DOI: 10.1002/chem.201404157
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Synthetic Methods
Titanium Salan Catalysts for the Asymmetric Epoxidation of
Alkenes: Steric and Electronic Factors Governing the Activity and
Enantioselectivity
Evgenii P. Talsi,[a, b] Denis G. Samsonenko,[b, c] and Konstantin P. Bryliakov*[a, b]
Abstract: A new insight into the highly enantioselective (up
to >99.5% ee) epoxidation of olefins in the presence of
chiral titanium(IV) salan complexes is reported. A series of 14
chiral ligands with varying steric and electronic properties
have been designed, and it was found that electronic effects
modulate the catalytic activity (without affecting the enan-
tioselectivity), whereas the steric properties account for the
enantioselectivity of the epoxidation. Competitive oxidations
of p-substituted styrenes reveal the electrophilic nature of
the oxygen-transferring active species, with a Hammett
1 value of ꢀ0.51; the enantioselectivity is unaffected by the
electron-donating (or withdrawing) ability of the p-substitu-
ents. Mechanistic studies provide evidence in favor of a step-
wise reaction mechanism: in the first (rate-determining)
stage, olefin most probably coordinates to the active spe-
cies, followed by intramolecular enantioselective oxygen
transfer. The enantioselectivity increases with decreasing
temperature. The modified Eyring plots for the epoxidation
of styrene and (Z)-b-methylstyrene are linear, indicating
a single, enthalpy-controlled mechanism of stereoselectivity,
¼
with DDH =ꢀ6.6 kJmolꢀ1 and ꢀ5.4 kJmolꢀ1, respectively.
Introduction
inertness toward redox processes and with rich possibilities of
tuning its activity and selectivity by rational ligand design, this
makes titanium a welcome protagonist for various enantiose-
lective catalytic transformations, including epoxidations.[5]
In 2005, Katsuki with co-workers introduced the first titani-
um-based family of salalen (dihydrosalen) catalysts that were
capable of epoxidizing unfunctionalized conjugated olefins
with H2O2 with high enantioselectivity.[6,7] Berkessel and co-
workers developed alternative procedures for the syntheses of
salalen ligands,[8,9] and demonstrated that titanium–salalen cat-
alysts can also catalyze the epoxidation of nonconjugated, in-
cluding terminal, olefins with high ee values.[10]
Alongside titanium–salalen,[11,12] more synthetically accessible
titanium–salan complexes have been studied in recent years as
catalysts for enantioselective epoxidations[13–18] and sulfoxida-
tions[19–25] with H2O2. In spite of the large amount of reported
catalytic data, to our knowledge, there have been no systemat-
ic studies of the influence of ligand structure on the catalytic
activity and oxidation selectivity. This work was initiated with
the aim of bridging this gap. Herewith, we report the effects of
the ligand structure (salalen vs. salan), symmetry, steric bulk,
and electronic properties on the epoxidation of conjugated
olefins. These studies have allowed us to delineate the steric
and electronic rules that govern the reaction outcome, so that
catalytic properties of titanium–salan catalysts can be predict-
ed for a particular combination of electron-donating (or with-
drawing), and bulky substituents. In addition, some general
conclusions on the mechanism of epoxidation can be drawn.
In particular, the epoxidation proceeds in a stepwise rather
than a concerted mechanism, with the process being most
Chiral epoxides containing one or two stereogenic centers are
versatile and reactive yet stable intermediates that can be
readily involved in further asymmetric transformations
through, for example, asymmetric ring-opening reactions.[1]
Since the milestone discoveries of organocatalyzed[2] and tran-
sition-metal-catalyzed[3,4] enantioselective epoxidations of ole-
finic substrates, catalytic approaches to the asymmetric synthe-
sis of chiral epoxides have developed greatly and they are
nowadays regarded as the most straightforward and reliable
ways of the producing enantiopure epoxides. More recently,
catalyst systems that rely on inexpensive and environmentally
benign hydrogen peroxide as terminal oxidant are of increas-
ing interest.
Titanium is one of the cheapest transition metals (7th most
abundant metal on Earth), and the products of its hydrolysis
are not toxic, which is in contrast to those of other available
transition metals such as Cr, Ni, and V. Together with its relative
[a] Prof. Dr. E. P. Talsi, Prof. Dr. K. P. Bryliakov
Boreskov Institute of Catalysis
Pr. Lavrentieva 5, Novosibirsk 630090 (Russia)
[b] Prof. Dr. E. P. Talsi, Dr. D. G. Samsonenko, Prof. Dr. K. P. Bryliakov
Novosibirsk State University
Pirogova 2, Novosibirsk 630090 (Russia)
[c] Dr. D. G. Samsonenko
Nikolaev Institute of Inorganic Chemistry
Pr. Lavrentieva 3, Novosibirsk 630090 (Russia)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201404157.
Chem. Eur. J. 2014, 20, 1 – 8
1
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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