Full Paper
Scheme 2. Synthesis of complexes L-Rh-Cl and L-Rh1.
the precursor complex L-Rh-Cl (Scheme 2). Interestingly,
unlike the common chloro-bridged dimers, L-Rh-Cl features a
mononuclear structure. As shown in Figure 1, each RhIII ion is
Table 1. Optimization of the reaction conditions.[a]
Entry
Catalyst
Solvent
T [8C]
t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7[d]
8[d]
9[d]
10[d]
11[d]
12[d]
L-Rh1
L-Rh1
L-Rh1
L-Rh1
L-Rh1
L-Rh1
L-Rh1
L-Rh-Cl
L-Rh2
L-Rh3
L-Rh4
none
THF
32
32
32
32
32
32
50
50
50
50
50
50
36
36
36
36
36
36
48
48
48
48
48
48
60
trace
31
32
35
56
85
0
90
91
60
0
99
n.d.
99
99
99
99
98
n.d.
82
85
toluene
CH2Cl2
DCE
MeCN
dioxane
THF
THF
THF
THF
THF
Figure 1. Crystal structures of L-Rh-Cl (left) and L-Rh1 (right).[12] The hexa-
fluorophosphate counterions of L-Rh1 are omitted for clarity; ORTEP draw-
ing with thermal ellipsoids drawn at the 35% probability level.
five-coordinated by two chiral cyclometalating pyridine ligands
and one chloride in a distorted trigonal bipyramidal configura-
tion. Notably, only the L-configuration of the rhodium center
is observed in L-Rh-Cl. The subsequent reaction of L-Rh-Cl
with AgPF6 in MeCN at 508C provides L-Rh1 through the ste-
reospecific substitution of the chloride by two acetonitrile mol-
ecules. The crystal structure of L-Rh1 indicates that the L-con-
figuration is completely retained during this process (Figure 1).
Thus, the ligand-based chirality permits the straightforward
synthesis of enantio- and diastereometrically pure complexes
in a stereospecific fashion. Both of the complexes display con-
stitutional and configurational stability without any significant
decomposition or isomerization upon leaving the complexes
on the benchtop for one week.
84
n.d.
THF
[a] Reaction conditions: 1a (0.20 mmol), 2a (0.30 mmol), catalyst (2.0 mol%)
in solvent (0.4 mL) under argon atmosphere. [b] Isolated yield. [c] Chiral
HPLC analysis, n.d.=not determined. [d] 0.4 mmol of 2a was used.
comparison, previously developed chiral-at-metal catalysts L-
Rh2,[6a] L-Rh3,[8g] and L-Rh4[8f] afforded the adduct 3aa in
moderate to good yields (60–91%), but with inferior enantiose-
lectivities (82–85% ee; entries 9–11). A control experiment in
the absence of catalyst failed to provide any product, thereby
demonstrating that this reaction crucially depends on the
chiral rhodium Lewis acid catalysts (entry 12).
Then, the Mukaiyama–Michael reaction of a,b-unsaturated 2-
acyl imidazoles with silyl enol ether was selected to examine
the performance of the complexes. To our delight, in the pres-
ence of 2 mol% L-Rh1 at 328C in THF, the reaction of 1a with
silyl enol ether 2a (1.5 equiv) afforded the desired product 3aa
in 60% yield with 99% ee (Table 1, entry 1). No product was
formed when THF was replaced with toluene, whereas other
solvents such as CH2Cl2, DCE, MeCN, and 1,4-dioxane could not
provide 3aa in satisfactory yields, although it did give excel-
lent enantioselectivities (entries 2–6). By increasing the loading
of 2a (2.0 equiv) and temperature (508C), the reaction led to
3aa in 85% yield with 98% ee within 48 h (entry 7). However,
L-Rh-Cl was not able to catalyze the reaction (entry 8). For
With the optimal reaction conditions in hand (Table 1,
entry 7), we next investigated the scope of a,b-unsaturated 2-
acyl imidazoles (Scheme 3). The introduction of electron-donat-
ing and electron-withdrawing groups on the phenyl ring of
a,b-unsaturated 2-acyl imidazoles had little influence on the
enantioselectivity. The desired products 3aa–3ia were ob-
tained in high yields (75–90%) with excellent enantioselectivi-
ties (95–98% ee). Heteroaromatic 1j–1k and ring-condensed
1l–1m were all converted to the corresponding adducts (3ja–
3ma) in moderate to good yields (50–98%) with excellent ee
values (96–99% ee).[13] Methyl or cyclopropyl-substituted a,b-
unsaturated 2-acyl imidazoles were also tolerated well, afford-
ing products 3na and 3oa in 71% and 80% yields with 96%
&
&
Chem. Asian J. 2018, 00, 0 – 0
2
ꢀ 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!