Lateral Lithiation of N′-(2-Methylbenzyl)-N,N-dimethylurea and N-(2-Methylbenzyl)pivalamide: Synthesis of Tetrahydroisoquinolines

 

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Abstract

Lithiation of N′-(2-methylbenzyl)-N,N-dimethylurea and N-(2-methylbenzyl)pivalamide with two mole equivalents of tert-butyllithium at -78 ˚C takes place on the nitrogen and on the methyl group at position 2. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding side-chain-substituted derivatives in high yields. Dehydration of the products obtained from reactions with carbonyl compounds in some cases gives the corresponding tetrahydroisoquinolines in excellent yields, while in other cases dehydration takes place within the substituted side chain to produce the corresponding alkenes in excellent yields.

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Full crystallographic data of compounds 15, 24, 26, and 28 have been deposited with the CCDC under reference numbers 737412, 737417, 737416, and 737414, respectively, and can be obtained free of charge via
http://www.ccdc.ac.uk/data_request/cif.

• Supplementary Material