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. 2010 Nov 10;132(44):15800-7.
doi: 10.1021/ja1071509.

Palladium-catalyzed dynamic kinetic asymmetric transformations of vinyl aziridines with nitrogen heterocycles: rapid access to biologically active pyrroles and indoles

Barry M Trost  1 , Maksim Osipov, Guangbin Dong
Affiliations

Palladium-catalyzed dynamic kinetic asymmetric transformations of vinyl aziridines with nitrogen heterocycles: rapid access to biologically active pyrroles and indoles

Barry M Trost et al. J Am Chem Soc. .

Abstract

We report that nitrogen heterocycles can serve as competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric alkylation of vinyl aziridines. The resulting alkylated products were obtained with high regio-, chemo-, and enantioselectivity. Both substituted 1H-pyrroles and 1H-indoles were successfully employed to give exclusively the branched N-alkylated products. The synthetic utility of this process was demonstrated by applying this method to the preparation of several medicinal chemistry lead compounds and bromopyrrole alkaloids including longamide B, longamide B methyl ester, hanishin, agesamides A and B, and cyclooroidin.

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Figures

Figure 1
Figure 1
Diphenylphosphino benzoic acid-based ligands
Figure 2
Figure 2
Representative bromopyrrole alkaloids
Figure 3
Figure 3
Representative medicinal chemistry lead compounds
Scheme 1
Scheme 1
Synthesis of medicinal chemistry lead compounds.
Scheme 2
Scheme 2
Concise synthesis of bromopyrrole alkaloids
Scheme 3
Scheme 3
Mechanistic rationale
Scheme 4
Scheme 4
Rationale for observed regioselectivity
See this image and copyright information in PMC

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