10.1002/anie.202105909
Angewandte Chemie International Edition
COMMUNICATION
solubility allowed crystallization of the isocyanide in the absence
of the Li-siloxide (Figure 3c). The N-C distance was 1.159(4) Å.
Scheme 3 Examples of gram-scale and one-pot reactions to isocyanides.
In conclusion, the reaction of silylamides with CO provides
a facile and low-pressure protocol to both KCN and isocyanides.
Understanding the mechanism using reliable DFT calculations
has allowed the adaptation of this reaction to the preparation of a
series of 19 isocyanides. This methodology is readily adapted to
the inclusion of 13C isotopic labeling at the cyano or isocyanide
carbons. In addition, it is shown to be viable in gram scale
preparations. We are continuing to explore the reaction chemistry
of alkali-metal species with small molecules.
Acknowledgements
D.W.S. is grateful to NSERC of Canada for research support and
the award of an NSERC Canada Research Chair and to the
Guggenheim Foundation for a 2020 Guggenheim Fellowship and
Killam foundation for the 2021 Killam Prize. Z.W.Q and S.G are
grateful to DFG (project SPP1807 and Gottfried Wilhelm Leibnitz
prize to S.G) for financial support. M.X. is grateful for the award of
Colin H. Bayley Scholarship. T.W. is grateful to China Scholarship
Council for financial support.
Figure
3
POV-ray depictions of the crystal structures of (a) [(2,6-
(b) [(THF)2(2,6-(Ph2CH)2-4-
Keywords: Cyanide • carbon monoxide • isotopic labelling •
small molecule activation• 13C labelled iso cyanides
(iPr)2C6H3NCLiOSiMe3)]4,
MeC6H2)NC)2(LiOSiMe3)4], and (c) 2,4,6-(tBu)3C6H2NC. Hydrogen atoms are
omitted for clarity, C: black, N: blue, O: red, Si: pink, Li: bronze.
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Several examples of these syntheses were performed on a
gram scale. Reactions of 1.1 g of [(Me3Si)(2,6-iPr2C6H3)N]Li or 1.0
g of [(Me3Si)(2,6-(Ph2CH)2-4-MeC6H2)N]Li in THF with CO
afforded the corresponding isocyanides in isolated yields 99 and
94% after recrystallization (Scheme 3), respectively. Similarly, 1
g of [(Me3Si)(tBu)N]Li in C6D6 led to quantitative conversion to
tBuNC, as evidenced by 1H NMR spectrum. Efforts to develop a
one-pot synthesis from the parent amines were also probed.
Using 1.88 g of 2,6-iPr2C6H3NH2 successive additions of 1.1
equivalent of nBuLi, 1 equivalent of Me3SiCl, and a second
equivalent of nBuLi and CO for 12 h in THF afforded the
isocyanide 2,6-iPr2C6H3NC in 47% isolated yield (Scheme 3).
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4
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