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

Santiago Fonzo; Didier F. Vargas; Teodoro S. Kaufman

doi:10.1055/s-0037-1610720

Synthesis, Table of Contents

Synthesis 2019; 51(20): 3908-3914
DOI: 10.1055/s-0037-1610720

paper

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

Santiago Fonzo

^aFacultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina

,

Didier F. Vargas ∗

^aFacultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina

^bInstituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario 2000, Argentina Email: vargas@iquir-conicet.gov.ar Email: kaufman@iquir-conicet.gov.ar

,

Teodoro S. Kaufman ∗

^aFacultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina

^bInstituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario 2000, Argentina Email: vargas@iquir-conicet.gov.ar Email: kaufman@iquir-conicet.gov.ar

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Abstract

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Dedicated to the memory of our treasured colleague and Master Prof. Dr. Edmundo A. Rúveda (03/1934–12/2018) and our beloved friend and co-worker Lic. María Virginia Méndez (02/1987–01/2019).

Abstract

A short and convenient total synthesis of 6,8-dimethoxy-1,3-dimethylisoquinoline, employing a C–H activation/alkenylation strategy, is reported. The approach involves 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 microwave-assisted 6π-azaelectrocylization to complete the sequence. This approach, which entails a shortcut in the synthetic management of the three-carbon 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.

Key words

C–H activation - one-pot transformation - total synthesis - natural product - ruthenium catalysis - 6,8-dimethoxy-1,3-dimethylisoquinoline

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References

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Supplementary Material

Supporting Information

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

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