ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Direct N‑Acylation of Lactams,
Oxazolidinones, and Imidazolidinones
with Aldehydes by Shvo’s Catalyst
Jian Zhang‡ and Soon Hyeok Hong*,†
Department of Chemistry, College of Natural Sciences, Seoul National University,
Seoul 151-747, Korea, and Division of Chemistry and Biological Chemistry,
School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
Received July 27, 2012
ABSTRACT
Direct N-acylation of lactams, oxazolidinones, and imidazolidinones was achieved with aldehydes by Shvo’s catalyst without using any other
stoichiometric reagent. The N-acylations with R,β-unsaturated aldehydes were achieved with excellent yields.
N-Acylated lactams, oxazolidinones, and imidazolidi-
nones are important organic molecules with a wide range
of biological activity. They are associated with certain
natural productsand drugs, suchasvariotin,1 aniracetam,2
piperlotine G,3 and imidapril.4 Functionalized chiral ox-
azolidinones are widely used as chiral auxiliaries and
ligands in asymmetric synthesis.5 A typical method for
the N-acylation of lactams, oxazolidinones, and imidazoli-
dinones is the usage of acyl chlorides or anhydrides in the
presence of a strong base such as nBuLi.6 Recent represen-
tative approaches are the N-acylation of oxazolidinones
with acid fluorides7 and mild bases, and the copper-
catalyzed coupling of aldehydes with free amides using
1.5 equiv of N-bromosuccinimide (NBS).8 These synthetic
methods are not environmentally friendly and atom eco-
nomical, as the reactions require more than stoichiometric
amounts of bases and generate halide and/or other wastes.
To develop a more versatile, operatively simple, and en-
vironmentally friendly synthetic route to the N-acylation
of cyclic amides from a readily available source, we envi-
sioned that the acylation could be carried out directly with
aldehydes generating hydrogen as the sole byproduct,
through generation of a hemiaminal intermediate and
dehydrogenation of the hemiaminal by a transition-metal
catalyst. Although there have been many reports on amide
‡ Nanyang Technological University.
† Seoul National University.
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10.1021/ol302087z
XXXX American Chemical Society