Abstract
The reaction of tryptamine and (2-oxocyclohexyl)acetic acid can be catalyzed by 3,3′-bis(triphenylsilyl)-1,1′-bi-2-naphthol phosphoric acid to give an asymmetric β-carboline. This reaction was first studied by Holloway et al. (Org. Lett. 2010, 12, 4720-4723), but their mechanistic work did not explain the high stereoselectivity achieved. This study uses density functional theory and hybrid quantum mechanics/molecular mechanics calculations to investigate this reaction and provide a model to explain its outcome. The step leading to diastereo- and enantioselectivity is an asymmetric Pictet-Spengler reaction involving an N-acyliminium ion bound to the catalyst in a bidentate fashion. This interaction occurs via hydrogen bonds between the two terminal oxygen atoms of the catalyst phosphate group and the hydrogen atoms at N and C2 of the substrate indole group. These bonds hold the transition structure rigidly and thus allow the catalyst triphenylsilyl groups to influence the enantioselectivity.
Original language | English |
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Pages (from-to) | 2634-2640 |
Number of pages | 7 |
Journal | Journal of Organic Chemistry |
Volume | 80 |
Issue number | 5 |
Early online date | 5 Feb 2015 |
DOIs | |
Publication status | Published - 6 Mar 2015 |
ASJC Scopus subject areas
- Organic Chemistry