Synthesis 2019; 51(20): 3908-3914
DOI: 10.1055/s-0037-1610720
paper
© Georg Thieme Verlag Stuttgart · New York

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

Santiago Fonzo
a  Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina
,
a  Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina
b  Instituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario 2000, Argentina   eMail: vargas@iquir-conicet.gov.ar   eMail: kaufman@iquir-conicet.gov.ar
,
a  Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina
b  Instituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, Rosario 2000, Argentina   eMail: vargas@iquir-conicet.gov.ar   eMail: kaufman@iquir-conicet.gov.ar
› Institutsangaben
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, PUE IQUIR-2016) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT, PICT 2017-0149) are thanked for funding this study.
Weitere Informationen

Publikationsverlauf

Received: 27. Mai 2019

Accepted after revision: 08. Juni 2019

Publikationsdatum:
16. Juli 2019 (online)


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.

Supporting Information

 
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