Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench

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 c...

Full description

Saved in:
Bibliographic Details
Published in:Organic & biomolecular chemistry 2016-06, Vol.14 (21), p.498-4917
Main Authors: Talk, Ruaa A, Duperray, Alexia, Li, Xiabing, Coldham, Iain
Format: Article
Language:English
Subjects:
Chemistry Techniques, Synthetic
Lithium - chemistry
Tetrahydroisoquinolines - chemical synthesis
Tetrahydroisoquinolines - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 LiAlH 4 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. Lithiation then electrophilic quench of tetrahydroisoquinolines provides access to 1-substituted products. Removal of the N -Boc group allows rapid access to natural products such as (±)-crispine A.
ISSN:1477-0520
1477-0539
DOI:10.1039/c6ob00577b