A one-pot synthesis of indenones is presented. The process involves palladium-catalyzed annulation of ortho-halobenzaldehydes with internal alkynes. Notably, it proceeded successfully in water as the sole, and green, solvent. Significantly, unlike in earlier reports, this protocol showed excellent regioselectivity with unsymmetrical alkylarylacetylenes. Further, the strategy was extended to a one-pot synthesis of a neolignan natural product. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim