Journal of the American Chemical Society
Herein, we report for the first time the enantioselective C−H
alkenylation of ferrocenes with various internal alkynes by a
chiral half-sandwich scandium catalyst (Scheme 1b). This
protocol offers an efficient and selective route for the synthesis
of a new family of planar-chiral ferrocenes bearing quinoline
and pyridine/alkene functionalities with high enantioselectiv-
ity. The mechanistic details have been clarified by DFT
calculations. The potential of a quinoline/alkene-function-
alized ferrocene product as a chiral ancillary ligand for
asymmetric rhodium catalysis is also demonstrated.
At first, we examined the reaction of a quinoline-substituted
ferrocene 1a with 1-phenyl-1-propyne 2a by using half-
sandwich scandium catalysts bearing various binaphthyl-
71−73
substituted cyclopentadienyl ligands (Table 1).
The Sc
Table 1. Asymmetric C−H Alkenylation of 1a with 2a by
a
Various Half-sandwich Scandium Catalysts
Figure 1. ORTEP drawing of Ph-TMS-Sc showing thermal ellipsoids
at the 30% probability level. Hydrogen atoms have been omitted for
clarity. Selected bond lengths [Å] and angles [°]: Sc1−Cp (av.)
2
.538(3), Sc1−C1 2.304(4), Sc1−C10 2.281(4), Sc1−N1 2.420(3),
Sc1−N2 2.464(3); C1−Sc1−N1 71.63(12), C1−Sc1−N2 87.03(13),
C10−Sc1−N2 72.05(12).
in sharp contrast with the analogous reactions catalyzed by
1
9
31
Pd or Ir catalysts, which either gave an alkyne-annulated
product or did not show significant enantioselectivity (see also
Scheme 1a).
b
c
entry
[Sc]
T (°C)
t (h)
yield (%)
e.r.
Having established the optimal conditions for the asym-
metric C−H alkenylation of 1a with 2a, we then examined the
reactions of 1a with various alkynes. Some representative
results are shown in Table 2. In addition to 2a, internal alkynes
bearing various aryl and alkyl substituents could generally serve
as efficient alkenylating reagents for 1a in the presence of Ph-
TMS-Sc. The C−C bond formation took place regioselectively
at the carbon atom of a CC unit bearing the alkyl
substituent, affording the corresponding alkenylated ferrocene
derivatives in high yields and excellent enantioselectivities (e.r.
1
2
3
4
5
6
OMe-Sc
TIPS-Sc
TBDPS-Sc
Ph-Sc
Ph-TMS-Sc
Ph-TMS-Sc
80
80
80
80
80
70
24
24
24
24
24
48
0
0
0
61
81
61
/
/
/
95:5
98:2
98:2
a
Reaction conditions: 1a (0.05 mmol), 2a (0.07 mmol), [Sc] (4 mol
b
%
), [Ph C][B(C F ) ] (4 mol %), toluene-d (0.5 mL). Yield of 3a
3 6 5 4 8
1
was determined by H NMR spectroscopy using CH Br as an
internal standard. Enantiomer ratio of 3a determined by HPLC
2
2
c
=
96:4−99:1). Phenyl (3e), naphthyl (3f), phenoxy (3g),
trimethylsilyl (3h), chloro (3i, 3k), bromo (3j), methylthio
3l), carbazolyl (3m), and vinyl (3o) functional groups in the
analysis on a chiral stationary phase.
(
alkyne substrates were all compatible with the catalyst, without
6
8
i
63
catalysts possessing OMe (OMe-Sc), OSi( Pr) (TIPS-Sc),
showing erosion of the enantioselectivity. Thiophenyl (3n),
3
t
63
i
and OSi BuPh (TBDPS-Sc) substituents at the 3,3′-
PhS (3q), and PrS (3r) groups directly bonded to the CC
2
positions of the binaphthyl group in the Cp ligand, which
were previously reported to show high activity and excellent
unit of the alkyne substrates did not hamper the reaction. The
sterically demanding diphenylacetylene (3p) also worked well
6
3,70
82
enantioselectivity in the hydroarylation
and hydrosilyla-
for the alkenylation of 1a. The absolute configuration of the
6
8
tion of alkenes, did not work in the C−H alkenylation of 1a
with 2a under the similar conditions (Table 1, entries 1−3). In
contrast, an analogous catalyst bearing phenyl substituents at
the binaphthyl group (Ph-Sc) afforded the desired C−H
alkenylation product 3a in 61% yield with an enantiomer ratio
of 95:5 (Table 1, entry 4). The introduction of a bulky SiMe3
substituent to the Cp ring of the catalyst (Ph-TMS-Sc, Figure
gave a further higher yield (81%) and higher
enantioselectivity (98:2 e.r.) (Table 1, entry 5).
the reaction temperature from 80 to 70 °C did not influence
the enantioselectivity, while a lower yield of 3a was observed
alkenylation product 3p was assigned to be S by spectroscopic
p
66
83
for details).
Table 3 shows the Ph-TMS-Sc catalyzed enantioselective
C−H alkenylation of various N-heterocycle-substituted
ferrocenes with alkynes. Methyl (3s), bromo (3t), and fluoro
(3u) substituents at the quinoline moiety of the ferrocene
substrates did not hamper the enantioselectivity (e.r. = 96:4−
98:2). A fused polycyclic quinoline unit (3v) was well
accommodated. n-Butyl (3w) or bromo (3x) substituent at a
Cp ring of the ferrocenes was also compatible with the C−H
alkenylation at the other Cp ring, without deteriorating the
enantioselectivity. In addition to quinoline substituents,
7
4
1
)
75−81
Lowering
(
Table 1, entry 6). The formation of 3a in the reaction of 1a
with 2a represents the first example of enantioselective C−H
alkenylation of a ferrocene compound with an alkyne, standing
2
471
J. Am. Chem. Soc. 2021, 143, 2470−2476
Lou, Shao-Jie
