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.
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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