COMMUNICATION
DOI: 10.1002/chem.201000960
A Tetranuclear-Zinc-Cluster-Catalyzed Practical and Versatile Deprotection
of Acetates and Benzoates
Takanori Iwasaki,[a] Kazushi Agura,[a] Yusuke Maegawa,[a] Yukiko Hayashi,[a]
Takashi Ohshima,*[b] and Kazushi Mashima*[a]
Acyl groups, especially acetyl groups, are one of the most
common and useful protecting groups in organic synthesis.[1]
Consequently, a number of acylation and deacylation meth-
ods have been developed[2] and are widely utilized in organ-
ic synthesis, such as natural product synthesis and industrial
processes.[3] The increased demand for an environmentally
benign process with high total efficiency, however, requires
the development of more operationally simple, safe, and en-
vironmentally friendly alternatives.[4] In this context, transes-
terifications are especially attractive, because they require
only a catalytic amount of reagent and have additional ad-
vantages, such as mild reaction conditions, high chemoselec-
tivity, ease of handling, and high ester stability.[5] Indeed,
several efficient transesterification catalysts for acetylation
have been reported, including a Zn-catalyzed acetylation we
developed using ethyl acetate as the acetyl donor.[6] In con-
trast, deacylation still relies largely on the classical basic hy-
drolysis because of its efficiency and irreversible nature.[1]
The disadvantage of this procedure, however, is the low tol-
erance to many functional groups and the potential occur-
rence of undesired side reactions, such as elimination and
epimerization.[5,7] Although catalytic cleavage of ester bonds
using simple alcohol nucleophiles, such as methanol and eth-
anol, is a more desirable method, it is not a trivial task; for
example, catalytic activity of most of Lewis acid catalysts
decreases in the presence of stoichiometric or excess
amounts of alcohol. Alkali metal alkoxides,[7] KCN,[8] Sc-
AHCTUNGTRENNUNG
(OTf)3,[9] organotin dimers,[10] proazaphosphatranes,[11] Yb-
AHCTUNGTRENNUNG
(OTf)3,[12] tris(2,4,6-trimethoxyphenyl)phosphine,[13] acetyl
chloride,[14] ZrCl4,[15] and enzymes[16] have been applied to
the deacetylation of aliphatic acetates. Among them, the
neutral organotin catalyst [{tBu2SnOH(Cl)}2] developed by
Otera et al.[10] is the most efficient catalyst in terms of mild
reaction conditions and catalytic activity, though it does re-
quire the use of a toxic heavy metal. Even under these neu-
tral conditions, however, undesired reactions such as elimi-
nation reactions sometimes occur. Low conversion of steri-
cally congested acetates of secondary and tertiary alcohol is
another problem. To date, the best result in deacetylation of
tertiary acetate[17] was a yield of only 22% and the harsh
conditions resulted in an elimination reaction.[10]
As part of our ongoing studies of environmentally friend-
ly, direct catalytic reactions, we recently developed an
m-oxo-tetranuclear zinc cluster [Zn4ACTHNUTRGNEUNG
(OCOCF3)6O] (1),[6,18,19]
which efficiently catalyzed the transesterification of various
methyl esters under mild conditions.[18b,c] The neutral and
mild reaction conditions enabled the transesterification of
esters and alcohols with various functional groups, affording
highly functionalized esters in good to excellent yield. More-
over, we successfully developed a chemoselective acylation
of hydroxyl groups in the presence of primary and secon-
dary aliphatic amino groups.[6,18b] This unusual selectivity of
1 can be ascribed to the simultaneous activation[20,21] of both
esters and hydroxyl groups by the two adjacent zinc ions in
cluster 1. This protocol is also applicable to the catalytic
acetylation of alcohols with various functionalities through
the use of ethyl acetate as the acetyl donor and solvent.[6]
Because the zinc cluster 1 retains the high catalyst activity
even in the presence of excess amounts of alcohol,[18a] we an-
ticipated that deacetylation, which is the reverse reaction of
the above-mentioned acetylation, would also be catalyzed
by 1 just by changing the solvent from ethyl acetate to meth-
anol. Here, we report that the zinc cluster 1 efficiently cata-
lyzed deacetylation and debenzoylation when methanol was
[a] Dr. T. Iwasaki, K. Agura, Y. Maegawa, Y. Hayashi,
Prof. Dr. K. Mashima
Department of Chemistry
Graduate School of Engineering Science
Osaka University, CREST, 1-3 Machikaneyama
Toyonaka, Osaka 560-8631 (Japan)
Fax : (+81)6-6850-6245
[b] Prof. Dr. T. Ohshima
Graduate School of Pharmaceutical Sciences
Kyushu University, CREST, 3-1-1 Maidashi
Higashi-ku, Fukuoka 812-8582 (Japan)
Fax : (+81)92-642-6650
Supporting information for this article is available on the WWW
Chem. Eur. J. 2010, 16, 11567 – 11571
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11567