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

Abstract

Two new strategies for the efficient synthesis of racemic 1,2,3,4-tetrahydroisoquinoline-3-phosphonic acid (Tic^P) (±)-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.

Keywords: N-Acyliminium ion; Phosphorylation; Radical fragmentation; Wittig–Horner and Pictet–Spengler reactions; α,β-Dehydroaminophosphonate; α-Aminophosphonic acids.