Table 3 Tris(2,2,2-trifluoroethyl) borate-promoted transamidation
Notes and references
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Entry
1
Product
Isolated yield (%)
73
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2
3
4
63
82
62
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alkenes, cyclopropanes, indoles, hydroxyl groups and esters were
also well tolerated (entries 7, 9–11, 15).
Given the fact that these borate ester reagents had proved
highly effective for the activation of carboxylic acids, we were
keen to expore their potential for activating other related systems.
Although esters did not undergo amidation (Table 2, entry 15),7
B(OCH2CF3)3 was observed to activate primary amides (Table 3).
This boron-mediated transamidation reaction gave good yields
of secondary amides, and shows very good functional group
tolerance (entries 3–4). Although a number of different procedures
for transamidation have been reported,13 there are few methods
available for the transamidation of primary amides without
a separate pre-activation step.13e–13f In contrast to these other
reports, this method is experimentally simple,13f and requires only
equimolar quantities of amine/amide.13e No transamidation was
observed in the absence of B(OCH2CF3)3, or in the presence of
B(OMe)3.
In summary, we have demonstrated that simple borates are
practical reagents for direct amide bond formation under both
thermal and microwave conditions. Unlike many other coupling
methods, this approach exhibits good functional group toler-
ance and purification is extremely straightforward. Tris(2,2,2-
trifluoroethyl) borate was also shown to activate amides toward
transamidation, providing a convenient and practical method for
the direct conversion of primary amides to secondary amides.
Further work on the development and application of other
boron-centered reagents is ongoing and will be reported in due
course.
13 For examples of amide activation/transamidation, see:(a) N. S.
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2009, 131, 10003–10008; (b) J. M. Hoerter, K. M. Otte, S. H. Gellman,
Q. Cui and S. S. Stahl, J. Am. Chem. Soc., 2008, 130, 647–654; (c) D.
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Acknowledgements
This work was supported by the EPSRC (EP/E052789/1: Ad-
vanced Research Fellowship to T.D.S. and PhD studentship to
P.S.). P.S. thanks the Estonian Ministry of Education and Research
and the Archimedes Foundation.
1322 | Org. Biomol. Chem., 2011, 9, 1320–1323
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