CONCEPT
In Lewis acid/Brønsted base catalysis, the most familiar
catalyst system is composed of metallic compounds and ex-
ternal basic compounds, such as tertiary amines. These spe-
cies do not interact significantly with each other and work
simultaneously to deprotonate substrates. On the other
hand, metallic compounds including basic counteranions are
also recognized as good candidates for Lewis acid/Brønsted
base catalysts, because in acid/base systems using external
bases, the deprotonation step proceeds in an intermolecular
fashion. However, the deprotonation step proceeds in an in-
tramolecular-like fashion when metallic compounds includ-
ing basic counteranions are used (Figure 1). This means that
Abstract: In this paper, new possibilities for metal
amides are described. Although typical metal amides
are recognized as strong stoichiometric bases for depro-
tonation of inert or less acidic hydrogen atoms, transi-
tion-metal amides, namely silver and copper amides,
show interesting abilities as one of the simplest acid/
base catalysts in stereoselective carbon–carbon bond-
forming reactions.
Keywords: asymmetric synthesis · Brønsted base · cata-
lyst · Lewis acid · metal amide
Introduction
Acid/base catalysis has been well explored in synthetic or-
ganic chemistry. Among these catalysts, Lewis acid/Brønsted
base catalysts can achieve atom-economical bond-forming
processes through only proton transfer.[1] In particular, a
combination of metal or metalloid Lewis acid and Brønsted
base is a promising catalyst system in carbon–carbon bond-
forming reactions, because control of reactivity and stereo-
selectivity by modified metal Lewis acid and deprotonation
of active hydrogen by Brønsted base under Lewis acid acti-
vation of substrates are quite efficient for the formation of
reactive and stereoselective carbanion species.
In the long history of metal catalysis, Lewis acid catalysis
has been of great interest because it enables unique reactivi-
ty and stereoselectivities, especially enantioselectivities, to
be attained under mild reaction conditions.[2] To obtain
higher reactivities and selectivities, a target is stronger
Lewis acids, which are prepared by combining more Lewis
acidic metals or metalloids with less nucleophilic centers.
Through this approach, ligands (counteranions) have
evolved from halides to perchlorate, triflate, triflimide, etc.,
leading to stronger Lewis acids. However, strong Lewis
acids are not always suitable for acid/base catalysis. In Lewis
acid catalysis using strong Lewis acids, electrophile/Lewis
acid complexes are formed in transition states, and if the
complexes are too stable, Lewis acid catalysts might be trap-
ped by electrophiles, which suppress the catalyst turnover.
Moreover, a strong Lewis acid could easily interact with
basic species to deactivate them and shut down the acid/
base-catalyzed reactions. To achieve efficient acid/base cat-
alysis, the use of an appropriate combination of Lewis acid
and Brønsted base species is crucial.
Figure 1. Intermolecular- and intramolecular-type deprotonation by
Lewis acid/base system.
a
metallic compounds including basic counteranions could
promote acid/base-mediated reactions much more smoothly.
The structures of those metallic compounds are very simple,
and much flexibility exists in modification of the metal
center by using coordinative ligands for reactivity and
stereoACTHNURTGNEUcGN hemical control of reactions. To date, several types of
Lewis acid/Brønsted base catalysts, such as metal acetates,
phenoxides, and alkoxides, have been developed and em-
ployed in several stereoselective acid/base catalyses;[3] how-
ever, metal amides have not received the same attention as
effective Lewis acid/Brønsted base catalysts in stereoselec-
tive carbon–carbon bond-forming reactions.
Metal amides, mainly alkaline metal amides, have been
used as stoichiometric strong Brønsted base species in or-
ganic transformation reactions.[4] However, the difficulty in
modification of alkaline metal amides by using external lig-
AHCTUNGTREGaNNNU nds because of the lower Lewis acidic nature of the metals,
and also the acidity of the conjugate acid, a secondary
amine, prevent the application of those metal amides to cat-
alytic stereoselective reactions. Other metal amides, such as
alkaline earth metal amides and transition-metal amides,
have also been employed in some catalytic reactions such as
hydroamination reactions[5] and hydroaminoalkylation reac-
tions;[6] however, use of those species in catalytic stereose-
lective carbon–carbon bond-forming reactions has been very
limited. Those metal amides may show a less Brønsted basic
nature because the Lewis acidic metal part and the basic
amide part sometimes interact with each other and are deac-
tivated; therefore, the choice of metals could be an impor-
tant factor in developing effective active metal amides as
catalysts. However, some combination of metal and amide
[a] Dr. Y. Yamashita, Prof. Dr. S. Kobayashi
Department of Chemistry, School of Science
The University of Tokyo
Hongo, Bunkyo-ku, Tokyo, 113-0033 (Japan)
Fax : (+81)3-5684-0634
Chem. Eur. J. 2013, 19, 9420 – 9427
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9421