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 05.07.2012   Карта сайта     Language По-русски По-английски
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Экология
Электротехника и обработка материалов
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05.07.2012

Direct and highly regioselective and enantioselective allylation of β-diketones





Journal name:

Nature

Volume:

487,

Pages:

86–89

Date published:

(05 July 2012)

DOI:

doi:10.1038/nature11189


Received


Accepted


Published online







The enantioselective allylation of ketones is a problem of fundamental importance in asymmetric reaction design, especially given that only a very small number of methods can generate tertiary carbinols. Despite the vast amount of attention that synthetic chemists have given to this problem1, 2, 3, 4, 5, 6, 7, 8, success has generally been limited to just a few simple ketone types. A method for the selective allylation of functionally complex ketones would greatly increase the utility of ketone allylation methods in the chemical synthesis of important targets. Here we describe the operationally simple, direct, regioselective and enantioselective allylation of β-diketones. The strong tendency of β-diketones to act as nucleophilic species was overcome by using their enol form to provide the necessary Brønsted-acid activation. This reaction significantly expands the pool of enantiomerically enriched and functionally complex tertiary carbinols that may be easily accessed. It also overturns more than a century of received wisdom regarding the reactivity of β-diketones.





Figures at a glance


left


  1. Figure 1: Origin and evolution of a proposal for a direct, enantioselective and regioselective allylation of β-diketones.
    Origin and evolution of a proposal for a direct, enantioselective and regioselective allylation of [bgr]-diketones.

    a, Retrosynthesis of the AB spiroketal of spongistatin 1 to β-hydroxyketone 1. Me, methyl group; Ac, acetyl group; R, unspecified group. b, A direct asymmetric allylation of acetylacetone would have to contend with the enol form of the diketone. c, The generalization of a direct method would require control of regioselectivity.





  2. Figure 2: Reaction design and proof of concept.
    Reaction design and proof of concept.

    a, The reaction design entails tethering the allylsilane to the enol form of the diketone and activation of the silane by the liberated hydrochloric acid (HCl). Ar, aryl group. b, First demonstration of the asymmetric allylation of acetylacetone.





  3. Figure 3: Scope of the regio- and enantioselective allylation of β-diketones.
    Scope of the regio- and enantioselective allylation of [bgr]-diketones.

    a, The β-diketone was treated with 1.2 equiv. of (S,S)-3 in chloroform (CHCl3) and the resultant mixture was stirred at ambient temperature for 13–27h. In all cases, the reported yield refers to the yield of isolated (greater than or equal to 20:1 regioisomeric purity) major product after workup and purification by flash chromatography, and the enantiomeric excess (e.e.) was determined by chiral high-performance liquid chromatography. d.r., diastereomer ratio. b, Enantioselective allylation of symmetrical β-diketones. Ph, phenyl group. c, Regio- and enantioselective allylation of unsymmetrical aryl, alkyl β-diketones (r.r.,regioisomer ratio). d, Regio- and enantioselective allylation of unsymmetrical diaryl β-diketones.





  4. Figure 4: Regio-, diastereo- and enantioselective crotylation of β-diketones.
    Regio-, diastereo- and enantioselective crotylation of [bgr]-diketones.

    a, The crotylation of β-diketones allows the establishment of a second stereocentre in the homoallylic alcohol products. OTf, triflate. b, α-Substitution on the β-diketone substrate may be parlayed into reactions that establish three stereocentres from simple starting materials.





  5. Figure 5: General mechanism and origin of regioselectivity.
    General mechanism and origin of regioselectivity.







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  • Chen Wev .  honorary member of ISSC science council

  • Harton Vladislav Vadim  honorary member of ISSC science council

  • Lichtenstain Alexandr Iosif  honorary member of ISSC science council

  • Novikov Dimirtii Leonid  honorary member of ISSC science council

  • Yakushev Mikhail Vasilii  honorary member of ISSC science council

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