Direct Synthesis of Protoberberine Alkaloids by Rh-Catalyzed C-H Bond Activation as the Key Step

Abstract

A one-pot reaction of substituted benzaldehydes with alkyne-amines by a Rh-catalyzed C-H activation and annulation to afford various natural and unnatural protoberberine alkaloids is reported. This reaction provides a convenient route for the generation of a compound library of protoberberine salts, which recently have attracted great attention because of their diverse biological activities. In addition, pyridinium salt derivatives can also be formed in good yields from α,β-unsaturated aldehydes and amino-alkynes. This reaction proceeds with excellent regioselectivity and good functional group compatibility under mild reaction conditions by using O2 as the oxidant. Rhoad to alkaloids! A Rh-catalyzed intramolecular C-H bond activation/annulation of aldehydes and alkyne-amines provides a novel efficient method for the synthesis of various protoberberine salts and natural products in high yield under mild reaction conditions.