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

ROMERO, BRENDA S.; VARGAS, DIDIER F.; KAUFMAN, TEODORO S.; LARGHI, ENRIQUE L.

SYNTHESIS-STUTTGART

GEORG THIEME VERLAG KG

Año: 2019 vol. 51

0039-7881

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, found in 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/CaCl2-mediated reduction of the resulting isoquinoline 3-carboxylate ester completed the sequence.