107382-95-6Relevant articles and documents
Regioselective Lithiation and Electrophilic Quenching of N-Boc-3-phenyltetrahydroisoquinoline
Talk, Ruaa A.,El-Tunsi, Ashraf,Robertson, Craig C.,Coldham, Iain
, p. 5294 - 5301 (2019)
Tetrahydroisoquinolines are found in many natural products and drug compounds and a convenient method to access 1-substituted derivatives is to carry out the lithiation at C-1 followed by trapping with an electrophile. Here we explore the feasibility of lithiation at C-3 by using a substrate with a benzylic proton on both sides of the nitrogen atom such that lithiation with nBuLi could occur at either C-1 or C-3 of the tetrahydroisoquinoline. The regioselectivity in the lithiation was determined using the substrate N-tert-butoxycarbonyl (Boc)-3-phenyltetrahydroisoquinoline. The lithiation could be followed by in situ ReactIR spectroscopy and the rate of rotation of the carbamate group was determined (barrier to rotation was approximately ΔG? 58 kJ/mol at –50 °C). Subsequent trapping of the organolithium species with an electrophile gave a mixture of two regioisomeric products with a preference for reaction at C-1. This led to the isolation of 1,3-disubstituted tetrahydroisoquinolines with trans relative stereochemistry. Removal of the Boc group from the nitrogen atom gave secondary and tertiary amine products.
