Organic Letters
Letter
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a modified Leuckart−Wallach procedure, with conversion in
situ into isocyanides, which can be reacted in the same pot in
different isocyanide-based MCRs. The broad applicability of the
procedure is exemplified with multiple highly diverse examples
of six different unrelated MCR scaffolds. We found the yields
and substrate scope to be comparable, or superior, to the
original procedures using isolated isocyanides. Highly stereo-
selective transformations are also possible. This in situ
procedure comprises a major milestone in the rapidly advancing
field of isocyanide chemistry in general, and specifically in
IMCR, since it avoids the isolation of the unpleasant
isocyanides and reduces the time to the product without
compromising structural and scaffold diversity.
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ASSOCIATED CONTENT
* Supporting Information
■
S
(14) (a) Ugi, I.; Steinbruckner, C. Chem. Ber. 1960, 72, 267−268.
̈
Optimization, screening results, general procedures, character-
ization data of all the compounds, and a multimedia file (AVI)
are included as Supporting Information. This material is
(b) Domling, A.; Ugi, I. Angew. Chem. 2000, 112, 3300−3344.
̈
(15) Mironov, M. A.; Mokrushin, V. S. Russian Journal of Organic
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̈
AUTHOR INFORMATION
Corresponding Author
(b) Schaffert, E. S.; Hofner, G.; Wanner, K. T. Bioorg. Med. Chem.
̈
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2011, 19, 6492−6504. (c) Patil, P.; Khoury, K.; Herdtweck, E.;
Domling, A. Org. Lett. 2014, 16, 5736−5739.
̈
Notes
(17) (a) Demharter, A.; Horl, W.; Herdtweck, E.; Ugi, I. Angew.
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Chem. 1996, 108, 185−187. (b) Demharter, A.; Horl, W.; Herdtweck,
E.; Ugi, I. Angew. Chem. 1996, 35, 173−175.
̈
The authors declare no competing financial interest.
(18) (a) Borthwick, A. D.; Liddle, J.; Davies, D. E.; Exall, A. M.;
Hamlett, C.; Hickey, D. M.; Mason, A. M.; Smith, I. E. D.; Nerozzi, F.;
Peace, S.; Pollard, D.; Sollis, S. L.; Allen, M. J.; Woollard, P. M.; Pullen,
M. A.; Westfall, T. D.; Stanislaus, D. J. J. Med. Chem. 2012, 55, 783−
796. (b) Borthwick, A. D. J. Med. Chem. 2010, 53, 6525−6538.
(19) (a) Khoury, K.; Sinha, M. K.; Nagashima, T.; Herdtweck, E.;
ACKNOWLEDGMENTS
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The work was financially supported from the NIH
(1R01GM097082-01) and by Innovative Medicines Initiative
(Grant Agreement No. 115489).
Domling, A. Angew. Chem., Int. Ed. 2012, 51, 10280−10283. (b) Sinha,
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M. K.; Khoury, K.; Herdtweck, E.; Domling, A. Org. Biomol. Chem.
̈
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