Synthesis of 1,2-Dihydroisoquinolines by a Modified Pomeranz-Fritsch Cyclization.
J Org Chem
; 85(2): 1062-1072, 2020 01 17.
Article
em En
| MEDLINE
| ID: mdl-31854981
ABSTRACT
Isoquinolines (IQs) and their derivatives are present in many natural products and biologically active small molecules. Herein, we report a modified procedure for the classical Pomeranz-Fritsch protocol, which expands the scope of 1,2-dihydroisoquinoline (DHIQ) products. 1,2-DHIQs are an attractive branch point for the synthesis of IQs, but because of their innate reactivity, they have remained difficult to prepare. We demonstrate that the Fujioka/Kita conditions, combining trimethylsiyltriflate (TMSOTf) and an amine base, activate dimethylacetals required for Pomeranz-Fritsch cyclization under sufficiently mild conditions to prepare a broad range of 1,2-DHIQ products. We also demonstrate the synthetic value of these DHIQs by further functionalization to either reduced tetrahydroisoquinoline (THIQ) or fully aromatized IQ natural products.
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MEDLINE
Idioma:
En
Ano de publicação:
2020
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Article