Asymmetric Hydrovinylation of Vinylindoles. A Facile Route to Cyclopenta[g]indole Natural Products (+)-cis-Trikentrin A and (+)-cis-Trikentrin B

Abstract

Vinylindoles undergo Ni(II)-catalyzed asymmetric hydrovinylation under very mild conditions (−78 °C, 1 atmosphere ethylene, 4 mol% catalyst) to give the corresponding 2-but-3-enyl derivatives in excellent yields and enantiose-lectivities. Hydroboration of the alkene, 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.

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…Treating 7-vinylindoles under ethylene in the presence of a Ni(II) catalyst and a phosphoramidite ligand provided hydrovinylation products 168 with excellent yields and ees, which were transformed to (+)-cis-166 and (+)-cis-167, respectively (Scheme 46). 78 rac-cis-Trikentrin B (167), was synthesized using regioselective indole aryne cycloaddition with cyclopentadiene to install the cyclopentan ring via annulation at the 6,7-position of the indole ring. The aryne intermediate 171 was generated regioselectively by metal-halogen exchange at the 7-position of 5,6,7-tribromoindole 170 (Scheme 47).…”

Catalytic Enantioselective Hetero-dimerization of Acrylates and 1,3-Dienes

“…4 In this context, we have reported highly enantioselective heterodimerization between ethylene and activated alkenes using nickel catalysts (Eq 1), 5a and, between ethylene and 1,3-dienes using cobalt catalysts (Eq 2). 6a,b While the reactions of ethylene are highly efficient and selective, and, applicable for the syntheses of several biologically important molecules (e. g., 2-arylpropionic acids, 7a steroid analogs, 7b pseudopterosins, 7c trikentrins 7d ) the utility of this reaction would be vastly enhanced if instead of ethylene a functionalized alkene such as methyl acrylate can be used. Even though acrylates are among the largest volume feedstocks (> 2,000,000 metric tons annual production), they are seldom used in catalytic enantioselective reactions, and, for known dimerization reactions involving acrylates and other alkenes, the reported substrate scope, yields and selectivities are somewhat limited.…”

Transition‐Metal‐Catalyzed Laboratory‐Scale Carbon–Carbon Bond‐Forming Reactions of Ethylene

“…It should be noted that nickel-catalyzed hydrovinylations have enabled the enantioselective synthesis of many other biologically active compounds, such as trikentrin, [37] various pyrrolidinoindolines, [38] and pseudopterosins. [39] …”