39964-92-6

Upstream product

• 21852-32-4 4-bromomethyl-1,2-dimethoxybenzene 
• 58754-95-3 N-(2,2-dimethoxyethyl)-p-toluenesulfonamide 
• 7306-46-9 4-chloromethyl-1,2-dimethoxy-benzene 
• 98-59-9 p-toluenesulfonyl chloride 
• 54879-76-4 N-(3,4-dimethoxybenzyl)aminoacetaldehyde dimethyl acetal 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 39964-87-9 N-(2,2-dimethoxyethyl)-1-(3,4-dimethoxyphenyl)methanimine 

Downstream Products

• 15248-39-2 6,7-dimethoxyisoquinoline 
• 54879-52-6 6,7-dimethoxy-2-(toluene-4-sulfonyl)-1,2-dihydro-isoquinoline 

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.

One substrate, two modes of C-H functionalization: A metal-controlled site-selectivity switch in C-H arylation reactions

A unique site-selectivity switch has been achieved in the ruthenium-catalyzed C-H arylation reaction of N-acetyl-1,2-dihydroisoquinolines. This metal-mediated switch is antipodal to the previous report on the palladium-mediated C-4 C-H arylation on the same substrate. Mechanistic details reveal interesting aspects of the reaction pathway, and kinetic studies bring out the difference in the modes of C-H activation adopted by the two catalytic systems.

LiCl-mediated preparation of highly functionalized benzylic zinc chlorides

In the presence of zinc dust (1.5-2.0 equiv) and LiCI(1.5-2.0 equiv), various benzylic chlorides bearing functional groups (iodide, cyanide, ester, ketone) are smoothly converted at 25°C to the corresponding zinc reagents without homo-coupling (≤5%). The utility of these benzylic zinc reagents is demonstrated by a short synthesis of papaverine.

A SIMPLIFIED ISOQUINOLINE SYNTHESIS

A simple variation of the Pomeranz-Fritsch cyclization provides a short, efficient route to isoquinolines.Treatment of benzylic halides or mesylates 1 with the sodium anion of N-tosyl aminoacetaldehyde dimethyl acetal (2) followed by acid-catalyzed cyclization provides an effective, two-step preparation of isoquinolines 4.