Angewandte
Chemie
DOI: 10.1002/anie.200703371
Supramolecular Catalysis
Catalytic Deprotection of Acetals in Basic Solution with a
Self-Assembled Supramolecular “Nanozyme”**
Michael D. Pluth, Robert G. Bergman,* and Kenneth N. Raymond*
Acetals are among the most commonly used protecting
groups for aldehydes and ketones in organic synthesis because
of their ease of installation and resistance to cleavage in
neutral or basic solution.[1] The common methods for hydro-
lyzing acetals almost always involve the use of either
Brønsted acid or Lewis acid catalysts.[2] A number of reports
have documented a variety of strategies for acetal cleavage
under mild conditions. These include the use of Lewis acids
such as bismuth(III)[3] or cerium(IV),[4,5] functionalized silica
gel, such as silica sulfuric acid[6] or silica-supported pyridinium
p-toluenesulfonate,[7] or the use of silicon-based reagents
such as triethylsilyltrifluoromethanesulfonyl-2,6-lutidine.[8]
Figure 1. Left: A schematic representation of the host M4L6 assembly.
Onlyone ligand is shown for clarity. Right: A model of the empty
assembly; Ga green, O red, N blue, C gray; hydrogen atoms are
omitted for clarity.
Despite these mild reagents, all of the above conditions
require either added acid or overall acidic media. Markó and
co-workers recently reported the first example of acetal
deprotection under mildly basic conditions using catalytic
cerium ammonium nitrate at pH 8 in a water/acetonitrile
mixture.[5] Also recently, Rao and co-workers described a
purely aqueous system at neutral pH for the deprotection of
acetals using b-cyclodextrin as the catalyst.[9] Herein, we
report the hydrolysis of acetals in basic aqueous solution using
a self-assembled supramolecular host as the catalyst.
imparts water solubility, the naphthalene walls of the
assembly provide a hydrophobic cavity which is isolated
from the bulk aqueous solution. This hydrophobic cavity has
been utilized to stabilize a variety of water-sensitive guests,
such as tropylium,[11] iminium,[12] diazonium,[13] protonated
amine,[14] and reactive phosphonium species.[15] Furthermore,
1 has been used to encapsulate catalysts[16] for organic
transformations as well as act as a catalyst for the 3-aza-
Cope rearrangement of enammonium substrates[17] and the
hydrolysis of acid-labile orthoformates.[18]
During the last decade, we have used metal–ligand
interactions for the formation of well-defined supramolecular
assemblies with the stoichiometry M4L6 (M = GaIII (1 refers to
K12[Ga4L6]), AlIII, InIII, FeIII, TiIV, or GeIV, L = N,N’-bis(2,3-
dihydroxybenzoyl)-1,5-diaminonaphthalene;
Figure 1).[10]
Our recent work using 1 as a catalyst for orthoformate
hydrolysis prompted our investigation of the ability of 1 to
catalyze the deprotection of acetals (Scheme 1). With the
The metal ions occupy the vertices of the tetrahedron and
the bisbidentate catecholamide ligands span the edges. The
rigid ligands transfer the chirality from one metal vertex to
the other, thereby requiring the DDDD or LLLL config-
urations of the assembly. Whereas the ꢀ12 overall charge
Scheme 1. Catalytic deprotection of acetals under basic conditions
using 1 as a catalyst.
[*] M. D. Pluth, Prof. R. G. Bergman, Prof. K. N. Raymond
Department of Chemistry
Universityof California
Berkeley, CA 94720–1460 (USA)
Fax: (+1)510-642-7714 (Bergman)
Fax: (+1)510-486-5283 (Raymond)
E-mail: rbergman@cchem.berkeley.edu
bergman.html
ability of 1 to favor encapsulation of monocationic guests, we
anticipated that acetal hydrolysis could be accelerated by
stabilization of any of the cationic protonated intermediates
along the mechanistic pathway upon encapsulation in 1. In
contrast to the stability of 2,2-dimethoxypropane in H2O at
pH 10, addition of the acetal to a solution of 1 at this pH
quickly yielded the products of hydrolysis. Addition of a
strongly binding inhibitor for the interior cavity of 1, such as
NEt4 (logKa = 4.55), inhibited the overall reaction, thus
confirming that 1 is active in the catalysis.
The hydrolysis reactions were screened by mild heating
(508C) of 5 mol% of 1 with respect to the acetal substrate at
pH 10 in H2O in a sealed NMR tube using dimethylsulfoxide
raymond.html
[**] We gratefullyacknowledge financial support from the Director,
Office of Science, Office of Basic EnergySciences, and the Division
of Chemical Sciences, Geosciences, and Biosciences of the US
Department of Energyat LBNL under Contract No. DE-AC02-
05CH11231 and an NSF predoctoral fellowship to M.D.P. We thank
Dr. D. Leung, Dr. S. Biros, Dr. M. Seitz, and C. Hastings for helpful
discussions.
+
Angew. Chem. Int. Ed. 2007, 46, 8587 –8589
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8587
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&