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. 2012 Sep 21;14(18):4890-3.
doi: 10.1021/ol302221s. Epub 2012 Sep 5.

An "aprotic" Tamao oxidation/syn-selective tautomerization reaction for the efficient synthesis of the C1-C9 fragment of fludelone

Tyler J Harrison  1 , Philippe M A Rabbat, James L Leighton
Affiliations

An "aprotic" Tamao oxidation/syn-selective tautomerization reaction for the efficient synthesis of the C1-C9 fragment of fludelone

Tyler J Harrison et al. Org Lett. .

Abstract

An efficient synthesis of the C(1)-C(9) fragment of fludelone has been developed. The key step is a tandem silylformylation-crotylsilylation/Tamao oxidation sequence that establishes the C(5) ketone, the C(6), C(7), and C(8) stereocenters, and the C(9) alkene in a single operation from a readily accessed starting material. The stereochemical outcome at C(6) depends critically on the development of an "aprotic" Tamao oxidation, which leads to a reversal in the intrinsic diastereoselectivity observed using "standard" Tamao oxidation conditions.

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Figures

Figure 1
Figure 1
Epothilones A and B, fludelone, and the three principal fragments from which fludelone is assembled.
Scheme 1
Scheme 1
Proposal for a Method to Reverse the Intrinsic Selectivity in the Tandem Tamao Oxidation/Diastereoselective Tautomerization Reaction.
Scheme 2
Scheme 2
Synthesis of Di-cis-crotylsilyl Ether 6
Scheme 3
Scheme 3
Performance of 6 in the Tandem Silylformylation/Crotylsilylation Reaction and in the tandem Tamao Oxidation/Diastereoselective Tautomerization Reaction.
Scheme 4
Scheme 4
Application of Optimized Conditions to Silane 6 for the Direct and Efficient Synthesis of the C(1)–C(9) Fragment of Fludelone
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