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Updated: Mar 21, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench
Ruaa A Talk1, Alexia Duperray, Xiabing Li
1Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
Abstract:
Substituted N-tert-butoxycarbonyl (Boc)-1,2,3,4-tetrahydroisoquinolines were prepared and treated with n-butyllithium in THF at -50 °C to test the scope of the metallation and electrophilic quench. The lithiation was optimised by using in situ ReactIR spectroscopy and the rate of rotation of the carbamate was determined. The 1-lithiated intermediates could be trapped with a variety of electrophiles to give good yields of 1-substituted tetrahydroisoquinoline products. Treatment with acid or reduction with LiAlH4 allows conversion to the N-H or N-Me compound. The chemistry was applied to the efficient total syntheses of the alkaloids (±)-crispine A and (±)-dysoxyline.
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