Talk, R., El-Tunsi, A., Robertson, C. et al. (1 more author) (2019) Regioselective lithiation and electrophilic quench of N‐Boc‐3‐phenyltetrahydroisoquinoline. European Journal of Organic Chemistry, 2019 (31-32). pp. 5294-5301. ISSN 1434-193X
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an author produced version of a paper subsequently published in European Journal of Organic Chemistry. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 02 Apr 2019 15:06 |
Last Modified: | 22 Nov 2021 14:22 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/ejoc.201900238 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:144362 |