title: 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.
authors.affiliation: Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
authors.forename: Ruaa A
authors.initials: RA
authors.lastname: Talk
authors.forename: Alexia
authors.initials: A
authors.lastname: Duperray
authors.forename: Xiabing
authors.initials: X
authors.lastname: Li
authors.forename: Iain
authors.initials: I
authors.lastname: Coldham
mesh_terms: D060326:Chemistry Techniques, Synthetic; D008094:Lithium / Q000737:chemistry*; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D008094:Lithium