New approaches towards the synthesis of 1,2,3,4-tetrahydro isoquinoline-3-phosphonic acid (TicP)

Two new strategies for the efficient synthesis of racemic 1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (TicP) (±)-2 have been developed. The first strategy involves the electron-transfer reduction of the easily obtained α,β-dehydro phosphonophenylalanine followed by a Pictet–Spengler cyclization. The second strategy involves a radical decarboxylation–phosphorylation reaction on 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic). In both strategies, the highly electrophilic N-acyliminium ion is formed as a key intermediate, and the target compound is obtained in good yield using mild reaction conditions and readily available starting materials, complementing existing methodologies and contributing to the easy accessibility of (±)-2 for further research.
This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACYT) through projects 286614 and 256985, and Gobierno de Aragon-FEDER (Grupo Aminoacidos y Peptidos E19-17R; FEDER 2014-2020 “Construyendo Europa desde Aragon”).