Synthesis of Highly Substituted Biaryls by the Construction of a Benzene Ring via In Situ Formed Acetals

Abstract

Herein, we present an interesting method for the construction of a benzene ring using propargylic alcohols and 1,3dicarbonyls, which involves three new C−C bond formations via cascade alkylation, formylation, annulation, and aromatization to make substituted biaryls. This one-pot Brønsted acid-promoted protocol utilizes the unique reactivity of the acetal formed under the reaction conditions. Alkynyl methyl ketones could be employed instead of 1,3-dicarbonyls as they are converted to 1,3-dicarbonyls by hydration under the reaction conditions.

Ag(i)-catalyzed cyclization of o-alkynylacetophenones facilitated through acetal formation: synthesis of C3-naphthyl indole derivatives

“…4 In this context, we disclosed the construction of naphthyl ketones and benzene rings from o -alkynylacetophenones and propargylated benzoylacetones respectively (Scheme 1, our earlier works). 5 These reactions proceeded through the formation of an α-formylated intermediate which cyclized on the alkyne. We were curious to study the reaction of o -alkynylacetophenones with indoles under acetalization conditions.…”

“…The reaction optimization was carried out on the unsubstituted o -alkynylacetophenone derivative 1a and N -benzylindole using different acid catalysts. Based on our earlier works, 5 the reaction was tested in the presence of Brønsted acids and 2 equivalents of TMOF. In the case of reactions involving TfOH and HClO 4 , indole got decomposed (Table 1, entries 1 and 2).…”