Ligand tuning in the chromium-salen-mediated asymmetric epoxidation of alkenes

Article abstract of DOI:10.1016/j.tetasy.2004.03.010

A series of Cr(salen) complexes have been synthesised from 5-substituted-3-bromosalicylaldehydes and trans-1,2-cyclohexanediamine. These have been used to probe the Cr(salen)-mediated asymmetric epoxidation of alkenes. No simple correlation was found between the electronic character of the salen-substituents and the enantioselectivity - multiple oxidation pathways are proposed as a possible explanation. Enantioselectivities of up to 90% have been achieved using a novel, synthetically accessible Cr(salen) complex.

Full text of DOI:10.1016/j.tetasy.2004.03.010

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1343–1354
Ligand tuning in the chromium–salen-mediated asymmetric
epoxidation of alkenes
E. M. McGarrigle, D. M. Murphy and D. G. Gilheany*
Centre for Synthesis and Chemical Biology, Conway Institute of Biomolecular and Biomedical Sciences, Chemistry Department,
University College Dublin, Belfield, Dublin 4, Ireland
Received 18 February 2004; accepted 4 March 2004
Abstract—A series of Cr(salen) complexes have been synthesised from 5-substituted-3-bromosalicylaldehydes and trans-1,2-cy-
clohexanediamine. These have been used to probe the Cr(salen)-mediated asymmetric epoxidation of alkenes. No simple correlation
was found between the electronic character of the salen-substituents and the enantioselectivity––multiple oxidation pathways are
proposed as a possible explanation. Enantioselectivities of up to 90% have been achieved using a novel, synthetically accessible
Cr(salen) complex.
Ó 2004 Elsevier Ltd. All rights reserved.
0
1
. Introduction
sary to have a substituent on the 3,3 -positions of the
salen ligand in order to obtain high enantioselectiv-
ity
17;20;23
The synthetic value of enantiopure epoxides is well
established and a very substantial amount of research on
synthetic methods for their production has been carried
out. Synthetic methods based on metal(salen) com-
plexes have been developed for both asymmetric
although this does not have to be bulky, again
in contrast to the Mn(salen) systems. More recently, we
detailed results from a comprehensive survey of all
22
positions of the aromatic ring of the salen ligand.
Although this yielded new information with respect to
the trajectories of approach of the substrate to the
alkene, it did not directly suggest further improvements
that might be made to the catalyst structure. We noted
1
–3
2
–4
epoxidation (AE) of alkenes and the asymmetric ring-
5
–13
opening of epoxides.
gated Cr(salen)-mediated AE,
We have specifically investi-
24–28
1
4–23
as have others.
0
We found it intriguing that the Cr-system shows high
enantioselectivity for the conversion of trans-1,2-disub-
stituted alkenes (trans-alkenes henceforth) in contrast to
almost all known Mn(salen) systems.
trast to the Mn(salen) system, with Cr(salen) it is pos-
sible to isolate the metal–oxo complex proposed as the
active oxidant in both systems.
to study the reaction of the alkene with the
salen)Cr @O species in isolation from other aspects of
that once the 3,3 -position was substituted, addition of
another group at any other position was detrimental to
the ee obtained. However, all of the complexes surveyed
were derived from salicylaldehydes with only one type of
substituent, for example, dimethyl, tetrachloro etc. In
29;30
Also in con-
3
4;35
light of the studies by Jacobsen et al.
we felt it would
be prudent to examine some cases where the substituents
31–33
This has allowed us
0
at the 3,3 -positions were different from those at the
other positions on the ring. Specifically, the decrease in
ee observed on going from, for example, 3,3 -dichloro-
substituted complex to 3,3 ,5,5 -tetrachlorosubstituted
complex, could be due to an increase in the reactivity of
the complex and an earlier transition state and therefore
less selectivity. Consistent with this, we note that Ra-
jagopal and co-workers have reported that reduction
potentials and reactivity of O@Cr(salen) complexes to-
wards sulfoxides correlate with Hammett constants of
V
(
the catalytic cycle.
0
0
0
We have concentrated much of our efforts on variation
of the substituents on the aromatic rings of the salen
ligand. Our first investigations showed that it is neces-
36
the salen-ring substituents. We report here our efforts
0
to synthesise a series of 3,3 -dibromosubstituted com-
plexes 1–3a–f, and the results from their subsequent use
in the asymmetric epoxidation of trans-b-methylstyrene.
*
0
Corresponding author. Tel.: +353-1-716-2308; fax: +353-1-716-2127;
e-mail: declan.gilheany@ucd.ie
957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.03.010

1344
E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
3,3' = Br
The results obtained in the epoxidation of trans-b-
methylstyrene are shown in Table 1. The Cr(III)salen
complexes were reacted with PhIO to form the green-
black O@Cr(V) species in situ. Excess PhIO was
removed by filtration and the substrate was added to the
solution of O@Cr(V)salen at 0 °C. The epoxidations
1
2
3
. A = Cl
a: 5,5' = Br
b: 5,5' = H
c: 5,5' = Me
d: 5,5' = Et
e: 5,5' = tBu
f: 5,5' = OMe
. A = NO
3
. A = PF
6
N
O
N
O
+
Cr
5
5
A-
3
3
3
were carried out in the absence and presence of Ph PO
21
since this has been shown to improve the ee. Pre-
liminary results with 2 and 3a,b have been previously
22
communicated.
2
. Results
Scheme 1 shows the synthesis of the requisite salicylal-
dehydes 4 and 5, which were not commercially available.
3. Discussion
4
b,d–f were synthesised using the method of Levin
37
et al. Although the unoptimised isolated yield of 21%
for 4b is low, it compares favourably with yields
reported in the literature using traditional methods such
The unusual behaviour of the methoxy-substituted cat-
alyst 3f makes it difficult to determine whether its per-
formance can be compared with the other catalysts. It
38
as the Duff reaction (14%) or the Reimer–Tiemann
would appear from the colour changes that a
39
reaction (17%). Indeed it is actually better than
expected because just 5% was reported by Levin and
co-workers for 3-fluorosalicylaldehyde. These poor
yields obtained can be partially attributed to the ability
of the fluoro group to chelate magnesium along with
phenoxide thereby preventing formation of the correctly
orientated complex between the magnesium phenolate
and the paraformaldehyde. This may be less of a prob-
lem with the softer halogens. 4d–f were isolated in good
yield as expected. The bromination of salicylaldehydes,
using a slight excess of elemental bromine in acetic acid,
O@Cr(salen) complex is formed initially but rapidly
decomposes. Therefore, a different species may be
responsible for the AE reaction. As such it would be
unwise to place any significance on the result obtained
with 3f. Aside from that, all the ees were moderate to
excellent as would be expected due to the presence of the
0
23
3,3 -bromo group. The addition of Ph PO increased
3
the ee obtained in all cases, confirming itself as the most
reliable additive we have studied.
21;22
In line with pre-
the effect of additive was most notice-
17;22
vious results,
able when the ee in its absence was relatively low. The
optimum choice of counterion varied with catalyst
structure.
40–42
proceeded in good yield using literature procedures.
The salicylaldehydes were converted to salen ligands by
standard methods in good yield and fully characterised
by normal methods (see experimental section). The
Yields were below 30% in all cases. This is not unex-
pected in the stoichiometric mode as the Cr(III)salen
generated can react with the O@Cr(V)salen to form a
ligands were reacted with CrCl
chromium(III) salen chloride complexes 1 using our
2
and oxidized to form
20;26
sink for the active complex.
The recovered mass is
20
standard procedure. After synthesis of the chloride
complexes it is necessary to change to a noncoordinating
also low and this is due to the fact that Cr(salen) com-
plexes can also act as polymerisation catalysts.
31;44
31
counterion to get an active epoxidation complex. The
Cr(salen) complexes were precipitated from the reaction
mixture and after washing with solvent were not purified
further. The paramagnetic complexes were characterised
by IR and ES-MS. Elemental analyses were not satis-
factory, however, this is not unusual for these com-
An attempt was made to correlate Hammett substituent
constants r and the ratio of enantiomers (ln(R/S)).
Assuming only one active oxidant, the latter should be
directly proportional to DDG , the free energy difference
between two diastereomeric transition states as a result
z
43
plexes and epoxidation results were reproducible from
batch to batch.
of two facial approaches of trans-b-methylstyrene
34;35
towards the Cr–oxo species.
Figures 1 and 2 show
1
2
. Mg(OMe) /MeOH
2
. (CH O) /toluene
O
2
n
4
b R = H; R' = Br (21%)
4d R = Et; R' = H (80%)
e R = tBu; R' = H (69%)
4f R = OMe; R' = H (58%)
+
R
OH 3. H
R
R
OH
4
R'
R'
O
O
5
c R = Me (42%)
Br2
5d R = Et (88%)
R
OH
OH
5
5
e R = tBu (90%)
f R = OMe (76%)
NaOAc/AcOH
H
Br
Scheme 1. Synthesis of salicylaldehydes (unoptimised isolated yields in parentheses).

E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
1345
V
III
Table 1. Results for the stoichiometric AE of trans-b-methylstyrene with oxo–Cr (salen) complexes generated in situ from Cr (salen) complexes 2,
a
3a–f
0
#
Complex
5,5
Time (h)
Additive L
trans-epoxide
Yield (%)
Unreacted
alkene (%)
Recovered
c
mass
b
Ee (%)
ꢀ
3a (PF )
6
1
2
3
4
5
Br
Br
Br
Br
H
3
3
None
71
79
63
77
79
84
81
86
73
79
77
82
77
79
Nd
Nd
87
90
82
88
41
––
2
14
2
10
22
3
––
––
––
––
6
3a
Ph
None
Ph PO
None
Ph PO
None
Ph PO
None
Ph PO
None
Ph PO
None
Ph PO
None
Ph PO
None
Ph PO
None
Ph PO
3
PO
ꢀ
2a (NO )
3
3
2a
ꢀ
3b (PF )
6
3
3
3
4
5.5
4.5
5
4
2
d
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
3b
H
3
27
7
21
8
52
17
42
38
32
24
15
30
30
––
––
22
34
40
45
15
––
ꢀ
2b (NO )
3
H
2b
ꢀ
3c (PF )
6
H
5
3
13
13
16
14
9
28
23
15
9
Me
Me
Me
Me
Et
7.7
8.3
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3c
3
ꢀ
2c (NO )
3
2c
9
3
5
e
e
f
ꢀ
3d (PF )
6
5
2
28
25
––
––
5
3d
Et
Et
3.25
2.5
2.5
9
3
4
ꢀ
2d (NO )
3
Nd
Nd
15
15
23
26
f
2d
ꢀ
3e (PF )
6
Et
3
g
t-Bu
t-Bu
t-Bu
t-Bu
OMe
OMe
3e
9
3
18
16
18
15
––
ꢀ
2e (NO )
3
10
10
9
2e
3
h
i
ꢀ
3f (PF )
6
None
None
0.3
––
ꢀ
2f (NO )
3
N/A
a
III
Alkene (1 equiv) was used w.r.t. Cr (salen). Solvent ¼ acetonitrile. Temperature ¼ 0 °C. Time ¼ time for green-black Cr(V) colour to discharge to
orange-brown Cr(III) colour. Benzaldehyde and phenylacetone were detected as side-products 6 1%, unless otherwise stated. (R,R)-trans-b-
Methlystyrene oxide was the major enantiomer when (R,R)-catalyst was used. Ees (ꢁ2%) were determined by chiral GC (see Section 5 for full
details).
b
c
d
e
f
Using n-decane as internal standard.
Sum of all organic material (%), excluding PhI.
Phenylacetone (4%) as side-product.
III
Cr (salen) complex had low solubility in acetonitrile but addition of PhIO gave a black solution.
III
Cr (salen) complex was sparingly soluble in acetonitrile. Addition of PhIO did not give a colour change. The standard protocol was followed but
only alkene was recovered. No PhI was detected.
Phenylacetone (2%) as side-product.
g
h
V
The black colour due to the O@Cr (salen) complex disappeared within 10 min of adding PhIO. The reaction was carried out with the resulting
brown solution and worked up after 9 h.
III
i
Cr (salen) complex was insoluble in acetonitrile, CH
2
Cl
2
, CHCl
3
and toluene. No reaction was carried out.
Hammett plots of the enantioselectivity versus the
substituent effect. The enantioselectivities of catalysts do
not show the expected linear correlation with the sub-
stituent electronics. In our previous communication we
had observed that addition of more halo substituents to
ferent results from the electronically similar 2 and 3c,d.
This may take the form of more effective blocking of the
alkene trajectory of approach over the 5,5 -positions of
0
the arene ring which otherwise would allow the forma-
tion of the disfavoured enantiomer of the epoxide. This
is not wholly unexpected since a similar role has been
0
a 3,3 -halo complex results in a decrease in ee. However,
0
on addition of an electron-donating groups (EDGs)
such as methyl or ethyl the ee also decreases, contrary to
what might have been predicted from work on
proposed for the tert-butyl group in the 5,5 -positions in
Jacobsen’s manganese(salen) catalyst while the effect of
methyl groups in the same positions could be fully ra-
35;45
36
O@Cr(salen) by Rajagopal et al. and the Mn(salen)
tionalised in terms of electronic considerations.
It is
3
4;35
systems of Jacobsen et al.
we discovered that placement of tert-butyl groups on the
5
On a more positive note,
noteworthy that this complex is less expensive and re-
quires less synthetic operations than the only other
Cr(salen) complex shown to be capable of epoxidising
0
,5 -positions leads to ees of up to 90%. Prior to con-
20
sidering the enantioselectivity obtained in the Cr(salen)-
mediated AE of alkenes in terms of possible substituent-
electronic effects, 2e and 3e would not have been con-
sidered good candidates for enantioselective complexes
because the chromium analogue of Jacobsen’s catalyst
was a mediocre epoxidation catalyst and EWGs were
an alkene in greater than 90% ee.
As regards the Hammett plots, one might speculate that
as EDGs are added to the ligand a different oxidation
pathway or alkene approach trajectory may become
competitive since EDGs are expected to reduce the
reaction rate. Imanishi and Katsuki found the sense of
the enantioselectivity in the AE by a given catalyst could
change depending on the solvent used, which led them
to suggest that two different oxidation pathways were
0
best for the 3,3 -positions. Thus, we have found that the
0
choice of optimum substituent for the 3,3 -positions and
0
the 5,5 -positions is quite different. The effect of the
bulky tert-butyl group would appear to be, at least
partly, of a steric nature since 2 and 3e give quite dif-
24
competing. Recently, we have also found evidence

1346
E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
5
. Experimental
(
(
a)
b)
1
1
0
0
0
0
.3
.1
.9
.7
.5
.3
5
.1. General
Melting points were determined using a Gallenkamp
melting point block, a Griffin melting point apparatus or
a Reichert Thermovar hot stage microscope and are
uncorrected. Elemental analyses were carried out by the
Microanalytical Laboratory, University College Dublin.
Infrared spectra were obtained on either a Mattson
Galaxy Series FTIR 3000 spectrometer or a Nicolet
Impact 410 FTIR Spectrometer and processed using
Omnic 4.1. Mass spectra were obtained by the Mass
Spectrometry Service, University College Dublin. Opti-
cal rotation values were obtained using a Perkin-Elmer
-
0.3
-0.2
-0.1
0
σ
0.1
0.2
0.3
Figure 1. Hammett plot of r vs log(er). Er ¼ enantiomeric ratio
obtained in the O@Cr(salen)-mediated AE of trans-b-methylstyrene
using 3a–f; (a) No additive; ee range: 41–87%. (b) Additive ¼ Ph
3
PO;
ee range: 79–90%.
2
41 polarimeter or a Bellingham and Stanley Polari-
meter ADP 220. ½aꢂ values are reported without units,
D
which are understood to be 10 deg cm g at 589 nm.
ꢀ
1
2
ꢀ1
1
.2
(
(
a)
b)
1
H NMR spectra were recorded at 300 MHz on a Varian
INOVA 300 spectrometer or, where stated, at 270 MHz
1
13
on a Jeol JNM-GX270 FT spectrometer. C NMR
spectra were recorded at 75 MHz (Varian). Chemical
shifts are reported as d-values in ppm relative to tetra-
methylsilane (TMS). Either TMS or a residual solvent
0
.8
.6
1
13
signal was used as an internal standard for H and C.
Chiral gas–liquid chromatography (GC) was performed
on either a Shimadzu GC-8A gas chromatograph, cou-
pled to a Shimadzu C-R3A integrator or a Perkin-Elmer
Autosystem Gas Chromatograph. Details of the chiral
column used are described in the relevant section.
0
-
0.3
-0.2
-0.1
0
σ
0.1
0.2
0.3
Figure 2. Hammett plot of r vs log(er). Er ¼ enantiomeric ratio
obtained in the O@Cr(salen)-mediated AE of trans-b-methylstyrene
using 2a–c, 2e. (a) No additive; ee range: 63–82%. (b) Addi-
tive ¼ Ph
3
PO; ee range: 77–88%.
All solvents were commercially available and used as
supplied, unless otherwise stated. All chemicals, were
obtained from the Aldrich Chemical Company and used
as received unless otherwise stated. The resolution and
liberation of (ꢁ)-trans-cyclohexane-1,2-diamine were
suggestive of competing oxidation cycles in the catalytic
20
mode of Cr(salen)-mediated AE. Daly et al. found that
using bleach as oxidant instead of PhIO favoured
epoxide of the opposite configuration and in catalytic
mode the level of enantioselectivity is less than that in
the stoichiometric mode. Last year, Bryliakov and
48–50
carried out according to literature procedures.
26
Talsi reported evidence that there were two semi-stable
oxygen-bearing Cr(salen) species present in solution
under catalytic conditions although they proposed that
only one of these was involved in transfer of oxygen to
the alkene. Interestingly, Linde et al. and Adam et al.
have recently published evidence to support the exis-
tence of multiple oxidation pathways in Mn(salen) AE
5
5
.2. Synthesis of salicylaldehydes
.2.1. Use of the method of Levin et al. for o-formyla-
51
tion. General method: The phenol (1 equiv) was added to
methanolic solution of magnesium methoxide
0.6 equiv) under a N atmosphere in a three-neck RB
a
(
2
flask equipped for reduced pressure distillation. The
solutions were made in situ by reaction of magnesium
turnings with freshly distilled dry MeOH (15–20 mL per
g of magnesium). Approximately half the MeOH was
removed by distillation. Dry toluene was added to
replace the distilled MeOH. Distillation continued until
the reaction mixture reached a specified temperature (see
below). A slurry of paraformaldehyde (3 equiv) in dry
toluene (1.8 mL per g of paraformaldehyde) was added
in small portions with washings over 1 h. Removal of the
azeotrope of toluene/MeOH by distillation was main-
tained between additions and for a further 1–3 h (see
below) at constant temperature. Extra toluene was
added if the heterogeneous mixture became viscous.
Sometimes the mixture developed a bright yellow col-
our. After a number of hours (see below), heating was
discontinued and the reaction left to cool down (some-
times this was done overnight for convenience). Sulfuric
46;47
reactions. Ultimately, more experimental results are
needed to establish the details of this reaction.
4. Conclusions
Investigations into salen-substituent effects in Cr(salen)-
mediated epoxidation have yielded nonlinear Hammett
plots and the involvement of multiple oxidation path-
ways has been suggested to explain this. These ligand-
tuning studies have also led to the development of a
synthetically accessible chromium–salen complex capa-
ble of mediating the asymmetric epoxidation of trans-b-
methylstyrene with high enantioselectivity. Further
studies are underway to use the knowledge gained to
further improve the design of Cr(salen) complexes.

E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
1347
acid (10%, ꢃ75 mL per 50 mmol of Mg) was added and
the reaction was stirred at 50 °C for 2 h. The reaction
was allowed to cool and the layers were separated. The
aqueous layer was extracted with toluene (2 ꢄ 50 mL per
spectroscopy with 1,4-dimethoxybenzene as internal
standard). Vacuum distillation of some of this oil
(19.7 g) gave the desired product as a clear liquid
[15.23 g, 80% yield (correcting for the amount distilled)].
53
1
2
00 mL of aqueous solution). The combined organic
Bp 50–52 °C (0.3 Torr); lit. 236 °C @ 760 mmHg; H
NMR (300 MHz) d (ppm): 10.84 (s, ArOH, 1H), 9.86 (d,
ArCHO, J ¼ 0:6 Hz, 1H), 7.38–7.34 (m, ArH, 2H), 6.91
layers were washed with water (2 ꢄ 25 mL per 100 mL of
toluene). The solvent was removed in vacuo to give the
crude product.
(m, ArH, 1H), 2.64 (q, ArCH
2
, J ¼ 7:6, 2H), 1.24 (t,
4
53
CH , J ¼ 7:6 Hz, 3H); lit. (CCl , 60 MHz) 10.90 (s),
3
13
Two basic variations of the method of Levin et al. were
used. The procedures used are typified by the o-formyl-
ation of alkylphenols (Method A) and 2-bromophenol
9.90 (s), 6.80–7.50 (m), 2.5 (q), 0.80 (t); C NMR
(75 MHz) (ppm): 196.8 (ArCHO), 160.0, 137.2 (ArCH),
135.9, 132.4 (ArCH), 120.7, 117.7 (ArCH), 27.9 (CH ),
2
(
Method B).
15.7 (CH ).
3
Method A: The reaction was carried out at 95 °C and
normal pressure. Two hours of further heating followed
the paraformaldehyde addition period.
5.2.4. 5-tert-Butylsalicylaldehyde 4e. Method A: 4-tert-
Butylphenol (10.0 g, 66.6 mmol) gave a bright canary
yellow coloured reaction mixture. Work-up yielded an
1
Method B: The reaction was carried out at 75 °C under
sufficient reduced pressure (using a water pump) to
allow removal of the azeotrope by distillation. Three
hours of further heating followed the paraformaldehyde
addition period. Pressure was decreased gradually so as
to maintain slow distillation and typically varied over a
range of 160–360 mmHg.
orange oil (12.2 g, 103% crude yield). H NMR indicated
that the desired product accounted for ꢃ83% of tert-
butyl signals. Distillation (82–84 °C @ 1 mmHg) gave a
yellow liquid (8.68 g). H NMR indicated that this was
1
>95% pure with just traces of 4-tert-butylphenol
remaining. The isolated yield was, therefore, >69%. This
was used without further purification.
54
Yellow liquid, bp 82–84 °C @ 1 mmHg, lit. 60–65 °C @
1
5
.2.2. 3-Bromosalicylaldehyde 4b. Method B: 2-Bromo-
phenol (6.2 mL, 10 g, 58 mmol) gave an orange oil
0.1 Torr; H NMR (300 MHz) d (ppm): 10.87 (s, ArOH,
1H), 9.90 (d, ArCHO, J ¼ 0:5 Hz, 1H), 7.59 (dd, ArH ,
4
1
(
9.65 g, 83% crude yield). H NMR indicated that the
J ¼ 8:8, 2.5 Hz, 1H), 7.53 (d, ArH , J ¼ 2:5 Hz, 1H),
6
ratio of product to starting material was 1.9:1 and that
there were only small amounts of unidentified material.
The yield was estimated at 40–50%. The oil mostly
solidified on standing. It was filtered and the residue
washed with hexane to give pale yellow crystals (1.61 g,
6.95 (dd, ArH
3
, J ¼ 0:5, 8.8 Hz, 1H), 1.35 (s, C
4 9
H , 9H);
55
13
lit. ; C NMR (75 MHz) d (ppm): 196.7 (ArCHO),
159.4, 142.7, 134.6 (ArCH), 129.7 (ArCH), 120.0, 117.2
(ArCH), 34.0 (CMe ), 31.2 ((CH ) ); lit.
3 3 3
56
1
(
4% yield). An additional crop of crystals was obtained
0.83 g, 7% yield). The combined isolated yield was 21%.
5.2.5. 5-Methoxysalicylaldehyde 4f. Method A at lower
temperature: 4-Methoxyphenol (10.0 g, 80.6 mmol) was
subjected to the standard reaction conditions except that
the internal temperature did not rise above 80 °C. A red
oil (11.5 g, 93% crude yield) was obtained. In addition to
unreacted starting material and the desired product,
there was a small amount (<10% relative to the desired
product) of an unidentified impurity characterised by
52
1
Mp 49–52 °C (lit. 49 °C); H NMR (300 MHz) d
ppm): 11.60 (d, ArOH, J ¼ 0:6 Hz, 1H), 9.86 (s, Ar-
6
CHO, 1H), 7.77–7.80 (m, ArH , 1H), 7.55 (dd, ArH ,
(
4
J ¼ 7:6, 1.5 Hz, 1H), 6.95 (apparent t, ArH
5
, J ¼ 7:9 Hz,
13
1
1
H); C NMR (75 MHz) d (ppm): 196.2 (ArCHO),
58.4, 140.2 (ArCH), 133.2 (ArCH), 121.6, 121.0
ꢀ
1
(
ArCH), 111.5; IR (cm ): 2855, 1654 (s, C@O), 1440,
1
1
6
365, 1292, 1218, 1172, 1129, 1073, 900, 819, 760, 732,
68, 601, 488; MS (EI) m=z (% relative intensity): 203 (4,
peaks @ 9.8 and 11.5 ppm in the H NMR. The starting
material to product ratio was 3:10. The yield of the
desired product is ꢃ69%. The oil darkened on standing.
Distillation yielded a nonviscous yellow liquid (7.88 g,
bp 88–90 °C @ 1.5 mmHg), which contained 5-meth-
þ
M þ 3), 202 (27, M þ 2), 201 (23, M ꢀ 1 þ 2), 200 (30,
þ
þ
M ), 199 (26, M ꢀ 1), 184 (6), 182 (6), 174 (3), 172 (4),
1
56 (5), 154 (5), 145 (14), 143 (16), 132 (2), 131 (2), 120
1
(
(
7), 119 (9), 117 (6), 103 (7), 92 (50), 86 (3), 81 (6, Br), 79
7, Br), 75 (29), 74 (16), 63 (100), 53 (44), 46 (10). Anal.
oxysalicylaldehyde (>90% pure by H NMR, >58%
yield) and a trace of unreacted substrate. Yellow liquid,
1
57
Calcd for C H BrO : C, 41.82; H, 2.51; Br, 39.75.
7
bp 88–90 °C @ 1.5 mmHg (lit. 80 °C @ 0.5 Torr); H
5
2
Found: C, 41.74; H, 2.43; Br, 39.71.
NMR (270 MHz) d (ppm): 10.67 (s, ArOH, 1H), 9.87 (d,
ArCHO, J ¼ 0:6 Hz, 1H), 7.15 (dd, ArH
4
, J ¼ 9:1,
3
.1 Hz, 1H), 7.01 (d, ArH , J ¼ 3:1 Hz, 1H), 6.94 (m,
6
58;59
5
.2.3. 5-Ethylsalicylaldehyde 4d. Method A with Dean–
3 3
ArH , 1H), 3.82 (s, ArCH , 3H); lit.
Stark apparatus: 4-Ethylphenol (20.0 g, 164 mmol) was
reacted as per the described procedure with the internal
temperature in the range 95–105 °C. A Dean–Stark
apparatus was used to ensure efficient solvent removal.
5.3. Bromination of salicylaldehydes
5.3.1. 3-Bromo-5-methoxysalicylaldehyde 5f. The proce-
dure of Rubenstein was followed with the modifica-
tions to the work-up as described by Swenton and
1
A red oil (25.5 g, 104% crude yield) was obtained. H
NMR indicated that the desired product was the major
60
1
component (estimated at 80% by mass using H NMR

1348
E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
6
1
Raynolds. Thus, 4f (1.50 g, 9.86 mmol) was dissolved
in glacial acetic acid (10 mL). Sodium acetate (0.90 g,
1
metabisulfite solution (50 mL, 10% w/v) and saturated
sodium bicarbonate solution (50 mL). After drying over
magnesium sulfate the solvent was removed in vacuo to
give a yellow solid (2.89 g, 127% crude yield). Recrys-
tallisation with light petroleum spirits (bp 40–60 °C)
yielded pale yellow crystals (1.90 g, 83% yield). A second
crop of crystals was obtained (0.15 g, 7% yield). Overall
yield ¼ 90%. Mp 89–90 °C (Light pet. spirits, 40–60 °C)
1 mmol) was added. The mixture was cooled on ice/
water. To this stirring slurry was added a solution of
bromine (0.5 mL, 9.8 mmol), in glacial acetic acid
3 mL), via syringe over 10 min. The deep red homoge-
neous solution that resulted was stirred for a further 3 h.
The mixture was then poured into a saturated solution
(
63
1
of SnCl (45 mL, ꢃ5 mol %). This was then filtered to
lit. 81–83 °C (CH Cl /hexane); H NMR (300 MHz) d
2
2
2
give a pale yellow solid (2.91 g, 128% crude yield). This
was recrystallised immediately (this is recommended by
Swenton and Raynolds) with EtOH. After leaving the
recrystallisation to stand overnight, filtration yielded
pale yellow fluffy crystals, 1.76 g, 76% yield. Mp 110–
(ppm): 11.39 (d, ArOH, J ¼ 0:6 Hz, 1H), 9.85 (s, Ar-
CHO, 1H), 7.81 (dd, ArH
, J ¼ 2:3, 0.6 Hz, 1H), 7.51 (d,
ArH, J ¼ 2:3 Hz, 1H), 1.33 (s, C H , 9H); lit. 11.39 (s),
4
63
4
9
9.82 (s), 7.79 (d, J ¼ 2:2 Hz), 7.48 (d, J ¼ 2:2 Hz), 1.30
13
(s); C NMR (75 MHz) d (ppm): 196.1 (CHO), 155.8,
143.8, 137.6 (CH), 129.3 (CH), 120.7, 110.8, 34.2
(CMe ), 31.1 (CH ).
1
1
1
12 °C (lit. 109–110.5 °C (Swenton and Raynolds) or
07 °C (Rubenstein)). H NMR (300 MHz) d (ppm):
1.11 (s, ArOH, 1H); 9.82 (s, ArCHO, 1H); 7.40 (d,
1
3
3
ArH, J ¼ 2:9 Hz, 1H); 7.03 (d, ArH, J ¼ 2:9 Hz, 1H);
61
13
3
1
.82 (s, OCH , 3H) (lit. ); C NMR (75 MHz) d (ppm):
5.3.4. 3-Bromo-5-ethylsalicylaldehyde 5d. The procedure
3
63
95.6 (CHO), 152.8, 152.4, 127.3 (CH), 120.4, 115.7
of Lam et al., as described above, was followed. 4d
(5.00 g, 33.3 mmol) gave a yellow liquid and a whitish
precipitate after heating for 12 h @ 50 °C. Work-up as
before gave a yellow liquid (7.18 g, 94% crude yield),
which was distilled to give 3-bromo-5-ethylsalicylalde-
hyde as a yellow liquid (6.68 g, 88% yield). Bp 116–
(
3
CH), 111.4, 56.1 (OCH ).
5
.3.2. 3-Bromo-2-hydroxy-5-methylbenzaldehyde 5c. The
60
method of Rubenstein (see above) was used. Thus,
sodium acetate (0.72 g, 8.78 mmol) was added to a
solution of 2-hydroxy-5-methylbenzaldehyde (1.04 g,
1
118 °C (0.9 Torr); H NMR (300 MHz) d (ppm): 11.38
(s, ArOH, 1H), 9.82 (d, ArCHO, J ¼ 0:6 Hz, 1H), 7.63
(dt, ArH, J ¼ 2:2, 0.6 Hz, 1H), 7.34 (m, ArH, 1H), 2.64
(qt, CH , J ¼ 7:6, 0.6 Hz, 2H), 1.25 (t, CH , J ¼ 7:6 Hz,
7
.64 mmol) in glacial acetic acid (5 mL). The resulting
suspension was cooled on ice and then removed from
the ice before dropwise addition of a solution of bro-
mine (1.32 g, 8.26 mmol) in glacial acetic acid (2.6 mL).
The yellow mixture was stirred for 3 h at room tem-
perature and then poured onto water (8 mL þ 16 mL
washings). The pale yellow solid was filtered and washed
with water (5 mL). This was dissolved in CH Cl
2
3
13
3H); C NMR (75 MHz) d (ppm): 195.9 (ArCHO),
156.0, 139.6 (ArCH), 136.9, 131.6 (ArCH), 121.0, 110.8,
ꢀ
1
27.4 (CH ), 15.3 (CH ); IR (cm ): 3097 (br, OH), 2967,
2
3
2933, 2872, 1660 (s, C@O), 1455, 1378, 1342, 1301, 1275,
1190, 1140, 935, 881, 779, 736, 696; GC–MS m=z (%
relative intensity): 230 (53, M þ 2), 229 (11, M þ 1), 228
2
2
(
(
20 mL) and washed with sodium metabisulfite solution
10% w/v, 10 mL) and saturated sodium bicarbonate
(55, M), 215 (80, M þ 2 ꢀ CH
3
), 214 (8, M þ 1 ꢀ CH
3
),
213 (100, M ꢀ CH
3
), 201 (5), 199 (5), 149 (6), 120 (17),
solution (10 mL). After drying over magnesium sulfate
the solvent was removed in vacuo to yield a yellow solid
105 (11), 103 (7), 92 (8), 91 (27), 89 (7), 78 (16), 77 (31),
65 (17), 63 (16). Anal. Calcd for C H BrO : C, 47.19; H,
3.96; Br, 34.88. Found: C, 46.89; H, 3.84; Br, 35.06.
9
9
2
(
1.46 g, 89% crude yield). A small amount of starting
1
material was still present (as detected by H NMR).
Recrystallisation with EtOH yielded fluffy yellow crys-
62
tals (0.69 g, 42%). Mp 63–64 °C (lit. 65–66 (aq EtOH));
5.4. Synthesis of salen ligands
1
H NMR (300 MHz) d (ppm): 11.36 (s, ArOH, 1H), 9.80
(
(
(
s, ArCHO, 1H), 7.61 (dd, ArH, J ¼ 2:1 Hz, 1H), 7.32
(R,R)-(ꢀ)-trans-Cyclohexane-1,2-diamine (0.5 equiv, as
a frozen white solid) was weighed into an appropriately
sized RB flask, immediately followed by EtOH (GR,
approximately 25 mL per 2 g of salicylaldehyde). This
solution was brought to reflux and salicylaldehyde
13
dd, ArH, J ¼ 2:1 Hz, 1H), 2.34 (s, CH
3
, 3H); C NMR
75 MHz) d (ppm): 195.9 (CHO), 155.9, 140.6 (CH),
1
32.8 (CH), 130.4, 120.9, 110.7, 19.9 (CH ).
3
(1 equiv) was added portionwise down the condenser
5.3.3. 3-Bromo-5-tert-butyl-2-hydroxybenzaldehyde 5e.
The procedure of Lam et al. was followed. A solu-
with washings of EtOH (ꢃ25 mL per 2 g of salicylalde-
hyde) resulting in an immediate development of a bright
yellow colour. After refluxing for 2 h the solution was
allowed to cool which, if it had not happened already,
usually led to precipitation of bright yellow crystals. The
crystals were then filtered and washed with ice-cold
EtOH (ꢃ5 mL) before air-drying at the pump. If insuf-
ficient product precipitated the filtrate or reaction
solution could be concentrated by removal of some
solvent in vacuo to obtain more. The bright yellow
powders/crystals were recrystallised from EtOH. These
were then powdered and dried under vacuum at 60 °C to
remove any residual solvent.
63
tion of 4e (1.58 g, 8.86 mmol) and sodium acetate (1.34 g,
1
6.3 mmol) in glacial acetic acid (40 mL) was made up.
A solution of bromine (1.44 g, 9.01 mmol) in glacial
acetic acid (15 mL) was added via a dropping funnel
over 30 min. The yellow solution was stirred at 50 °C for
1
2 h. After cooling this resulted in a colourless liquid
with a whitish precipitate. The solvent was removed in
vacuo and water (50 mL) and CH Cl (40 mL) were
added. After separation of the layers the aqueous layer
2
2
was extracted with a further 2 ꢄ 30 mL CH Cl . The
2
2
combined organic layers were washed with sodium

E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
1349
0
þ
þ
þ
5
.4.1.
cyclohexane-1,2-diamine 6b. Compound 4b (2.01 g,
.00 mmol) gave yellow crystals (EtOH, 1.81 g, 75%).
(R,R)-())-N,N -Bis(3-bromosalicylidene)-trans-
(M þ 2 þ Na , 16), 557 (M þ Na , 10), 539 (MH þ 4,
þ
þ
62), 538 (15), 537 (MH þ 2, 100), 536 (4), 535 (MH ,
2þ
2þ
1
55), 270 ((M þ 4)H , 4), 269 ((M þ 2)H , 11), 268
2
2
1
2þ
Mp 150–153 °C; H NMR (300 MHz) d (ppm): 14.4 (s,
br, ArOH, 2H), 8.20 (s, ArCH@NR, 2H), 7.50 (dd,
ArH, J ¼ 1:5, 7.9 Hz, 2H), 7.10 (dd, ArH, J ¼ 1:5,
(MH
2
, 4); Anal. Calcd for C24
H
28Br
2
N
H, 5.26; Br, 29.80; N, 5.22. Found: C, 53.72; H, 5.14; Br,
2
O
2
: C, 53.75;
34
30.00; N, 5.15; ½aꢂ ¼ ꢀ450 (c ¼ 1:06, CH Cl ).
D
2
2
7
.6 Hz, 2H), 6.70–6.64 (m, ArH, 2H), 3.35–3.32 (m,
C@N–CH, 2H), 1.97–1.41 (m, cyclohexyl–CH
2
’s, 8H);
C NMR (75 MHz) d (ppm): 164.3 (C@N), 158.5, 135.6
ArCH), 130.8 (ArCH), 119.1 (ArCH), 118.9, 111.0, 71.9
13
0
5.4.4. (R,R)-())-N,N -Bis(3-bromo-5-tert-butylsalicylid-
ene)-trans-cyclohexane-1,2-diamine 6e. Compound 5e
(1.81 g, 7.04 mmol) gave yellow crystals (EtOH, 1.61 g,
(
(
2
1
4
(
(
(
ꢀ
1
cyclohexyl–CH), 32.9 (CH
2
), 23.9 (CH
937, 2857, 1627 (s, C@N), 1568, 1490, 1445, 1271, 1181,
146, 855, 771, 736; MS (EI) m=z (% relative intensity):
2
); IR (cm ):
1
77%). Mp 202–203 °C; H NMR (300 MHz) d (ppm):
14.2 (s, br, ArOH, 2H), 8.21 (s, ArCH@NR, 2H), 7.53
(d, ArH, J ¼ 2:3 Hz, 2H), 7.10 (d, ArH, J ¼ 2:3 Hz,
2H), 3.34–3.31 (m, C@N–CH, 2H), 1.96–1.43 (m, cy-
þ
þ
82 (M þ 4, 4), 481 (3), 480 (M þ 2, 16), 479 (3), 478
þ
M , 9), 283 (6), 282 (22), 281 (279 þ 2, 90), 280 (55), 279
þ
13
M ꢀ C H BrNO, 100), 278 (42), 264 (9), 252 (8), 238
clohexyl–CH ’s, 8H), 1.23 (s, ArC H , 18H); C NMR
7
6
2
4
9
8), 226 (5), 212 (9), 202 (47), 200 (69), 198 (23), 185 (14),
(75 MHz) d (ppm): 164.6 (C@N), 155.9, 142.4, 132.9
(ArCH), 127.4 (ArCH), 118.4, 110.4, 72.2 (cyclohexyl–
CH), 34.0 (CMe ), 33.0 (CH ), 31.2 (CH ), 24.0 (CH );
IR (cm ): 2960 (s), 2931 (s), 2861, 1630 (s, C@N), 1574,
1466, 1447, 1378, 1362, 1281, 1263, 1170, 701; MS (EI)
1
(
C
72 (4), 146 (6), 132 (7), 120 (14), 105 (27), 91 (16), 81
39), 77 (29), 67 (24), 54 (24), 41 (47). Anal. Calcd for
Br : C, 50.02; H, 4.20; N, 5.83; Br, 33.28.
Found: C, 50.28; H, 4.18; N, 5.70; Br, 33.41;
3
2
3
2
ꢀ
1
20
H
20
N
2
O
2
2
2
5
þ
½
aꢂ ¼ ꢀ578 (c ¼ 0:601, CH Cl ).
m=z (% relative intensity): 594 (M þ 4, 6), 593 (4), 592
D
2
2
þ
þ
(
3
M þ 2, 17), 590 (M , 7), 338 (27), 337 (335 þ 2, 98),
þ
36 (40), 335 (M ꢀ C11
H14BrNO, 100), 322 (27), 320
0
5
trans-cyclohexane-1,2-diamine 6c. Compound 5c (0.64 g,
.4.2. (R,R)-())-N,N -Bis(3-bromo-5-methylsalicylidene)-
(40), 308 (3), 294 (6), 282 (18), 281 (26), 280 (16), 258
(21), 257 (15), 256 (30), 255 (14), 242 (32), 241 (15), 240
(38), 225 (8), 212 (6), 200 (4), 161 (9), 146 (8), 133 (7),
117 (12), 105 (6), 96 (12), 91 (9), 82 (13), 81 (33), 80 (14),
79 (19), 57 (63), 56 (15), 55 (12), 41 (32). Anal. Calcd for
3
1
.0 mmol) gave yellow crystals (EtOH, 0.63 g, 83%). Mp
1
67–168 °C; H NMR (300 MHz) (d ppm): 14.1 (s, br,
ArOH, 2H), 8.14 (s, ArCHNR, 2H), 7.33 (d, ArH,
J ¼ 1:8 Hz, 2H), 6.89 (d, ArH, J ¼ 1:8 Hz, 2H), 3.32–
C H36Br N O : C, 56.77; H, 6.13; N, 4.73. Found:
28 2 2 2
32
C, 56.67; H, 6.00; N, 4.63; ½aꢂ ¼ ꢀ396 (c ¼ 1:19,
3
.29 (m, C@NCH, 2H), 2.20 (s, ArCH
3
, 6H), 1.96–1.45
D
13
(
m, cyclohexyl–CH ’s, 8H); C NMR (75 MHz) (d
CH Cl ).
2
2
2
ppm): 164.1 (C@N), 155.9, 136.1 (ArCH), 130.9
(
(
(
1
1
ArCH), 128.6, 118.6, 110.3, 72.2 (cyclohexyl–CH), 32.9
cyclohexyl–CH ), 24.3 (cyclohexyl–CH ), 19.9
); IR (cm ): 2945, 2924, 2847, 1633 (s, C@N),
575, 1445, 1367, 1274, 1245, 1203, 1152, 1098, 1065,
045, 975, 942, 862, 787, 741, 703, 571; MS (ES) m=z (%
0
5.4.5. (R,R)-())-N,N -Bis(3-bromo-5-methoxysalicylid-
ene)-trans-cyclohexane-1,2-diamine 6f. Compound 5f
(1.00 g, 4.33 mmol) gave orange crystals (EtOH, 0.88 g,
2
2
ꢀ
1
ArCH
3
1
75%). Mp 183–185 °C; H NMR (300 MHz) d (ppm):
relative intensity) (0.1 mg/mL in MeOH): 533
13.8 (s, br, ArOH, 2H), 8.16 (s, ArCH@NR, 2H), 7.15
(d, ArH, J ¼ 2:9 Hz, 2H), 6.67 (d, ArH, J ¼ 2:9 Hz,
þ
þ
(
(
(
(
M þ Na þ 4, 10), 531 (M þ Na þ 2, 11), 529
þ þ
M þ Na , 5), 511 (MH þ 4, 32), 510 (13), 509
3
2H), 3.71 (s, OCH , 6H), 3.34–3.31 (m, C@N–CH, 2H),
13
þ
þ
MH þ 2, 100), 508 (3), 507 (MH , 36), 256
1.97–1.43 (m, cyclohexyl–CH ’s, 8H);
C NMR
2
2þ
2þ
2þ
(M þ 4)H
2
, 5), 255 ((M þ 2)H
2
, 8), 254 (MH
: C, 51.99; H, 4.76; N,
2
, 5).
(75 MHz) d (ppm): 164.0 (C@N), 152.2, 151.9, 122.5
(ArCH), 118.4, 114.9 (ArCH), 110.7, 72.4 (cyclohexyl–
CH), 56.0 (CH ), 32.9 (CH ), 24.0 (CH ); IR (cm ):
3
Anal. Calcd for C22
5
(
H
24Br
2
N
2
O
2
31
ꢀ1
.51. Found: C, 51.99; H, 4.73; N, 5.44; ½aꢂ ¼ ꢀ498
D
2
2
c ¼ 1:03, CH
2
Cl
2
).
2941, 2859, 1632 (s, C@N), 1574, 1471, 1434, 1369, 1286,
1
253, 1177, 1142, 1096, 1052, 964, 852, 778, 716; MS
þ
(
EI) m=z (% relative intensity): 542 (M þ 4, 10), 541 (5),
0
þ
þ
5
.4.3. (R,R)-())-N,N -Bis(3-bromo-5-ethylsalicylidene)-
540 (M þ 2, 28), 538 (M , 6), 312 (14), 311 (309 þ 2,
þ
trans-cyclohexane-1,2-diamine 6d. Compound 5d
6.00 g, 26.2 mmol) gave yellow crystals (EtOH, 4.65 g,
100), 309 (M ꢀ C
8 8 2
H BrNO , 85), 294 (22), 268 (10),
(
6
232 (17), 231 (42), 230 (30), 229 (50), 214 (36), 186 (8),
161 (5), 135 (9), 94 (12), 82 (15), 81 (38, Br), 80 (17), 79
(35, Br), 77 (21), 67 (17), 56 (16), 55 (16), 54 (17), 53 (26),
41 (32). Anal. Calcd for C22
4.48; N, 5.19; Br, 29.58. Found: C, 48.99; H, 4.59; N,
1
6%). Mp 71–74 °C; H NMR (300 MHz) d (ppm): 14.1
(
(
s, broad, ArOH, 2H), 8.17 (s, ArCH@NR, 2H), 7.36
dd, ArH, J ¼ 2:1, 0.5 Hz, 2H), 6.92 (d, ArH,
2 2 4
H24Br N O : C, 48.91; H,
J ¼ 2:1 Hz, 2H), 3.33–3.30 (m, C@NCH, 2H), 2.51 (q,
2
D
3
CH
H), 1.15 (t, CH
d (ppm): 164.3 (C@N), 156.1, 135.2, 135.1 (ArCH),
29.8 (ArCH), 118.7, 110.4, 72.2 (cyclohexyl–CH), 32.9
2
, J ¼ 7:6 Hz, 4H), 1.96–1.43 (m, cyclohexyl-CH
2
’s,
4.89; Br, 29.61; ½aꢂ ¼ )432 (c ¼ 0:41, CH
2 2
Cl ).
13
8
3
, J ¼ 7:6 Hz, 6H); C NMR (75 MHz)
1
5.5. Synthesis of chromium(III) salen complexes
5.5.1. General procedure. The complexes were prepared
following the method described by Mabbs et al.
Chromium(salen) chloride complexes were synthesised
ꢀ
1
(
2
8
CH ), 27.4 (CH ), 24.0 (CH ), 15.4 (CH ); IR (cm ):
2 2 2 3
930, 2858, 1629 (s, C@N), 1573, 1462, 1371, 1278, 1151,
64
77, 772, 741, 702; MS (ES) m=z (% relative intensity)
þ
(
0.1 mg/mL in MeOH): 561 (M þ 4 þ Na , 10), 559

1350
E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
by reacting chromium(II) chloride with the appropriate
salen ligand. The chromium(II) chloride was made by
reducing chromium(III) with zinc amalgam and used
immediately. The general procedure is described below,
along with procedures for exchanging the chloride
counter-ion for either nitrate or hexafluorophosphate.
CAUTION: There is evidence that Cr(III)salen com-
plexes are genotoxic and carcinogenic and thus due care
(ES, 0.1 mg/mL in HPLC grade MeOH unless stated),
elemental analysis and mp.
5
5
.6. Counterion exchange protocols
.6.1. Exchange of chloride to nitrate 2b. Compound 1b
(0.657 g, 1.16 mmol) was dissolved in MeOH (116 mL).
A 0.01 M solution of complex is typically used. In some
cases it was necessary to use more MeOH or a 1:5 ace-
tone/MeOH solution to obtain dissolution. If any solid
was still insoluble, after doubling the volume of MeOH
or adding acetone, the mixture was filtered and the
residue discarded. An aqueous solution of silver nitrate
65
should be taken to avoid contact.
5.5.2. Preparation of zinc amalgam. This preparation
was adapted from the method of Caesar. Granular
66
zinc was stored under N when not in use. Exposure to
2
(
398 mg, 2.34 mmol in 8.5 mL, ꢃ0.3 M, 2 equiv) was
air led to deactivation of the zinc due to oxidation of the
surface. Concd HCl (3.3 mL) was added to a suspension
of mercury(II) chloride (4.38 g, 16.1 mmol) in distilled
water (42 mL) in a 100 mL conical flask resulting in a
homogeneous solution. Granular zinc (20 mesh, 99.8%,
added dropwise to the stirring homogeneous solution of
complex. A white precipitate of silver chloride could be
observed immediately. The reaction was stirred for a
further hour before gravity filtration was performed to
remove the silver chloride. The filtrate was concentrated
in vacuo to ꢃ10 mL to yield a brown precipitate, which
was collected by filtration, washed with water
2
1.93 g, 0.335 mol) was then added and stirring contin-
ued for 30 min. Stirring was sufficiently slow that air did
not come into contact with the solid amalgam. The zinc
amalgam was then filtered and washed with water,
(
2 ꢄ 10 mL) and Et O (10 mL), and dried in the same
2
manner as the chloride complex.
EtOH and Et O (10 mL each). It was immediately
2
2
placed under an atmosphere of N in a three-necked RB
flask equipped as described in the next section. It is
important to minimise any contact with air during this
procedure.
5.6.2. Exchange of chloride to hexafluorophosphate 3b. In
the same manner as for the synthesis of nitrate com-
plexes a ꢃ0.01 M solution of 1c (0.605 g, 1.07 mmol in
1
07 mL) was prepared in a 250 mL RB flask. To this
solution was added an aqueous solution of potassium
hexafluorophosphate (0.394 g, 2.14 mmol in 7.1 mL,
ꢃ0.3 M, 2 equiv). The resulting solution was stirred
overnight before concentration in vacuo to just over
5
.5.3. Reduction of chromium(III) chloride to chro-
mium(II) chloride. The zinc amalgam and stirring bar
were transferred into a waiting three-necked RB flask
equipped with a pressure equalizing dropping funnel
and nitrogen inlet/outlet, under a positive flow of N2.
The dropping funnel contained a green solution of
chromium(III) chloride in water (1.83 g, 6.87 mmol, in
1
0 mL to yield a brown precipitate, which was collected
by filtration. The complex was washed with water
50 mL) and Et O (10 mL) before drying in the same
(
2
manner as for the chloride and nitrate complexes.
1
2 mL), which was added slowly to the stirring amal-
gam. Within 30 min of commencing stirring, a sky blue
colour characteristic of chromium(II) chloride persisted.
The mixture was stirred for a further hour before use.
After removal of the chromium(II) solution the amal-
gam was transferred to a plastic vessel for safe disposal.
0
5
cyclohexane-1,2-diamine chromium(III)] chloride 1b. 1st
.6.3.
[(R,R)-())-N,N -Bis(3-bromosalicylidene)-trans-
precipitate, 26% yield; 2nd precipitate, 51% yield. Total
ꢀ
1
yield ¼ 77%. Mp dec >320 °C; IR (cm ): 3253 (br),
2
1
6
932, 2856, 1631 (s, C@N), 1589, 1530, 1435, 1394, 1346,
332, 1227, 1182, 1135, 1084, 1021, 932, 845, 738, 703,
43, 625, 567, 472, 446; MS (ES) m=z (% relative
5.5.4. Complex generation. A solution of 6b (2.20 g,
4.58 mmol) was prepared in acetone/MeOH (5:1 ratio,
90 mL) in a three-necked RB flask under a nitrogen
intensity) (all peaks >2%): 526 (2), 528 (53), 529 (16),
ꢀ
5
5
30 (100, M ꢀ Cl ), 531 (31), 532 (50), 533 (15), 546 (5),
atmosphere. The chromium(II) chloride solution pre-
pared as described above was added dropwise with
stirring, via syringe through a septum, under a positive
ꢀ
47 (5), 548 (9, M ꢀ Cl þ H
2
O), 549 (2), 550 (4), 559
ꢀ
(
5
6
11), 561 (21, M ꢀ Cl þ OMe), 562 (6), 563 (7), 564 (2),
ꢀ
82 (2), 584 (4, M ꢀ Cl þ OMe þ Na), 586 (2), 606 (10),
flow of N
brown colour. The reaction was stirred for 1 h and then
the N flow was stopped. After leaving to stir overnight
under a N blanket, the reaction was exposed to air and
2
. The solution immediately changed to a
ꢀ
07 (3), 608 (20, M ꢀ Cl þ MeOH þ 2Na), 609 (6), 610
ꢀ
(
6
10), 611 (3), 626 (3, M ꢀ Cl þ MeOH þ 2Na þ H
2
O),
2
ꢀ
39 (2, M ꢀ Cl þ MeOH þ 2Na þOMe), 686 (2,
2
ꢀ
M ꢀ Cl þ 2(MeOH þ 2Na)).
Anal.
Calcd
for
left to stir for 4 h. At this point, any brown precipitate
present was removed by filtration and worked-up sepa-
rately from the later precipitate. The solution was then
concentrated in vacuo to yield a brown precipitate,
which was removed by filtration. The precipitate(s) were
20 2 2 2
C H18Br ClCrN O : C, 42.47; H, 3.21; N, 4.95; Br,
2
4
8.25; Cl, 6.27; Cr, 9.19. Found: C, 41.03; H, 3.51; N,
.55; Br, 27.91; Cl, 5.79; Cr, 8.33.
2
washed with water and Et O (10 mL each) and dried at
0
the pump before being placed in an oven overnight. For
analysis, the samples were further dried under vacuum
at 60 °C for ꢃ12 h. Samples were analysed by IR, MS
5.6.4.
cyclohexane-1,2-diamine chromium(III)] nitrate 2b.
[(R,R)-())-N,N -Bis(3-bromosalicylidene)-trans-
Compound 1b (657 mg, 1.16 mmol) yielded a brown

E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
1351
ꢀ
1
powder (476 mg, 69%). Mp dec >280 °C; IR (cm ):
150 (br), 2928, 2857, 1626 (s, C@N), 1589, 1532, 1434
s), 1394, 1345, 1315, 1286, 1225, 1184, 1136, 1064, 1021,
33, 846, 777, 741, 707, 649, 568; MS (ES) m=z (% rel-
378 (3), 554 (4), 555 (4), 556 (53), 557 (26), 558 (100,
ꢀ
3
(
9
M ꢀ NO
3
), 559 (41), 560 (50), 561 (20), 562 (4), 572 (3),
ꢀ
573 (4), 574 (6, M ꢀ NO þ O), 575 (5), 576 (3), 587 (9),
3
ꢀ
588 (6), 589 (24, M ꢀ NO
3
þ OMe), 590 (6), 591 (11),
þ OMe þ Na), 614 (4). Anal.
ꢀ
ative intensity) (all peaks >2%): 526 (3), 527 (2), 528
610 (4), 612 (7, M ꢀ NO
3
ꢀ
(
56), 529 (22), 530 (100, M ꢀ NO3 ), 531 (36), 532 (49),
Calcd for C H Br CrN O : C, 42.60; H, 3.58; N, 6.77.
22 22 2 3 5
5
33 (17), 534 (4), 545 (4), 546 (6), 547 (3), 548 (11,
O), 549 (4), 550 (5), 559 (13), 560 (7),
Found: C, 37.03; H, 3.35; N, 6.07.
ꢀ
M ꢀ NO
3
þ H
2
ꢀ
5
61 (30, M ꢀ NO þ OMe), 563 (17), 564 (4), 569 (3),
3
ꢀ
0
5
(
71 (4, M ꢀ NO
3
þ H
2
O þ Na), 572 (2), 573 (3), 582
5.6.8.
[(R,R)-())-N,N -Bis(3-bromo-5-methylsalicylid-
ꢀ
5), 583 (2), 584 (10, M ꢀ NO
3
þ OMe þ Na), 585 (3),
ene)-trans-cyclohexane-1,2-diamine chromium(III)] hexa-
fluorophosphate 3c. Compound 1c (113 mg, 0.190 mmol)
gave a brown solid (117 mg, 87%). Mp dec >280 °C; IR
ꢀ
5
Anal. Calcd for C H Br CrN O : C, 40.56; H, 3.06; N,
86 (4), 587 (2), 612 (3, M ꢀ NO þ H O þ 2MeOH).
3
2
20
18
2
3
5
ꢀ
1
7
6
.10; Br, 26.99; Cr, 8.78. Found: C, 38.04; H, 3.40; N,
.34; Br, 25.22; Cr, 7.91.
(cm ): 3228 (br), 2939, 2861, 1629 (s, C@N), 1533,
1450, 1387, 1306, 1288, 1232, 1154, 1029, 855, 813, 747,
5
2
47; MS (ES) m=z (% relative intensity) (all peaks > 3%):
73 (4), 296 (4), 310 (3), 328 (3), 554 (3), 556 (55), 557
0
ꢀ
5
.6.5.
[(R,R)-())-N,N -Bis(3-bromosalicylidene)-trans-
cyclohexane-1,2-diamine chromium(III)] hexafluorophos-
(27), 558 (100, M ꢀ PF
6
), 559 (43), 560 (55), 561 (21),
ꢀ
562 (6), 573 (3), 574 (4), 575 (4, M ꢀ PF þ OH), 587
6
ꢀ
phate 3b. Compound 1b (323 mg, 0.571 mmol) gave a
ꢀ
(12), 588 (3), 589 (23, M ꢀ PF
6
þ OMe), 590 (3), 591
1
brown powder (251, 65%). Mp dec >300 °C; IR (cm ):
(11). Anal. Calcd for C22
H
22Br
2
CrF
6
N
2
O
H, 3.15; N, 3.98. Found: C, 35.57; H, 3.37; N, 3.58.
2
P: C, 37.58;
2
1
8
936, 2862, 1629 (s, C@N), 1589, 1535, 1434 (s), 1394,
349, 1313, 1282, 1227, 1187, 1138, 1083, 1016, 934, 916,
45 (s), 774, 738, 709, 646, 616, 556, 491, 443; MS (ES)
0
m=z (% relative intensity) (all peaks >2%): 526 (2), 528
5.6.9. [(R,R)-())-N,N -Bis(3-bromo-5-ethylsalicylidene)-
þ
ꢀ
(
5
52), 529 (19), 530 (100, M ꢀ PF ), 531 (34), 532 (48),
trans-cyclohexane-1,2-diamine chromium(III)] chloride
1d. Compound 6d (3.01 g, 5.61 mmol) gave brown
powders (1.11 g, 32%) and (1.37 g, 39%). Total
6
33 (3), 534 (3), 545 (3), 546 (6), 547 (3), 548 (11,
þ
ꢀ
M ꢀ PF
6
þ H
2
O), 549 (3), 550 (5), 559 (8), 560 (5), 561
17, M ꢀ PF þ OMe), 562 (11), 563 (10), 564 (2), 582
þ
ꢀ
ꢀ1
(
yield ¼ 71%. Mp dec >325 °C; IR (cm ): 3201 (br),
6
þ
ꢀ
(
7), 584 (11, M ꢀ PF
6
þ MeO þ Na), 585 (3), 586 (6),
2956, 2929, 2855, 1634 (s, C@N), 1534, 1449, 1391, 1347,
1307, 1224, 1147, 854, 795, 746, 716, 541, 447; MS (ES)
þ
ꢀ
6
Calcd for C H Br CrF N O P: C, 35.58; H, 2.69; Br,
12 (5, M ꢀ PF
6
þ H
2
O þ 2MeOH), 614 (2). Anal.
(% relative intensity) (all peaks >3%): 310 (5), 324 (3),
569 (10), 570 (4), 571 (21, M ꢀ Cl ꢀ CH
2
0
18
2
6
2
2
ꢀ
2
3
4
3.67; Cr, 7.70; F, 16.88; N, 4.15; P, 4.59. Found: C,
5.22; H, 3.15; Br, 23.86; Cr, 7.05; F, 11.39; N, 3.90; P,
.38.
3
), 572 (7), 573
(10), 574 (3), 582 (3), 583 (3), 584 (52), 585 (30), 586
ꢀ
(100, M ꢀ Cl ), 587 (46), 588 (56), 589 (24), 590 (6), 602
ꢀ
ꢀ
(
(
5, M ꢀ Cl þ O), 603 (3), 604 (3), 615 (20), 616 (6), 617
28, M ꢀ Cl þ OMe), 618 (8), 619 (15), 620 (3), 638 (3),
0
ꢀ
5
.6.6.
[(R,R)-())-N,N -Bis(3-bromo-5-methylsalicylid-
640 (6, M ꢀ Cl þ OMe þ Na), 642 (5), 644 (3); Anal.
ene)-trans-cyclohexane-1,2-diamine chromium(III)] chlo-
ride (C22 ClCrN ) 1c. Compound 6c (0.58 g,
.1 mmol) gave brown solids in two precipitates (198 mg,
Calcd for C H Br ClCrN O : C, 46.36; H, 4.22; N,
2
24
26
2
2
H
22Br
2
2
O
2
4.51. Found: C, 44.84; H, 4.34; N, 4.21.
1
2
9% and 315 mg, 47%). Total yield ¼ 75%. Mp
ꢀ
1
0
dec >270 °C; IR (cm ): 3427 (br), 2925, 2857, 1630 (s,
5.6.10.
ene)-trans-cyclohexane-1,2-diamine
nitrate 2d. Compound 1d (596 mg, 0.959 mmol) gave a
brown powder (522 mg, 84%). Mp dec >250 °C; IR
(cm ): 2928, 2856, 1627 (s, C@N), 1593, 1519, 1449,
1385, 1315, 1259, 1224, 1146, 1058, 876, 852, 793, 751,
[(R,R)-())-N,N -Bis(3-bromo-5-ethylsalicylid-
C@N), 1528, 1452, 1389, 1341, 1307, 1229, 1151, 1032,
chromium(III)]
8
(
5
5
56, 812, 746, 542; MS (ES) m=z (% relative intensity)
all peaks >3%): 296 (6), 326 (3), 328 (3), 378 (3), 554 (4),
ꢀ
ꢀ1
55 (3), 556 (54), 557 (26), 558 (100, M ꢀ Cl ), 559 (42),
60 (53), 561 (19), 562 (5), 574 (3), 575 (4,
ꢀ
ꢀ
ꢀ
M ꢀ Cl þ OH), 576 (3), 587 (12), 588 (4), 589 (21,
717, 548; MS (ES) (% relative intensity) (all peaks >5%):
310 (8), 328 (5), 340 (5), 342 (8), 391 (8), 392 (5), 506 (5),
M ꢀ Cl þ OMe), 590 (5), 591 (8), 612 (3,
ꢀ
M ꢀ Cl þ OMe þ Na), 614 (3). Anal. Calcd for
508 (5), 569 (16), 570 (5), 571 (21, M ꢀ NO
3
ꢀ CH
3
),
C H Br ClCrN O : C, 44.51; H, 3.74; N, 4.72. Found:
2
572 (8), 573 (12), 574 (7), 582 (8), 583 (7), 584 (63), 585
(36), 586 (100, M ꢀ NO ), 587 (40), 588 (57), 589 (19),
22
22
2
2
ꢀ
C, 41.64; H, 3.75; N, 4.25.
3
90 (7), 598 (10), 599 (7), 600 (16), 601 (9), 602 (15,
5
ꢀ
M ꢀ NO þ O), 603 (8), 604 (5), 605 (5), 607 (5), 608
3
0
5
ene)-trans-cyclohexane-1,2-diamine
.6.7.
[(R,R)-())-N,N -Bis(3-bromo-5-methylsalicylid-
(7), 609 (9), 610 (5), 611 (8), 613 (6), 614 (5), 615 (22),
þ OMe), 618 (11), 619 (10),
ꢀ
chromium(III)]
nitrate 2c. Compound 1c (178 mg, 0.300 mmol) gave a
616 (10), 617 (30, M ꢀ NO
3
620 (5), 625 (5), 626 (5), 628 (6), 629 (5), 630 (5), 638
ꢀ
ꢀ
1
brown solid (157 mg, 84%). Mp dec >240 °C; IR (cm ):
(12), 639 (9), 640 (28, M ꢀ NO
3
þ OMe þ Na), 641
3
1
5
2
421 (br), 2932, 2859, 1626 (s, C@N), 1530, 1494, 1449,
384, 1306, 1284, 1234, 1153, 1031, 851, 813, 746, 717,
47; MS (ES) m=z (% relative intensity) (all peaks >3%):
96 (8), 300 (3), 302 (3), 310 (4), 326 (5), 328 (5), 377 (3),
(12), 642 (17), 643 (6), 646 (5), 652 (5), 654 (10,
M ꢀ NO þ MeOH þ 2H O), 655 (5), 656 (5). Anal.
ꢀ
3
2
Calcd for C H Br CrN O : C, 44.46; H, 4.04; N, 6.48.
5
24
26
2
3
Found: C, 41.92; H, 3.54; N, 4.83.

1352
E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
0
5
.6.11. [(R,R)-())-N,N -Bis(3-bromo-5-ethylsalicylidene)-
1518, 1449 (s), 1393, 1362 (w), 1257, 1165, 837, 740, 548;
MS (ES) m=z (% relative intensity) (all peaks >3%): 638
trans-cyclohexane-1,2-diamine chromium(III)] hexaflu-
orophosphate 3d . Compound 1d (718 mg, 1.15 mmol),
gave a brown powder (630 mg, 75%). Mp dec >275 °C;
ꢀ
(4), 640 (58), 641 (23), 642 (100, M ꢀ PF ), 643 (42),
6
644 (55), 645 (19), 646 (5), 671 (12), 672 (5), 673 (21,
M ꢀ PF
ꢀ
1
ꢀ
IR (cm ): 2961, 2933, 2861, 1630 (s, C@N), 1524, 1448,
6
þ MeO), 674 (7), 675 (7), 718 (19), 719 (8),
ꢀ
1
relative intensity) (all peaks >3%): 310 (7), 314 (5), 316
391, 1311, 1225, 1147, 872, 854, 796, 551; MS (ES) (%
720 (33, M ꢀ PF þ MeOH þ 2Na), 721 (15), 722 (20),
6
ꢀ
723 (6), 749 (3), 751 (6, M ꢀ PF
6
þ MeOH
ꢀ
(
(
4), 324 (3), 340 (5), 342 (5), 354 (3), 356 (3), 391 (4), 393
3), 506 (4), 507 (3), 508 (4), 539 (7), 569 (15), 570 (7),
þ 2Na þ MeO), 753 (3), 796 (3), 798 (6, M ꢀ PF
6
þ 2(MeOH þ 2Na)), 800 (3). Anal. Calcd for C H Br -
28
34
2
ꢀ
571 (28, M ꢀ PF
5
5
6
ꢀ CH
3
), 572 (12), 573 (13), 574 (7),
ꢀ
CrF
H, 4.75; N, 3.39.
6 2 2
N O P: C, 42.71; H, 4.35; N, 3.56. Found: C, 43.36;
82 (4), 583 (3), 584 (57), 585 (27), 586 (100, M ꢀ PF
6
),
87 (41), 588 (54), 589 (19), 590 (5), 600 (6), 601 (5), 602
ꢀ
(
7, M ꢀ PF6 þ O), 603 (5), 604 (4), 605 (3), 615 (14),
ꢀ
6
6
3
3
16 (9), 617 (23, M ꢀ PF
6
þ OMe), 618 (5), 619 (13),
0
5
.6.15. (R,R)-())-N,N -Bis(3-bromo-5-methoxysalicylid-
2 6 2 2
20 (3). Anal. Calcd for C24H26Br CrF N O P: C,
ene)-trans-cyclohexane-1,2-diamine chromium(III) chlo-
ride 1f. Compound 6f (0.500 g, 0.925 mmol) gave brown
precipitates (205 mg, 35% and 136 mg, 23%). Total
9.42; H, 3.58; N, 3.83. Found: C, 41.47; H, 3.80; N,
.91.
ꢀ
1
yield ¼ 58%. Mp dec >340 °C; IR (cm ): 3442, 2934,
2
1
854, 1629 (s, C@N), 1535, 1454, 1435, 1392, 1335, 1307,
279, 1222, 1137, 1040, 854, 808, 737, 671, 550, 470; MS
0
5
.6.12. [(R,R)-())-N,N -Bis(3-bromo-5-tert butylsalicylid-
ene)-trans-cyclohexane-1,2-diamine chromium(III)] chlo-
ride 1e. No initial precipitate was obtained. Compound
(ES) m=z (% relative intensity) (all peaks >3%): 286 (17),
3
4
12 (3), 394 (3), 422 (5), 424 (3), 450 (3), 465 (5), 467 (5),
68 (3), 532 (4), 545 (3), 547 (6), 549 (3), 560 (3), 573
6e (1.53 g, 2.58 mmol) gave a brown solid (1.60 g, 91%)
after concentration of the homogeneous reaction solu-
tion. Mp dec >300 °C; IR (cm ): 2952, 2861, 1628 (s,
C@N) 1516, 1449, 1392, 1362, 1310, 1257, 1234, 1206,
164, 1129, 1028, 876, 856, 837, 740, 718, 546; MS
ꢀ
(
5
13), 574 (5), 575 (28, M ꢀ Cl ꢀ CH ), 576 (9), 577 (15),
3
ꢀ
1
78 (4), 586 (3), 587 (3), 588 (55), 589 (27), 590 (100,
ꢀ
M ꢀ Cl ), 591 (39), 592 (55), 593 (20), 594 (5), 619 (11),
1
ꢀ
6
20 (6), 621 (20, M ꢀ Cl þ OMe), 622 (7), 623 (10), 624
(
(
(
(
(
(
(
ES)m=z (% relative intensity) (all peaks >3%): 638
ꢀ
(
3), 644 (3, M ꢀ Cl þ OMe þ Na), 646 (3). Anal. Calcd
ꢀ
3), 640 (51), 641 (21), 642 (100, M ꢀ Cl ), 643 (37), 644
for C22
Found: C, 41.65; H, 4.16; N, 3.39.
2 2 4
H22Br ClCrN O : C, 42.23; H, 3.54; N, 4.48.
51), 645 (19), 646 (5), 671 (11), 672 (5), 673
18, M ꢀ Cl þ MeO), 674 (8), 675 (7), 676 (3), 696
ꢀ
ꢀ
ꢀ
3, M ꢀ Cl þ MeO þ Na), 718 (17), 719 (7), 720
33, M ꢀ Cl þ MeOH þ 2Na), 721 (12), 722 (18), 723
0
5
.6.16. [(R,R)-())-N,N -Bis(3-bromo-5-methoxysalicylid-
6), 724 (3), 749 (3), 750 (3), 751 (5,
ꢀ
ene)-trans-cyclohexane-1,2-diamine chromium(III)] ni-
trate 2f. Compound 1f (151 mg, 0.241 mmol) gave a
M ꢀ Cl þ MeOH þ 2Naþ MeO), 752 (3), 753 (3), 796
ꢀ
(
(
5
3), 798 (7, M ꢀ Cl þ 2(MeOH þ 2Na)), 799 (3), 800
ꢀ
1
brown solid (118 mg, 75%). Mp dec >210 °C; IR (cm ):
4). Anal. Calcd for C28
H
.06; N, 4.13. Found: C, 44.28; H, 4.88; N, 3.46.
34Br
2
ClCrN
2 2
O : C, 49.61; H,
3
1
448, 2933, 2854, 1628 (s, C@N), 1535, 1455, 1435, 1372,
337, 1309, 1226, 1139, 1053, 854, 808, 634; (ES)m=z
(
% relative intensity) (all peaks >3%): 424 (3), 547 (3),
ꢀ CH
ꢀ
0
573 (12), 574 (4), 575 (22, M ꢀ NO
3
3
), 576 (7),
5
.6.13. [(R,R)-())-N,N -Bis(3-bromo-5-tert-butylsalicy-
5
77 (11), 578 (4), 586 (3), 587 (4), 588 (55), 589 (26), 590
lidene)-trans-cyclohexane-1,2-diamine chromium(III)]
nitrate 2e. Compound 1e (739 mg, 1.09 mmol) gave a
ꢀ
(
100, M ꢀ NO ), 591 (42), 592 (49), 593 (19), 594 (6),
3
ꢀ
ꢀ
1
606 (3), 607 (3, M ꢀ NO
3
þ OH), 619 (11), 620 (3), 621
brown solid (643 mg, 84%). Mp dec >300 °C; IR (cm ):
ꢀ
(
19, M ꢀ NO
3
þ OMe), 622 (6), 623 (7), 624 (3), 644 (8,
2956, 2864, 1628 (s, C@N), 1518, 1449, 1385, 1362, 1310,
1258, 1235, 1207, 1165, 1129, 1028, 878, 856, 837, 740,
719, 549; MS (ES) m=z (% relative intensity) (all
ꢀ
M ꢀ NO þ OMe þ Na), 646 (3), 653 (3), 666 (11), 668
3
ꢀ
(
(
22, M ꢀ NO þ MeOH þ 2Na), 670 (11), 744 (3), 746
3
ꢀ
7, M ꢀ NO
3
þ 2(MeOH þ 2Na)), 747 (4), 748 (4).
2 3 7
peaks >3%): 638 (4), 640 (56), 641 (22), 642 (100,
ꢀ
Anal. Calcd for C22H22Br CrN O : C, 40.51; H, 3.40; N,
6.44. Found: C, 38.87; H, 3.64; N, 5.51.
M ꢀ NO
3
), 643 (40), 644 (52), 645 (20), 646 (5),
ꢀ
6
6
71 (10), 672 (4), 673 (11, M ꢀ NO
3
þ MeO), 674 (6),
75
(8),
718
(18),
719
(7),
720 (32,
ꢀ
M ꢀ NO þ MeOH þ 2Na), 721 (13), 722 (20), 723 (5),
3
ꢀ
0
7
(
(
49 (3), 751 (6, M ꢀ NO
3
þ MeOH þ 2Na þ MeO), 752
5.6.17. [(R,R)-())-N,N -Bis(3-bromo-5-methoxysalicylid-
ꢀ
3), 796 (3), 798 (5, M ꢀ NO þ 2(MeOH þ 2Na)), 800
ene)-trans-cyclohexane-1,2-diamine chromium(III)] hexa-
fluorophosphate 3f. Compound 1f (100 mg, 0.160 mmol)
gave a brown solid (60 mg, 51%). Mp dec >270 °C; IR
3
3). Anal. Calcd for C H Br CrN O : C, 47.74; H,
28
34
2
3
5
4
.87; N, 5.97. Found: C, 45.37; H, 4.59; N, 5.17.
ꢀ
1
(
cm ): 3447, 2940, 2860, 1631 (s, C@N), 1537, 1456,
1
434, 1391, 1335, 1225, 1140, 1052, 844, 809, 558; MS
0
5
idene)-trans-cyclohexane-1,2-diamine
.6.14. [(R,R)-())-N,N -Bis(3-bromo-5-tert-butylsalicyl-
(ES) m=z (% relative intensity) (all peaks >3%): 312 (3),
424 (3), 547 (4), 573 (13), 574 (4), 575 (21,
chromium(III)]
ꢀ
hexafluorophosphate 3e. Compound 1e (792 mg,
.17 mmol) gave a brown solid (751 mg, 82%). Mp
M ꢀ PF ꢀ CH ), 576 (7), 577 (11), 578 (5), 586 (5), 588
6
3
ꢀ
1
(52), 589 (24), 590 (100, M ꢀ PF ), 591 (42), 592 (49),
6
ꢀ
1
dec >300 °C; IR (cm ): 2960 (s), 2866, 1631 (s, C@N),
593 (19), 594 (5), 619 (12), 620 (5), 621 (18,

E. M. McGarrigle et al. / Tetrahedron: Asymmetry 15 (2004) 1343–1354
1353
ꢀ
ꢀ
M ꢀ PF
6
6
þ OMe), 622 (7), 623 (8), 624 (3), 668 (6,
þ MeOH þ 2Na) 670 (3). Anal. Calcd for
5.7.3.2. Yield determinations. The compositions of the
reaction mixtures were determined by comparison of
individual peak areas to the peak area due to n-decane,
the internal standard. GC analysis of authentic samples
of possible products and by-products confirmed that the
components of a typical chromium-mediated epoxida-
tion of trans-b-methlystyrene were: the alkene and
epoxide, iodobenzene, benzaldehyde and phenylacetone.
The relative burn ratios of each of these were calculated
by injecting 1 lL samples of solutions of known com-
position. The values determined were trans-b-methly-
styrene oxide (1.41), trans-b-methylstyrene (1.09),
iodobenzene (1.54), benzaldehyde (1.30) and phenylac-
etone (1.12). All yields were calculated using these
ratios.
M ꢀ PF
C H Br CrF N O P: C, 35.94; H, 3.02; N, 3.81.
4
22
22
2
6
2
Found: C, 34.11; H, 3.40; N, 2.98.
5
5
.7. Asymmetric epoxidation of alkenes
.7.1. Preliminary notes. Iodosylbenzene was synthesised
67
using the procedure of Saltzmann and Sharefkin. (ꢁ)-
(
E)-methlystyrene oxide was synthesised by reacting
trans-b-methylstyrene with mCPBA. CAUTION: There
is evidence that chromium(III)(salen) and oxo-chro-
mium(V)(salen) complexes are genotoxic and carcino-
genic and thus due care should be taken to avoid
65
contact.
5.7.3.3. Determination of absolute configurations. The
absolute configuration of trans-b-methlystyrene oxide
was assigned by comparison with the data of Witkop and
68
69
5
.7.2. Procedure for stoichiometric epoxidations with
Foltz and of Shi et al. On the cyclodextrin-a column
the (R,R)-trans-b-methlystyrene oxide eluted after the
(S,S)-isomer.
þ
OCr(salen) . Iodosylbenzene (1.5 equiv) was added to a
solution of the chromium salen complex (30 mg, 1 equiv)
in acetonitrile (4 mL) and the mixture stirred for 30 min.
A deep green-black colour developed rapidly. The
mixture was then filtered through a cotton wool-plugged
Pasteur pipette, to remove excess iodosylbenzene, into a
Acknowledgements
1
0 mL RB, which contained the donor ligand (1 equiv),
if required. An additional 2 mL of acetonitrile was used
as washings. The solution was stirred for 30 min in an
ice/water bath to cool it to 0 °C. The alkene substrate
We thank Enterprise Ireland (Grants SC/93/213, SC/94/
569 and SC/97/536, Scholarship for EMM) University
College Dublin for Demonstratorship (E.M.M.) and
Swords Laboratories Ltd (Bristol Myers Squibb) for a
Scholarship (E.M.M.).
(
typically 5–10 lL, 1 equiv unless stated) was then added
by microlitre syringe. The reaction was stirred at 0 °C
until the brown colour of the original complex was
adjudged to have returned (reaction times varied from
1
h to overnight). The solvent was removed in vacuo and
the residue washed onto a short alumina pad (sometimes
in a Pasteur pipette) using Et O (50 mL) as eluent. This
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