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. 2021 Oct 15;23(20):7916-7920.
doi: 10.1021/acs.orglett.1c02914. Epub 2021 Oct 5.

Palladium-Catalyzed, Enantioselective Desymmetrization of N-Acylaziridines with Indoles

Kinney Van Hecke  1 , Tyler R Benton  1 , Michael Casper  1 , Dustin Mauldin  1 , Brandon Drake  1 , Jeremy B Morgan  1
Affiliations

Palladium-Catalyzed, Enantioselective Desymmetrization of N-Acylaziridines with Indoles

Kinney Van Hecke et al. Org Lett. .

Abstract

Ring opening reactions of meso-aziridines generate chiral amine derivatives where the control of stereochemistry is possible through enantioselective catalysis. We report the use of a diphosphine-palladium(II) catalyst for the highly enantioselective desymmetrization of N-acylaziridines with indoles. The β-tryptamine products are isolated in moderate to high yield across a range of indole and aziridine substitution patterns. The synthetic utility of β-tryptamine products is demonstrated by conversion to the brominated pyrroloindoline derivative.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Natural products containing the tryptamine core.
Figure 2.
Figure 2.
[(R)-DM-SEGPHOS]Pd(H2O)2(BF4)2 crystal structure.
Figure 3.
Figure 3.
Proposed catalytic cycle.
Scheme 1.
Scheme 1.
New Method for Aziridine Desymmetrization with Indoles
Scheme 2.
Scheme 2.
Gram-Scale Reaction Conditions
Scheme 3.
Scheme 3.. Tryptamine Deprotection and Functionalization
aReaction conditions: 1) Boc2O, DMAP, THF, 60 °C, 6 h: 2) K2CO3, MeOH, 23 °C, 1 h, 88% over 2 steps. bNBS, PPTS CH2Cl2, −10 °C, 6 h, 76%, 5:1 dr.
See this image and copyright information in PMC

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