Angewandte
Chemie
DOI: 10.1002/anie.201202327
Organocatalysis
Nucleophilic Reactivities of Deoxy Breslow Intermediates: How Does
Aromaticity Affect the Catalytic Activities of N-Heterocyclic
Carbenes?**
Biplab Maji, Markus Horn, and Herbert Mayr*
Dedicated to Professor George A. Olah on the occasion of his 85th birthday
N-Heterocyclic carbenes[1] (NHCs, 1) are widely used as
umpolung reagents[2] in organocatalysis.[3] In benzoin con-
densations[4] and Stetter reactions[5] the initially formed
Breslow intermediate A,[6] a nucleophilic acyl anion equiv-
alent, reacts with an aldehyde or Michael acceptor to give 1,2-
or 1,4-functionalized products. Recently, Fu, Matsuoka, and
Glorius independently reported the umpolung of the b-
position of Michael acceptors, where 1,1-diaminoalkenes B
act as key intermediates.[7] Since the structure of B is closely
related to A, it has been named “deoxy Breslow intermedi-
ate” (Scheme 1).[7c,8]
As the different catalytic activities of unsaturated and
saturated carbenes thus cannot be assigned to the different
properties of the carbenes themselves, the question arose
whether it is due to the different reactivities of the corre-
sponding Breslow intermediates. While characterizations of
Breslow intermediates by spectroscopic and theoretical
methods have been reported,[10] we are not aware of any
kinetic investigations comparing the reactivities of 1,1-di-
aminoethenes derived from different classes of NHCs. There-
fore, we have now synthesized compounds 2[11] and deter-
mined the kinetics of their reactions with electrophiles.
The reactions of 1a and 1b with benzyl or 4-nitrobenzyl
bromide, and subsequent deprotonation of the resulting
amidinium ions with NaH in the presence of a catalytic
amount of KOtBu in THF afforded 2a–2b’ in yields of 30–
90% (Scheme 2). While 2a and 2a’ could also be generated
Scheme 1. Reactions of NHCs with aldehydes and Michael acceptors
to give intermediates A and B, respectively.
Most suitable for these reactions were 1,2,4-triazol-5-
ylidenes, 1,3-thiazol-2-ylidenes, and imidazol-2-ylidenes,
while imidazolidin-2-ylidenes are not effective as umpolung
reagents.[3,8] This observation is surprising, because in recent
work we have shown that the imidazol-2-ylidene 1a and
imidazolidin-2-ylidene 1b have almost the same nucleophi-
licities and Lewis basicities, while Endersꢀs carbene 1c
reacted 103 times more slowly and 55 kJmolꢀ1 less exothermic
with C-electrophiles.[9]
Scheme 2. Synthesis of deoxy Breslow intermediates 2.
[*] M. Sc. B. Maji, Dr. M. Horn, Prof. Dr. H. Mayr
Department Chemie, Ludwig-Maximilians-Universitꢀt Mꢁnchen
Butenandtstrasse 5–13 (Haus F), 81377 Mꢁnchen (Germany)
E-mail: herbert.mayr@cup.uni-muenchen.de
with stoichiometric amounts of KOtBu in the absence of
NaH,[8] this procedure did not allow the synthesis of 2b and
2b’. Attempts to synthesize 2c’ analogously resulted in
complex reaction mixtures. However, 2c’ was synthesized in
60% yield from 4-nitrobenzyl bromide and 2 equivalents of
1c in toluene, the second molecule of 1c acting as the base.
For details of the synthetic procedures see the Supporting
Information.
[**] We thank the Deutsche Forschungsgemeinschaft (SFB 749) for
financial support, Dr. Peter Mayer for the determination of the X-ray
structures, and Dr. Sami Lakhdar, Dr. Guillaume Berionni, Dr. Armin
R. Ofial, Prof. Paul von Raguꢂ Schleyer, and Dr. Judy Wu for helpful
discussions.
In order to quantify the nucleophilic reactivities of 2 we
have studied the kinetics of their reactions with the benzhy-
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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