Trading N and O. Part 3: Synthesis of 1,2,3,4-tetrahydroisoquinolines from α-hydroxy-β-amino esters
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- 作者：Stephen G. Davies ; steve.davies@chem.ox.ac.uk" class="auth_mail" title="E-mail the corresponding author ; Ai M. Fletcher ; Aileen B. Frost ; Matthew S. Kennedy ; Paul M. Roberts ; James E. Thomson
- 关键词：Tetrahydroisoquinoline ; α-Hydroxy-β-amino ester ; Aziridinium ; Asymmetric synthesis
- 刊名：Tetrahedron
- 出版年：2016
- 出版时间：28 April 2016
- 年：2016
- 卷：72
- 期：17
- 页码：2139-2163
- 全文大小：2697 K
文摘
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.