54879-52-6

Upstream product

• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 54879-76-4 N-(3,4-dimethoxybenzyl)aminoacetaldehyde dimethyl acetal 
• 39964-92-6 N-(3,4-dimethoxybenzyl)-N-(2,2-dimethoxyethyl)-4-methylbenzenesulfonamide 

Downstream Products

• 71521-93-2 6,7-dimethoxy-2-(toluene-4-sulfonyl)-2,3-dihydro-1H-isoquinolin-4-one 
• 208848-88-8 6,7-Dimethoxy-2-(toluene-4-sulfonyl)-1,2,3,4-tetrahydro-isoquinoline-3,4-diol 

Relevant academic research and scientific papers

Synthesis of 1,2-Dihydroisoquinolines by a Modified Pomeranz-Fritsch Cyclization

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.