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. 2010 Nov 10;132(44):15559-61.
doi: 10.1021/ja1082798.

Total synthesis of (+)-roxaticin via C-C bond forming transfer hydrogenation: a departure from stoichiometric chiral reagents, auxiliaries, and premetalated nucleophiles in polyketide construction

Soo Bong Han  1 , Abbas Hassan, In Su Kim, Michael J Krische
Affiliations

Total synthesis of (+)-roxaticin via C-C bond forming transfer hydrogenation: a departure from stoichiometric chiral reagents, auxiliaries, and premetalated nucleophiles in polyketide construction

Soo Bong Han et al. J Am Chem Soc. .

Abstract

A total synthesis of the oxo-polyene macrolide (+)-roxaticin is achieved in 20 steps from 1,3-propanediol. In this approach, 9 of 10 C-C bonds formed in the longest linear sequence are made via metal catalysis, including 7 C-C bonds formed by iridium catalyzed alcohol C-C coupling. Notably, the present synthesis, which represents the most concise preparation of any oxo-polyene macrolide reported to date, is achieved in the absence of chiral reagents and chiral auxiliaries with minimal use of premetalated C-nucleophiles.

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Figures

Scheme 1
Scheme 1
Representative oxo-polyene macrolides and retrosynthetic analysis of the (+) roxaticin.a aSee supporting information for a graphical summary of prior syntheses.
Scheme 2
Scheme 2
Total synthesis of the oxo-polyene macrolide (+)-roxaticin via C-C bond forming transfer hydrogenation.a aYields are of material isolated by silica gel chromatography and represent the average of two runs. Enantiomeric excess of 1 was determined by chiral stationary phase HPLC analysis. See Supporting Information for preparation of homoallylic ether A and other experimental details.
See this image and copyright information in PMC

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