α-Vinylation of Haloquinones with Methyl Acrylate and MVK under Baylis-Hillman Reaction Conditions

Abstract

The Baylis-Hillman reaction has been one of the most intensively studied carbon-carbon bond-forming reactions in organic synthesis. In our earlier paper, we demonstrated that DABCO-attached enolate anion of activated olefins were useful in substitution reaction of 2,3-dihalo-1,4naphthoquinone leading to the formation of the α-vinylnaphthoquinones under the Baylis-Hillman reaction conditions as shown in Scheme 1. We desired to extend this method to other haloquinone derivatives. General methods for introducing α-vinyl unit into substrates involve palladium-catalyzed cross-coupling reactions of α-stannyl acrylate with aryl iodides or triflates, ethyl 2-bromoacrylate with arylboronic acids and ethyl 2-bromoarylate with aryl halides using electro-generated reactive zinc metal. First, we investigated the effect of an resonance electrondonating methoxy group on the regiochemistry of the vinylation reaction using 2,3-dichloro-6-methoxy-1,4naphthoquinone (4) as a substrate. Reaction of 4 with methyl acrylate (6 equiv) in the presence of 1.2 equiv of DABCO in THF at room temperature provided 3-chloro-6-methoxy-2vinyl-1,4-naphthoquinone 5a (71%) and unexpected 1,4dicarbomethoxy-6-methoxyanthraquinone 6a (4%). When the reaction was carried out using excess methyl acrylate (10 equiv) and DABCO (2.5 equiv), vinylnaphthoquinone 5a (35%) and anthraquinone 6a (21%) were produced. Also, treatment of 4 with methyl vinyl ketone (MVK) (6 equiv) and DABCO (1.2 equiv) in THF at 10-15 °C gave the corresponding vinylnaphthoquinone 5b (53%) and anthraquinone 6b (9%). Use of excess MVK (10 equiv) and DABCO (2.5 equiv), no increase of yields was observed (Scheme 2 and Table 1). We assumed that the major compounds 5 were formed by addition of the DABCOattached enolate anion to the more electrophilic C-2 carbon on the quinone core of 4 by the influence of methoxy substituent. The minor compounds 6 were presumably produced through the second vinylation, 6π-electrocyclization and oxidation reaction under the reaction conditions. Secondly, we studied α-vinylation of 2-bromo-1,4naphthoquinone (7) with methyl acrylate or MVK. Interestingly, we observed that vinylation with methyl acrylate proceeded exclusively at the carbon bearing hydrogen to provide the 2-bromo-3-vinylnaphthoquinone 8 in 58% yield. But, vinylation with MVK proceeded at the carbon bearing bromine to afford the 2-vinylnaphthoquinone 10 and Scheme 1