Enantioselective Diarylcarbene Insertion into Si-H Bonds Induced by Electronic Properties of the Carbenes

Article abstract of DOI:10.1021/jacs.0c04725

Catalytic enantioselection usually depends on differences in steric interactions between prochiral substrates and a chiral catalyst. We have discovered a carbene Si-H insertion in which the enantioselectivity depends primarily on the electronic characteristics of the carbene substrate, and the log(er) values are linearly related to Hammett parameters. A new class of chiral tetraphosphate dirhodium catalysts was developed; it shows excellent activity and enantioselectivity for the insertion of diarylcarbenes into the Si-H bond of silanes. Computational and mechanistic studies show how the electronic differences between the two aryls of the carbene lead to differences in energies of the diastereomeric transition states. This study provides a new strategy for asymmetric catalysis exploiting the electronic properties of the substrates.

Full text of DOI:10.1021/jacs.0c04725

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Article
Enantioselective Diarylcarbene Insertion into Si-H
Bonds Induced by Electronic Properties of the Carbenes
Liang-liang Yang, Declan Evans, Bin Xu, Wen-Tao Li, Mao-Lin Li, Shou-Fei Zhu, K. N. Houk, and Qi-Lin Zhou
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c04725 • Publication Date (Web): 16 Jun 2020
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Enantioselective diarylcarbene insertion into Si−H bonds induced by
electronic properties of the carbenes
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Liang-Liang Yang,† Declan Evans,‡ Bin Xu,† Wen-Tao Li,† Mao-Lin Li,† Shou-Fei Zhu,*,† K. N.
Houk,*,‡ Qi-Lin Zhou*,†
† State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin
300071, China
‡ Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA
ABSTRACT: Catalytic enantioselection usually depends on differences in steric interactions between prochiral substrates and a
chiral catalyst. We have discovered a carbene Si–H insertion in which the enantioselectivity depends primarily on the electronic
characteristics of the carbene substrate, and the log(er) values are linearly related to Hammett parameters. A new class of chiral
tetraphosphate dirhodium catalysts was developed that shows excellent activity and enantioselectivity for the insertion of
diarylcarbenes into the Si–H bond of silanes. Computational and mechanistic studies show how the electronic differences between
the two aryls of the carbene lead to differences in energies of the diastereomeric transition states. This study provides a new strategy
for asymmetric catalysis exploiting the electronic properties of the substrates.
INTRODUCTION
= −94.7°) to stabilize the lone pair of the carbene that also
donates to the Rh dz2 orbital. In this way, the electronic
properties of the substituents determine the degree of the
conjugation between the aryl rings and the p or lone pair orbitals
of the carbene center. Based on this property, we speculated that
enantioselective transformation could be achieved by a chiral
catalyst that distinguishes the conformations of a prochiral
carbene intermediate. This strategy provides a new method for
the enantiocontrol for chiral transformations of substrates
which have sterically similar substituents. While
stereoselectivity has been achieved in carbene reactions
catalyzed by Cu, Fe, and Rh catalysts,12 the carbenes generally
have one ester group and one aryl or alkenyl group, or in the
work by Shaw, very different substitution patterns on the two
aryl groups of diaryl carbenes that cause large steric
differences.13 We have now found that dirhodium catalysts
modified with chiral spiro phosphate ligands (Fig. 1B,
Rh2(SPA)4) can differentiate the conformations of
Enantiomers of chiral molecules often exhibit biological
activities distinct from one another due to the homochirality of
biological molecules (e.g. L-amino acids and D-saccharides).
As a result, industrial compounds such as pharmaceuticals,
pesticides, flavors and fragrances often must be a single
enantiomer.1 In the past several decades, asymmetric catalysis
has become
a reliable method for the synthesis of
enantiomerically-enriched chiral compounds.2 Most current
methods of asymmetric catalysis rely on the spatial interactions
between the catalyst and substrate for enantiocontrol. Many
sterically crowded chiral catalysts have been developed that
utilize this principle to achieve high enantioselectivity.3 For
unsaturated substrates, the chiral catalyst is often able to
achieve enantiocontrol by discriminating between the two
prochiral faces of the substrate.4 It is difficult to identify
prochiral faces when the reactive center is attached to two
sterically similar substituents (Fig. 1A). For this reason, only
limited successes have been achieved in the catalytic
enantioselective reactions such as hydrogenations of diaryl5 or
dialkyl ketones,6 or of diaryl or dialkyl ethylenes,7 and
cycloadditions of diaryl ethylenes.8
diarylcarbenes
to
achieve
highly
enantioselective
transformations even though the substituents are in positions
where they have no different direct interactions with the
catalyst.
Transition-metal-catalyzed carbene insertion into Si−H
bonds is a powerful method for the synthesis of optically active
silanes. However, high enantioselectivity has only been
achieved using carbenes with markedly different substituents
(e.g. one substituent is an alkyl, alkenyl, or aryl group and the
other substituent is an electron-withdrawing group).14
Enantioselective Si−H bond insertion of diarylcarbenes remains
undeveloped. The challenge in the enantioselective Si−H bond
insertion of diarylcarbene stems from the difficulty of precisely
distinguishing the Re and Si faces of the carbene. We sought to
overcome this limitation using a chiral catalyst capable of
distinguishing the electronic-induced conformations of the
prochiral carbene intermediate (Fig. 1B).
Many active intermediates of organic reactions, such as
carbocations, carbon radicals, carbenes, and conjugated
carbanions have planar structures. Asymmetric reactions that
proceed via these active intermediates often rely on the steric
differences between the substituents connected to the prochiral
center.9 Catalytic enantiocontrol by discriminating substituent
electronics is very rare.10 Recently, Fürstner and coworkers11
studied the structures of rhodium-diphenylcarbenes by X-ray
single crystal diffraction: the electron-rich phenyl ring (4-
Me2NC6H4) adopts a coplanar orientation with carbene plane (Θ
= 0.9°) to maximize the overlap of the π cloud of phenyl ring
with the (empty) carbene p orbital. The electron-deficient
phenyl ring (4-CF3C6H4) lies orthogonal to the carbene plane (Θ
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A) Chiral differentiation via spatial interactions of substrate and catalyst
A variety of diphenyl diazomethylenes D1−D12 bearing
reagent A
chiral catalyst
R1
R2
R1
A
X
1
2
3
4
5
6
7
8
electronically different para substituents were evaluated in the
reaction with silane S1 catalyzed by C2 (Table 1). The
substrates with a strong electron-withdrawing group or a strong
electron-donating group at the para position of one phenyl ring
exhibited high enantioselectivity (entries 1−4 and 12), while the
substrates having a moderate or weak electronic effect exhibited
lower enantioselectivity (entries 5−11). Moreover, the
substrates with electron-withdrawing groups (D3, R = CF3) or
electron-donating groups (D11, R = OMe) afforded Si−H bond
insertion products with opposite absolute configurations (entry
3 and entry 11). When the Hammett substituent constant (σp)17
differences of the para substituents of two phenyl rings are over
0.5, the ee values of the corresponding Si−H bond insertion
products are over 90%. Moreover, a plot of log(er) values
against Hammett’s σp values is shown in Figure S1 (slope 2.86,
C
C
X
R2
chiral product
prochiral substrate
X
C
X
C
X
C
easy
hard
chiral differentiation
B) Enantioselective Si-H bond insertion induced by electronic properties of the diarylcarbenes
9
SiPhMe2
N2
PhMe2SiH
Ph
*
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0.1 mol% Rh2(SPA)4
W
W
D
D
O
O
O
Rh
Rh
electron-
withdrawing
group
P
electron-
donating
group
up to 99% ee
O
W
4
Ph
Rh2(SPA)4
*Rh
R2
= 0.96). These results clearly indicate that the
enantioselectivity of this reaction is directly related to the
electronic properties of carbene intermediates.
D
Figure 1. Chiral differentiations of prochiral faces and
enantioselective diarylcarbene insertion into Si−H bonds.
Table 1. Rhodium-Catalyzed Enantioselective Si−H Bond
Insertions of Diphenyl Diazomethylenes D1−D12
RESULTS AND DISCUSSION
SiPhMe2
N2
The insertion of 4-nitrophenyl phenyl diazomethane (D1)
into dimethylphenylsilane (S1) was performed using several
chiral dirhodium catalysts commonly used in asymmetric
carbene transformations15 (see the Supporting Information for
more details). The best performing catalyst for this reaction,
Rh2(S-PTTL)4, gave high yield but only modest
enantioselectivity, prompting further investigation. A new type
of dirhodium catalysts was developed which contain spiro
phosphate ligands C1−C5 (see Supporting Information for
details).16 Of the spiro phosphate dirhodium catalysts, C2
afforded both good yield and the highest enantioselectivity
(Scheme 1). Even 0.01 mol% catalyst is sufficient for excellent
results.
C2
0.1 mol%
*
+
PhMe2SiH
(1.2 equiv)
DCM, 0 oC, < 3 min
R
R
S1
D1 D12
P1 P12
entrya
R
Δσp (R-H)b
0.78
product
P1
yield (%)
ee (%)
1
NO2
92
96
91
68
66
95
79
62
88
51
47
45
>99
98
95 (S)d
2
CN
CF3
SCF3
OCF3
Cl
0.66
P2
3c
4c
5c
6
0.54
P3
0.50
P4
97
0.35
P5
76
0.28
P6
66
7
Br
0.23
P7
77
8
I
0.18
P8
82
9c
10
11
12
F
0.06
P9
25
Scheme 1. Enantioselective Si−H Bond Insertion of 4-
Nitrophenylphenyl Diazomethane Catalyzed by Chiral
Dirhodium Catalystsa
Me
OMe
NMe2
−0.17
−0.27
−0.60
P10
P11
P12
18
64 (R)d
91
N2
SiPhMe2
0.1 mol% Catal.
a
*
+
PhMe2SiH
Reaction conditions: Condition A (for entries 1−3, 6−7, and
DCM, 0 oC, < 3 min
10−11): diazo compound (0.2 mmol), PhMe2SiH (1.2 equiv), C2
(0.1 mol%), DCM, 0 °C; Condition B (for entries 4, 5, 8, 9 and 12):
hydrazone (0.2 mmol), MnO2 (3.5 equiv), MgSO4, DCM, rt, 5−6 h;
then, PhMe2SiH (1.2 equiv), C2 (0.1 mol%), DCM, 0 °C. Isolated
yields were given. The ee values were determined by chiral HPLC.
b Hammett substituent constant for para substituents. c The ee value
was determined by the corresponding alcohol obtained through the
O2N
O2N
D1
S1
P1
O
N
Ph
Ph
tBu
H
O
S
(S)
N
H
O
(S)
O
O
Rh
O
C12H25
(R)
O
O
O
O
Rh
4
Rh Rh
Rh Rh
d
oxidation of Si−H insertion product. The absolute configuration
Br
Rh2(S-PTTL)4
was assigned by analogy with the reported data (see Supporting
Information for details).
Rh2(S-DOSP)4
85% yield, 17% ee
Rh2(R-BTPCP)4
92% yield, 83% ee
trace
R1
R2
Next, various diphenyl diazomethanes bearing different para
substituents were studied (Table 2). These results show that the
enantioselectivity of the reaction is directly correlated with the
differences in substrate electronics. Again, when the difference
of Hammett substituent constant of the two para substituents is
equal or greater than 0.5, the ee of the corresponding Si−H bond
insertion product is equal or greater than 90% (entries 1−6,
9−11, and 14−16). Moreover, sterically similar substituents
(e.g. para-NO2 vs para-NMe2, entry 1; para-CF3 vs para-CH3,
entry 10; para -OCF3 vs para-OCH3, entry 14) were precisely
R1 = H
R2 = H
C1
56% yield 95% ee
R1 = C6H5
R1 = 3,5-Me2C6H3
R1 = H
R2 = H
C2
C3
C4
C5
92% yield >99% ee
94% yield 97% ee
56% yield 66% ee
33% yield 82% ee
O
O
O
Rh
Rh
R2 = H
R2 = Br
R2 = C6H5
P
O
R1 = H
4
R2
R1
Rh2(SPA)4
C2
84% yield and >99% ee were obtianed using 0.01 mol%
!
a Reaction conditions: Catal/D1/S1= 0.0002:0.2:0.24 (mmol), 1 mL
solution of D1 was dropped into 2 mL solution of S1 and catalyst
at 0 ℃, < 3 min, isolated yield.
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differentiated indicating that the observed enantioselectivity is
enantioselectivity can be obtained. Excellent enantioselectivity
can also been achieved when the diaryl diazomethane substrates
have an ortho substituent (P39 and P40). Presumably due to
small radius of fluorine atom, the 2-fluoro-substituted diazo
compound afforded relatively lower ee (83% ee, P41).
However, the enantioselectivity can be increased by introducing
an electron-donating group (4-OMe) at the other aryl ring of the
substrate (91% ee, P42). In addition to dimethylphenylsilane
(S1), other silanes can also be used in the Si−H bond insertion
reaction with diaryl diazomethane D1, affording Si−H bond
insertion products with excellent enantioselectivtiy (P43−P49).
It is worth mentioning that the alkynyl silane underwent Si−H
bond insertion reaction, giving the corresponding product P47
with high yield (93%) and excellent enantioselectivity (>99%
ee). The absolute configuration of (S)-P47 was determined by a
single crystal X-ray diffraction analysis.
1
not a result of steric effects.
2
3
4
5
6
7
8
9
Table 2. Rhodium-Catalyzed Enantioselective Si−H Bond
Insertion of Diphenyl Diazomethanes D13−D30
SiPhMe2
N2
C2
0.1 mol%
*
+
PhMe2SiH
(1.2 equiv)
DCM, 0 oC, < 3 min
R1
R2
R1
R2
S1
D13 D30
R1
P13 P30
entrya
1
R2
Δσp (R1-R2)b
product
P13
P14
P15
P16
P17
P18
P19
P20
P21
P22
P23
P24
P25
P26
P27
P28
P29
P30
yield(%) ee (%)
10
11
12
13
14
15
16
17
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60
NO2
NO2
NO2
NO2
NO2
NO2
NO2
CN
NMe2 1.38
66
78
87
86
80
88
58
42
78
85
63
71
73
58
58
59
43
40
96
2
OMe
Me
F
1.05
0.95
0.72
0.55
0.5
99
3
99
4
98
5
Br
95
6
Cl
96
Scheme 2. Substrate Scope of Diarylcarbene Insertion into
7
CF3
CF3
OMe
Me
F
0.24
0.12
0.81
0.71
0.48
0.31
0.26
0.62
0.50
0.55
0.33
0.10
86
Si−H Bondsa
N2
SiR3
8
36
C2
0.1 mol%
+
R3SiH
(1.2 equiv)
*
R2
R1
R2
DCM, 0 oC, < 3 min
9
CF3
98
R1
10c
11c
12c
13c
14
15
16
17c
18
CF3
94(S)
92
S1 S8
D31 D49
P31 P49
CF3
SiPhMe2
SiPhMe2
SiPhMe2
OMe
*
*
*
CF3
Br
67
R
R
MeO
O2N
P35
CF3
Cl
76(R)
93
73% yield, 99% ee
P31
P32
P33
P34
R = H, 85% yield, 53% ee
R = H, 60% yield, 32% ee
OCF3 OMe
R = NO2, 89% yield, 96% ee
R = NO2, 45% yield, >99% ee
SiPhMe2
Br
Cl
F
OMe
OMe
OMe
OMe
94
SiPhMe2
SiPhMe2
O
*
*
*
93
N
H
O
O
F3C
O2N
F3C
P37
77(R)
56
P36
49% yield, 97% ee
P38 44% yield, 99% ee
82% yield, 98% ee
Me
P39 R1 = Cl, R2 = H, 92% yield, 99% ee
R1 SiPhMe2
Correlations of ee and p
R
1 = Br, R2 = H, 82% yield, 98% ee
1 = F, R2 = H, 69% yield, 83% ee
ee/%
100
P40
p
*
P41
R
1.2
R2 P42 R1 = F, R2 = OMe, 36% yield, 91% ee
80
60
1.0
0.8
Ph
Me
40
20
[Si]
Me Si
0.4
*
O2N
O2N
P47
R1
NO2
CF3
CN
CF3
CF3 CF3 CF3 CF3 OCF3 Br
Cl
F
NO2 NO2 NO2 NO2 NO2 NO2
Me2 OMe Me Br Cl
Me
P43
[Si] = SiMe2OEt, 76% yield, 99% ee
Me
93% yield, >99% ee
Me
N
R2
CF3 OMe Me
F
Br Cl OMe OMe OMe OMe
P44b
P45
P46
N
F
OMe
[Si] = SiMe2OH, 56% yield, 98% ee
[Si] = SiEt3, 64% yield, 96% ee
[Si] = SiPh2Me, 62% yield, 94% ee
Me
Me Si
Cl
Me Si
a
Reaction conditions: hydrazone (0.2 mmol), MnO2 (3.5 equiv),
*
*
MgSO4, DCM, rt, 5−6 h; then, PhMe2SiH (1.2 equiv), C2 (0.1
O2N
P48
O2N
mol%), DCM, 0 °C. Isolated yields were given. The ee values were
89% yield, 99% ee
P49
53% yield, 99% ee
b
determined by chiral HPLC analysis. The Hammett substituent
a
c
Reaction conditions: hydrazone (0.2 mmol), MnO2 (3.5 equiv),
constant difference for para substituents. The ee value was
MgSO4, DCM, rt, 5−6 h; then, PhMe2SiH (1.2 equiv), C2 (0.1
determined by the corresponding alcohol obtained through the
oxidation of Si−H insertion product. A plot of log(er) vs Δσp (R1-
R2) is shown in Figure S2.
mol%), DCM, 0 °C. Isolated yields were given. The ee values were
b
determined by chiral HPLC analysis. Dimethylchlorosilane was
used and the hydrolysis product was isolated after work-up.
The chiral spiro phosphate dirhodium catalyst C2 is also
efficient for the enantioselective Si−H bond insertion of other
diazo compounds containing two different aryl groups (Scheme
2). In every case, the electronic property of the substituents on
the aryl rings significantly affected the enantioselectivity of
reaction. For instance, the naphthyl phenyl diazomethane
afforded the Si−H bond insertion product P31 with 53% ee;
MECHANISTIC STUDIES
A kinetic isotopic study was carried out; in a competition
experiment using dimethylphenylsilane and deuterated
dimethylphenylsilane, the kinetic isotope effect (KIE) was
found to be 1.5 (see Supporting Information for details). This
result is similar to the values reported in the Si−H insertions of
however, introducing
a para-NO2 at the phenyl ring
aryl diazoesters catalyzed by transition metals such as Ir14c
,
dramatically increased the ee value of product P32 to 96%.
Similarly, 4-nitrophenyl 2'-methoxylphenyl diazomethane
provided much higher enantioselectivity (P34, >99% ee) than
2-methoxylphenyl phenyl diazomethane (P33, 32% ee).
Moreover, if one aryl ring of the substrates has a strong
electron-withdrawing para substituent (e.g. NO2 or CF3), and
the other aryl ring is a heteroaryl ring (P36−P38), excellent
Rh14d and Cu18; these reactions proceed through concerted
three-center transition states. In order to gain insights about the
origin of enantioselectivity from the catalyst and the electronic
effects of substrates, we also conducted a computational
investigation. C1 was used as the model catalyst.19 X-ray
structure analysis of the catalyst C1 reveals that the presence of
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Journal of the American Chemical Society
four identical chiral ligands around the dirhodium core results
in a rigid catalyst with higher symmetry (D4 symmetry) than the
ligands themselves (C2 symmetry).16 This symmetry causes
both sides of the dirhodium catalyst to be identical, limiting the
number of possible conformations for the transition state of
Si−H insertion.
Page 4 of 7
(R1 = NO2, R2 = OMe) from its Re face (TS-3) is the lowest in
energy (Fig. 2B, 2C). This transition state is favored by 5.6 kcal
mol-1 over TS-5 due to the different steric effects of the two aryl
substituents on carbene; this steric difference originates from the
electronic effects of substituents that orients electron-rich and
electron-deficient aryl rings differently. Moreover, TS-3 is
favored by 2.2 kcal mol-1 over TS-4 (which would lead to the
opposite enantiomer) due to steric effects the chiral catalyst has
on the transition state conformations. In these structures, the
electron-rich aryl ring (R2=OMe) is able to adopt a more
coplanar orientation in TS-3 (Θ = 19.5°) than in TS-4 (Θ =
31.6°). The last possible transition state, TS-6, is 7.4 kcal mol-1
higher in energy than TS-3 due to both unfavorable electronics
and steric clashes with the catalyst. Moreover, when two aryls
of the carbene have similar electronic property, as in the case
for R1 = CN, R2 = CF3, the energy difference between TS'-3 and
TS'-5 is smaller (2.4 kcal/mol), which is consistent with the low
enantioselectivity observed in the experiment (see Supporting
Information for details).20
1
2
3
4
5
6
7
8
Initially, a dirhodium-tetraformate catalyst (Rh2(O2CH)4)
was computed to observe transition state geometries in the
absence of any steric effects caused by the ligands (see
Supporting Information for details). Fig. 2A shows that the
Si−H insertion proceeds via a concerted three-center transition
state. Calculated transition state geometries for diphenyl
carbene insertion into the Si−H bond of dimethylphenylsilane
show that one aryl ring rotates to a near-coplanar orientation
with the carbene empty p orbital while the other phenyl ring
rotates to a near orthogonal orientation. For substituted
diphenyl carbenes, two transition state geometries are possible
depending on whether the substituted aryl ring is conjugated
(TS-1) or orthogonal (TS-2) to the empty p orbital. These two
transition states are not equal in energy and the favored
transition state always results when the electron-rich aryl ring
is nearly coplanar with carbene plane. Plotting the energy
difference (ΔΔG‡) vs the corresponding Hammett substituent
constant σp shows a linear correlation (Fig. 2A), indicating that
this energy difference is greater when the electronic difference
between aryl rings is more pronounced.
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These calculations show that the chiral environment of the
catalyst C1 can fix the conformations of the transition state in
the Si−H bond insertion reaction. On this basis, the energy
difference of the transition states, which relates to the
enantioselectivity of reaction, is primarily due to the electronic
difference between two aryls of carbene.
CONCLUSION
A
B
H
R
R
H
R1 = NO2, R2 = OMe
In summary, we have achieved a method for highly
enantioselective carbene insertion into Si−H bonds that relies
primarily on the electronic properties of the substrates. It
represents the first highly enantioselective diarylcarbene
insertion into the heteroatom-hydrogen bonds. A new class of
D4-symmetric dirhodium catalysts bearing chiral spiro
phosphate ligands was developed, and computational studies
demonstrate that the chiral environment of these catalysts can
differentiate the various possible transition state conformations.
The chiral induction observed in this study not only enables the
unprecedented enantioselective transformations of carbenes
having spatially similar groups, but also inspires the
development of new strategies for chiral transformations of
charged active intermediates, such as carbocations, carbanions,
as well as carbon radicals.
Si
Si
Me
Me
Me
Me
H
H
Rh
Rh
Rh
Rh
O
O
O
O
H
H
H
H
O
O
O
O
TS-2
TS-1
y = 3.4491x + 0.6970
R2 = 0.9216
TS-3
TS-5
TS-4
TS-6
0.0
5.6
2.2
7.4
R = NMe2, OMe, Me, H, F, I, Br, Cl, OCF3, SCF3, CF3, CN, NO2.
C
R1 = NO2, R2 = OMe
ASSOCIATED CONTENT
90o
Supporting Information.
The data supporting the findings of this study are available within
the paper and its Supplementary Information. Geometrical
parameters for the structure of reagents C3 and P47 (see
Supplementary Information) are available from the Cambridge
Crystallographic Data Centre (https://www.ccdc.cam.ac.uk/) under
reference numbers CCDC 1888695 and CCDC 1888689,
respectively. This material is available free of charge via the
Internet at http://pubs.acs.org.
TS-3
Favorable enantio-determining transition state
Figure 2. Computational studies. A) Optimized transition state
structures for carbene insertion into Si−H bond with a tetraformate
dirhodium (Rh2(O2CH)4) as a model catalyst. B) Structures of
optimized transition states for the Si−H bond insertion of
asymmetrically substituted diphenyl carbene formed from C1.
ONIOM partitioning of the transition state geometry, with the
atoms shown opaque modelled with density functional theory
(DFT), and the atoms shown transparent modelled with the
universal force field (UFF). The relative Gibbs free energies with
single point corrections are given in kcal mol-1. C) Favorable
enantio-determining transition state structure for the Si−H bond
insertion of asymmetrically substituted diphenyl carbene (R1 =
NO2, R2 = OMe) formed from C1.
AUTHOR INFORMATION
Corresponding Author
Shou-Fei Zhu − State Key Laboratory and Institute of Elemento-
Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China; orcid.org/0000-0002-6055-3139; Email:
sfzhu@nankai.edu.cn
In the chiral environment of C1, the transition state for the
Si−H bond approaching to the asymmetrical diphenyl carbene
K. N. Houk − Department of Chemistry and Biochemistry,
University of California, Los Angeles, California 90095-1569,
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Journal of the American Chemical Society
(7) (a) Mazuela, J.; Verendel, J. J.; Coll, M.; Schäffner, B.; Börner,
USA; orcid.org/0000-0002-8387-5261; Email: houk@chem.ucla.
edu
Qi-Lin Zhou − State Key Laboratory and Institute of Elemento-
Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China; orcid.org/0000-0002-4700-3765; Email:
qlzhou@nankai.edu.cn
A.; Andersson, P. G.; Pàmies, O.; Diéguez, M. Iridium Phosphite-
Oxazoline Catalysts for the Highly Enantioselective Hydrogenation of
Terminal Alkenes. J. Am. Chem. Soc. 2009, 131, 12344–12353. (b)
Mazuela, J.; Norrby, P.-O.; Andersson, P. G.; Pàmies, O.; Diéguez, M.
Pyranoside Phosphite-Oxazoline Ligands for the Highly Versatile and
Enantioselective Ir-Catalyzed Hydrogenation of Minimally
Functionalized Olefins. A Combined Theoretical and Experimental
Study. J. Am. Chem. Soc. 2011, 133, 13634–13645. (c) Besset, T.;
Gramage-Doria, R.; Reek, J. N. H. Remotely Controlled Iridium-
Catalyzed Asymmetric Hydrogenation of Terminal 1,1-Diaryl Alkenes.
Angew. Chem. Int. Ed. 2013, 52, 8795–8797.
1
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8
Author
Liang-Liang Yang − State Key Laboratory and Institute of
Elemento-Organic Chemistry, College of Chemistry, Nankai
University, Tianjin 300071, China
Declan Evans − Department of Chemistry and Biochemistry,
University of California, Los Angeles, California 90095-1569,
USA
Bin Xu − State Key Laboratory and Institute of Elemento-Organic
Chemistry, College of Chemistry, Nankai University, Tianjin
300071, China
Wen-Tao Li − State Key Laboratory and Institute of Elemento-
Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China
9
(8) Wiest, J. M.; Conner, M. L.; Brown, M. K. Allenoates in
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15943–15949.
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(9) For a review, see: Mohr, J. T.; Hong, A. Y.; Stoltz, B. M.
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Copper-Catalyzed C−N Cross-Couplings Induced by Visible Light.
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Wang, D.; Chen, P.; Stahl, S. S.; Liu, G. Enantioselective Cyanation of
Benzylic C−H Bonds via Copper-Catalyzed Radical Relay. Science
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N. Quaternary Stereocentres via an Enantioconvergent Catalytic SN1
Reaction. Nature 2018, 556, 447–451.
Mao-Lin Li − State Key Laboratory and Institute of Elemento-
Organic Chemistry, College of Chemistry, Nankai University,
Tianjin 300071, China
Notes
(10) (a) Legros, J.-Y.; Fiaud, J.-C. Electronic Control of
Enantioselectivity in the Palladium-Catalyzed Asymmetric Allylic
Substitution of trans 4-tButyl-1-vinylcyclohexyl Benzoates.
Tetrahedron 1994, 50, 465–474.; (b) Corey, E. J.; Helal, C. J. Novel
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S. Enantioselectivity Increases with Reactivity: Electronically
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Aldehydes Catalyzed by a Chiral Pyridylphenol. J. Org. Chem. 1996,
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Controlled Asymmetric Cyclopropanation Catalyzed by a New Type
of Chiral 2,2’-Bipyridine. Tetrahedron Lett. 2000, 41, 7723–7726.
(11) Werlé, C.; Goddard, R.; Philipps, P.; Farès, C.; Fürstner, A.
Structures of Reactive Donor/Acceptor and Donor/Donor Rhodium
Carbenes in the Solid State and Their Implications for Catalysis. J. Am.
Chem. Soc. 2016, 138, 3797–3805.
(12) For reviews, see: (a) Zhu, S.-F.; Zhou, Q.-L. Transition-Metal-
Catalyzed Enantioselective Heteroatom-Hydrogen Bond Insertion
Reactions. Acc. Chem. Res. 2012, 45, 1365–1377. (b) Keipour, H.;
Carreras, V.; Ollevier, T. Recent Progress in the Catalytic Carbene
Insertion Reactions into the Silicon−Hydrogen Bond. Org. Biomol.
Chem. 2017, 15, 5441–5456.
(13) (a) Soldi, C.; Lamb, K. N.; Squitieri, R. A.; González-López,
M.; Di Maso, M. J.; Shaw, J. T. Enantioselective Intramolecular C−H
Insertion Reactions of Donor–Donor Metal Carbenoids. J. Am. Chem.
Soc. 2014, 136, 15142–15145.
(14) For representative examples, see: (a) Davies, H. M. L.; Hansen,
T.; Rutberg, J.; Bruzinski, P. R. Rhodium(II) (S)-N-
(Arylsulfonyl)prolinate Catalyzed Asymmetric Insertion of Vinyl- and
Phenylcarbenoids into the Si−H Bond. Tetrahedron Lett. 1997, 38,
1741–1744. (b) Zhang, Y.-Z.; Zhu, S.-F.; Wang, L.-X.; Zhou, Q.-L.
Copper-Catalyzed Highly Enantioselective Carbenoid Insertion into
Si–H Bonds. Angew. Chem. Int. Ed. 2008, 47, 8496–8498. (c)
Yasutomi, Y.; Suematsu, H.; Katsuki, T. Iridium(III)-Catalyzed
Enantioselective Si−H Bond Insertion and Formation of an
Enantioenriched Silicon Center. J. Am. Chem. Soc. 2010, 132, 4510–
4511. (d) Chen, D.; Zhu, D.-X.; Xu, M.-H. Rhodium(I)-Catalyzed
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Hydrogen Bonds with Trifluorodiazoalkanes. Angew. Chem. Int. Ed.
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The authors declare no competing interests.
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China
(21625204, 21790332, 21532003, 21971119), the “111” project
(B06005) of the Ministry of Education of China, and the National
Program for Special Support of Eminent Professionals, the
National Science Foundation of the USA (CHE-176328 to KNH)
and the National Institute of Health (T32GM008496 to DE) for
financial support.
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(20) During submission of this manuscript, Davies and coworkers
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TOC
1
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SiPhMe2
N2
PhMe2SiH
*
0.1 mol% Rh2(SPA)4
W
W
D
D
electron-
withdrawing
group
electron-
donating
group
up to 99% ee
W
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*Rh
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D
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