Catalase and epoxidation activity of manganese salen complexes bearing two xanthene scaffolds

Article abstract of DOI:10.1021/ja070358w

A series of manganese Hangman salen ligand platforms functionalized by tert-butyl groups in the 3 and 3′ positions using the Suzuki cross-coupling methodology are presented. The Hangman platforms support multielectron chemistry mediated by proton-coupled

Full text of DOI:10.1021/ja070358w

Published on Web 06/07/2007
Catalase and Epoxidation Activity of Manganese Salen
Complexes Bearing Two Xanthene Scaffolds
Jenny Y. Yang and Daniel G. Nocera*
Contribution from the Department of Chemistry, 6-335, Massachusetts Institute of Technology,
77 Massachusetts AVenue, Cambridge, Massachusetts 02139-4307
Received January 17, 2007; E-mail: nocera@mit.edu
Abstract: A series of manganese Hangman salen ligand platforms functionalized by tert-butyl groups in
the 3 and 3′ positions using the Suzuki cross-coupling methodology are presented. The Hangman platforms
support multielectron chemistry mediated by proton-coupled electron transfer (PCET), as demonstrated
by their ability to promote the catalytic disproportionation of hydrogen peroxide to oxygen and water via a
high-valent metal oxo. The addition of the steric groups to the salen macrocycle leads to enhanced catalase
activity by circumventing side reactions that sequester the catalyst off pathway. The stereochemistry imposed
by the cyclohexanediamine backbone of the salen platform is revealed by the epoxidation of 1,2-
dihydronapthalene by a variety of oxidants. Improved enantiomeric excess and catalase activity as compared
to sterically unmodified counterparts establishes the efficacy of the tert-butyl groups in promoting PCET
catalysis on the Hangman platform.
by at least an order of magnitude.7 The increased catalase
activity by the Hangman salens is particularly compelling in
Introduction
Metallocofactors of proteins and enzymes are the sites of
confluence for coupling the protons and electrons needed for
the activation of small molecule substrates.1,2 We have captured
the proton-coupled electron transfer (PCET) reactivity of
metallocofactors by designing “Hangman” constructs.3-7 In the
Hangman architecture, the proton-transfer function of the
secondary coordination sphere of the enzyme is assumed by an
acid-base functional group that is suspended over the face of
a redox-active macrocycle, which serves as the site for both
the redox and substrate binding functions.8-10 We previously
reported the synthesis of a series of Hangman salen ligands that
incorporated two functionalized xanthene scaffolds and a chiral
cyclohexanediamine backbone in the macrocyclic ring.7 Com-
pared to the redox-only salen complex, the Hangman salen
complexes, HSX* and HphSX*, (Chart 1) catalytically enhance
the dismutation of hydrogen peroxide
view of the efficacy of manganese salen complexes as thera-
peutic agents of reactive oxygen species (ROS) in biological
systems.11 The removal of cytotoxic amounts of hydrogen
peroxide in animals12-16 and human tissue17 by manganese bis-
(3-methoxysalicylidene)-1,2-ethylenediamine chloride (EUK-
134) and manganese bis(salicylidene)-1,2-ethylenediamine chlo-
ride (EUK-8) has prompted structure-reactivity11,18 and
computational19,20 investigations aimed at elucidating key
intermediates in the catalytic cycle. To this end, the ability to
control catalase reactivity with the hanging group of Hangman
salens establishes this platform as an ideal venue in which to
define the structural and electronic properties of salen complexes
that are critical to enhanced ROS activity. We now show that
the superior catalase activity of Hangman salen complexes is
(11) Doctrow, S. R.; Adinolfi, C.; Baudry, M.; Huffman, K.; Malfroy, B.;
Marcus, C. B.; Melov, S.; Pong, K.; Rong, Y.; Smart, J. L.; Tocco, G. In
Critical ReViews of OxidatiVe Stress and Aging: AdVances in Basic Science,
Diagnostics, and InterVention, Vol. 2; Cutler, R. G., Rodriquez, H., Eds.;
World Scientific: Hackensack, NJ, 2003; pp 1324-1343.
(12) Gonzalez, P. K.; Zhuang, J.; Doctrow, S. R.; Malfroy, B.; Benson, P. F.;
Menconi, M. J.; Fink, M. P. J. Pharmacol. Exp. Ther. 1995, 275, 798-
806.
2 H2O2 catalase8 2 H2O + O2
(1)
(13) McDonald, M. C.; d’Emmanuele di Villa Bianca, R.; Wayman, N. S.; Pinto,
A.; Sharpe, M. A.; Cuzzocrea, S.; Chatterjee, P. K.; Thiemermann, C. Eur.
J. Pharmacol. 2003, 466, 181-189.
(1) Reece, S. Y.; Hodgkiss, J. M.; Stubbe, J.; Nocera, D. G. Philos. Trans. R.
Soc. London, Ser. B 2006, 361, 1351-1364.
(2) Cukier, R. I.; Nocera, D. G. Annu. ReV. Phys. Chem. 1998, 49, 337-369.
(3) Yeh, D.-Y.; Chang, C. J.; Nocera, D. G. J. Am. Chem. Soc. 2001, 5, 1513-
1514.
(14) Olcott, A. P.; Tocco, G.; Tian, J.; Zekzer, D.; Fukuto, J.; Ignarro, L.;
Kaufman, D. L. Diabetes 2004, 53, 2574-2579.
(15) Baker, K.; Marcus, C. B.; Huffman, K.; Kruk, H.; Malfroy, B.; Doctrow,
S. R. J. Pharmacol. Exp. Ther. 1998, 284, 215-221.
(16) d’Emmanuele di Villa Bianca, R.; Wayman, N. S.; McDonald, M. C.; Pinto,
A.; Sharpe, M. A.; Chatterjee, P. K.; Thiemermann, C. Med. Sci. Monit.
2002, 8, BR1-7.
(17) Decraene, D.; Smaers, K.; Gan, D.; Mammone, T.; Matusi, M.; Maes, D.;
Declercq, L.; Garmyn, M. J. InVest. Dermatol. 2004, 122, 484-491.
(18) Doctrow, S. R.; Huffman, K.; Marcus, C. B.; Tocco, G.; Malfroy, E.;
Adinolfi, C. A.; Kruk, H.; Baker, K.; Lazarowych, N.; Mascarenhas, J. J.
Med. Chem. 2002, 45, 4549-4558.
(19) Abashkin, Y. G.; Burt, S. K. J. Phys. Chem. B 2004, 108, 2708-2711.
(20) Abashkin, Y. G.; Burt, S. K. Inorg. Chem. 2005, 44, 1425-1432.
(4) Chng, L. L.; Chang, C. J.; Nocera, D. G. Org. Lett. 2003, 5, 2421-2424.
(5) Chang, C. J.; Chng, L. L.; Nocera, D. G. J. Am. Chem. Soc. 2003, 125,
1866-1876.
(6) Liu, S.-Y.; Nocera, D. G. J. Am. Chem. Soc. 2005, 127, 5278-5279.
(7) Yang, J. Y.; Bachmann, J.; Nocera, D. G. J. Org. Chem. 2006, 71, 8706-
8714.
(8) Yeh, C.-Y.; Chang, C. J.; Nocera, D. G. J. Am. Chem. Soc. 2001, 123,
1513-1514.
(9) Chang, C. J.; Yeh, C.-Y.; Nocera, D. G. J. Org. Chem. 2002, 67, 1403-
1406.
(10) Liu, S.-Y.; Nocera, D. G. J. Am. Chem. Soc. 2005, 127, 5278-5279.
9
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J. AM. CHEM. SOC. 2007, 129, 8192-8198
10.1021/ja070358w CCC: $37.00 © 2007 American Chemical Society

Catalase and Epoxidation Activity of Mn Salen Complexes
A R T I C L E S
Chart 1
Scheme 1
augmented by structurally imposing a bulky tert-butyl group
ortho to the phenol (HSX*-tBu and HphSX*-tBu in Chart 1).
The initial step of catalase reactivity involves the PCET
activation of the O-O bond of hydrogen peroxide within the
Hangman cleft by heterolysis to produce the high-valent metal
oxo species,21 which reacts with a second molecule of hydrogen
peroxide to complete the dismutation reaction. Kinetically stable
intermediates that are deleterious to dismutation are averted by
the presence of the bulky tert-butyl groups. Moreover, we show
that this structural modification is general to enhanced enanti-
oselective reactivity of the high-valent manganese oxo. Because
the ligand also incorporates a chiral cyclohexanediamine bridge,
which has proven to be extremely effective in the transfer of
chiral information in oxygen atom transfer chemistry,22 the
Hangman salens are capable of converting olefins to epoxides
enantoselectively. Improved enantiomeric excess of the epoxide
products for the manganese HSX*-tBu and HphSX*-tBu catalysts
as compared to their unmodified manganese HSX* and Hph-
SX* congeners establishes the benefits of a sterically circum-
scribed Hangman salen platform for the PCET activation of
small molecule substrates.
One of the bromides can be selectively functionalized to the
carboxylic acid with 1 equiv of phenyllithium, followed by
treatment with carbon dioxide and an acidic workup to furnish
3.5 Methyl ester 4 is obtained smoothly by using a catalytic
amount of sulfuric acid in methanol.5 Incorporation of the
phenylene spacer between the xanthene scaffold and carboxylic
acid requires the stepwise functionalization of the xanthene to
deliver the benzoic acid methyl ester 6,6 which can be
deprotected with sodium hydroxide to give the corresponding
acid 5.7 The acid- and ester-functionalized xanthene spacers 3-6
retain a bromo group, which serves as the site for addition of
the boronic ester derivative of 3-tert-butylsalicylaldehyde (2)
using Suzuki cross-coupling methodology.23 Synthesis of the
boronic ester 2 required a two-step procedure. First, the
commercially available 3-tert-butyl-2-hydroxybenzaldehyde was
functionalized with a bromo group in the 5 position as described
in the literature.24 The bromo was then replaced with a boronic
ester functionality by palladium-catalyzed cross-coupling meth-
ods25 to give 2. Synthon 2 serves as a good nucleophilic
substrate for the conversion of xanthene precursors 3-6 to
7-10, respectively.26 Hangman ligands 11-14 are provided by
the condensation of 7-10 with 0.5 equiv of (1R,2R)-(-)-1,2-
diaminocyclohexane. The amount of product depends critically
on the stoichiometry of (1R,2R)-(-)-1,2-diaminocyclohexane.
If more than 0.5 equiv is used, varying amounts of product with
an incompletely formed macrocycle are obtained; only one imine
forms to make an -(ONN)- tridentate ligand impurity. This
Results and Discussion
The synthesis of the Hangman family of salens substituted
with tert-butyl groups in the 3 and 3′ positions is presented in
Scheme 1. Ligand construction begins with the commercially
available 4,5-dibromo-2,7-di-tert-butyl-9,9-dimethylxanthene.
(23) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483.
(24) Cavazzini, M.; Manfredi, A.; Montanari, F.; Quici, S.; Pozzi, G. Eur. J.
Org. Chem. 2001, 4639-4649.
(25) Ishiyama, T.; Ishida, K.; Miyaura, N. Tetrahedron 2001, 57, 9813-9816.
(26) Chang, C. J.; Yeh, C.-Y.; Nocera, D. G. J. Org. Chem. 2002, 67, 1403-
1406.
(21) Liu, S.-Y.; Soper, J. D.; Yang, J. Y.; Rybak-Akimova, E. V.; Nocera, D.
G. Inorg. Chem. 2006, 45, 7572-7574.
(22) Jacobsen, E. N.; Wu, M. H. Epoxidation of Alkenes Other than Allylic
Alcohols. In ComprehensiVe Asymmetric Catalysis, Jacobsen, E. N., Pfaltz,
A., Yamamoto, H., Eds.; Springer: New York, 1999; pp 649-677.
9
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A R T I C L E S
Yang and Nocera
Table 1. Observed TON and Initial Rate Constant (kinit) for H2O2
manganese salen complexes with the methyl ester deprotected
(Figure S2.2). Deprotection of methyl esters to give the acid
derivative with hydrogen peroxide is possible owing to the high
pKa of the conjugate acid. Moreover, it has been shown that
HOO- can nucleophilically cleave the methyl ester in some
cases.28
Disproportionation by Manganese Hangman Catalystsa
1
catalyst
TON
k
init (M-1 s-
)
Mn(HSX*-COOH)Cl
1574b
5328
792b
2495
59
1207
164
182
6
14
5
Mn(HSX*-tBu-COOH)Cl (15)
Mn(HphSX*-COOH)Cl
Mn(HphSX*-tBu-COOH)Cl (17)
Mn(HSX*-tBu-COOMe)Cl (16)
Mn(HphSX*-tBu-COOMe)Cl (18)
Mn(salen)Clc
10
The effect of substitution at the 3 and 3′ positions is revealed
by comparison of the activity of 15 and 17 to Mn(HSX*-
COOH)Cl and Mn(HphSX*-COOH)Cl, respectively. An ap-
proximately 3-fold increase in the catalase activity is observed
upon substitution of the tert-butyl groups. The overall TONs
are closely tied with the reaction rates in the first 2 min of the
reaction. The initial rate constants (kinit) for H2O2 consumption
by the four acid-functionalized manganese Hangman complexes
are listed in Table 1. 15 and 17 display kinit values that are
roughly double that of their respective unsubstituted congeners.
Though the reactions are run under biphasic conditions with
methanol serving as a phase transfer reagent between dichlo-
romethane/catalyst solution and the aqueous hydrogen peroxide
phase, reaction rates and TON are not limited by the biphasic
nature of the reaction. Dissolution of the more soluble 15 in
tetrahydrofuran and methanol yields a homogeneous reaction
mixture. Addition of the aqueous hydrogen peroxide to this
solution results in TONs that are commensurate to those
obtained under the biphasic conditions (see Figure S3).
Experimental21 and theoretical19,20 studies have led to the
proposal that the catalase reaction at Mn salens proceeds by
the cycle shown in Scheme 2. Oxidation of the metal by
hydrogen peroxide forms a high-valent manganyl oxo and water.
Evidence for the oxo is provided by stopped flow studies; spectra
consistent with an oxo intermediate are obtained when the
catalytic cycle is arrested by the replacement of hydrogen
peroxide by aryl peroxide.21 Whereas a proton transfer to the
coordinated aryl peroxide is necessary to promote cleavage of
the O-O bond to form the Mn(V) oxo, this step does not show
rate-determining kinetics. Alternatively, oxidation of the second
Mn(salen)Clc,d
a In 2:1 dichloromethane/methanol at 25 °C. b Data taken from ref 9.
c salen ) (1R,2R)-(-)-[1,2-cyclohexanediamino-N,N’-bis(3,5-di-tert-butyl-
salicylidene)]. d Two equivalents of benzoic acid.
1
unintended product can be identified by H NMR and mass
spectrometry; spectra for the incomplete macrocycle resulting
from the condensation reaction to produce 13 can be found in
Figures S1.1 and S1.2. When 0.5 equiv of (1R,2R)-(-)-1,2-
diaminocyclohexane is employed, 1H NMR integrations of 11-
14 establish the presence of one cyclohexanediamine per two
xanthene scaffolds.
Manganese acetate serves as an efficient metalation agent of
11-14. The oxidized Mn(III) products 15-19 are obtained
when the metalation is performed in air followed by a workup
in aqueous sodium chloride. Computations on the analogous
compounds lacking the tert-butyl groups suggest that the
carboxylic acids on the Hangman ligand (17) can easily span
the face of the macrocycle to form a carboxylic acid dimer.7
Solid state infrared spectra of 17 are congruent with this finding;
a doublet at ν ) 1285 and 1272 cm-1 is indicative of the C-O
stretching band in carboxylic acid dimers.27 The band is not
seen in the spectra of the methyl ester analogue (18).
Hangman complexes 15-18 were examined for their catalytic
activity. Table 1 shows the turnover numbers (TON) for
hydrogen peroxide dismutation by the Hangman systems over
the course of 1 h. These results are compared to two control
system: a manganese salen lacking a xanthene scaffold but with
the tert-butyl groups in the 3 and 3′ positions and a Hangman
platform in which the proton is absent from the hanging group
(achieved by the replacement of the acid by a methyl ester).
The unsubstituted control, [1,2-cyclohexanediamino-N,N’-bis-
(3,5-di-tert-butylsalicylidene)] manganese chloride, demonstrates
negligible TONs, even with the addition of 2 equiv of benzoic
acid to serve as an intermolecular proton source. Conversely,
Hangman platforms show high TONs, but only if a proton is
present on the hanging group; 15 exhibits TONs that are
appreciably higher than 16, where the acid functionality has
been replaced by an ester. The activity of 17, with the acid
extended from the xanthene with a phenylene group, also
demonstrates increased activity with respect to its methyl ester
analogue 18, albeit to a lesser extent. We note that the activity
of 18 (Figure S2.1 in the Supporting Information) is complicated
by ester hydrolysis. Oxygen evolution is initially slow and ceases
completely within 15 min of hydrogen peroxide addition. At
this point, a marked increased in activity is observed and TONs
are obtained that are higher than expected from the initial rate.
Mass spectrometry of Mn-containing species obtained from
quenched reaction mixtures (∼20 min) reveals the presence of
equivalent of peroxide appears to be rate-determining.20,21
A
detailed theoretical study on this step has concluded that the
orientation of the second hydrogen peroxide to the Mn(V) oxo
center is critical to catalysis.20 An end-on approach leads to
substrate oxidation in a one-step, low activation energy process.
Alternatively, the side-on approach was computed to form an
intermediate (depicted as B in Scheme 2), which is stabilized
by hydrogen bond formation with a ligand oxygen. Propagation
of the side-on intermediate requires several high-energy steps,
making it an “energetic trap”; this trap is avoided by an end-on
approach.20 The temporary deactivation of the catalyst from the
formation of intermediate B limits overall catalase efficiency.
It is at this step that the hanging acid-base group of the
Hangman platform is manifest to increased catalase activity.
The Hangman construct can maintain the catalyst on cycle by
promoting the end-on assembly of H2O2 via a hydrogen-bonding
network (intermediate A in Scheme 2). Geometry-optimized
calculations on the manganese Hangman salens7 support the
contention that the carboxylic acid in both the acid and benzoic
acid-functionalized xanthenes is sufficiently proximate to the
metal center to hydrogen bond with a ligated hydroperoxide.
The presence of the large tert-butyl groups at the 3 and 3′
(27) Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. Infrared Spectroscopy. In
Spectrometric Identification of Organic Compounds; Wiley: New York,
1991; p 118.
(28) Nomura, Y.; Kubozono, T.; Hidaka, M.; Horibe, M.; Mizushima, N.;
Yamamoto, N.; Takahashi, T.; Komiyama, M. Bioorg. Chem. 2004, 32,
26-37.
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Catalase and Epoxidation Activity of Mn Salen Complexes
A R T I C L E S
Scheme 2
positions provides a further bias for intermediate A vs inter-
mediate B by preventing hydrogen peroxide approach to the
Mn(V) oxo near the phenolic oxygens.20 We believe that it is
the confluence of the hydrogen-bonding scaffold of the Hang-
man platform and the steric blocking groups in the 3 and 3′
positions of 15 and 17 that keeps the system on cycle and leads
to the enhanced rates and TONs for catalase activity.
The Mn(V) oxo generated in the catalase cycle is believed
to be the enantioselective oxidant in manganese salen epoxi-
dation reactions.29 This manganyl oxo is formed by the
activation of the O-X bond of various oxidants.30 Computa-
tional31 studies performed on the O-O bond cleavage of
acylperoxo manganese salen complexes in acidic and neutral
media identify the proton as a means to promote O-O bond
heterolysis and prevent O-O bond homolysis to produce the
less reactive Mn(IV) oxo. Such acid-base-induced bond activa-
tion chemistry, classically known as the “pull effect” in heme
oxidations,32-37 is responsible for the enhanced olefin epoxi-
dation observed in Hangman porphyrin complexes.5 Similar
oxygen atom transfer chemistry has been observed for doubly
strapped Hangman salen complexes. However, in the absence
of 3 and 3′ substitution, these oxidations proceed with small
enantiomeric excess (ee).7
(-)-[1,2-cyclohexanediamino-N,N’-bis(3,5-di-tert-
butylsalicylidene)]manganese(III) chloride (Jacobsen’s catalyst22).
Table 2 lists the TONs measured by GC/MS for the various
catalysts and oxidants. In view of the foregoing catalase studies,
hydrogen peroxide is limited in its utility as an oxidant owing
to its proclivity to disproportionate.38,39 Hence, low TONs are
observed for H2O2 as an oxidant even when dilute hydrogen
peroxide was added by a syringe pump to high concentrations
of substrate. Conversely, the more commonly used oxidants,
sodium hypochlorite (NaOCl) under biphasic reaction conditions
of dichloromethane and water, and iodosobenzene (PhIO) in
dichloromethane, result in higher TONs that are commensurate
with the unmodified platform. Both acid-functionalized Hang-
man complexes 15 and 17 give products with 53% ee. By
comparison, the analogous Hangman compounds lacking the
tert-butyl groups in the 3 and 3′ positions on the macrocycle
yield epoxidized product at 23% ee.7 Steric functionalities at
the 3 and 3′ positions on the salicylide have been shown to be
a critical element for good enantioselectivity by maximizing
stereochemical communication between the manganyl oxo and
substrate.22,40 As with the unmodified Mn salen catalysts, the
Hangman systems gain a considerable boost to the enantiose-
lectivity when the salen macrocycle is substituted with steric-
directing tert-butyl groups.
In summary, the activity of the oxo catalyst of Mn salens is
enhanced by the positioning of an acid-base group over the
salen that is modified with steric blocking groups at the 3 and
3′ positions of the macrocycle. These design principles are
general for the oxidation catalysis of Mn salens, as demonstrated
by the variant oxidation chemistry of catalase-like oxygen
evolution and mono-oxygenase epoxidation. For catalase con-
version, the hydrogen-bonding network established by the
Hangman scaffold and the steric blocking groups work in
concert to promote the end-on assembly of the second equivalent
of the hydrogen peroxide in conformation that is productive
for its subsequent oxidation by the manganyl oxo. Similarly,
the tert-butyl groups on the macrocycle confer the chirality of
the diamine backbone of the macrocycle to substrate. These
design principles should find utility for the construction of
To investigate whether the presence of the acid Hangman
moiety in conjunction with 3 and 3′ substitution leads to an
increase in yield of enantiomeric oxidation products, a compara-
tive study was undertaken of the epoxidation of the prochiral
olefin, 1,2-dihydronapthalene by 15 and 17 versus the unsub-
stituted Hangman salens, Mn(HSX*-COOH)Cl and Mn(Hph-
SX*-tBu-COOH)Cl, and the non-Hangman catalyst (1R,2R)-
(29) Srinivasan, K.; Michaud, P.; Kochi, J. K. J. Am. Chem. Soc. 1986, 108,
2309-2320.
(30) Allain, E. J.; Hager, L. P.; Deng, L.; Jacobsen, E. N. J. Am. Chem. Soc.
1993, 115, 4415-4416.
(31) Khavrutskii, I. V.; Musaev, D. G.; Morokuma, K. Inorg. Chem. 2005, 44,
206-315.
(32) Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. ReV. 1996,
96, 2841-2887.
(33) Watanabe, Y. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M.,
Guilard, R., Eds.; Academic Press: San Diego, CA, 2000; Vol. 4, pp 97-
117.
(34) Veitch, N. C.; Smith, A. T. In AdVances in Inorganic Chemistry; Academic
Press: New York, 2001; Vol. 51, pp 107-162.
(35) Poulos, T. L. In AdVances in Inorganic Biochemistry; Eichhorn, G. L.,
Marzilli, L. G., Eds.; Elsevier: New York, 1988; Vol. 7, pp 1-36.
(36) Dawson, J. H. Science 1988, 240, 433-439.
(37) Soper, J. D.; Kryatov, S. V.; Rybak-Akimova, E. V.; Nocera, D. G. J. Am.
Chem. Soc. 2007, 129, 5069-5075.
(38) Irie, R.; Hosoya, N.; Katsuki, T. Synlett 1994, 1994, 255-256.
(39) McGarrigle, E. M.; Gilheany, D. C. Chem. ReV. 2005, 105, 1563-1602.
(40) Lin, G.-Q.; Li, Y.-M.; Chan, A. S. C. In Principles and Applications of
Asymmetric Synthesis; Wiley: New York, 2001; pp 237-249.
9
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A R T I C L E S
Yang and Nocera
84.15, 35.04, 30.40, 29.44, 25.08. HRESI-MS ([M + H]+) calcd for
C17H26BO4 m/z, 305.1933, found 305.1922.
Table 2. TON for Epoxidation of 1,2-Dihydronapthalene in
Dichloromethane
catalyst
2,7-Di-tert-butyl-5-(3-tert-butyl-5-formyl-4-hydroxyphenyl)-9,9-
dimethyl-9H-xanthene-4-carboxylic Acid (7). Under nitrogen, 4-hy-
droxycarbonyl-5-bromo-2,7-di-tert-butyl-9,9-dimethylxanthene (3) (0.400
g, 0.898 mmol), 3-tert-butyl-2-hydroxy-5-(4,4,5,5-tetramethyl-[1,3,2]-
dioxaborolan-2-yl)-benzaldehyde (2) (0.300 g, 0.988 mmol), sodium
carbonate (0.139 g, 1.35 mmol), and tetrakis(triphenylphosphine)-
palladium(0) (0.062 g, 0.053 mmol) were combined with 18 mL of
DMF and 2 mL of deionized water, and the mixture was heated to 90
°C for 36 h. Upon cooling, 30 mL of dichloromethane was added and
the solution was washed with 10 mL of water. The aqueous layer was
then extracted with 2 × 10 mL of dichloromethane, and the combined
organic portions were dried over MgSO4. The solvent was removed
by rotary evaporation, and the residue was purified by column
chromatography (silica gel, 3:7 diethyl ether/pentane) to give the desired
product (0.265 g, 54%). 1H NMR (500 MHz, CDCl3, 25 °C): δ 11.92
(s, 1H), 9.95 (s, 1H), 8.06 (d, J ) 2 Hz, 1H), 7.71 (d, J ) 2 Hz, 1H),
7.63 (d, J ) 2 Hz, 1H), 7.57 (d, J ) 2 Hz, 1H), 7.51 (d, J ) 2 Hz,
1H), 7.24 (d, J ) 2 Hz, 1H), 1.76 (s, 6H), 1.48 (s, 9H), 1.40 (s, 9H),
1.37 (s, 9H). 13C NMR (500 MHz, CDCl3, δ): 197.29, 165.26, 161.25,
148.08, 147.57, 146.93, 144.52, 139.44, 135.25, 132.60, 131.19, 130.14,
129.00, 128.73, 128.54, 128.33, 126.68, 122.34, 120.88, 116.29, 35.32,
35.16, 34.91, 32.11, 31.72, 31.52, 29.32. HRESI-MS ([M + H]+) calcd
for C35H43O5 m/z, 543.3105, found 534.3109.
oxidant
t (h)
Mn(salen)Cla
Mn(HSX*-tBu)Cl (15)
Mn(HphSX*-tBu)Cl (17)
NaOCl
NaOCl
PhIO
3
24
3
24
3
24
4
4
21
76
22
89
24
80
3
12
59
28
79
31
75
2
29
69
25
85
25
85
2
PhIO
PhIOb
PhIOb
H2O2
b
H2O2
6
9
4
a salen ) (1R,2R)-(-)-[1,2-cyclohexanediamino-N,N’-bis(3,5-di-tert-
butylsalicylidene)]. b With 1 equiv of N-methylimidazole.
general Mn salen catalysts displaying enhanced ROS and
organic substrate oxidation activity.
Experimental Methods
Materials. Silica gel 60 (70-230 and 230-400 mesh) was used
for column chromatography. Analytical thin layer chromatography was
performed using F254 silica gel (precoated sheets, 0.2-mm thick).
Solvents for synthesis were reagent grade or better and used as received
or dried according to standard methods.41 3-tert-Butyl-2-hydroxyben-
zaldehyde, potassium acetate, (1R,2R)-(-)-1,2-diaminocyclohexane,
1,2-dihydronapthalene, and dodecane (Aldrich), bis(pinacolato)diboron
(Frontier Scientific), bis(tricyclohexylphosphine)palladium(0), tetrakis-
(triphenylphosphine)palladium(0), sodium carbonate, manganese(II)
acetate tetrahydrate, and (1R,2R)-(-)-[1,2-cyclohexanediamino-N,N’-
bis(3,5-di-tert-butylsalicylidene)]manganese(III) chloride (Strem Chemi-
cals), 30% aqueous solution of hydrogen peroxide (Alfa Aesar), and
iodosobenzene (TCI America) were used as received. The following
compounds were obtained using published protocols and their purity
was confirmed by 1H NMR: 5-bromo-3-tert-butylsalicylaldehyde (1),42
4-hydroxycarbonyl-5-bromo-2,7-di-tert-butyl-9,9-dimethylxanthene (3),5
4-methoxycarbonyl-5-bromo-2,7-di-tert-butyl-9,9-dimethylxanthene (4),5
4-(5-bromo-2,7-di-tert-butyl-9,9-dimethyl-9H-xanthen-4-yl)-benzoic acid
(5),7 and 4-(5-bromo-2,7-di-tert-butyl-9,9-dimethyl-9H-xanthen-4-yl)-
benzoic acid methyl ester (6).6
Physical Measurements. 1H NMR spectra were recorded on CDCl3
(Cambridge Isotope Laboratories) solvents at 25 °C on an Inova 500
spectrometer housed in the MIT Department of Chemistry Instrumenta-
tion Facility (DCIF). All chemical shifts are reported using the standard
δ notation in parts-per-million relative to tetramethylsilane, and spectra
have been internally calibrated to the monoprotio impurity of the
deuterated solvent used. High-resolution mass spectral analyses were
carried out by the MIT DCIF on a Bruker APEXIV47e.FT-ICR-MS
using an Apollo ESI source.
2,7-Di-tert-butyl-5-(3-tert-butyl-5-formyl-4-hydroxyphenyl)-9,9-
dimethyl-9H-xanthene-4-carboxylic Acid Methyl Ester (8). Under
nitrogen, 4-methoxycarbonyl-5-bromo-2,7-di-tert-butyl-9,9-dimethyl-
xanthene (4) (0.100 g, 0.218 mmol), 3-tert-butyl-2-hydroxy-5-(4,4,5,5-
tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (2) (0.073 g, 0.239
mmol), sodium carbonate (0.034 g, 0.327 mmol), and tetrakis-
(triphenylphosphine)palladium(0) (0.015 g, 0.013 mmol) were added
to 9 mL of DMF and 1 mL of deionized water. The mixture was heated
to 90 °C for 24 h. Upon cooling, 10 mL of deionized water was added,
and the solution was extracted with 3 × 20 mL of dichloromethane.
The combined organic portions were washed with 10 mL of deionized
water and dried over MgSO4. The solvent was removed by rotary
evaporation, and the residue was purified by column chromatography
(silica gel, 1:9 diethyl ether/pentane) to give the desired product (0.084
1
g, 69% yield). H NMR (500 MHz, CDCl3, 25 °C): δ 11.87 (s, 1H),
10.03 (s, 1H), 7.78 (d, J ) 2.5 Hz, 1H), 7.68 (d, J ) 2.5 Hz, 1H), 7.57
(d, J ) 2.5 Hz, 1H), 7.56 (d, J ) 2.5 Hz, 1H), 7.44 (d, J ) 2.5 Hz,
1H), 7.22 (d, J ) 2.5 Hz, 1H), 3.46 (s, 3H), 1.71 (s, 9H), 1.49 (s, 9H),
1.38 (s, 9H), 1.33 (s, 9H). 13C NMR (500 MHz, CDCl3, δ): 198.41,
198.12, 167.24, 160.40, 147.40, 146.11, 145.31, 145.28, 137.72, 136.22,
134.02, 130.92, 129.98, 129.46, 128.44, 126.50, 126.16, 125.81, 121.99,
120.30, 120.28, 119.65, 52.04, 35.14, 35.08, 34.78, 34.72, 32.47, 31.75,
31.58, 29.45. HRESI-MS ([M + Na]+) calcd for C36H44NaO5 m/z,
579.2903, found 579.2911.
3-tert-Butyl-2-hydroxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-
2-yl)-benzaldehyde (2). Under nitrogen, a mixture of 5-bromo-3-tert-
butylsalicylaldehyde (1) (1.00 g, 3.89 mmol), bis(pinacolato)diboron
(1.087 g, 4.28 mmol), potassium acetate (0.572 g, 5.83 mmol), and
bis(tricyclohexylphosphine)palladium(0) (0.130 g, 0.194 mmol) was
combined with 24 mL of dry dioxane and heated to 85 °C for 36 h.
Upon cooling, 20 mL of water was added and the mixture was extracted
with 4 × 50 mL of benzene. The organic portions were combined and
dried over MgSO4. The solvent was removed by rotary evaporation,
and the residue was purified by column chromatography (silica gel,
7:3 hexane/dichloromethane) to give the desired product (0.715 g,
60.4%). 1H NMR (500 MHz, CDCl3, 25 °C): δ 12.00 (s, 1H), 9.90 (s,
1H), 7.93 (s, 1H), 7.91 (s, 1H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR
(500 MHz, CDCl3, δ): 197.72, 163.81, 140.21, 140.18, 137.62, 120.61,
4-[2,7-Di-tert-butyl-5-(3-tert-butyl-5-formyl-4-hydroxyphenyl)-9,9-
dimethyl-9H-xanthen-4-yl]-benzoic Acid (9). Under nitrogen, 4-(5-
bromo-2,7-di-tert-butyl-9,9-dimethyl-9H-xanthen-4-yl)-benzoic acid (5)
(0.312 g, 0.598 mmol), 3-tert-butyl-2-hydroxy-5-(4,4,5,5-tetramethyl-
[1,3,2]dioxaborolan-2-yl)-benzaldehyde (2) (0.200 g, 0.657 mmol),
sodium carbonate (0.092 g, 0.897 mmol), and tetrakis(triphenylphos-
phine)palladium(0) (0.041 g, 0.036 mmol) were added to 18 mL of
DMF and 2 mL of deionized water. The mixture was heated to 90 °C
for 36 h. Upon cooling, 30 mL of dichloromethane was added, and the
solution was washed with 10 mL of water. The aqueous layer was then
extracted with 2 × 15 mL of dichloromethane, and the combined
organic portions were dried over MgSO4. The solvent was removed
by rotary evaporation, and the residue was purified by column
chromatography (silica gel, 2:8 ethyl acetate/pentane) to give the desired
1
(41) Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory Chemicals,
4th ed.; Butterworth-Heinemann: Oxford, 1966.
(42) Cavazzini, M.; Manfredi, A.; Montanari, F.; Quici, S.; Pozzi, G. Eur. J.
Org. Chem. 2001, 24, 4639-4649.
product (0.273 g, 68% yield). H NMR (500 MHz, CDCl3, 25 °C): δ
11.72 (s, 1H), 9.36 (s, 1H), 7.80 (d, J ) 8 Hz, 2H), 7.50 (m, 2H), 7.48
(d, J ) 2 Hz, 1H), 7.32 (d, J ) 8 Hz, 2H), 7.22 (J ) 2 Hz, 1H), 7.20
9
8196 J. AM. CHEM. SOC. VOL. 129, NO. 26, 2007

Catalase and Epoxidation Activity of Mn Salen Complexes
A R T I C L E S
(m, 2H), 1.78 (s, 6H), 1.45 (s, 9H), 1.40 (s, 9H), 1.38 (s, 9H). 13C
NMR (500 MHz, CDCl3, δ): 196.78, 170.83, 160.39, 145.95, 145.89,
145.78, 145.72, 143.74, 138.02, 135.02, 135.33, 133.63, 130.69, 130.38,
129.75, 129.62, 128.90, 128.69, 128.20, 127.69, 125.59, 122.75, 121.90,
120.39, 35.39, 35.08, 34.81, 31.14, 31.80, 31.77, 29.45. HRESI-MS
([M + H]+) calcd for C41H47O5 m/z, 619.3418, found 619.3414.
4-[2,7-Di-tert-butyl-5-(3-tert-butyl-5-formyl-4-hydroxyphenyl)-9,9-
dimethyl-9H-xanthen-4-yl]-benzoic Acid Methyl Ester (10). The
addition of 4-(5-bromo-2,7-di-tert-butyl-9,9-dimethyl-9H-xanthen-4-
yl)-benzoic acid methyl ester (6) (0.100 g, 0.187 mmol), 3-tert-butyl-
2-hydroxy-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzalde-
hyde (2) (0.063 g, 0.205 mmol), sodium carbonate (0.029 g, 0.280
mmol), and tetrakis(triphenylphosphine)palladium(0) (0.013 g, 0.011
mmol) to 9 mL of DMF and 1 mL of deionized water was performed
under N2. The mixture was heated to 90 °C for 24 h. Upon cooling, 10
mL of deionized water was added, and the solution was extracted with
3 × 20 mL of dichloromethane. The combined organic portions were
washed with 10 mL of deionized water and dried over MgSO4. The
solvent was removed by rotary evaporation, and the residue was purified
by column chromatography (silica gel, 1:9 diethyl ether/pentane) to
6.92 (s, 2H), 3.74 (m, 2H), 3.66 (bs, 2H), 3.51 (bs, 2H), 2.02 (bs, 4H),
1.76 (s, 12H), 1.56 (s, 18H), 1.39 (s, 18H), 1.38 (s, 18H). HRESI-MS
([M + H]+) calcd for C88H103N2O8 m/z, 1315.7709, found 1315.7704.
H2[HphSX*-tBu-COOMe] (14). 4-[2,7-Di-tert-butyl-5-(3-tert-butyl-
5-formyl-4-hydroxyphenyl)-9,9-dimethyl-9H-xanthen-4-yl]-benzoic acid
methyl ester (10) (0.050 g, 0.080 mmol) was added to (1R,2R)-(-)-
1,2-diaminocyclohexane (0.004 g, 0.040 mmol) to 6 mL of absolute
ethanol, and the mixture was refluxed for 12 h. Upon cooling, the
solvent was removed by rotary evaporation and the residue was washed
with 1 mL of cold deionized water and dried under vacuum to give
1
the yellow product (0.053 g, 100%). H NMR (500 MHz, CDCl3, 25
°C): δ 13.71 (bs, 2H), 7.48 (d, J ) 8 Hz, 4H), 7.42 (d, J ) 2.5 Hz,
2H), 7.39 (d, J ) 2.5 Hz, 2H), 7.09 (m, 6H), 7.02 (d, J ) 2 Hz, 2H),
6.97 (d, J ) 2 Hz, 2H), 6.87 (d, J ) 2 Hz, 2H), 2.91 (s, 6H), 3.32 (J
) 10 Hz, 2H), 2.07 (bs, 2H), 2.04 (bs, 2H), 1.97 (d, J ) 10 Hz, 2H),
1.72 (s, 6H), 1.70 (s, 6H), 1.55 (m, 2H), 1.34 (s, 18H), 1.31 (s, 18H),
1.14 (s, 18H). HRESI-MS ([M + H]+) calcd for C90H107N2O8 m/z,
1343.8022, found 1343.8016.
Mn[HSX*-tBu-COOH]Cl (15). H2[HSX*-tBu-COOH] (11) (0.105
g, 0.093 mmol) was added to manganese(II) acetate tetrahydrate (0.033
g, 0.140 mmol) in 6 mL of absolute ethanol, and the solution was
refluxed in air for 2 h. Upon cooling, 1 mL of an aqueous saturated
sodium chloride solution was added and the mixture was stirred for 10
min and then extracted with 3 × 10 mL of dichloromethane. The
organic layers were combined and washed with 10 mL of water and
then dried over MgSO4. The solvent was removed by rotary evaporation
to leave the brown product (0.112 g, 99%). HRESI-MS ([M - Cl]+)
calcd for C76H92ClMnN2O8 m/z, 1215.6229, found 1215.6241. Anal.
Calcd for C76H92ClMnN2O8: C, 72.91; H, 7.41; N, 2.24. Found: C,
72.84; H, 7.46; N, 2.35.
Mn[HSX*-tBu-COOMe]Cl (16). H2[HSX*-tBu-COOMe] (12) (0.020
g, 0.017 mmol) was added to manganese(II) acetate tetrahydrate (0.006
g, 0.025 mmol) in 4 mL of absolute ethanol, and the solution was
refluxed in air for 2 h. Upon cooling, 0.5 mL of an aqueous saturated
sodium chloride solution was added and the mixture was stirred for 10
min and then extracted with 3 × 10 mL of dichloromethane. The
organic layers were combined and washed with 10 mL of water and
then dried over MgSO4. The solvent was removed by rotary evaporation
to leave the brown product (0.021 g, 98%). HRESI-MS ([M - Cl]-)
calcd for C78H96MnN2O8 m/z, 1243.6542, found 1243.6582. Anal. Calcd
for C78H96ClMnN2O8: C, 73.19; H, 7.56; N, 2.19. Found: C, 73.01;
H, 7.76; N, 2.30.
1
give the desired product (0.106 g, 90% yield). H NMR (500 MHz,
CDCl3, 25 °C): δ 11.66 (s, 1H), 9.29 (s, 1H), 7.67 (s, 1H), 7.65 (s,
1H), 7.49 (d, J ) 2.5 Hz, 1H), 7.47 (dd, J ) 2.5 Hz, 7 Hz, 2H), 7.27
(d, J ) 2.5 Hz, 1H), 7.25 (s, 1H), 7.18 (m, 2H), 7.16 (d, J ) 2.5 Hz,
1H), 3.98 (s, 3H), 1.76 (s, 6H), 1.42 (s, 9H), 1.39 (s, 9H). 13C NMR
(500 MHz, CDCl3, δ): 197.00, 196.93, 166.84, 160.27, 145.93, 145.87,
145.70, 142.88, 137.86, 135.39, 133.71, 130.64, 130.39, 129.63, 129.06,
128.92, 128.57, 128.40, 128.26, 125.76, 125.54, 122.64, 121.93, 120.35,
52.20, 35.38, 35.03, 34.79, 32.13, 31.78, 31.75, 29.43. HRESI-MS ([M
+ Na]+) calcd for C42H48O5Na m/z, 655.3185, found 655.3196.
H2[HSX*-tBu-COOH] (11). 2,7-Di-tert-butyl-5-(3-tert-butyl-5-
formyl-4-hydroxyphenyl)-9,9-dimethyl-9H-xanthene-4-carboxylic acid
(7) (0.100 g, 0.184 mmol) was added to (1R,2R)-(-)-1,2-diaminocy-
clohexane (0.010 g, 0.092 mmol) to 6 mL of absolute ethanol. The
mixture was heated to reflux for 12 h. Upon cooling, the solvent was
removed by rotary evaporation and the residue was washed with 1 mL
of cold methanol and then dried under vacuum to give the bright yellow
1
product (0.105 g, 98%). H NMR (500 MHz, CDCl3, 25 °C): δ 8.61
(s, 2H), 7.66 (s, 2H), 7.58 (bs, 2H), 7.51 (s, 2H), 7.46 (d, J ) 2 Hz,
2H), 7.41 (d, J ) 2 Hz, 2H), 7.31 (d, J ) 2 Hz, 2H), 3.16 (bs, 2H),
2.97 (m, 2H), 2.31 (m, 2H), 1.83 (s, 12H), 1.52 (s, 18H), 1.50 (s, 4H),
1.39 (18H), 1.35 (18H). HRESI-MS ([M - H]-) calcd for C76H93N2O8
m/z, 1161.6926, found 1161.6884.
Mn[HphSX*-tBu-COOH]Cl (17). H2[HphSX*-tBu-COOH] (12) (0.025
g, 0.019 mmol) was combined with manganese(II) acetate tetrahydrate
(0.007 g, 0.028 mmol) in 3 mL of absolute ethanol and refluxed in air
for 2 h. Upon cooling, 0.5 mL of an aqueous saturated sodium chloride
solution was added and the mixture was stirred for 10 min and then
extracted with 3 × 10 mL of dichloromethane. The organic layers were
combined and washed with 5 mL of water and dried over MgSO4. The
solvent was removed by rotary evaporation to give the brown product
(0.027 g, 100%). HRESI-MS ([M - Cl]+) calcd for C88H100MnN2O8
m/z, 1367.6860, found 1367.7056. Anal. Calcd for C88H100ClMnN2O8:
C, 75.27; H, 7.18; N, 2.00. Found: C, 75.15; H, 7.38; N, 2.13.
Mn[HphSX*-tBu-COOMe]Cl (18). H2[HphSX*-tBu-COOMe] (14)
(25 mg, 0.019 mmol) was combined with manganese(II) acetate
tetrahydrate (6.8 mg, 0.028 mmol) in 4 mL of absolute ethanol and
refluxed in air for 2 h. Upon cooling, 0.5 mL of an aqueous saturated
sodium chloride solution was added and the mixture was stirred for 10
min and then extracted with 3 × 10 mL of dichloromethane. The
organic layers were combined and washed with 5 mL of water and
dried over MgSO4. The solvent was removed by rotary evaporation to
give the brown product (0.026 g, 98%). HRESI-MS ([M - Cl]+) calcd
for C90H104MnN2O8 m/z, 1395.7168, found 1395.7136. Anal. Calcd for
C90H104ClMnN2O8: C, 75.48; H, 7.32; N, 1.96. Found: C, 75.34; H,
7.45; N, 2.03.
H2[HSX*-tBu-COOMe] (12). 2,7-Di-tert-butyl-5-(3-tert-butyl-5-
formyl-4-hydroxyphenyl)-9,9-dimethyl-9H-xanthene-4-carboxylic acid
methyl ester (8) (0.040 g, 0.072 mmol) was added to (1R,2R)-(-)-1,2-
diaminocyclohexane (0.004 g, 0.036 mmol) in 4 mL of absolute ethanol
and heated to reflux for 12 h. Upon cooling, the solvent was removed
by rotary evaporation and the residue was washed with 1 mL of cold
deionized water and then dried under vacuum to give the bright yellow
product (0.042 g, 98%). 1H NMR (500 MHz, CDCl3, 25 °C): δ 13.92
(bs, 2H), 8.46 (s, 2H), 7.55 (d, J ) 2.5 Hz, 2H), 7.51 (d, J ) 2.5 Hz,
2H), 7.37 (m, 4H), 7.29 (d, J ) 2 Hz, 2H), 7.15 (d, J ) 2 Hz, 2H),
3.46 (d, J ) 10 Hz, 2H), 3.18 (s, 6H), 2.02 (d, J ) 7 Hz, 2H), 1.92 (d,
J ) 10 Hz, 2H), 1.80 (d, J ) 7 Hz, 2H), 1.69 (s, 6H), 1.68 (s, 6H),
1.53 (m, 2H), 1.40 (s, 18H), 1.34 (s, 18H), 1.33 (s, 18H). HRESI-MS
([M + H]+) calcd for C78H99N2O8 m/z, 1191.7396, found 1191.7342.
H2[HphSX*-tBu-COOH] (13). 4-[2,7-Di-tert-butyl-5-(3-tert-butyl-
5-formyl-4-hydroxyphenyl)-9,9-dimethyl-9H-xanthen-4-yl]-benzoic acid
(9) (0.050 g, 0.081 mmol) was added to (1R,2R)-(-)-1,2-diaminocy-
clohexane (0.005 g, 0.040 mmol) to 5 mL of absolute ethanol. The
mixture was refluxed for 12 h. Upon cooling, the solvent was removed
by rotary evaporation and the residue was washed with 1 mL of cold
methanol and dried under vacuum to give the yellow product (0.051
1
g, 96%). H NMR (500 MHz, CDCl3, 25 °C): δ 7.82 (m, 6H), 7.49
(d, J ) 2 Hz, 2H), 7.43 (d, J ) 2 Hz, 2H), 7.34 (m, 6H), 7.22 (m, 4H),
9
J. AM. CHEM. SOC. VOL. 129, NO. 26, 2007 8197

A R T I C L E S
Yang and Nocera
Disproportionation Reactions. Dismutation reactions were per-
formed at room temperature in a sealed (PTFE septum) 20-mL reaction
vial equipped with a magnetic stir bar and a capillary gas delivery tube
linked to an inverted graduated burette filled with water. The reaction
vial was charged with a stock solution of the corresponding catalyst in
CH2Cl2 (1.0 mL). MeOH (0.5 mL) was added followed by H2O2 (790
µL, 8.22 mmol; 10.4 M (30%) aqueous solution), and the reaction
mixture was stirred vigorously. The time was set to zero immediately
after addition of H2O2. The conversion was monitored volumetrically,
and the amount of O2 (n) produced was calculated using the ideal gas
law.
of a 0.0104 M solution (42.7 mg in 50 mL of dichloromethane) of
N-methylimidazole was added to each reaction. For H2O2, the oxidant
solution was prepared by diluting 1 mL of 30% H2O2 solution with 9
mL of H2O. A 40 mM solution of 1,2-dihydronapthalene and 10 mM
of dodecane was prepared (130 mg 1,2-dihydronapthalene and 43 mg
of dodecane in 25 mL of dichloromethane). A quantity of 0.5 mL of
this was added to 0.5 mL of each catalyst solution. The diluted solution
of H2O2 was added over 3 h. Upon completion of the oxidant addition,
the reaction was stirred for an additional hour before being sampled.
The concentration of the substrate and epoxide product was determined
by GC/MS with dodecane as the internal standard to determine the
TON.
The amount of catalyst used to obtain the results of Table 1: (1R,2R)-
(-)-[1,2-cyclohexanediamino-N,N’-bis(3,5-di-tert-butylsalicylidene)]-
manganese(III) chloride (1.0 mL from 6.0 mg into 10 mL of CH2Cl2
solution or 0.00095 mmol) to give an average of 3.7 mL of O2 in 1 h.
(1R,2R)-(-)-[1,2-Cyclohexanediamino-N,N’-bis(3,5-di-tert-butylsali-
cylidene)]manganese(III) chloride with 2 equiv of benzoic acid (1.0
mL from 6.0 mg). (1R,2R)-(-)-[1,2-cyclohexanediamino-N,N’-bis(3,5-
di-tert-butylsalicylidene)]manganese(III) chloride and 1.2 mg of benzoic
acid into 10 mL of CH2Cl2 solution or 0.00095 and 0.0019 mmol,
respectively, to give on average 4.2 mL of O2 in 1 h. Mn(HSX*-tBu-
COOH)Cl (15) (1.0 mL from 3.0 mg into 5 mL of CH2Cl2 solution or
0.000475 mmol) to give 60.7 mL of O2 in 1 h. Mn(HSX*-tBu-COOMe)-
Cl (16) (1.0 mL from 2.4 mg into 2 mL of CH2Cl2 solution or 0.00095
mmol) to give 1.4 mL of O2 in 1 h. Mn(HphSX*-COOH)Cl (19) (1.0
mL from 1.3 mg into 2 mL of CH2Cl2 solution or 0.00095 mmol) to
give 56.9 mL of O2 in 1 h. Mn(HphSX*-COOMe)Cl (20) (1.0 mL from
2.7 mg into 2 mL of CH2Cl2 solution or 0.00095 mmol) to give 27.5
mL of O2 in 1 h. The standard deviations on the TON measurements
are derived from at least three data points and are as follows: compound
15 ((113), 16 ((11), 17 ((178), and 18 ((49).
Epoxidation of 1,2-Dihydronapthalene. The data from Table 2
were determined as follows: 0.2 mM solutions of the catalyst (1R,2R)-
(-)-[1,2-cyclohexanediamino-N,N’-bis(3,5-di-tert-butylsalicylidene)]-
manganese(III) chloride (1.3 mg in 10 mL of dichloromethane), 15
(2.5 mg in 10 mL of dichloromethane), and 17 (2.8 mg in 10 mL of
dichloromethane) were prepared. A 20 mM solution of 1,2-dihy-
dronapthalene and 10 mM dodecane (65 mg of 1,2-dihydronapthalene
and 43 mg of dodecane in 25 mL) was prepared. For NaOCl as the
oxidant, the oxidant solution was prepared by mixing 2 mL of 0.05 M
NaHPO4 and 5 mL of commercial bleach (Clorox) and 0.1 mL of 1 M
NaOH solution and then cooling to 0 °C. A quantity of 1.5 mL of this
solution was added to 0.5 mL of each catalyst solution and 0.5 mL of
the 1,2-dihydronapthalene/dodecane solution, precooled to 0 °C. For
PhIO as the oxidant, 4.0 mg of PhIO was added to 0.5 mL of each
catalyst solution with 0.5 mL of the 1,2-dihydronapthalene/dodecane
solution. For the trial with an equivalent of N-methylimidazole, 10 µL
For the determination of ee, the epoxidation method and conditions
were modified from that employed for previous epoxidation studies
using manganese salen complexes for comparison to previous literature
work.43 Five milliliters of a 0.05 M solution of Na2HPO4 was added to
12.5 mL of commercial bleach (Clorox). The pH of this solution (∼55
M in NaOCl) was adjusted to pH 12 by the dropwise addition of 1.0
M NaOH solution and cooled to 0 °C. A quantity of 4.8 mL was added
to a precooled 0 °C solution of 1,2-dihydronapthalene (104 mg, 0.800
mmol) and Mn(HSX*-tBu-COOH) (15) (10 mg, 0.008 mmol, 1%
catalyst loading) in 8 mL of dichloromethane. A quantity of 3.6 mL of
the prepared bleach solution was added to a precooled 0 °C solution
of 1,2-dihydronapthalene (78 mg, 0.600 mmol) and Mn(HphSX*-tBu-
COOH) (17) (8.4 mg, 0.006 mmol, 1% catalyst loading) in 6 mL of
dichloromethane. Upon being stirred for 12 h, the layers were separated
and the aqueous layer was extracted with 2 × 6 mL of dichloromethane.
The combined organic layers for each reaction were washed with 10
mL of water and 10 mL of a saturated sodium chloride solution and
dried over MgSO4. After solvent removal by rotary evaporation, the
crude products were purified by column chromatography (silica gel,
98:2 pentane/ethyl acetate) to yield the epoxide product.
Acknowledgment. We thank Professor Timothy Jamison for
the use of his chiral gas chromatograph, Chudi Ndubaku and
Ryan Moslin for instrument assistance, and Shih-Yuan Liu and
Julien Bachmann for fruitful discussions. This work was
supported by funding from the DOE DE-FG02-05ER15745.
Supporting Information Available: 1H NMR and MS of the
potential ligand impurity from synthesis of 13, O2 evolution
and MS of 18 in the catalase reaction, and O2 evolution by 15
under two different solvent conditions. This material is available
free of charge via the Internet at http://pubs.acs.org.
JA070358W
(43) Zheng, W.; Jacobsen, E. N. J. Org. Chem. 1991, 56, 2296-2298.
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