Asymmetric synthesis of substituted 2-aminotetralins
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- Institutt for kjemi 
Presented in this thesis are the results obtained from the project: Asymmetric synthesis of substituted 2-aminotetralins. The initial goal was to establish new or improved routes to enantiopure 2-aminotetralin (2-AT) derivatives. The motivation for this project was based on the diverse applications various 2-ATs represent as biologically active compounds. Despite the role of 2-aminotetralins as interesting target molecules, reflected by the massive research activity in the field, no general and cost efficient route has really been established. Chapter 1 in this thesis gives an introduction to 2-ATs as biologically active compounds, as well as a brief survey of the concepts of chirality and asymmetric synthesis. Aziridines are also presented, given their role as key intermediates in our developed strategies (chapters 2-4). In chapter 2, a total synthesis of substituted (S)-2-ATs is presented, starting from natural L-aspartic acid. Two 2-AT derivatives were successfully synthesised, but especially one step (ring-closing to tetralones) proved difficult, providing up to 41% yield only. Chapter 3 is directly based on the experiences we made in the former chapter, and presents an improved route from the same starting point (chiral pool strategy utilising L-aspartic acid). Again we struggled with one specific cyclisation reaction (up to 36% yield), but the remaining steps provided overall good yields. In Chapter 4, a different approach has been targeted, i.e. asymmetric aziridination of 1,2-dihydronaphthalenes. Here, various copper, rhodium and ruthenium catalytic systems were tested with alternative nitrogen sources. While we were able to achieve quite good results for non-substituted 1,2-dihydronaphthalene, substituted substrates provided only mediocre yields and enantioselectivity. Aziridines were selectively ring-opened by catalytic hydrogenation to their respective N-protected 2-ATs in good yields.
Består avAaseng, J. E.; Gautun, O. R.. Synthesis of substituted (S)-2-aminotetralins via ring-opening of aziridines prepared from L-aspartic acid ß -tert-butyl ester.. Tetrahedron. (ISSN 0040-4020). 66: 8982-8991, 2010. 10.1016/j.tet.2010.09.025.
Aaseng, J. E.; Gautun, O. R.. Synthesis of (S)-2-amino-7-methoxytetralin and isoindolo[1,2-a]isoquinolinone derivatives from L-aspartic acid.. .