Amidation of silyl enol ethers and cholesteryl acetates with chiral ruthenium(II) Schiff-base catalysts: Catalytic and enantioselective studies

Article abstract of DOI:10.1039/b109272c

Chiral ruthenium(II)-salen complexes [Ru^II(salen)(PPh₃)₂] catalyse asymmetric aziridination of alkenes with up to 83% ees, asymmetric amidation of silyl enol ethers with up to 97% ees, and allylic amidation of cholesteryl

Full text of DOI:10.1039/b109272c

Amidation of silyl enol ethers and cholesteryl acetates with chiral
ruthenium(II) Schiff-base catalysts: catalytic and enantioselective studies†
Jiang-Lin Liang,ab Xiao-Qi Yuab and Chi-Ming Che*ab
a Department of Chemistry and Open Laboratory of Chemical Biology of The Institute of Molecular
Technology for Drug Discovery and Synthesis‡, The University of Hong Kong, Pokfulam Road, Hong
Kong. E-mail: cmche@hku.hk
b Shanghai-Hong Kong Joint laboratory on Chemical Synthesis, Shanghai Institute of Organic Chemistry,
Shanghai, China
Received (in Cambridge, UK) 16th October 2001, Accepted 31st October 2001
First published as an Advance Article on the web 9th January 2002
Chiral ruthenium(II)–salen complexes [RuII(salen)(PPh3)2]
catalyse asymmetric aziridination of alkenes with up to 83%
ees, asymmetric amidation of silyl enol ethers with up to 97%
ees, and allylic amidation of cholesteryl acetates with good
regioselectivity.
(1-cyclohexenyloxy)trimethylsilane with PhI = NTs was slow.
After 12 h reaction, all the PhI = NTs was consumed, but about
10% 2-[N-(p-tolylsulfonyl)amino]cyclohexanone (based on
starting substrate) was obtained.
Amino ketones are of importance in natural products, drugs,
and are useful building blocks for organic synthesis. To our
knowledge, there are two reports6,7 on asymmetric catalytic
amidation of silyl enol ethers to give a-amino ketones. In this
work, silyl enol ethers were chosen as substrates, and target
products were a-amino ketones. As shown in Table 1, the
conversions range from 23 to 92% when different substrates are
used. The best conversion was 92% with yield 73% for
amidation of (1-styrenyloxy)trimethylsilane catalysed by 2
Metal-catalysed aziridination and amidation of hydrocarbons
offer useful means for the synthesis of aziridines, amides, and
amines.1 In contrast to the numerous studies on asymmetric
organic oxidations, asymmetric C–N bond formations, partic-
ularly those involving amidation of C–H bonds, are less
developed. Recent studies by us1 and others2 demonstrated the
usefulness of chiral metalloporphyrin catalysts for asymmetric
nitrene transfer reactions. However, the reported ee values are
moderate. Because synthesis of chiral porphyrin ligands
requires tedious steps, improvement of ee through structural
modification of chiral metalloporphyrin catalysts would be a
difficult task. In this context, we turn our attention to salen
ligands, which are easily synthesised and modified. Jacobsen3
Table 1 Asymmetric amidation of silyl enol ethers and aziridination of
alkenes catalysed by RuII–salen complexesa
Sub-
Entry strates
Con-
Catalyst version
Products
Yieldb
Eec
and Katsuki4 have reported chiral Cu(
) and Mn(III) salen
I
1
1
1
1
1
1
2
3
28
15
22
23
40
25
23
78
71
75
75
75
74
75
74
24
50
16
79
71
97
complexes for asymmetric alkene aziridination and amidation
of saturated hydrocarbons. Because high valent ruthenium–
tosylimido complexes are reactive,5 we envision that chiral
ruthenium–salen complexes should hold promising prospects in
developing new catalysts for enantioselective C–N bond
formation. We describe here the aziridination of alkenes and
amidation of silyl enol ethers and cholesteryl acetates catalysed
by chiral ruthenium(II)–salen complexes.
2d
3e
4f
5g
6
7
8
9
10
1
2
3
41
43
27
72
73
73
—
—
—
The catalysts 1–3 were obtained in high yields ( ~ 80%) by
reacting the H2 salen ligands with [RuII(PPh3)3Cl2] in ethanol.§
11
12
13
1
2
3
23
25
37
76
72
85
59
29
66
14
15
16
1
2
3
53
60
47
75
74
73
33
58
74
17
18
19
1
2
3
52
56
40
76
83
73
14h
10h
58h
They are effective catalysts for asymmetric amidation of silyl
enol ethers and aziridination of alkenes using PhI = NTs as
nitrogen source. The results obtained for a series of substrates
are summarised in Table 1. Using (1-cyclohexenyloxy)trime-
thylsilane as substrate and 12.5 mol% of complex 1 (based on
substrate) as catalyst, all the conversion, yield and ee values
were improved when dichloromethane was the solvent (entries
1, 2 and 3). When only 5 mol% catalyst was used, the ee value
decreased from 74% (entry 1) to 16 % (entry 4), and when
catalyst loading was 20 mol%, the ee value slightly increased
(79%, entry 5). In absence of catalyst, the reaction of
20
21
1
2
74
92
73
73
—
—
22
23
24
1
2
3
34
30
31
68
74
74
83
42
19
25
26
27
1
2
3
46
31
31
84
74
75
45
51
19
a Reaction conditions: catalyst+substrate+PhINNTs = 1+8+12 (molar ratio),
rt, 2 h, CH2Cl2.b Yield (%) based on substrate consumed.c Ee (%)
determined by HPLC using chiral whelk-ol column.d Acetonitrile as
solvent.e Benzene as solvent.f 5% catalyst was added.g 20% catalyst was
added.h Determiend by HPLC using chiral OJ column.
† Electronic supplementary information (ESI) available: experimental
details. See http://www.rsc.org/suppdata/cc/b1/b109272c/
‡ Area of Excellence Scheme (AoE/P-10/01), University Grants Committee
of the Hong Kong Special Administrative Region, China.
124
CHEM. COMMUN., 2002, 124–125
This journal is © The Royal Society of Chemistry 2002

View Online
Table 2 Allylic amidation of cholesteryl acetate catalysed by RuII–salen complexesa
c
Entry
Catalyst
Conversion
Yield (%)b
Ratio of b/a
1
2
3
1
2
3
24
26
28
73
74
71
1.6+1
2.3+1
1.1+1
a Reaction conditions: catalyst+substrate+PhINNTs = 1+8+12 (molar ratio), rt, 2 h, CH2Cl2.b Yield based on substrate consumed.c Ratio was determined by
1H NMR.
(entry 21). For [1-(4A-methyl)cyclohexenyloxy]trimethylsilane,
Notes and references
§ General procedure for ruthenium-catalysed asymmetric aziridina-
tion and amidation with PhI = NTs. A solution of substrate (0.16 mmol)
in dry dichloromethane (4 mL) was added through syringe to a Schlenk flask
(1-naphthalenyloxy)trimethylsilane, and (1-cyclopentenyloxy-
)trimethylsilane, the ee values are moderate to good with 3 as
catalyst. Notably, the amidation of (1-cyclohexenyloxy)trime-
thylsilane catalysed by 3 afforded 97% ee, which represents the
containing ruthenium catalyst (0.02 mmol) and molecular sieves (4 Å, 150
highest ee value reported for such a reaction.6,7 The amidation
mg). The mixture was stirred at rt for 10 min, then treated with PhI = NTs
of
D
(+)-camphor trimethylsilyl enol ether gave only endo-
(0.24 mmol) for 2 h. The molecular sieves were filtered and washed with
DCM. The filtrate and washings were evaporated to dryness and the solid
was purified by column chromatography (silica gel, 230–400 mesh; n-
hexane+EtOAc = 4+1 as eluent).1 FAB-MS: m/z 1126 [M]+, 864 [M 2
PPh3]+; Calcd. for C56H46N6O10P2Ru·4H2O C 56.14, H 4.54, N 7.01; found:
amino ketone, and the exo product was undetectable.
The aziridination of indene and chromene has also been
investigated. The conversion is moderate (30–46%), and yield is
good (68–84%). The ee values range from 19 to 83%. The
highest ee of 83% was found with 1. Unlike the amidation of
silyl enol ethers, 3 gave low ee values in aziridination of indene
and chromene. When cis-ß-methylstyrene was used as substrate
with 2 as catalyst, the cis aziridine was the main product
(conversion 24%, yield 73%) with the molar ratio of cis to trans
aziridines being 84+16, showing that a stepwise pathway
analogous to that proposed by Mansuy and co-workers8 should
be operative for the aziridination. The reaction is almost non-
enantioselective (ee ~ 2%), in sharp contrast to related
rhodium-catalysed aziridination reported by Muller (73%).9
Amino steroids have been shown to have noteworthy
pharmacological activity, for instance, as anesthetics and
enzyme inhibitors on the central nervous system.10 Dodd and
Dauban11 demonstrated the copper-catalysed aziridination of
11-pregnene-3,20-dione in 53% yield with PhI = NSes (Ses =
2-(trimethylsilyl)ethanesulfonyl). Breslow12 reported the ami-
dation of equilenin acetate with PhI = NTs catalysed by
[Mn(TPFPP)Cl] (TPFPP = meso-tetrakis(pentafluorophenyl-
)porphyrinato dianion) in 47% yield. In this work, we reported
the first amidation of steroids such as cholesteryl acetate by
PhI = NTs with metal salen catalysts. As shown in Table 2, the
catalysts exhibited good regioselectivity as the amidation only
occurred at the 7-substituted position of the cholesteryl ring, and
there was no 4-site amidation or 5,6-site aziridination product.
The amidation products have two isomers with a and b
configurations (the spectral data of the a isomer are identical
with those reported in the literature13), respectively. Catalyst 2
showed the best b selectivity with a b+a ratio of 2.3 +1 (Table
2, entry 2).
1
C 56.08, H 4.25, N 6.74%. H NMR (CDCl3) d 8.31 (d, 2H, J = 3 Hz,
CH = N), 7.10–7.40 (m, 34H, Ar-H), 3.15 (2H, m, CH-N), 1.2–2.6 (6H, m,
CH2); 31P NMR (CDCl3) d 31.06.2 FAB-MS: m/z 1450 [M]+, 1188 [M 2
PPh3]+, 926 [M 2 2PPh3]+; Calcd. for C56H46I4N2O2P2Ru·0.5C6H14: C
47.47, H 3.58, N 1.88; found: C 47.02, H 3.55, N 1.45%; 1H NMR (CDCl3)
d 8.02 (d, 2H, J = 2.2 Hz, CH = N), 6.80–7.60 (m, 34H, Ar-H), 3.77 (2H,
m, CH-N), 1.2–2.6 (6H, m, CH2); 31P NMR (CDCl3) d 29.57.3 FAB-MS: m/
z 1262 [M]+, 1000 [M 2 PPh3]+, 738 [M 2 2PPh3]+; 1H NMR (CDCl3) d
7.86 (d, 2H, J = 2.1 Hz, CH = N), 6.80–7.51 (m, 34H, Ar-H), 3.68 (2H, m,
CH-N), 1.2–2.6 (6H, m, CH2); 31P NMR (CDCl3) d 29.56.
1 (a) T.-S. Lai, H.-L. Kwong, C.-M. Che and S.-M. Peng, Chem.
Commun., 1997, 2373; (b) X.-G. Zhou, X.-Q. Yu, J.-S. Huang and C.-
M. Che, Chem. Commun., 1999, 2377; (c) S.-M. Au, J.-S. Huang, C.-M.
Che and W.-Y. Yu, J. Org. Chem., 2000, 65, 7858.
2 J.-P. Simonato, J. Pecaut, W. R. Scheidt and J.-C. Marchon, Chem.
Commun., 1999, 989.
3 Z. Li, K. R. Conser and E. N. Jacobsen, J. Am. Chem. Soc., 1993, 115,
5326.
4 Y. Kohmura and T. Katsuki, Tetrahedron Lett., 2001, 42, 3339.
5 S.-M. Au, J.-S. Huang, W.-Y. Yu, W.-H. Fung and C.-M. Che, J. Am.
Chem. Soc., 1999, 121, 9120.
6 P. Phukan and A. Sudalai, Tetrahedron Asymmetry, 1998, 9, 1001.
7 W. Adam, K. J. Roschmann and C. R. Saha-Moller, Eur. J. Org. Chem.,
2000, 557.
8 J. P. Mahy, G. Bedi, P. Battioni and D. Mansuy, J. Chem. Soc., Perkin
Trans. 2, 1988, 1517.
9 P. Muller, C. Baud and Y. Jacquier, Can. J. Chem, 1998, 76, 738.
10 M. Gasior, R. B. Carter and J. M. Witkin, Trends Pharmacol. Sci., 1999,
20, 107.
11 P. H. D. Chenna, P. Dauban, A. Ghini, G. Burton and R. H. Dodd,
Tetrahedron Lett., 2000, 41, 7041.
12 J. Yang, R. Weinberg and R. Breslow, Chem. Commun., 2000, 531.
13 D. H. R. Barton, R. S. Hay-Motherwell and W. B. Motherwell, J. Chem.
Soc., Perkin Trans. 1, 1983, 445.
We acknowledge support from the Hong Kong Research
Grants Council (HKU 7096/97P and HKU 7099/00P), Generic
Drug Program of the University of Hong Kong.
CHEM. COMMUN., 2002, 124–125
125