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. 2012 Mar 28;134(12):5496-9.
doi: 10.1021/ja3004733. Epub 2012 Mar 13.

Asymmetric hydrovinylation of vinylindoles. A facile route to cyclopenta[g]indole natural products (+)-cis-trikentrin A and (+)-cis-trikentrin B

Wang Liu  1 , Hwan Jung Lim, T V RajanBabu
Affiliations

Asymmetric hydrovinylation of vinylindoles. A facile route to cyclopenta[g]indole natural products (+)-cis-trikentrin A and (+)-cis-trikentrin B

Wang Liu et al. J Am Chem Soc. .

Abstract

Vinylindoles undergo Ni(II)-catalyzed asymmetric hydrovinylation under very mild conditions (-78 °C, 1 atm ethylene, 4 mol % catalyst) to give the corresponding 2-but-3-enyl derivatives in excellent yields and enantioselectivities. Hydroboration of the alkene and oxidation to an acid, followed by Friedel-Crafts annulation, gives an indole-annulated cyclopentanone that is a suitable precursor for the syntheses of cis-trikentrins and all known herbindoles. For example, the cyclopentanone from 4-ethyl-7-vinylindole is converted into (+)-cis-trikentin A in four steps (Wittig reaction, alkene isomerization, diastereoselective hydrogenation, and nitrogen deprotection). The previous synthesis of this molecule from (S)-(-)-malic acid involved more than 20 steps and a preparative HPLC separation of diastereomeric intermediates.

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Figures

Figure 1
Figure 1
Biologically Active Indole Derivaties.
Figure 2
Figure 2
Ligands for Asymmetric Hydrovinylation of Vinylindoles.
Figure 3
Figure 3
Major Products from HV of Vinylindoles Using Ligands L1-L3
Scheme 1
Scheme 1
Selected Examples of Asymmetric Hydrovinylation of Alkenes,
Scheme 2
Scheme 2
Synthesis and Asymmetric Hydrovinylation of a Prototypical Vinylindole
Scheme 3
Scheme 3
Enantioselective Synthesis of (+)-cis-Trikentrin A
Scheme 4
Scheme 4
Enantioselective Synthesis of cis-Trikentrin B
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