Enantioselective epoxidation of chromenes using chiral Mn(III) salen catalysts with built-in phase-transfer capability

Article abstract of DOI:10.1016/S0040-4039(02)00112-0

New chiral Mn(III) salen epoxidation catalysts 1 and 2 (a catalyst loading in the range of 2.0-0.4 mol%) have been investigated for enantioselective epoxidation of chromene derivatives to chromene epoxides using pyridine N-oxide as a proximal ligand with excellent conversions and chiral induction.

Full text of DOI:10.1016/S0040-4039(02)00112-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2665–2668
Enantioselective epoxidation of chromenes using chiral Mn(III)
salen catalysts with built-in phase-transfer capability
Rukhsana I. Kureshy,* Noor-ul H. Khan, Sayed H. R. Abdi, Sunil T. Patel, Parameswar K. Iyer
and Raksh V. Jasra
Silicates and Catalysis Discipline, Central Salt and Marine Chemicals Research Institute, Bhavnagar 364 002, India
Received 23 October 2001; revised 18 December 2001; accepted 14 January 2002
Abstract—New chiral Mn(III) salen epoxidation catalysts 1 and 2 (a catalyst loading in the range of 2.0–0.4 mol%) have been
investigated for enantioselective epoxidation of chromene derivatives to chromene epoxides using pyridine N-oxide as a proximal
ligand with excellent conversions and chiral induction. © 2002 Elsevier Science Ltd. All rights reserved.
The design of a new chiral metal catalyst for enantiose-
lective epoxidation of alkenes constitutes an important
strategy for the synthesis of chiral pharmaceuticals and
dioctylamine (b), to give 2-hydroxy-3-t-butyl-5-(N,N-
dioctylmethylene)benzaldehyde hydrochloride 5. Com-
pound 5 on condensation with 1S,2S-(+)-cyclohexa-
nediamine and 1R,2R-(+)-diphenyldiamine in a 2:1
molar ratio gave ligands 6 and 7, respectively. Finally,
ligands 6 and 7 were complexed with manganese to give
chloro - (S,S) - [[2,2%] - (1,2 - cyclohexanediyl)bis(nitrilo-
methylidyne)]bis[4 - (methylene - N,N% - dioctylamino) - 6-
1
fine chemicals. Among several catalytic methods, chiral
Mn(III) salen complexes have been reported to give
high enantioselectivity in the epoxidation of non-func-
tionalised cis or cyclic alkenes using NaOCl as oxidant
2
under biphasic reaction conditions. Furthermore, it
3
has been observed that the use of N-oxides, specifically
(
(
1,1 - dimethylethyl)phenolato] - [N,N%,O,O%]manganese-
III) 1 and chloro-(R,R)-[[2,2%]-(1,2-diphenyl-1,2-ethane-
4
4
-phenyl pyridine N-oxide (PPNO) and 4-phenyl-
5
propyl pyridine N-oxide, (PPPNO) as proximal ligand
not only stabilises the catalytically active intermediate
species Mn(V)-oxo, but also act as phase-transfer
reagents. Although, PPNO and PPPNO have imparted
the best results, these are expensive and get degraded
under the reaction conditions. In the present study, we
report the new chiral Mn(III) salen complexes 1 and 2
with built-in phase-transfer capability due to the meth-
ylene aminoalkyl groups at the 5,5%-positions of the
substituted salicylaldehyde moiety so that simple N-
oxides can be used effectively. With these new catalysts,
chromene and substituted chromenes were used as
model substrates as their epoxides are useful in the
synthesis of selective potassium channel activator
diyl)bis(nitrilomethylidyne)]bis[4-(methylene-N,N-dio-
ctylamino)-6-(1,1-dimethylethyl)phenolato]-[N,N%,O,O%]-
manganese(III) 2, respectively.
Asymmetric epoxidation reactions were performed with
2
mol% of the complexes 1 and 2 with 2,2-dimethyl-
chromene, 6-cyano-2,2-dimethylchromene, 6-methoxy-
,2-dimethylchromene and spiro[cyclohexane-1,2%-[2H]-
2
10
[
1]chromene] as substrates in dichloromethane using
buffered NaOCl (pH 11.3) as the oxidant at 0°C in the
presence of pyridine N-oxide as a proximal ligand. As
shown in Table 1, high conversions (>99%) were
obtained with all chromenes (entries 1–8) in 3.5–9.5 h,
using the complexes 1 and 2. Both catalysts gave 98–
99% chiral induction with 6-cyano-2,2-dimethyl-
chromene (entries 3 and 4). Catalyst 2 gave a lower ee
6
drugs. The complexes were prepared as shown in
Scheme 1. Thus, in a stepwise manner, 3-t-butyl salicyl-
7
aldehyde was chloromethylated (a), and reacted with
(
65%) for 6-methoxy-2,2-dimethylchromene (entry 6)
and moderate ee’s for spiro[cyclohexane-1,2%-
2H][1]chromene] (entry 8) and 2,2-dimethylchromene
entry 2) while the ee’s were better in the case of
[
(
Keywords: Mn(III) salen; chiral; epoxidation; chromene; phase trans-
fer.
*
Corresponding author. Fax: +91-0278-566970; e-mail: salt@
catalyst 1 (81–87%) (entries 1, 5 and 7). Overall, cata-
lyst 1 seems to be better than the catalyst 2.
csir.res.in
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00112-0

2
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R. I. Kureshy et al. / Tetrahedron Letters 43 (2002) 2665–2668
Scheme 1. Reagents and conditions: (a) HCHO, conc. HCl, rt, 48 h, 97%; (b) N,N-dioctylamine, benzene, reflux, 6 h, 97%; (c)
8
a
(
8
1S,2S)-(+)-1,2-diaminocyclohexane, abs. EtOH, reflux, 7 h, 95%; (d) (1R,2R)-(+)-diphenyldiamine, abs. EtOH, reflux, 8 h,
8b
9a
3 2 2 2 3 2 2 2
6%; (e) (1) Mn(CH COO) ·4H O, EtOH, N , reflux, 7 h, (2) LiCl, rt, 4 h, 92%; (f) (1) Mn(CH COO) ·4H O, EtOH, N ,
9b
reflux, 8 h, (2) LiCl, rt, 4 h, 91%.
In all the catalytic runs where the catalyst 1 (S,S
configuration) was used the dominant enantiomer of
the product epoxides was S,S, whilst with catalyst 2
salicylaldehyde moiety of the catalyst. As a result the
transportation of HOCl to the organic phase as
required with Jacobsen’s catalyst, may not be neces-
5
11
(
R,R configuration), it was R,R. Jacobsen complex
sary with the present system. Moreover, 0.4 mol% of
catalyst 1 is sufficient to achieve similar conversion
and selectivity for cyanochromene within 10 h. Fur-
ther reduction in catalyst loading (0.2 mol%) caused a
reduction in the reaction rate with a decrease in the
ee value (92% in the case of the cyanochromene) in
20 h. Below 0.2 mol% of catalyst loading, the reac-
tion rate and selectivity deteriorated rapidly.
with 2 mol% catalyst loading gave 96% conversion
with 97% ee’s in 6-cyano-2,2-dimethylchromene in 9 h
(
with 10 mol% of 4-phenyl pyridine N-oxide). How-
ever, under similar reaction conditions, even with sim-
ple pyridine N-oxide, the complexes 1 and 2 take
only 6–6.5 h with >99% conversion and 98 and 99%
ee’s, respectively. It has been found that by replacing
the pyridine N-oxide with 10 mol% of 1,4-dioxane as
a proximal ligand under similar reaction conditions,
the reactivity and selectivity were comparable (epoxi-
dation of 6-cyano-2,2-dimethylchromene with conver-
sion >99%, ee’s >97%, time 8 h). This shows that
even water-soluble O-coordinating proximal ligands
are able to impart the requisite activity and selectivity
in the catalyst. This feature may be attributed to the
built-in phase-transfer capability in the catalytic sys-
tem created by way of introducing the N,N-dioctyl-
aminomethylene at the 5,5%-position of the substituted
In conclusion, we have developed new, efficient
Mn(III) salen complexes with a built-in phase-transfer
capability as epoxidation catalysts for chromene
derivatives. Excellent conversions were obtained with
all chromenes, but 98, 99% chiral induction was
1
obtained only with cyanochromene by H NMR and
HPLC. Furthermore, a catalyst loading of 0.4 mol%
under similar epoxidation conditions, works well with
some loss of activity, however, the ee’s remain unal-
tered.

R. I. Kureshy et al. / Tetrahedron Letters 43 (2002) 2665–2668
2667
Table 1. Data for the enantioselective epoxidations of chromene derivatives catalysed by complexes 1 and 2 with pyridine
N-oxide
Reactions conditions: catalyst (2 mol% in 1 ml CH Cl ), substrate (1.29 mmol), pyridine N-oxide (0.13 mmol), NaOCl (2.75 mmol).
2
2
a
b
c
Determined by GC.
By 1H NMR using the shift reagent (+)-Eu(hfc) /HPLC-Chiralcel OJ.
3
The configuration of the major enantiomer was determined by comparing the chemical shifts/retention time (using HPLC) with that of an
authentic sample of (3S,4S)-CN-chromene oxide. For other oxides, the absolute configuration was assigned by analogy to (3R,4R)-CN-
chromene oxide. In all the cases where catalyst 1 was used, the configuration of the product epoxides was 3S,4S whilst with catalyst 2, it was
3
R,4R.
Acknowledgements
6. Lee, N. H.; Muci, A. R.; Jacobsen, E. N. Tetrahedron
Lett. 1991, 38, 5055–5058.
R.I.K. would like to thank the DST for financial assis-
tance and also Dr. P. K. Ghosh, Director of the
Institute, for providing instrumentation facilities.
7. (a) White crystalline solid, mp 63–65°C; IR and NMR
data is in accordance with the reported data in Refs. 7b
and 7c; (b) Viscous oil, 96%. See: Minutolo, F.; Pini, D.;
Petri, A.; Salvadori, P. Tetrahedron: Asymmetry 1996, 7,
2
6
293–2302; (c) Yellow crystalline solid, yield 99% mp
2.2–62.9°C. See: Canali, L.; Cowan, E.; Deleuze, H.;
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8
3
1
996, 52, 12971–12978; (b) Sch u¨ rig, V.; Betschinger, F.
1
2
4.25, 13.66, 11.94, 9.48 (4 bs, 4H exchangeable), 8.42 (s,
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(
bs, 16H), 1.89 (bs, 8H), 1.38–1.43 (bs, 40H), 1.39 (s,
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−
1
2365, 1627, 1446, 1270, 1207, 1165, 899, 785 cm . Anal.
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62 110
2
4
2
Found: C, 73.46, H, 10.88; N, 5.49; (b) Mp 138–139°C;
1
H NMR (200 MHz, CDCl ): l 14.20, 12.18, 12.01,
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3
1
1.88, 9.43 (5bs, 4H exchangeable), 8.43 (s, 2H), 8.38 (s,
H), 7.98 (s, 2H), 7.31–7.22 (m, 10H), 4.17–4.14 (m, 2H),
.98–2.91 (bs, 20H), 1.82–1.71 (m, 40H), 1.37 (s, 18H),
.86 (t, J=6 Hz, 12H); IR (KBr): 3428, 2944, 2863, 2362,
2
2
0
1
−
1
625, 1442, 1276, 1206, 1164, 893, 785 cm . Anal. calcd
: C, 75.61; H, 10.08; N, 5.04. Found:
C, 75.57; H, 10.03; N, 5.02.
9. (a) Complex 1: Anal. calcd for C62
3
4
for C70H112Cl N O
2 4 2
. (a) Brandes, B. D.; Jacobsen, E. N. J. Org. Chem. 1994,
5
9, 4378–4380; (b) Brandes, B. D.; Jacobsen, E. N.
H
106ClMnN
4
O
; C,
2
Tetrahedron Lett. 1995, 36, 5123–5126.
72.34; H, 10.31; N, 5.45. Found: C, 72.36; H, 10.27; N,
5
. Senanayke, C. H.; Smith, G. B.; Fredenburgh, L. E.; Liu,
J.; Ryan, K. M.; Roberts, F. E.; Larsen, R. D.; Verho-
even, T. R.; Reider, P. J. Tetrahedron Lett. 1996, 37,
5.40. IR (KBr): wmax 3402, 2928, 2858, 1616, 1543, 1344,
−
1
1312, 1169, 830 cm ; UV–vis (MeOH): umax (m) 234
(6334), 260 (6244), 290 (4264), 404 (1332), 408 (1324); CD
umax Dm (CH Cl ): 284 (+8.8), 318 (+9.6), 414 (+5.3), 505
3
271–3274.
2
2

2
668
R. I. Kureshy et al. / Tetrahedron Letters 43 (2002) 2665–2668
+1.0), 623 (−1.0); [h] =+240 (c 0.104, CH Cl );
2
5
25
D
(
(CH Cl ): 440 (−2.5), 500 (+0.5), 625 (+4.2); [h] =
D
2
2
2
2
configuration (S); v (BM): 4.85; LM (MeOH): 3 mho
+123 (c 0.114, CH Cl ); configuration (R); v (BM):
eff.
2
2
eff.
−
1
−1
−1
−1
cm mol ; MS (FAB): m/z (1028); (b) Complex 2:
4.8; LM (MeOH): 3 mho cm mol ; MS (FAB): m/z
+
Anal. calcd for C H ClMnN O : C, 74.57; H, 9.59;
(1126) [Mn−Cl)]. .
70
108
4
2
N, 4.97. Found: C, 74.52; H, 9.54; N, 4.93. IR (KBr):
10. Bergmann, R.; Gericke, R. J. Med. Chem. 1990, 33,
492–504.
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Eur. J. 1996, 2, 974–980.
3
8
422, 2927, 2856, 1611, 1541, 1458, 1386, 1309, 1167,
−
1
51 cm ; UV–vis (MeOH): u
(m) 234 (7574), 266
max
(7322), 286 (6789), 304 (6967), 418 (3026); CD umax Dm