Noncovalent secondary interactions in Co(II)salen complexes: O2 binding and catalytic activity in cyclohexene oxygenation

Article abstract of DOI:10.1021/jo026118a

The O₂ affinity of Co(II)Salen complexes 1-4 and their reactivity in cyclohexene oxygenation reactions of Co(II)Salen complexes 1-4 are modulated by noncovalent interactions such as hydrogen bonding and steric hindrance using a functionalized diamino bridge. Higher O₂ affinity is observed in the case of efficient hydrogen-bonding interactions (complex 1), while increased steric hindrance (cis vs trans diamino bridge) around the Co-coordinated O₂ is influencing the reactivity of the complexes.

Full text of DOI:10.1021/jo026118a

Non cova len t Secon d a r y In ter a ction s in Co(II)Sa len Com p lexes: O2
Bin d in g a n d Ca ta lytic Activity in Cycloh exen e Oxygen a tion
Roberto Fiammengo, Christiaan M. Bruinink, Mercedes Crego-Calama,* and
David N. Reinhoudt*
Laboratory of Supramolecular Chemistry and Technology, MESA+ Research Institute, University of
Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands
m.crego-calama@ct.utwente.nl
Received J une 28, 2002
The O2 affinity of Co(II)Salen complexes 1-4 and their reactivity in cyclohexene oxygenation
reactions of Co(II)Salen complexes 1-4 are modulated by noncovalent interactions such as hydrogen
bonding and steric hindrance using a functionalized diamino bridge. Higher O2 affinity is observed
in the case of efficient hydrogen-bonding interactions (complex 1), while increased steric hindrance
(cis vs trans diamino bridge) around the Co-coordinated O2 is influencing the reactivity of the
complexes.
In tr od u ction
epoxidation of unfunctionalized alkenes using the easily
obtainable (R,R)-[N,N′-bis(3,5-di-tert-butylsalicylidene)-
1,2-cyclohexanediamine]Mn(III).11 Nevertheless, more
research in ligand design is of fundamental importance
in the field of Salen complexes as a valuable alternative
to metal porphyrins for the development of biomimetic
heme-protein models.12,13 Moreover, only recently it has
been shown that noncovalent secondary interactions such
as metal coordination are very important to obtain highly
efficient and selective catalysts based on Salen com-
plexes.14
Here, we report the preparation of three novel Co(II)-
Salen complexes 1-3 bearing (for 1 and 2) an OH-
functionalized diamino bridge. The presence of the hy-
droxyl groups in 1 increases the affinity for oxygen due
to hydrogen bonding with the Co-coordinated O2 (Figure
1). To the best of our knowledge, this is the first time
that hydrogen bonding as a noncovalent secondary
The oxygen binding abilities of Co(II)Salen (Salen )
bis(salicylidene)ethylenediamine) complexes have long
been established and have stimulated the research
toward reversible O2 carriers1,2 and their use as catalysts
in oxidation of organic substrates with O2.3-7 Variations
on the two aromatic rings of the Salen ligand have been
introduced to investigate the electronic and the steric
factors affecting O2 binding and the reactivity of the
metal-O2 complex. However, modification of the Salen
structure via introduction of functionalized diamino
bridges has been rarely attempted.8-10 This is probably
as a consequence of the already excellent results obtained
by J acobsen and co-workers in the enantioselective
(1) For an X-ray structure of a 1:1 O2-Co(II)Salen complex carrying
1-MeIm as axial base, see: Avdeef, A.; Schaefer, W. P. J . Am. Chem.
Soc. 1976, 98, 5153-5159.
(2) For review articles, see: J ones, R. D.; Summerville, D. A.; Basolo,
F. Chem. Rev. 1979, 79, 139-179 and Niederhoffer, E. C.; Timmons,
J . H.; Martell, A. E. Chem. Rev. 1984, 84, 137-203. For more recent
works see: Miyokawa, K.; Kinoshita, S.; Etoh, T.; Wakita, H. Bull.
Chem. Soc. J pn. 1992, 65, 3374-3377. Bhattacharya, S.; Mandal, S.
S. J . Chem. Soc., Chem. Commun. 1995, 2489-2490. Krebs, J . F.;
Borovik, A. S. Chem. Commun. 1998, 553-554. Nishide, H.; Mizuma,
H.; Tsuchida, E.; McBreen, J . Bull. Chem. Soc. J pn. 1999, 72, 1123-
1127. Sharma, A. C.; Borovik, A. S. J . Am. Chem. Soc. 2000, 122, 8946-
8955.
(11) J acobsen, E. N. In Catalytic Asymmetric Synthesis; Ojima, I.,
Ed.; VCH: New York, 1993; pp 159-199.
(12) For covalent superstructered porphyrins as model systems for
heme-proteins, see: Collman, J . P.; Fu, L. Acc. Chem. Res. 1999, 32,
455-463. Collman, J . P. Inorg. Chem. 1997, 36, 5145-5155. Momen-
tau, M.; Reed, C. A. Chem. Rev. 1994, 94, 659-698. For supramolecular
modified porphyrins, see: Weiss, J . J . Incl. Phenom. 2001, 40, 1-22.
Robertson, A.; Shinkai, S. Coord. Chem. Rev. 2000, 205, 157-199. Tani,
F.; Matsu-ura, M.; Nakayama, S.; Ichimura, M.; Nakamura, N.;
Naruta, Y. J . Am. Chem. Soc. 2001, 123, 1133-1142. Gazeau, S.;
Pe`caut, J .; Marchon, J .-C. Chem. Commun. 2001, 1644-1645. Starnes,
S. D.; Rudkevich, D. M.; Rebek, J ., J r. J . Am. Chem. Soc. 2001, 123,
4659-4669.
(3) For review articles, see: Mukayama, T.; Yamada, T. Bull. Chem.
Soc. J pn. 1995, 68, 17-35. Bailey, C. L.; Drago, R. S. Coord. Chem.
Rev. 1987, 79, 321-332.
(4) Bernardo, K.; Leppard, S.; Robert, A.; Commenges, G.; Dahan,
F.; Meunier, B. Inorg. Chem. 1996, 35, 387-396.
(5) Rhodes, B.; Rowling, S.; Tidswell, P.; Woodward, S.; Brown, S.
M. J . Mol. Catal. A 1997, 116, 375-384.
(13) For Co(II) Schiff base “lacunar complexes” as biomimetic O2
carriers, see: Busch, D. H.; Alcock, N. W. Chem. Rev. 1994, 94, 585-
623. Rybak-Akimova, E. V.; Marek, K.; Masarwa, M.; Busch, D. H.
Inorg. Chim. Acta 1998, 270, 151-161. See also ref 2.
(14) For a cooperative bimetallic mechanism in epoxide ring-opening
reaction catalyzed by Co(III)Salen and Cr(III)Salen complexes, see:
J acobsen, E. N. Acc. Chem. Res. 2000, 33, 421-431. Ready, J . M.;
J acobsen, E. N. J . Am. Chem. Soc. 2001, 123, 2687-2688. Ready, J .
M.; J acobsen, E. N. Angew. Chem., Int. Ed. 2002, 41, 1374-1377. For
supramolecular metallocleft catalysts (UO2Salophen), see: van Axel
Castelli V.; Dalla Cort, A.; Mandolini, L.; Reinhoudt, D. N.; Schiaffino,
L. Chem. Eur. J . 2000, 6, 1193-1198. van Axel Castelli, V.; Dalla Cort,
A.; Mandolini, L. J . Am. Chem. Soc. 1998, 120, 12688-12689.
(6) Kureshi, R. I.; Khan, N. H.; Abdi, S. H. R.; Bhatt, A. K.; Iyer, P.
J . Mol. Catal. 1997, 121, 25-31.
(7) Kholdeeva, O. A.; Vanina, M. P. React. Kinet. Catal. Lett. 2001,
73, 83-89.
(8) Zanello, P.; Cini, R.; Cinquantini, A.; Orioli, P. L. J . Chem. Soc.,
Dalton Trans. 1983, 2159-2166.
(9) Corden, B. B.; Drago, R. S.; Perito, R. P. J . Am. Chem. Soc. 1985,
107, 2903-2907.
(10) Blaauw, R.; Kingma, I. E.; Laan, J . H.; van der Baan, J . L.;
Balt, S.; de Bolster, M. W. G.; Klumpp, G. W.; Smeets, W. J . J .; Spek,
A. L. J . Chem. Soc., Perkin 1 2000, 1199-1210.
10.1021/jo026118a CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/05/2002
8552
J . Org. Chem. 2002, 67, 8552-8557

Noncovalent Interactions in Co(II)Salen Complexes
respectively, in refluxing ethanol in moderate to good
yields.20 Subsequent metalation with CoAc2 afforded
Co(II)Salen 1-3 in 93-95% yield (Scheme 2).
Structural diversity is introduced in Co(II)Salen com-
plexes 1-4 via the 1,2-diaminocyclohexane bridge. The
stereochemistry of the two amino groups is (meso)-cis in
1-3 and (R,R)-trans in 4. As a result, 1-3 have nonplanar
structures, with the cyclohexyl ring being roughly at 90°
to the Co(II)-N2O2 plane.21 Therefore, this spatial ar-
rangement should shield the Co-coordinated O2. In
contrast, as evident from an earlier X-ray crystal struc-
ture,22 the commercially available Co(II)Salen 4 is roughly
planar. Additionally, two cis-hydroxyl groups have been
introduced on the cyclohexane ring of 1 and 2 in position
4 and 5. The orientation of these two OH groups is either
syn or anti to the two amino groups (see Scheme 1). A
CPK model of Co(II)Salen 1 shows that the syn arrange-
ment of the cis-4,5-hydroxyl groups is necessary for one
OH to point directly toward the Co-O2 moiety, thus
having the required orientation to form a hydrogen bond
with O2. No hydrogen bond is possible when the hydroxyl
groups are arranged anti as in Co(II)Salen 2 and 3
(Figure 1).
F IGURE 1. Schematic representation of ternary complexes
1‚O2‚B and 2‚O2‚B showing hydrogen-bonding stabilization of
Co-coordinated O2 (left). B ) base (1-MeIm or propionaldehyde
in the text).
interaction in Salen complexes has been considered.15
This design mimics the hydrogen-bonding interaction
operated by the distal His residue in hemoglobin and
myoglobin or by Tyr in O2 avid Ascaris hemoglobin.16,17
Moreover, Co(II)Salen 1-3 and the commercially avail-
able 4 have been tested in the aerobic oxidation of
cyclohexene (Scheme 3). Reduced catalytic activity is
observed as a consequence of the Co-O2 complex stabi-
lization.
Oxygen -Bin d in g Stu d ies. The reversible binding of
O2 to Co(II)Salen complexes 1-4 in CH3CN or 1:1
toluene/CH3CN in the presence of 1-methylimidazole
[1-MeIm, (6-7) × 10-3 M] was studied by following the
UV-vis spectral changes (Figures 2 and 3) occurring
upon equilibration of the solution with O2/N2 gas mix-
tures of varying composition (expressed as O2 partial
pressure pO ). The experimental data were treated in
2
terms of a 1:1:1 equilibrium23 between CoL (2-4), 1-MeIm,
and O2 (eq 1) to evaluate the binding constants,24 KO
2
(eq 2).
Resu lts a n d Discu ssion
CoL + 1-MeIm + O2 a CoL‚1-MeIm‚O2
(1)
Syn th esis. Co(II)Salenes 1 and 2 were prepared
starting from the two diastereomeric cis-1,2-diamino-cis-
4,5-dihydroxycyclohexanes (5 and 6). The corresponding
dihydrochloride salts (5-Cl and 6-Cl) were synthesized
from cis-1,2,3,6-tetraphthalic anhydride 12 following a
slightly modified literature procedure (Scheme 1).18 Cata-
lytic osmylation of Cbz-protected 1,2-diaminocyclohex-
4-ene 15 using NMO (4-methylmorpholine N-oxide) as
primary oxidant and DABCO as ligand afforded a mix-
ture of diastereomeric cis-diols 16 and 17 in a 36:64 ratio
(80% yield) at room temperature.19 Deprotection via
catalytic hydrogenation and precipitation with HCl in
EtOH afforded the desired salts.
KO ) [CoL‚1-MeIm‚O2]/([CoL][1-MeIm]pO ) (2)
2
2
For complexes 2-4, KO values close to 10 M-1 Torr-1
2
have been determined at 10 °C (Table 1), while 1, under
identical conditions, showed much higher O2 affinity. The
complexation is so strong that saturation was obtained
already at pO < 12 Torr, which precluded the measure-
2
ment of the binding constant with our experimental
setup. Nevertheless, considering 1‚1-MeIm‚O2 > 90% at
12 Torr, a lower limit of 100 M-1 Torr-1 can be estimated
(20) J udged from NMR spectra, condensation of diamino diols 5 and
6 with aldehyde 8 was quantitative. Poor crystallization from methanol
lowered the yield in isolated products 9 and 10 in comparison to 11.
(21) van Doorn, A. R.; Schaafstra, R.; Bos, M.; Harkema, S.; van
Eerden, J .; Verboom, W.; Reinhoudt, D. N. J . Org. Chem. 1991, 56,
6083-6084.
Salen ligands 9, 10, and 11 were prepared by conden-
sation of 3,5-di-tert-butyl-2-hydroxybenzaldehyde 8 with
diamine 5 or 6 or with cis-1,2-diaminocyclohexane 7,
(15) Hydrogen-bond stabilization of the Co-coordinated O2 has been
considered for a Co(II)-Schiff base complex obtained from salicyl
aldehyde and L-serine. However, no binding studies have been
performed to quantify the interaction; see: Punniyamurthy, T.; Bhatia,
B.; Reddy, M. M.; Maikap, G. C.; Iqbal, J . Tetrahedron 1997, 53, 7649-
7670.
(22) Leung, W.-H.; Chan, E. Y. Y.; Chow, E. K. F.; Williams, I. D.;
Peng, S.-M. J . Chem. Soc., Dalton Trans. 1996, 1229-1236.
(23) Binding of O2 has often been considered as a 1:1 equilibrium
between O2 and CoL‚B. Experimentally, [B] is required to be high
enough to have CoL‚B as the predominant species in solution before
O2 addition. This condition is difficult to achieve with complexes 1-4
in CH3CN solution. For instance, binding constants <10 M-1 for
pyridine to CoL complexes similar to 3 and 4 in CHCl3 are reported;
see ref 24.
(24) O2 binding constants for Co(II)Salen complexes similar to 3 and
4 have been reported for pyridine and DMF solutions at 20 °C.
However, [O2] ) 1 M was assumed as standard state, and therefore
the values are not directly comparable with our results; see: Cesarotti,
E.; Gullotti, M.; Pasini, A.; Ugo, R. J . Chem. Soc., Dalton Trans. 1977,
757-763.
(16) Goldberg, D. E. Chem. Rev. 1999, 99, 3371-3378.
(17) Hydrogen-bonding interactions and reactivity of coordinated O2
in natural and biomimetic porphyrin systems: Harris, D. L.; Loew,
G. H. J . Am. Chem. Soc. 1994, 116, 11671-11674. Chang, C. K.; Avile´s,
G.; Bag, N. J . Am. Chem. Soc. 1994, 116, 12127-12128.
(18) Witiak, D. T.; Rotella, D. P.; Filippi, J . A.; Gallucci, J . J . Med.
Chem. 1987, 30, 1327-1336.
(19) No further attempt to increase the diastereoselectivity of the
osmylation reaction was made.
J . Org. Chem, Vol. 67, No. 24, 2002 8553

Fiammengo et al.
SCHEME 1a
a
TMS-N3, THF, reflux, 3 h. b SOCl2, CCl4, cat. DMF, 50 °C, 2.5 h. c Concentrated HCl, THF/acetone, rt, 14 h. d Cbz-Cl, N,N-diisopropyl-
N-ethylamine, THF/H2O, 0 °C, 3 h. e NMO, OsO4 (0.02 equiv), DABCO (0.2 equiv) acetone/H2O, rt, 72 h. Separation of 16 and 17 by
column chromatography. f 10% Pd/C, H2, EtOH, rt, 5 h. HCl/EtOH, rt.
g
SCHEME 2
for KO , 1 order of magnitude higher than for the
diastereomeric complex 2.
rangement of the diamino bridges of these complexes has
no appreciable influence on O2 binding.
2
This result agrees with the proposed hydrogen-bonding
stabilization of Co-coordinated O2, which, according to
the three-dimensional arrangement of its hydroxyl groups,
In the absence of 1-methylimidazole, O2 binding to 1-4
was not observed either at 10 or at -10 °C. This result
confirms that strong O2 complexation to 1 is due to
secondary interactions (hydrogen bonding) stabilizing the
ternary complex 1‚1-MeIm‚O2 and not to alteration of the
metal center’s electronic properties.
is specific for 1. Moreover, the similar and lower KO
2
values determined for 2-4 show that the spatial ar-
Oxygen a t ion of Cycloh exen e. Co(II) Schiff’s base
complexes3 as well as Co(II)porphyrins25 catalyze the
F IGURE 3. Absorbance changes at 416 nm (2) and at 424
nm (b) as function of the pO2 in equilibrium with an 11 × 10-5
M solution of 2 in CH3CN; [1-MeIm] ) 7 × 10-3. Solid lines
are the best fitting according to a 1:1:1 model (see the text).
F IGURE 2. Spectral changes as function of increasing pO2 in
equilibrium with a solution of 2 at 10 °C. [2] ) 11 × 10-5 M,
in CH3CN; [1-MeIm] ) 7 × 10-3 M. Maximum pO2 ) 152 Torr.
8554 J . Org. Chem., Vol. 67, No. 24, 2002

Noncovalent Interactions in Co(II)Salen Complexes
TABLE 1. F or m a tion Con sta n ts of Ter n a r y Com p lexes
TABLE 2. Ca ta lytic Oxid a tion of Cycloh exen e w ith
CoL‚1-MeIm ‚O2 in CH3CN Solu tion s a t 10°Ca
Co(II)Sa len 1-4: In d u ction Tim es (tin d ), In itia l Ra tes for
Cycloh exen e Con su m p tion a n d P r od u ct F or m a tion (r i),
KO (M-1 Torr-1
)
KO (M-1 Torr-1
)
a
2
2
a n d Cycloh exen e Ha lf-life Tim es (t1/2
)
1
2
g100b
8.4
3
4
13.6
9.5c
a
[CoL] ) (6-11) × 10-5 M, [1-MeIm] ) (6-7) × 10-3 M.
Estimated value (see the text). c 1:1 toluene/acetonitrile.
b
SCHEME 3
a
Typical reaction conditions are as in Figure 4.
oxidation of organic substrates (e.g. alkenes and alkanes)
with O2 as the bulk oxidant in the presence of reducing
agents such as aldehydes. Therefore, oxidation of cyclo-
hexene with O2 in the presence of propanal (Scheme 3)
was chosen as a model reaction to study the relationship
between noncovalent secondary interactions stabilizing
O2 binding and the catalytic activity of complexes 1-4.
A mechanistic study of the oxygenation of cyclohexene
with Co(II)Salens 1-4 is beyond the scope of this work.
However, it has been reported for similar systems that
the reaction probably starts with the formation of a CoL‚
B‚O2 complex (where B ) aldehyde)26 in close analogy
with the formation of CoL‚1-MeIm‚O2 under the equilib-
rium conditions reported here.
Complexes 1-4 efficiently catalyze cyclohexene oxida-
tion under mild conditions (20 °C, 1 atm of O2, 0.5 mol %
of catalyst, propionaldehyde as coreductant), affording,
independently from the catalyst used, two oxygenation
products,27 viz. cyclohexene oxide 18 and 2-cyclohexene-
1-one 19 in 4.7 ( 0.5 ratio (18/19) at 70% conversion.28
The constant product selectivity observed for different
metal catalyst shows a common catalytic pathway for all
the reactions, which probably involves radical chain
reactivity, a well-documented pathway for Co complex-
catalyzed oxidations.5,7,29 Nevertheless, different catalysts
exhibit distinct reactivities, as evident from the measured
induction times (tind), initial reaction rate (ri), and half-
life times for cyclohexene conversion (t1/2) (Table 2). These
differences can be related to the catalyst structure and,
in particular, to the hydrogen-bonding ability of 1 vs 2-4
and possibly to the sterical hindrance around the metal
center caused by the orientation of the cyclohexyl ring
with respect to the Co(II)-N2O2 plane (coplanar as in 4
vs bent as in 1-3).
of color changes from brick red to brown and finally
green, which is similar to previous observations for
analogous reactions.30 The color change to green has been
attributed to the formation of Co(III)-hydroperoxide
complexes in solution from the starting CoL‚B‚O2 com-
plexes via radical reaction with the aldehyde (H-abstrac-
tion) during the initiation step. The longest tind (8800 s)
is observed for Co(II)Salen 1 and indicates a retarded
formation of the Co(III)-hydroperoxide intermediate.
Thus, the hydrogen bond reduces the radical reactivity
of 1‚B‚O2 in comparison to complexes (2-4)‚B‚O2. The
shortest tind (400 s) is observed for 4, which is consistent
with the absence of hydrogen bond and of steric hin-
drance that protects the Co-O2 moiety due to its planar
structure. The tind for 2 and 3 are somewhere between,
as expected for complexes without hydrogen bond pos-
sibilities but with a nonplanar structure. The relative
order of these values remains still unclear. Furthermore,
the initial reaction rate (ri) and the half-life time for
cyclohexene conversion (t1/2, time at which 50% of the
cyclohexene is converted minus tind) are different within
the series of catalyst 1-4 (Table 2). It is generally
accepted that acylperoxy radicals and Co-coordinated
acylperoxy complexes are the active oxygen transfer
species formed during propagation of the oxidation reac-
tion catalyzed by Co(II) complexes.7,31,32 Thus, the results
reported in Table 2 suggest that Co(II)Salens 1-4
participate to some extent in the oxygen transfer to the
substrate, possibly as Co-coordinated acylperoxy species,
and not only in the initiation step. Consequently, hydro-
gen bonding and steric hindrance also play an important
role in stabilizing these intermediate species during the
propagation step of the reaction. In fact 1 is the least
reactive catalyst presenting the smallest ri and the
longest t1/2, while 4 is the most reactive one having the
shortest t1/2. The ri values for 4 are somehow smaller than
expected. However, this catalyst also exhibits a slightly
different concentration vs time profile when compared
to catalysts 1-3.33
During tind no oxygenation products were detected in
the reaction mixture via gas chromatographic analysis
(GC). However, the reaction mixture underwent a series
(25) Mandal, A. K.; Iqbal, J . Tetrahedron 1997, 53, 7641-7648.
(26) Kalra, S. J . S.; Punniyamurthy, T.; Iqbal, J . Tetrahedron Lett.
1994, 35, 4847-4850.
(27) 2-Cyclohexen-1-ol (product of allylic oxidation) was not detected
by GC in all the cases reported here.
(28) GC analysis showed that conversion up to 98% could be reached
by extension of the reaction time (overnight). A control experiment
was carried out using the same reaction conditions in the absence of
catalyst. No oxidation of the cyclohexene or aldehyde was observed.
(29) Sheldon, R. A.; Kochi, J . K. Metal-Catalyzed Oxidations of
Organic Compounds; Academic Press: New York, 1981.
(30) Hamilton, D. E.; Drago, R. S.; Zombeck, A. J . Am. Chem. Soc.
1987, 109, 374-379.
(31) Mastrorilli, P.; Nobile, C. F.; Suranna, G. P.; Lopez, L. Tetra-
hedron 1995, 51, 7943-7950.
(32) Nam, W.; Kim, H. J .; Kim, S. H.; Ho, R. Y. N.; Valentine, J . S.
Inorg. Chem. 1996, 35, 1045-1049.
J . Org. Chem, Vol. 67, No. 24, 2002 8555

Fiammengo et al.
126.40, 117.86, 69.96, 67.90, 35.23, 34.30, 31.64, 29.59. IR:
(cm-1) 3369, 2958, 2910, 2870, 1629, 1467, 1439, 1391, 1362,
1274, 1251, 1203, 1173, 1100, 1039, 968, 773. FAB-MS: m/z
578.3 ([M]+, calcd 578.4). Anal. Calcd for C36H54N2O4: C 74.70,
H 9.40, N 4.84. Found: C 74.25, H 9.50, N 4.75.
(1R,2S,3S,4R)-[N,N′-Bis(3,5-d i-ter t-bu tylsa licylid en e)-
4,5-dih ydr oxy-1,2-cycloh exan ediam in e 9. Yield: 65% yield.
1H NMR (400 MHz, CDCl3): δ (ppm) 13.46 (bs, 2H), 8.40 (s,
2H), 7.37 (d, 2H, J ) 2.3 Hz), 7.07 (d, 2H, J ) 2.3 Hz), 4.38-
4.31 (m, 2H), 3.90-3.80 (m, 2H), 2.25 (bs, 2H), 2.21-2.10 (m,
4H), 1.40 (s, 18H), 1.29 (s, 18H). 13C NMR (100 MHz, CDCl3):
δ (ppm) 166.64, 158.22, 140.28, 136.82, 127.34, 126.31, 118.01,
68.71, 35.22, 34.31, 34.01, 31.67, 29.64. IR: (cm-1) 3422, 2957,
2909, 2871, 1628, 1459, 1439, 1390, 1362, 1274, 1250, 1202,
1174, 1088, 1027. FAB-MS: m/z 578.3 ([M]+, calcd 578.4). Anal.
Calcd for C36H54N2O4: C 74.70, H 9.40, N 4.84. Found:
73.99, H 9.52, N 4.76.
C
F IGURE 4. Concentration vs time profile for cyclohexene
(0.18 M in CH3CN) oxidation catalyzed by Co(II)Salen 1 (0.005
equiv). Conditions: 20 °C, O2 1 atm, propanal (4 equiv).
P r ep a r a tion of (1R,2S)-[N,N′-Bis(3,5-d i-ter t-bu tylsa li-
cylid en e)-1,2-cycloh exa n ed ia m in e 11. 3,5-Di-tert-butyl-2-
hydroxybenzaldehyde 8 (490 mg, 2.1 mmol) was added to a
solution of cis-1,2-diaminocyclohexane 7 (120 µL, 1.0 mmol)
in 20 mL of EtOH at room temperature. The reaction mixture
was stirred for 1 h at 75 °C and gradually cooled to room
temperature to allow precipitation of the product. The bright
yellow solid was then filtrated and washed several times with
cold CH3OH. Yield: 81% (445 mg, 0.81 mmol).
1H NMR (400 MHz, CDCl3): δ (ppm) 13.77 (bs, 2H), 8.37
(s, 2H), 7.36 (d, 2H, J ) 2.3 Hz), 7.07 (d, 2H, J ) 2.3 Hz),
3.63-3.57 (m, 2H), 2.09-1.92 (m, 2H), 1.82-1.73 (m, 2H),
1.67-1.55 (m, 2H), 1.42 (s, 18H), 1.29 (s, 18H). 13C NMR (100
MHz, CDCl3): δ (ppm) 165.41, 158.40, 140.00, 136.80, 127.03,
126.17, 118.15, 69.53, 35.24, 34.30, 31.70, 30.65, 29.67, 22.94.
IR: (cm-1) 2997, 2955, 2864, 1630, 1598, 1459, 1441, 1390,
1362, 1273, 1251, 1204, 1174, 1134, 1083, 989, 879, 853, 827,
773. FAB-MS: m/z 546.3 ([M]+, calcd 546.4), 547.3. Anal. Calcd
for C36H54N2O2: C 79.07, H 9.95, N 5.12. Found: C 78.99, H
10.13, N 5.25.
Con clu sion s
We have demonstrated via O2 affinity studies on novel
Co(II)Salen complexes 1-3 (and on commercially avail-
able 4) that noncovalent secondary interactions and
especially hydrogen bonding largely increase O2 binding
(1 vs 2-4). The observed enhanced O2 binding for 1 is
also reflected in the lower catalytic reactivity in the
cyclohexene oxidation. The simple variations introduced
on the Salen ligand skeleton, and in particular on the
diamino bridge, show substantial control on the binding
properties of Co(II)Salen complexes by secondary interac-
tions. These results might allow introduction of an
alternative model to the heavily exploited field of bio-
mimetic superstructured porphyrins.
Gen er a l P r oced u r e for th e Syn th esis of Co(II)Sa len s
1-3. Salens 9-11 (1 equiv) were dissolved under nitrogen in
degassed EtOH (typically 0.7 mmol in 10 mL). A Co(Ac)2‚4H2O
solution in degassed EtOH (1.5 equiv in 5 mL) was then added,
causing an immediate turning of the solution from bright
yellow to deep red. The reaction mixture was refluxed for 1 h
under nitrogen and dried in vacuo. The product was extracted
from the solid residue with CHCl3, dried under vacuum, and
washed with CH3OH, affording 1-3 as brick red/dark red
solids which were always stored under nitrogen at -30 °C.
Exp er im en ta l Section
1H NMR chemical shift values (300 MHz) are expressed in
ppm relative to residual CHD2OD (δ 3.30) or CHCl3 (δ 7.26).
13C NMR chemical shift values (100 MHz) are expressed in
ppm relative to residual CD3OD (δ 49.0) or CDCl3 (δ 76.9).
Infrared spectra were recorded on KBr pellets. MS FAB
spectra were measured with m-nitrobenzyl alcohol (NBA) as
the matrix. GC analysis was performed on a gas chromato-
graph equipped with a flame ionization detector (FID), using
a capillary column (30 m, 0.25 µm film thickness) with DB-
5MS stationary phase (for temperature program and response
factor determination, see Supporting Information).
Gen er a l P r oced u r e for th e Syn th esis of Sa len es 9 a n d
10. 3,5-Di-tert-butyl-2-hydroxybenzaldehyde 8 (280 mg, 1.2
mmol) was added to a solution of cis-1,2-diamino-cis-4,5-
dihydroxycyclohexane dihydrochloride salt 5-Cl18 (or 6-Cl)18
(120 mg, 0.55 mmol) and NaHCO3 (100 mg, 1.2 mmol) in 10
mL of EtOH at room temperature. The reaction mixture was
stirred for 1 h at 75 °C, and the solvent was removed under
vacuum. The product was extracted from the solid residue with
CHCl3 and recrystallized from CH3OH.
Co(II)Sa len 1. Yield: 97%. FAB-MS: m/z 635.3 ([M]+,
calcd. 635.3). Anal. Calcd for C36H52N2O4Co: C 68.01, H 8.24,
N 4.41. Found: C 67.74, H 8.36, N 4.35.
Co(II)Sa len 2. Yield: 100%. FAB-MS: m/z 635.3 ([M]+,
calcd. 635.3). Anal. Calcd for C36H52N2O4Co: C 68.01, H 8.24,
N 4.41. Found: C 67.60, H 8.51, N 4.26.
Co(II)Sa len 3. Yield: 93%. FAB-MS: m/z 603.3 ([M]+,
calcd. 603.3). Anal. Calcd for C36H52N2O2Co: C 71.62, H 8.68,
N 4.64. Found: C 72.03, H 8.45, N 4.80.
Oxygen -Bin d in g Mea su r em en ts. . O2 affinities were
measured spectrophotometrically under equilibrium conditions
with a UV-vis spectrophotometer equipped with a optical fiber
probe (path length ) 1.000 cm), using solvents of spectroscopic
grade. Solutions of Co(II)Salenes 1-4 [(6-10) × 10-5 M] in
CH3CN containing 1-MeIm [(6-7) × 10-3 M] were prepared
under nitrogen using degassed solvent. The solutions were
transferred to a measuring chamber thermostated at 10 °C
and equipped with the UV-vis optical probe. O2 content in
the gas layer in equilibrium with the solution in the chamber
(1R,2S,3R,4S)-[N,N′-Bis(3,5-d i-ter t-bu tylsa licylid en e)-
4,5-d ih yd r oxy-1,2-cycloh exa n ed ia m in e 10. Yield: 26%. 1H
NMR (400 MHz, CDCl3): δ (ppm) 12.88 (bs, 2H), 8.26 (s, 2H),
7.27 (d, 2H, J ) 2.2 Hz), 6.96 (d, 2H, J ) 2.2 Hz), 3.95-3.86
(m, 2H), 3.59-3.52 (m, 2H), 2.56 (bs, 2H), 2.35-2.25 (m, 2H),
1.98-1.90 (m, 2H), 1.28 (s, 18H), 1.18 (s, 18H). 13C NMR (100
MHz, CDCl3): δ (ppm) 166.59, 158.08, 140.38, 137.01, 127.62,
was varied using the flow method.34 pO was varied between
2
3.9 and 152 Torr.
(33) The oxidation time course obtained for catalyst 4 resembles that
of an autocatalytic reaction (Supporting Information, Figure S2).
Probably for this reason the initial rates (ri) for 4 (Table 2) are the
smallest in the series, while t1/2 is the shortest, indicating higher
reactivity.
(34) Collman, J . P.; Brauman, J . I.; Doxsee, K. M.; Halbert, T. R.;
Hayes, S. E.; Suslick, K. S. J . Am. Chem. Soc. 1978, 100, 2761-2766.
8556 J . Org. Chem., Vol. 67, No. 24, 2002

Noncovalent Interactions in Co(II)Salen Complexes
Gen er a l P r oced u r e for th e Ca ta lytic Oxid a tion of
Cycloh exen e. In an external-cooling-jacketed reactor at 20
°C with vigorous stirring, a freshly prepared solution of Co-
(II)Salen (1-4, 0.005 equiv respect to cyclohexene) and 1,2-
dichlorobenzene as internal standard (200 µL) in CH3CN (25
mL) was equilibrated (2-5 min) with O2 (1 atm). Propanal (1.4
mL, 20 mmol) and cyclohexene (500 µL, 5.0 mmol) were then
added simultaneously to start the reaction. The reaction course
was monitored via GC analysis: 50 µL samples were with-
drawn from the reaction mixture and diluted with 250 µL of
CH2Cl2 before injection. The detected products were epoxide
18, unsaturated ketone 19, propionic acid, and traces of
propionaldehyde.
Ack n ow led gm en t. This work has been supported
by The Netherlands Research Council for Chemical
Sciences (CW) with financial aid from the Technology
Foundation STW. The research of M.C.-C. has been
possible by a fellowship of the Royal Netherlands
Academy of Arts and Sciences.
Su p p or tin g In for m a tion Ava ila ble: GC analysis of the
catalytic oxidation of cyclohexene. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O026118A
J . Org. Chem, Vol. 67, No. 24, 2002 8557