Rhodium(III)-Catalyzed C–H Activation-Based First Total Synthesis of 6-O-Methyl Anciscochine, an Alkaloid Isolated from Ancistrocladus tectorius

Abstract

The concise and efficient first total synthesis of 6-O-methyl anciscochine, employing a tandem C–C/C–N formation approach via a rhodium-catalyzed C–H activation/alkenylation/annulation strategy, is reported. This heterocycle was isolated from the liana Ancystrocladus tectorius and features a unique 3-hydroxymethylisoquinoline core that is found in a few other natural products and in some bioactive synthetic compounds. The synthesis, which was executed in four high-yielding steps and a global yield of 43%, involved the oximation of commercial 2,4-dimethoxyacetophenone under CeCl₃·7H₂O-promotion, followed by pivaloylation of the oxime. A one-pot pivaloxime-directed alkenyl­ation/annulation stage with methyl acrylate, furthered by a NaBH₄/ CaCl_2­-mediated reduction of the resulting isoquinoline 3-carboxylate ester completed the sequence.

Key words

C–H activation - natural product - rhodium catalysis - 6-O-methyl anciscochine - Ancystrocladus tectorius - one-pot alkenylation/ annulation­

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