Trading N and O. Part 3: Synthesis of 1,2,3,4-tetrahydroisoquinolines from α-hydroxy-β-amino esters
| Autor: | Matthew S. Kennedy, Paul M. Roberts, Stephen G. Davies, Aileen B. Frost, James E. Thomson, Ai M. Fletcher |
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| Rok vydání: | 2016 |
| Předmět: |
Amino esters
010405 organic chemistry Stereochemistry Aryl Organic Chemistry Diastereomer Enantioselective synthesis Regioselectivity 010402 general chemistry 01 natural sciences Biochemistry 0104 chemical sciences Carbenium ion chemistry.chemical_compound Enantiopure drug chemistry Drug Discovery Moiety |
| Zdroj: | Tetrahedron. 72:2139-2163 |
| ISSN: | 0040-4020 |
| Popis: | All rights reserved.A range of enantiopure 1,2,3,4-tetrahydroisoquinolines have been prepared directly from α-hydroxy-β-amino esters. Activation of the α-hydroxy group upon treatment with Tf2O and 2,6-di-tert-butyl-4-methylpyridine promotes aziridinium formation, which is then followed by rupture of the C(3)-N bond and Friedel-Crafts alkylation-type cyclisation of an N-benzyl moiety onto the resultant benzylic carbenium ion. The nature of the N-protecting group was varied and it was found that superior yields were obtained for reactions employing two benzylic groups. In the cases where two different N-benzyl groups were used, the regioselectivity resulting from competitive cyclisation of either N-benzyl group was addressed by the introduction of a p-trifluoromethyl group on one of the N-benzyl moieties, which retarded the rate of cyclisation via this electron poor aryl ring. This methodology was employed in the asymmetric synthesis of a range of enantiopure 1,2,3,4-tetrahydroisoquinolines, which were isolated in good yields as single diastereoisomers. |
| Databáze: | OpenAIRE |
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