Mechanistic insights into a BINOL-derived phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction

Lois M. Overvoorde, Matthew N. Grayson, Yi Luo, Jonathan M. Goodman

Research output: Contribution to journalArticlepeer-review

48 Citations (SciVal)


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 languageEnglish
Pages (from-to)2634-2640
Number of pages7
JournalJournal of Organic Chemistry
Issue number5
Early online date5 Feb 2015
Publication statusPublished - 6 Mar 2015

ASJC Scopus subject areas

  • Organic Chemistry


Dive into the research topics of 'Mechanistic insights into a BINOL-derived phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction'. Together they form a unique fingerprint.

Cite this