yield for the two steps. Interestingly, use of the diastereomeric
(CO)3Fe-protected dienoic acid 15b in the esterification-decom-
plexation sequence did not provide 16.20
Formation of the C5-C6 olefin and closure of the 19-membered
macrocycle was achieved by treating 16 with 20 mol % of Grubbs’
first generation olefin metathesis catalyst (Scheme 5). The (E,E)-
diene 17 was isolated in 73% yield. In addition, an inseparable
mixture of eneyne metathesis products was isolated in 10% yield.
Use of the more active Grubbs’ second generation or Grubbs-
Hoveyda catalysts only resulted in decompostition of polyene 16.
Stannylalumination-protonolysis21 of the alkyne unit of 17 gave
vinylstannane 18 (58%) which was transformed into vinyl iodide
19 by treatment with NIS (96% yield). Acidic hydrolysis of both
the triethylsilyl and acetonide protecting groups afforded triol 20
(77% yield). Stille22 cross coupling of 20 with vinylstannane 215
under the Corey23 conditions completed the synthesis of (-)-
amphidinolide E (59% yield). The spectroscopic properties of
synthetic (-)-1 were in excellent agreement with the literature data
reported by Kobayashi and co-workers. Because optical rotation
data for natural 1 were unavailable, we repeated the tris-Mosher
ester analysis of (-)-1 as described by Kobayashi.4b Our 1H NMR
data were in perfect agreement with published NMR data for the
tris-Mosher ester derivatives of 1,4b thereby confirming that
synthetic (-)-1 is in fact the naturally occurring enantiomer of
amphidinolide E.
(18) For synthesis of 15 see the SI and (a) Donaldson, W. A.; Craig, R.;
Spanton, S. Tetrahedron Lett. 1992, 33, 3967. (b) Wasicak, J. T.; Craig,
R. A.; Henry, R.; Dasgupta, B.; Li, H.; Donaldson, W. A. Tetrahedron
1997, 53, 4185.
(19) Hikota, M.; Sakurai, Y.; Horita, K.; Yonemitsu, O. Tetrahedron Lett. 1990,
31, 6367.
(20) Details of the divergent behavior of 15a and 15b in the esterification of
13 will be published separately: Va, P.; Roush, W. R. Submitted for
publication.
(21) Sharma, S.; Oehlschlager, A. C. J. Org. Chem. 1989, 54, 5064.
(22) Stille, J. K.; Groh, B. L. J. Am. Chem. Soc. 1987, 109, 813.
(23) Han, X.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 7600.
In summary, a convergent and highly stereocontrolled synthesis
of amphidinolide E has been accomplished. Key steps of this
synthesis include a highly diastereoselective BF3‚Et2O promoted
[3+2] annulation reaction between aldehyde 3 and allylsilane 4
and a ring closing metathesis reaction of polyene 16. In addition,
we have shown that the -Fe(CO)3 protecting group in 15 is vital
to the successful esterification of the hindered hydroxyl group of
13.
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J. AM. CHEM. SOC. VOL. 128, NO. 50, 2006 15961