Organic Letters
Letter
(7) An alternative approach towards sterically hindered N-acylated
Aib-derivatives was disclosed by Obrecht and Heimgartner. Obrecht,
D.; Heimgartner, H. Helv. Chim. Acta 1987, 70, 102−115.
(8) Seminal work: (a) Leuchs, H. Ber. Dtsch. Chem. Ges. 1906, 39,
857−861. (b) Leuchs, H.; Manasse, W. Ber. Dtsch. Chem. Ges. 1907,
40, 3235−3249. (c) Leuchs, H.; Geiger, W. Ber. Dtsch. Chem. Ges.
1908, 41, 1721−1726.
(9) Selected reviews: (a) Kricheldorf, H. R. Angew. Chem., Int. Ed.
2006, 45, 5752−5784. (b) Hadjichristidis, N.; Iatrou, H.; Pitsikalis, M.;
Sakellariou, G. Chem. Rev. 2009, 109, 5528−5578. (c) Deming, T. J.
Adv. Mater. 1997, 9, 299−311.
(10) α-Isocyanatocarboxylic acids were speculated to be intermedi-
ates in base initiated NCA polymerizations. However, several studies
excluded their existence, e.g. Kricheldorf treated Bn-Glu NCA with the
strong base HMDS, but no isocyanate absorption could be observed
by FTIR. Kricheldorf, H. R.; Greber, G. Chem. Ber. 1971, 104, 3131−
3145.
Figure 1. React-IR differential spectrum.
(11) The majority of Grignard reagents bearing sensitive functional
groups were prepared according to: Krasovskiy, A.; Knochel, P. Angew.
Chem., Int. Ed. 2004, 43, 3333−3336.
(12) We cannot completely rule out the possibility that the
isocyanate is only a resting state of the reaction and the amide
formation proceeds via a different mechanism.
addition of organometallic reagents to N-carboxyanhydrides
(NCA). The reaction proceeds via an intermediate α-
isocyanatocarboxylate, whose existence was demonstrated by
react-IR. This method is compatible with a wide range of
functional groups and the use of enantiomerically pure amino
acid derived NCAs.
́
(13) Daly, W. H.; Poche, D. Tetrahedron Lett. 1988, 29, 5859−5862.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and characterization data for all
compounds. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by ETH Research Grant ETH-12 11-
1. We thank the ETH Mass Spectroscopy Service for high-
■
resolution mass spectrometry data, Claudio Grunenfelder
̈
(group Prof. Helma Wennemers, ETH) for assistance with
react-IR measurements, and Lukas Leu (ETH) for experimental
assistance.
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