Organic Letters
Letter
reaction was carried out at below 0 °C, and the peroxide 13
decomposed readily at a temperature over 10 °C in the
presence of sun-lamp irradiation. Due to the decomposition of
ASSOCIATED CONTENT
Supporting Information
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*
S
1
,2-dioxane 13, we used 13 without further purification in the
18
next step. A further mild diimide reduction of the double
bond in crude 1,2-dioxane 13 afforded 14 in 41% yield over two
chemical operations.
Crystallographic data for 16 (CIF)
As shown in Scheme 4, according to the proposed biogenetic
pathway, we turned our attention toward the total synthesis of
Scheme 4. Total Synthesis of Gracilioether F
AUTHOR INFORMATION
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*
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported by a grant to the State Key
Laboratory of Synthetic Chemistry from the Innovation and
Technology Commission. Grants from the National Natural
Science Foundation of China/Research Grants Council Joint
Research Scheme (N_CUHK451/13), the Research Grants
Council of the Hong Kong SAR, China (GRF Project 403012
and CRF Project PolyU C5023-14G with The Hong Kong
Polytechnic University), The Chinese Academy of Sciences-
Croucher Foundation Funding Scheme for Joint Laboratories,
and the National Natural Science Foundation of China (No.
gracilioether F. Peroxide 14 was then treated with zinc in acetic
acid to generate 1,4-diol 15 in an excellent yield through a
proposed reductive cleavage of the O−O bond in 14. This
transformation was proven to be an efficient and practical
pathway to provide 1,4-diol 15 with the desired hydroxyl
groups for the gracilioether family, matching with their desired
stereochemical homology. Moreover, upon selective protection
of the primary alcohol in 15, compound 16 was obtained in
2
1272199), Shenzhen Science and Technology Innovation
Committee for the Municipal Key Laboratory Scheme
ZDSY20130401150914965), and the Shenzhen Basic Re-
(
search Program (JCYJ20140425184428455) are also gratefully
acknowledged.
8
9% yield. After many trials, compound 16 gave eventually
satisfactory single crystals from CH Cl . Gratifyingly, an X-ray
2
2
diffraction study convincingly showed that the molecular
structure of compound 16 contained a desired stereochemistry
consistent with that of gracilioether F. Afterward, we set out to
complete the total synthesis of gracilioether F (1). Although
considerable attempts were devoted to form the lactone moiety
REFERENCES
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(
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using either in situ generated RuO (RuCl ·6H O/NaIO ) or
4
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0
21
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3
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3
(
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2
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2
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(
(
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4
6
F (1) reported by Zampella, Carreira, and Brown.
In summary, we have first illustrated a synthetic pathway
toward the total synthesis of (±)-gracilioether F (1) via a
reductive cleavage of the 1,2-dioxane moiety, starting from
readily available allenic ester 5 in 11 steps. The key 1,2-dioxane
species (13, 14), derived from the [4 + 2] cyclization of singlet
oxygen with a diene, should be useful as common synthetic
precursors for the total synthesis of other gracilioethers. The
rapid stereocontrolled access to the crucial 1,4-diol moiety 15
was secured by strategic application of a reductive cleavage of
9
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1,2-dioxane 14. Notably, with efficient completion of the total
synthesis of gracilioether F (1) by this concise pathway, we
believe that other members of the Plakortin polyketides could
also be likewise obtained.
C
Org. Lett. XXXX, XXX, XXX−XXX