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nary stereocenter[19] as the reac-
tion of tert-butyl 2-oxocyclopen-
tane-1-carboxylate with 2-acyl
imidazole 9a afforded (S,S)-16 in
85% yield, with 96% ee, and
1.5:1 d.r.. The related Michael
addition of 2,3-dihydro-1-oxo-
1H-indene-2-carboxylic acid tert-
butyl ester to 2-acyl imidazole
9a provided (S,S)-17 in 93%
yield with 97% ee and 22:1 d.r..
As found for the Friedel–Crafts
reactions, the stereoselectivity of
the related catalyst L-IrO was
generally slightly lower.
Table 1. Friedel–Crafts alkylation with a,b-unsaturated 2-acyl imidazoles: Effects of substituents, catalyst load-
ing, and temperature.[a]
Substrate
Product
Cat. loading [mol%]
2.0
T [8C]
t [h]
66
Yield [%][b]
ee [%][c]
R=Me (9a)
(S)-11 a
RT
30
40
50
60
40
40
40
40
97
99
48
25
<20
5
94
99
95 (83)[d]
99
99 (99)[d]
98
96
98
0.5
2.0
2.0
2.0
32
18
24
48
96
99
95
81
98
99
99
96
R=Ph (9b)
R=CO2Et (9c)
R=nBu (9d)
(R)-11 b
(S)-11 c
(S)-11 d
[a] Reaction conditions: 2-acyl imidazoles 9a–d (0.20 mmol), 3-dimethylaminoanisole (0.60 mol), THF (0.1 mL).
[b] Isolated yields. [c] Enantiomeric excess determined by HPLC analysis on chiral stationary phase. [d] Yield
and enantioselectivity for the analogous reaction performed under air shown in brackets.
Asymmetric cycloadditions
We next investigated cycloaddi-
tions with a,b-unsaturated 2-acyl
11 a from room temperature to 608C leads to full conversion
in just 5 h with only a slightly diminished enantioselectivity of
98% ee (Table 1). Interestingly, the reaction is insensitive to air
(Table 1). It is also noteworthy that the catalyst loading can be
decreased for this reaction to 0.5 mol% and that the acyl imi-
dazole substrates 9b–d also provide the respective Friedel–
Crafts alkylation products (R)-11 b, (S)-11 c, and (S)-11 d with
high enantioselectivities (Table 1).
imidazoles (Figure 4). Accordingly, the reaction of 9a with the
nitrone 18 catalyzed by 2.0 mol% of L-IrS provided the 1,3-di-
polar cycloaddition product 19 in a yield of 86% and with ex-
cellent 98% ee, while virtually forming just one diastereomer
(endo/exo>100:1).[20,21] The enantioselectivity was significantly
lower using L-IrO (92% ee). In contrast, for the hetero-Diels–
Alder reaction between 9a or 9e with 2,3-dihydrofurane under
formation of the dihydropyrans 20 and 21, respectively, L-IrO
(2 mol%) turned out to be the catalyst of choice, providing
high diastereo- and enantioselectivities.[22,23] At last, the Diels-
Alder reaction of 9a with isoprene provided the desired prod-
uct 22 with high enantio- and diastereoselectivity.[24]
Asymmetric Michael additions
Next, we investigated the addition of CH-acidic malonodinitrile
and 1,3-dicarbonyl compounds to the Michael acceptor 9a as
shown in Figure 3. By using L-IrS at a loading of 1.0 or
2.0 mol%, the malonodinitrile[18] addition product (S)-14 was
formed in a yield of 95% with 90% ee and the Meldrum’s acid
addition product (S)-15 in a yield of 94% with 91% ee. L-IrS is
also suitable to catalyze the formation of an all-carbon quater-
Scope of acceptor-substituted alkenes
After we revealed that IrO and IrS catalyze the asymmetric
conjugate addition of a wide variety of nucleophiles to a,b-un-
saturated 2-acyl imidazoles, we next investigated the scope
with respect to acceptor substituted alkenes and
used the enantioselective Friedel–Crafts alkylation
with 3-dimethylaminoanisole as our model reaction
(Figure 5). We were pleased to find that a significant
number of the tested acceptor-substituted alkenes
9 f–p[15a,b,25–33] proved to be suitable substrates, pro-
viding the expected products in high yields and high
enantioselectivities, such as the benzimidazole 9 f
(86% yield, 96% ee),[25] 2-thiazole 9g (99% yield,
98% ee),[26] pyridine 9h (87% yield, 97% ee),[27] pyra-
zoles 9k (86% yield, 98% ee), and 9l (99% yield,
95% ee),[30] and a-ketoester 9n (99% yield,
95% ee).[32] Apparently, only substrates that can effi-
ciently coordinate to the iridium catalyst in a biden-
tate fashion give satisfactory results, whereas the
simple a,b-unsaturated carboxylic ester 9p does not
afford any product even at higher catalyst loadings
Figure 3. Chiral octahedral iridium(III) Lewis acid catalysis applied to Michael additions
with a,b-unsaturated 2-acyl imidazole 9a. [a] Reaction performed at 408C instead of
room temperature.
of 5 mol% and an elevated temperature of 608C. On
the other hand, we do not have an explanation for
Chem. Eur. J. 2015, 21, 9720 – 9726
9722
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