Edge Article
Chemical Science
not unique to iron and further understanding of ways to control
scrambling outside of reagent selection will greatly expand the
substrate scope and applicability of metal-mediated unsym-
metric urea formation.
Scheme 4 Formamide-dependent synthesis of 1,1,3-tripentylurea.
Conflicts of interest
amide intermediate to undergo dehydrogenation to the isocy-
anate, although steric hindrance in generating a putative ami-
nal intermediate cannot be ruled out. Therefore, a similar
analysis was performed using two synthetic routes for the
preparation of 1,1,3-tripentylurea (Scheme 4). While the NMR-
scale reaction of pentylformamide and dipentylamine dis-
played approximately 80% conversion to the desired urea,46 the
alternative combination of dipentylformamide and pentyl-
amine did not produce any coupling product (Fig. S7–S8†). The
main difference between these two routes is the ability of the
starting formamide to form an isocyanate intermediate, as the
sterics of the nal product are identical. Further evidence for an
isocyanate intermediate was obtained through the reaction of
cyclohexylformamide with 1 in the absence of other reagents. In
this reaction the iron-dihydride species (presumably generated
from formamide dehydrogenation) was observed by NMR
spectroscopy, along with cyclohexyl isocyanate (conrmed by
GC analysis) as the sole organic product (Fig. S9†). These results
indicate that iron-catalyzed dehydrogenative ureation most
likely proceeds through an isocyanate intermediate as shown in
Scheme 3b.
There are no conicts to declare.
Acknowledgements
This work was supported by the U.S. Department of Energy,
Office of Science, Basic Energy Sciences, Catalysis Science
Program, under Award DE-SC0018222 and the Curators of the
University of Missouri.
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