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. 2012 Jan 25;134(3):1396-9.
doi: 10.1021/ja210837b. Epub 2012 Jan 11.

Total synthesis of oxidized welwitindolinones and (-)-N-methylwelwitindolinone C isonitrile

Kyle W Quasdorf  1 , Alexander D Huters, Michael W Lodewyk, Dean J Tantillo, Neil K Garg
Affiliations

Total synthesis of oxidized welwitindolinones and (-)-N-methylwelwitindolinone C isonitrile

Kyle W Quasdorf et al. J Am Chem Soc. .

Abstract

We report the total synthesis of (-)-N-methylwelwitindolinone C isonitrile, in addition to the total syntheses of the 3-hydroxylated welwitindolinones. Our routes to these elusive natural products feature the strategic use of a deuterium kinetic isotope effect to improve the efficiency of a late-stage nitrene insertion reaction. We also provide a computational prediction for the stereochemical configuration at C3 of the hydroxylated welwitindolinones, which was confirmed by experimental studies.

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Figures

Figure 1
Figure 1
Welwitindolinones 1–5.
Figure 2
Figure 2
Nitrene insertion of substrates 10a and 10b.
Figure 3
Figure 3
Total synthesis of oxidized welwitindolinones 3 and 4.
Figure 4
Figure 4
Structures of 3 and 4, in addition to C3 epimers, and summary of computational findings.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Scheme 3
Scheme 3
See this image and copyright information in PMC

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