American Chemical Society
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Catalytic Direct Dehydrogenative Cross-Couplings of C–H (Pro)Nucleophiles and Allylic Alcohols without an Additional Oxidant

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journal contribution
posted on 2015-01-02, 00:00 authored by Marcel Weiss, René Peters
Transition-metal-catalyzed cross-coupling reactions between sp2-hybridized C atoms are of prime importance in both target and diversity oriented synthesis. Ideal cross-coupling reactions would neither require any leaving groups nor stoichiometric reagents. In this article, we report the first direct dehydrogenative cross-couplings between aromatic C–H bonds (in most cases using indole substrates) and allylic alcohols, which do not require an additional classical stoichiometric oxidizing agent and provide β-arylketones as value-added products. Ruthenocene- or ferrocene-based bismetallacycles, in which either Pd­(II) or Pt­(II) are the catalytically active centers, were found to be particularly efficient catalysts. Control experiments suggest that the bismetallacycles initially transform the allylic alcohols into vinylketones, which then alkylate the aromatic substrate in the presence of the catalyst. The fact that the dehydrogenative coupling does not require a classical stoichiometric oxidizing agent is explained either by protonolysis of a metallacyclic M­(II)-H intermediate or by a mechanism in which an excess of the allylic alcohol substrate serves as a sacrificial hydrogen acceptor. The title reaction is supported by cocatalytic amounts of Ni­(OAc)2. In preliminary studies, it was observed that the title reaction can as well be applied to prochiral CH-acidic pronucleophiles such as α-cyanoacetates, representing the first examples for direct enantioselective β-ketoalkylations via allylic alcohols in the absence of an additional oxidant.