A Ruthenium-Catalyzed C–H Activation Strategy as an Efficient Shortcut in the Total Synthesis of 6,8-Dimethoxy-1,3-dimethyl­isoquinoline

VARGAS, DIDIER F.; KAUFMAN, TEODORO S.; FONZO, SANTIAGO

SYNTHESIS-STUTTGART

GEORG THIEME VERLAG KG

Año: 2019 vol. 51 p. 3908 - 3914

0039-7881

A short and convenient total synthesis of 6,8-dimethoxy-1,3-dimethylisoquinoline, employing a C‒H activation/alkenylation strategy, is reported. It involved the CeCl3.7H2O-promoted methoximation of 2,4-dimethoxyacetophenone and a methoxime-directed ruthenium-catalyzed allylation. This was followed by a one-pot ruthenium-catalyzed allyl to propenyl isomerization and a microwaves-assisted 6π-azaelectrocylization to complete the sequence. This approach, which entails a shortcut in the synthetic management of the three-carbon atom side chain, is an improved and more efficient route toward the natural product, which facilitated its access in just three steps and 27.3% overall yield.