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Review
. 2010;49(1):34-44.
doi: 10.1002/anie.200904491.

Catalytic enantioselective olefin metathesis in natural product synthesis. Chiral metal-based complexes that deliver high enantioselectivity and more

Amir H Hoveyda  1 , Steven J Malcolmson, Simon J Meek, Adil R Zhugralin
Affiliations
Review

Catalytic enantioselective olefin metathesis in natural product synthesis. Chiral metal-based complexes that deliver high enantioselectivity and more

Amir H Hoveyda et al. Angew Chem Int Ed Engl. 2010.

Abstract

Chiral olefin metathesis catalysts enable chemists to access enantiomerically enriched small molecules with high efficiency; synthesis schemes involving such complexes can be substantially more concise than those that would involve enantiomerically pure substrates and achiral Mo alkylidenes or Ru-based carbenes. The scope of research towards design and development of chiral catalysts is not limited to discovery of complexes that are merely the chiral versions of the related achiral variants. A chiral olefin metathesis catalyst, in addition to furnishing products of high enantiomeric purity, can offer levels of efficiency, product selectivity and/or olefin stereoselectivity that are unavailable through the achiral variants. Such positive attributes of chiral catalysts (whether utilized in racemic or enantiomerically enriched form) should be considered as general, applicable to other classes of transformations.

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Figures

Scheme 1
Scheme 1
Enantioselective synthesis of antifungal agent fluvirucin B1 through a late-stage macrocyclic Mo-catalyzed RCM.
Scheme 2
Scheme 2
Total synthesis of aspidospermine through catalytic diastereoselective RCM.
Scheme 3
Scheme 3
Total synthesis of (−)-longithorone A involving a diastereoselective enyne RCM. The silylether-bearing stereogenic carbon centers, installed for control of planar stereogenicity and subsequently removed, are highlighted.
Scheme 4
Scheme 4
Control of atropisomerism in total syntheses of rac-coleophomones B and C. Ar = pBrC6H4; Mes = 2,4,6-Me3C6H2.
Scheme 5
Scheme 5
Synthesis of (+)-endo-brevicomin through enantioselective RCM.
Scheme 6
Scheme 6
Total synthesis of coniine through enantioselective RCM.
Scheme 7
Scheme 7
Synthesis of africanol through an enantioselective ring-opening/ring-closing metathesis (RORCM) reaction. Ar = 2,4,6-(iPr)3C6H2, TBS = t-butyldimethylsilyl
Scheme 8
Scheme 8
Enantioselective synthesis of the lactone fragment of HIV-protease inhibitor tipranivir through a Mo-catalyzed ring-opening/ring-closing metathesis (RORCM) reaction. Ar = 2,4,6-(iPr)3C6H2
Scheme 9
Scheme 9
Catalyst development spurred by total synthesis: A stereogenic-at-Mo complex as a highly effective chiral catalyst developed for enantioselective RCM in total synthesis of quebrachamine.
Scheme 10
Scheme 10
Total synthesis of baconipyrone C through an enantioselective Ru-catalyzed ring-opening/cross-metathesis (ROCM) reaction. PMB = pmethoxybenzyl; Mes = 2,4,6-Me3C6H2
Scheme 11
Scheme 11
A stereogenic-at-Mo complex serving as a uniquely efficient RCM catalyst.
Scheme 12
Scheme 12
A racemic stereogenic-at-Ru catalyst used to promote sequence-selective polymerization; success of this strategy is due to energy differences between the two carbene diastereomers of the chiral complex.
Scheme 13
Scheme 13
Chiral olefin metathesis catalysts are not only valuable for obtaining enantiomerically enriched products; they can also offer other types of selectivity. Mes = 2,4,6-Me3-C6H2.
Scheme 14
Scheme 14
Chiral Pd- and Cu-based complexes generate product-selectivity, site-selectivity and efficiency levels that are superior to those afforded by the corresponding achiral catalysts.
Scheme 15
Scheme 15
Natural product synthesis often underlines significant deficiencies in catalyst development, as indicated by an inefficient cross-metathesis reaction in an enantioselective synthesis of elenic acid.
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References

    1. Grubbs RH, editor. Handbook of Metathesis. Wiley–VCH; Weinheim: 2003.
    1. Schrock RR, Hoveyda AH. Angew Chem Int Ed. 2003;42:4592–4633. - PubMed
    2. Deiters A, Martin SF. Chem Rev. 2004;104:2199–2238. - PubMed
    3. Nicolaou KC, Bulger PG, Sarlah D. Angew Chem Int Ed. 2005;44:4490–4527. - PubMed
    1. Hoveyda AH, Zhugralin AR. Nature. 2007;450:243–251. - PubMed
    1. Houri AF, Xu Z, Cogan DA, Hoveyda AH. J Am Chem Soc. 1995;117:2943–2944.
    2. Xu Z, Johannes CW, Salman SS, Hoveyda AH. J Am Chem Soc. 1996;118:10926–10927.
    3. Xu Z, Johannes CW, Houri AF, La DS, Cogan DA, Hofilena GE, Hoveyda AH. J Am Chem Soc. 1997;119:10302–10316.

    1. For two noteworthy applications to natural product synthesis wherein the reversible nature of catalytic cross-metathesis is utilized, see: Smith AB, III, Adams CM, Kozmin SA, Paone DV. J Am Chem Soc. 2001;123:5925–5937.Fürstner A, Thiel OR, Ackermann L. Org Lett. 2001;3:449–451.

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