Issue 21, 2016

Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench

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.

Graphical abstract: Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench

Supplementary files

Article information

Article type
Paper
Submitted
16 Mar 2016
Accepted
04 May 2016
First published
04 May 2016

Org. Biomol. Chem., 2016,14, 4908-4917

Author version available

Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench

R. A. Talk, A. Duperray, X. Li and I. Coldham, Org. Biomol. Chem., 2016, 14, 4908 DOI: 10.1039/C6OB00577B

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