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. 2008 Sep 10;130(36):11970-8.
doi: 10.1021/ja804105m. Epub 2008 Aug 15.

An atom-economic and selective ruthenium-catalyzed redox isomerization of propargylic alcohols. An efficient strategy for the synthesis of leukotrienes

Barry M Trost  1 , Robert C Livingston
Affiliations

An atom-economic and selective ruthenium-catalyzed redox isomerization of propargylic alcohols. An efficient strategy for the synthesis of leukotrienes

Barry M Trost et al. J Am Chem Soc. .

Abstract

Catalytic ruthenium complexes in conjunction with an indium cocatalyst and Bronsted acid isomerize primary and secondary propargylic alcohols in good yields to provide trans enals and enones exclusively. Readily available indenylbis(triphenylphosphine)ruthenium chloride, in the presence of indium triflate and camphorsulfonic acid, gives the best turnover numbers and reactivity with the broadest range of substrates. Deuterium labeling experiments suggest that the process occurs through propargylic hydride migration followed by protic cleavage of the resultant vinylruthenium intermediate. Application of this method to the synthesis of leukotriene B4 demonstrates its utility and extraordinary selectivity.

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Figures

Figure 1
Figure 1
Commercial Catalysts for Redox Isomerization of Propargylic Alcohols
Scheme 1
Scheme 1
Deuterium Labeling Experiments
Scheme 2
Scheme 2
Proposed Catalytic Cycle for Redox Isomerization
Figure 2
Figure 2
Indium Activation of Cationic Ruthenium Species
Figure 3
Figure 3
Other Ruthenium Complexes for Redox Isomerization
Figure 4
Figure 4
Retrosynthesis of Leukotriene B4
Scheme 3
Scheme 3
Isomerization of 2,4-Diyn-1-ols
Scheme 4
Scheme 4
Synthesis of Leukotriene B4a a Reaction conditions: a) NaH, TBDMSCl, 62%; b) Red-Al, 88%; c) (COCl)2, DMSO, Et3N, 84%; d) borane 18, then NaOH, H2O2, 67%; e) TBDPSCl, imidazole, DMAP; f) CSA, MeOH, 81% over 2 steps; g) 2, In(OTf)3, CSA, 92%; h) [(Ph3PCH2Br]Br, t-BuOK, 65%; i) n-BuLi, OHC(CH2)3COOCH3, 27%, 67%brsm; j) TBDPSCl, imidazole, DMAP; k) H2, Lindlar, quinoline, 92%; l) TBAF, 87%.
Scheme 5
Scheme 5
Preparation of Allenylborane 18
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