Enantioselective Hydroboration of Ketones Catalyzed by Rare-Earth Metal Complexes Containing Trost Ligands

Article abstract of DOI:10.1021/acs.joc.0c00877

Four chiral dinuclear rare-earth metal complexes [REL1]2 (RE = Y(1), Eu(2), Nd(3), La (4)) stabilized by Trost proligand H3L1 (H3L1 = (S,S)-2,6-bis[2-(hydroxydiphenylmethyl)pyrrolidin-1-ylmethyl]-4-methylphenol) were first prepared, and all were characterized by X-ray diffraction. Complex 4 was employed as the catalyst for enantioselective hydroboration reaction of substituted ketones, and the corresponding secondary alcohols with excellent yields and high ee values were obtained using reductant HBpin. The same result was also achieved using the combination of lanthanium amides La[N(SiMe3)2]3 with Trost proligand H3L1 in a 1:1 molar ratio. The experimental findings and DFT calculation revealed the possible mechanism of the enantioselective hydroboration reaction and defined the origin of the enantioselectivity in the current system.

Full text of DOI:10.1021/acs.joc.0c00877

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Article
Enantioselective Hydroboration of Ketones Catalyzed by
Rare-Earth Metal Complexes Containing Trost Ligands
Yuli Sun, Chengrong Lu, Bei Zhao, and Mingqiang Xue
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00877 • Publication Date (Web): 26 Jun 2020
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Enantioselective Hydroboration of Ketones Catalyzed by Rare-Earth
Metal Complexes Containing Trost Ligands
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Yuli Sunb, Chengrong Lu*a,b, Bei Zhao*a,b, and Mingqiang Xueb
Key Laboratory of Organic Synthesis of Jiangsu Province,a College of Chemistry, Chemical
Engineering and Materials Science,b Soochow University, Suzhou 215123, People’s Republic of China
Supporting Information
ABSTRACT: Four chiral dinuclear rare-earth metal complexes [REL1]2
8 mol% La[N(SiMe3)2]3
8 mol% H3L1
(RE = Y(1), Eu(2), Nd(3), La (4)) stabilized by Trost proligand H3L1
O
OH
SiO2/EA
THF, 8 h, 0 o
4 mol% cat.
C
O
O
(H3L1
=
(S,S)-2,6-bis[2-(hydroxyl-diphenylmethyl)-pyrrolidin-1-
B
R1 R2
R1 R2
or
4
H
ylmethyl]-4-methylphenol) were firstly prepared and all characterized by
X-ray diffraction. Complex 4 was employed as the catalyst for
enantioselective hydroboration reaction of substituted ketones, and the
corresponding secondary alcohols with excellent yields and high ee
values were obtained using reductant HBpin. The same result was also
achieved using the combination of lanthanium amides La[N(SiMe3)2]3
with Trost proligand H3L1 in 1:1 molar ratio. The experimental findings
and DFT calculation revealed the possible mechanism of the
enantioselective hydroboration reaction and defined the origin of the
enantioselectivity in the current system.
5a-z, 7a-e
6a-z, 8a-e
2 equiv
Ph
Ph
Ph
Ph
31 examples
O
N
O
up to 99% yield
La
O
N
N
up to 99% ee
O
La
computational support
Ph
Ph
O
N
O
Ph
Ph
4
cat.
INTRODUCTION
reactions to give excellent yields and ee values, including aldol
reaction,10 Mannich reaction,11 Henry condensation,12 conjugate
addition,13 Darzens reaction,14 alkyne addition,15 desymmetrization
reaction,16 alkylation reaction,17 allylation reaction,18 and
polymerization reaction.19 Hence, the efficient Zn-Zn, Zn-Mg and
Mg-Mg complexes provide atom-economic methods to valuable
chemicals or building blocks.
Metal-catalyzed enantioselective reactions are one of the important
strategies for the synthesis of chiral compounds. The design and
preparations of chiral ligands are critical. During the last decades,
prolinol and its derivatives were proved to be a kind of efficient
chiral ligands, which were used in asymmetric alkyne addition,1
transfer hydrogenation,2 epoxidation3 and Henry condensation4
(Fig. 1a). Meanwhile, a series of chiral phenoxy-functionalized
prolinolates were developed and successfully employed in
Bronsted Basic
Lewis Acidic
R
O
Ar
Ar
Ar
O
N
Ar
M
M
asymmetric
Michael
addition,5
epoxidation,6
hydrophosphonylation7 and hydroboration8 (Fig. 1b).
N
O
R
R
M = Zn, Mg
OR''
N
R'
N
R
R''
R''
Figure 2. M-prophenol model
OH
R'
HO
a
Rare-earth metal complexes, as active catalysts, play an important
role in a range of transformations.20 Recently, several successful
cases about the applications of chiral rare-earth metal complexes
bearing phenoxy-functionalized prolinolates were published.5-8 If
the prolinolates we used are replaced by the above Trost ligands
with semi-crown structure, can we obtain the similar dual-core rare-
earth metal complexes, and what are the enantioselectivities when
they are used in the asymmetric catalytic reactions? To find the
answer, modification of chiral phenoxy-functionalized prolinolates
with semi-crown structure was carried out in our group.
b
R = alkyl, aryl
R = H, alkyl, X
R' = H, alkyl, X
R' = H, alkyl
R'' = H, alkyl
R" = alkyl, aryl
Figure 1. Prolinols and phenoxy-functionalized prolinolates
Another kind of phenoxy-functionalized prolinolates, the chiral
Trost ligands with semi-crown structure usually used to form chiral
dimetallic complexes when treated with appropriate precursors,
such as dialkylzinc and dibutyl magnesium.9 The complexes
obtained have Lewis acidic and Bronsted basic sites to activate an
electrophile and deprotonate a pronucleophile simultaneously (Fig.
2). The bimetallic complexes facilitate diverse enantioselective
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It is a simple method to gain chiral alcohols via enantioselective
Figure 3. ORTEP diagram of complex 4 was shown in the atom-
hydroboration, which is a common asymmetric hydrogenation,
safer and easier to handle.21 As early as late 1980s, a notable
reaction called CBS reduction was introduced by Corey and co-
workers, that is an enantioselective borane reduction of ketones
using oxazaborolidines as catalysts. Afterwards, the pioneering
investigation on CBS catalyst was well developed and it was
widely applied in enantioselective hydroborations.22 Recently,
metal-based catalytic enantioselective hydroboration of ketones
was developed, using Co,23a,b Mn,23c Mg,23d,e and RE8 complexes
supporting by iminopyridine oxazoline ligands, bis(oxazolinyl-
methylidene)isoindoline pincer ligands, BINOLs and phenoxy-
functionalized prolinolates, respectively. In view of the successful
cases of catalytic enantioselective hydroboration of ketones are
valuable supplements for the development of synthetic
methodology on the useful optically pure secondary alcohols,24 the
applications on enantioselective hydroboration of ketones were
tested herein.
numbering scheme. Thermal ellipsoids are drawn at the 30%
probability level. Hydrogen atoms except H68, H67 and solvent are
omitted for clarity. Dummy1-4 are the geometric centers of the
benzene rings.
To investigate the catalytic behavior of the chiral dinuclear
complexes 1-4, the enantioselective hydroboration reduction of
acetophenone 5a was carried out as a model reaction. Delightfully,
using HBpin as a reducing agent, acetophenone was transferred to
chiral 1-phenyl-1-ethanol quantitatively with good to high ee
values, varied from 65-89% ee (Table 1, entries 2-5). The
enantioselectivities of complexes 1-4 improved while the atomic
radii of the central rare-earth metal atoms increased. It can be
attributed to the better spatial match for the ketone with La-based
catalyst 4, which comes from the optimal angles of dummy3-La1-
dummy4 (Fig. S1-S4). No better enantioselectivities of 6a were
obtained after screening of many additives in the presence of
catalyst 4 (SI, Table S2). However, it makes more sense that the
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RESULTS AND DISCUSSION
comparable
high
ee
value
was
received
when
bis(trimethylsilyl)amide HN(SiMe3)2 was added deliberately,
meanwhile the yield of 6a maintained (Table 1, entries 5-7). It
means that the existence of HN(SiMe3)2 has no negative impact on
the reaction. More conveniently, treatment of lanthanum amide
La[N(SiMe3)2]3 with chiral ligand H3L1 in equal molar ratio to
generate the catalyst in-situ is a straightforward method to catalyze
the enantioselective hydroboration reduction of acetophenone.
A Trost ligand with semi-crown structure H3L1 was prepared
according the previous work.12a With the ligand in hand, four new
chiral rare-earth metal complexes [REL1]2 (RE = Y(1), Eu(2),
Nd(3), La(4)) were synthesized by the treatment of rare-earth metal
amides RE[N(SiMe3)2]3 with H3L1 in equal amount with high
isolated yields (Scheme 1). The structures of complexes 1-4 were
characterized by X-ray diffraction analysis, as well as NMR
spectroscopies when allowed.
Table 1. Enantioselective hydroboration of acetophenone catalyzed
by complexes 1-4a
Scheme 1. Synthesis of complexes 1-4
OH
O
Ph
Ph
SiO2/EA
4 mol % cat.
Ph
Ph
O
O
O
N
HO
OH
Ph
Ph
Ph
Ph
OH
C
O
B
THF, 8 h, 0
H
RE
O
O
RE[N(SiMe3)2]3
THF, 24 h
6a
5a
2 equiv
N
N
N
N
Entry Cat.
Additiveb
Yield (%)c ee (%)d
O
RE
Ph
Ph
N
O
1
2
3
4
5
6e
7
-
-
trace
>99
>99
>99
>99
>99
nd
65
80
83
89
89
Ph
H3L1
Ph
Y-1
Eu-2
Nd-3
La-4
La-4
-
1
2
3
4
RE = Y( , 67%), Eu( , 85%), Nd( , 87%), La( , 91%)
-
Unexpectedly, isomorphic complexes 1-4 are dinuclear structures
bearing two Trost ligands L1. The crystallographic data are listed in
Table S1 (SI). As shown in Fig. 3the bond angle of dummy3-La1-
dummy4 is 101.4(6)o, while the dummy1-La2-dummy2 is 57.6(1)o.
Furthermore, the vertical distance from H67 to benzene ring
containing dummy1 is 2.87Å, which indicating a weak H-
intramolecular attractive force.Similarly, the bond angles of
dummy3-RE1-dummy4 are 97.5(1)o of 1, 98.0(1)o of 2, and
98.4((5)o of 3, which are bigger than the corresponding angles of
dummy1-RE2-dummy2 significantly. The H- intramolecular
attractive forces in complexes 1-3 are also observed. Such dual-
core structures indicate that the two metal nuclei will behave
differently in the reaction, and RE1 center is most likely the active
site.
-
-
HN(SiMe3)2
La[N(SiMe3)2]3
/H3L1
-
>99
92
o
aReaction conditions: 5a (0.3 mmol), THF (1 mL), 25 C, 20 h;
d
bThe amount of additives was 8 mol%; cHPLC yield; Determined
by chiral HPLC; eThe amount of HN(SiMe3)2 was 24 mol%.
In general, the structure of ligands has decisive effects on the
enantioselectivity. A series of Trost ligands H3L2-H2L14 were
prepared, followed by the previous work12a, 18b (SI, Fig. S5). The
hydroborations of acetophenone 5a were used to optimize the
reaction conditions, and the results are summarized in Table S4.
Unfortunately, no further improvement on the enantioselectivity of
the target alcohol was achieved (SI, Table S3, entries 1-14).
Proligand H3L1 remains the best choice in the current
transformation. After routine screening, the enantioselective
hydroboration of acetophenone underwent smoothly for 8 h at 0 oC
in the presence of 8 mol% precatalyst La[N(SiMe3)2]3 combined
with 8 mol% chiral Trost proligand H3L1 (SI, Table S3-S4).
Various readily available aryl methyl ketones were reduced by 2
equivalent HBpin under the optimal condition and the results are
listed in Scheme 2. To our delight, most of the aryl methyl ketones,
including electron-rich heteroaryl ketone 5y, were reduced to the
corresponding chiral secondary alcohols in excellent yields with the
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satisfied enantioselectivities, varied from 74%-99% ee (Scheme 2,
aReaction conditions: 5 or 7 (0.3 mmol), La[N(SiMe3)2]3 (0.024
2
3
4
5
6a-6y). The reaction outcomes are better than our published work,8
in terms of both the yields and ee values. Regarding the methyl
pyridyl ketones 5z, excellent yield was obtained, albeit with very
poor enantioselectivity (15% ee), showing a limitation on the scope
of this lanthanum system.
mmol), Trost ligand H3L1 (0.024 mmol), THF (1 mL), 8 h, 0 C;
o
bIsolated yield; cDetermined by chiral HPLC.
The starting ketone 5c was reduced by HBPin on a gram scale to
get a satisfactory yield and the absolute configuration of the
reduced products 6c was unambiguously determined by the X-ray
diffraction analysis from the single crystal, and further supported
by both chiral HPLC and optical rotation analysis (SI, Fig. S6). The
stereochemistry was assigned to all products by analogy.
6
7
8
9
Encouraged by the good performance of La-catalyzed
enantioselective hydroboration of aryl methyl ketones, a few
ketones other than methyl ketones, for instance cyclic ketone 7a,
steric hindered ketone 7b, diaryl ketones 7c, and ,-unsaturated
ketones 7d-7e were investigated with reductant HBpin. The yields
of the corresponding alcohols are still high (82-99%), nevertheless,
a dramatically decrease of the enantioselectivities were observed,
for 56% ee of 8a, 16% ee of 8b, 17% ee of 8c, and 58% ee of 8d,
and 30% ee of 8e. It is speculated that the mismatching of the
relative bulky ketones with the catalytic species may cause the poor
enantioselectivities. The catalyst 4 exhibited high to excellent
chemoselectivity in the hydroboration of a variety of unsaturated
groups, substrates containing –NO2, CN, CO2Et, C=C and CC
group tolerated (6s-6v, and 8d-8e). In general, the results of
enantioselective hydroboration of methyl ketones catalyzed by our
chiral rare-earth metal catalyst are comparable to a few published
work,23d but a bit less than others.23a-d
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In order to gain a deeper insight into the mechanism of the
hydroboration, the structure of complex 1 in THF was confirmed
by a DOSY NMR analysis. The 1H DOSY spectrum (Fig. S7,
diffusion coefficient Dt determined as 4.368 × 10−10 m2/s) shows
that the hydrodynamic radius (rh) of complex 1 in THF-d8 is
9.10.4 Å (calculated by Stocks-Einstein equation), which is
comparable to the corresponding value of 9.10.4 Å, calculated
from crystals 1 according to the known method25. It reveals that
complex 1 has the same binuclear structure whether in THF or be
solid-state. To make clear of the existing way of the catalyst during
the reaction, treatment of complex 1 and acetophenone was
1
monitored by an in situ DOSY NMR analysis, too. The H DOSY
spectrum (Fig. S8, diffusion coefficient Dt determined as 4.762 ×
10−10 m2/s) shows that the hydrodynamic radius of the complex in
THF-d8 is 9.70.5 Å, which can be roughly inferred that the
catalyst does not dissociate and maintains a dual-core structure
during the reaction.
Scheme 2. Enantioselective hydroboration of ketones catalyzed by
La[N(SiMe3)2]3 combined with H3L1a
8 mol% La[N(SiMe3)2]3
8 mol% H3L1
O
OH
SiO2/EA
O
O
R1 R2
R1 R2
6a-z: R1= Ar, R2 = CH3
B
C
THF, 8 h, 0
H
Following the experimental results, the DFT calculations with
Gaussian 16 software package26 were performed to gain insight into
the reaction pathway and to define the origin of the
enantioselectivity. The reaction profiles were determined in silico
for acetophenone and HBPin promoted by catalyst 4 in THF (Fig.
4). Based on the previous work27, the coordination of ketone with
the catalyst via O⋯La interaction is more likely to occur. Nominally,
the direction of the coordination of ketone 5 to La center has two
possibilities. Complex AS, compared with complex AR, is
calculated to be thermodynamically favored with an energy span of
3.2 kcal∙mol-1, which is supposed to rationalize the stereoinduction
(Fig. 5). Subsequently, the reductant HBPin coordinate to the
alkoxy oxygen atom of complex AS to give complex BS with a
relative energy of -2.5 kcal∙mol-1, which surmounts an energy
barrier (TS1S) of 16.8 kcal∙mol-1 to realize the hydride transfer,
giving IntS with a relative energy of -20.5 kcal∙mol-1. Then, the
borate moiety in IntS transfers to the oxygen atom of the original
ketone to construct complex CS via a tetracyclic TS2S, overcoming
an energy barrier of 4.4 kcal∙mol-1. Finally, the liberation of the
target borate PS from complex CS overcomes the energy barrier of
0.9 kcal∙mol-1. The computed energy profile reveals that the
hydride transfer (complex BS  IntS) is predicted to be the rate-
determining step (Fig. 4). The red curve in Fig.5 shows the
formation of the R- product, obviously, each complex AR, complex
BR, complex CR, TSR, and IntR has higher energy barrier than the
corresponding S- enantiomer’s. Thus, the S-enantiomer is the major
product.
5a-z
7a-e
2 equiv
8a-e: R1= Ar, R2 = alkyl, alkenyl, alkynyl, or aryl
OH
OH
OH
OH
OH
OH
6a
6b
6f
6c
6d
6e
yield: 99%
ee: 90%
yield: 99%
ee: 92%
yield: 99%
ee: 84%
yield: 99%
ee: 82%
yield: 99%
ee: 90%
yield: 99%
ee: 95%
OMe
OEt OH
OH
OH
OH
F
OH
MeO
MeO
6h
yield: 99%
ee: 83%
6i
6j
6g
6k
yield: 98%
ee: 84%
yield: 98%
ee: 87%
yield: 99%
ee: 93%
yield: 99%
ee: > 99 %
OH
Cl
OH
OH
OH
Cl
OH
Cl
F
Cl
Cl
6p
6l
6o
6m
6n
yield: 98%
ee: 90%
yield: 98%
ee: 93%
yield: 99%
ee: 74%
yield: 99%
ee: 88%
yield:98%
ee:93%
NO2 OH
CF3 OH
OH
Br OH
CN OH
O2N
OH
6q
6r
6s
6t
6u
yield: 99%
ee: 88%
yield: 99%
ee: 82%
yield: 99%
ee: 91%
yield: 99%
ee: 89%
yield: 96%
ee: 75%
OH
HO
OH
N
OH
S
MeOOC
6y
6z
6x
6v
6w
yield: 99%
ee: 78%
yield:98%
ee:86%
yield: 99%
ee: 92%
yield: 99%
ee: 83%
yield: 99%
ee: 15%
Thus, a possible mechanism of the catalytic transformation in
current system was depicted in Scheme 3. As we mentioned before,
the steric hindrance of RE1 atom is significantly less than that of
the RE2 atom, which lead to the unique opportunity of ketone 5a to
coordinate with catalyst 4 by RE1 atom. So catalysts are simplified
as [REL], while the second half containing RE2 is omitted for
clarity. Initially, the substrate ketone 5a coordinates to the rare-
earth metal to give complex AS, followed by the coordination of
reducing agent HBPin with the alkoxy oxygen via boron atom to
OH
OH
OH
OH
OH
8a
8b
8c
8d
8e
yield: 94%
ee: 56%
yield: 82%
ee: 16%
yield: 87%
ee: 17%
yield: 83%
ee: 58%
yield: 99%
ee: 30%
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generate complex BS. Hydride migration to carbonyl carbon takes
place to produce IntS through TS1S, then -bond metathesis of O-B
and O-RE occurs to yield complex C via a tetracyclic TS2S. Finally,
the dissociation of the desired borate PS is concerted with the
regeneration of catalyst 4.
5
6
7
8
9
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15.4
TS1R
14.3
TS1S
-2.1
0.0
HBPin
-2.4
Complex BR
Complex AR
[LaL]2
-3.9
TS2R
-2.5
Complex BS
5a
-5.6
Complex AS
-13.8
IntR
-16.1
TS2S
-20.5
IntS
-21.9
Complex CR
PR
-26.0
-27.1
Complex CS
PS
[LaL]2
Figure 4. Plausible reaction profile of reduction of acetophenone to 1-phenyl-1-ethanol promoted by catalyst 4: blue curve for the formation
of S-enantiomer and red for R-enantiomer. The hydrogen atoms except for the transferring
H
are omitted for clarity.
O
O
O
H3C
5a
Ph
O
RE
N
O
O
O
O
N
O
O
[REL]
O
RE
N
RE
N
PinB
O
Ph
CH3
N
N
O
O
O
Ph
CH3
H
P
Ph
O
B
HBPin
H
O
O
CH3
Complex AS
Complex CS
O
O
O
O
O
3.3 Kcal/mol Disfavored
OH
RE
0 Kcal/mol Favored
N
O
RE
N
N
N
Figure 5. Optimized geometries of complex AS (left) and complex
AR (right)
Ph
O
O
Ph
O
O
B
O
O
H
CH3
B
H
CH3
O
TS2S
Complex BS
O
O
N
O
O
O
O
RE
N
O
RE
N
N
Ph
O
O
Ph
O
O
B
O
O
H
H
CH3
B
CH3
O
IntS
TS1S
Scheme 3. The possible mechanism of enantioselective
hydroboration of ketones catalyzed by [REL]2
CONCLUSION
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In summary, four novel chiral dinuclear rare-earth metal complexes
12.1 Hz, 4H), 2.54 – 2.43 (m, 4H), 2.21 (s, 6H), 2.09 – 1.95 (m,
2
3
4
5
6
7
8
9
stabilized by Trost ligand were synthesized in high yields and
structurally as well as spectroscopically characterized. The La-
based complex 4 showed excellent catalytic activities and high
enantioselectivities in asymmetric hydroboration of various methyl
ketones. The same outcome was also achieved using the
combination of lanthanium amides La[N(SiMe3)2]3 and Trost
proligand H3L1 in 1:1 molar ratio. The absolute configuration of the
desired alcohols was determined by the X-ray diffraction analysis
for the first time. A detailed reaction mechanism fully confirming
our empirical observations is proposed on the basis of
computational studies.
4H), 1.72 (dq, J = 13.1, 6.9 Hz, 4H), 1.54 – 1.26 (m, 8H);
13C{1H} NMR (101 MHz, C6D6) δ 156.0, 153.4, 151.8, 132.9,
127.3, 127.1, 127.0, 126.9, 125.7, 125.5, 125.4, 83.1, 80.0, 59.1,
53.2, 28.8, 20.9, 20.8; Anal. calcd for C86H86Y2N4O6∙2DME: C,
69.28; H, 6.56; N, 3.44; Found C, 70.17; H, 6.43; N, 3.52; IR
(KBr, cm-1)  2953, 2870, 1473, 1446, 1300, 1273, 1256, 1064,
971, 796, 756, 741, 704, 696.
Complex Eu2L1 (2): colorless crystals, 0.67 g, yield 85%;
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Anal. calcd for C86H86Eu2N4O6∙DME: C, 64.90; H, 5.81; N, 3.36;
Found C, 64.56; H, 5.84; N, 3.33; IR (KBr, cm-1)  3054, 3016,
2849, 1595, 1470, 1446, 1297, 1259, 1225, 1063, 973, 891, 795,
762, 740, 705, 669.
EXPERIMENTAL SECTION
General Procedures. All reagents are commercially available,
reagent grade, and used as received unless otherwise noted.
Experiments involving air and moisture sensitive components
were performed in glovebox or using the standard Schlenk
techniques with freshly distilled solvents. Solvents, such as THF,
DME and hexane, were degassed and distilled from sodium
benzophenone ketyl before use. Various readily available ketones
were distilled after treatment with calcium hydride. Flash
chromatography was performed using 200-300 mesh silica gel
Complex Nd2L1 (3): yellow crystals, 0.68 g, yield 87%; Anal.
calcd for C86H86Nd2N4O6∙2DME: C, 64.87; H, 6.14; N, 3.22;
Found C, 64.32; H, 6.04; N, 3.31; IR (KBr, cm-1)  2973, 2848,
1469, 1446, 1296, 1260, 1064, 973, 891, 796, 753, 740, 705, 669.
2
Complex La2L1 (4): colorless crystals, 0.71 g, yield 91%; H
1
2
NMR (500 MHz, C6D6) δ 7.59 (dd, J = 26.1, 7.2 Hz, 8H), 7.06 –
6.97 (m, 8H), 6.91 (s, 4H), 6.71 (t, J = 6.8 Hz, 2H), 4.09 (s, 2H),
3.88 (d, J = 11.9 Hz, 2H), 3.36 (d, J = 1.5 Hz, 2H), 3.09 (s, 2H),
2.78 (d, J = 12.0 Hz, 2H), 2.48 (d, J = 8.5 Hz, 2H), 2.21 (s, 3H),
2.11 (d, J = 6.1 Hz, 3H), 1.91 (s, 4H); 13C{1H} NMR (126 MHz,
C6D6) δ 157.12, 153.4, 134.7, 129.0, 128.1, 127.9, 127.6, 127.5,
127.3, 126.1, 125.9, 86.0, 80.9, 69.1, 59.2, 54.5, 32.6, 30.1, 26.1,
23.6, 22.4, 21.3, 15.1; Anal. calcd for C86H86La2N4O6∙DME∙THF:
C, 65.96; H, 6.12; N, 3.27; Found C, 65.08; H, 6.02; N, 3.27; IR
(KBr, cm-1)  2961, 1558, 1467, 1446, 1363, 1304, 1263, 1065,
974, 904, 870, 797, 746, 704, 668.
with freshly distilled solvents with
a SepaBean machine
instrument. Different types of commercial silica flash columns
were used and equilibrated with the appropriate solvent system
prior to use. Carbon, hydrogen and nitrogen analyses were
performed by direct combustion with Thermo Scientific Flash
Smart Elemental Analyzer instrument. IR spectra were recorded
with a VERTEX 70+HYPERION 2000 instrument. Melting points
of all solid compounds were measured by the SGW-630 automatic
image melting point instrument. Nuclear magnetic resonance
spectra were obtained on a Bruker-400/500 MHz apparatus
(CDCl3, C6D6 and THF-d8 were used as solvents). Chemical shifts
for NMR spectra are reported in units of parts per million (ppm)
downfield from SiMe4 (0.0) and relative to the signal of the
deuterated solvent. Multiplicities were given as s (singlet); d
(doublet); t (triplet); q (quartet); dd (doublets of doublet); or m
(multiplets). High Resolution Mass spectra were obtained using
Bruker ESI-TOF. HPLC analysis was performed on SHIMADZU
General Procedure for the Hydroboration Reaction of
Ketones. RE[N(SiMe3)2]3 (0.024 mmol) was added to a solution
of H3L1 (0.024 mmol) in THF (0.5 mL). The reaction was stirred
at room temperature for 1 h. HBpin (0.6 mmol) was added in one
portion and the mixture was stirred at room temperature for
additional 30 min before the corresponding ketone (0.3 mmol) in
o
o
0.5 mL THF was added at 0 C. After stirring for 8 h at 0 C, the
reaction mixture was quenched with SiO2 (1 g) and the solvent
was evaporated. The residue was purified by flash column
chromatography on silica gel to afford the pure chiral alcohol. The
enantiomeric excess of the alcohol was determined by HPLC
analysis on a chiral stationary phase. Or simply add complexes 1-
4 in the system to replace the treatment of RE[N(SiMe3)2]3 with
chiral ligand H3L1.
LC-20AD instrument equipped with
a quaternary pump,
o
employing a Daicel Chiralcel column at 35 C. Optical rotation
was measured using a SGW-2 Polarimeter equipped with a
sodium vapor lamp at 589 nm. Absolute configuration of the
products was determined by the crystal structure of product 6c
and comparison with known compounds in literature.8, Hence,
28
6g, 6p, 6s was assigned by analogy, assuming a common reaction
pathway. Suitable single crystals of complexes 1-4 and 6c were
loaded quickly and directly on the Rigaku Mercury CCD
instrument.
General Procedure for Gram-scale Hydroboration of 5c. A
THF (1 mL) solution of La[N(SiMe3)2]3 (0.4960 g, 0.8 mmol)
was added to a solution of H3L1 (0.5110 g, 0.8 mmol) in THF (1.0
mL). The reaction was stirred at room temperature for 1 h. HBpin
(2.92 mL, 20.2 mmol) was added in one portion and the mixture
was stirred at room temperature for additional 30 min before the
ketone 5c (1.50 g, 10.1 mmol) in THF (1.0 mL) was added at 0
oC. After stirring for 8 h at 0 oC, the reaction mixture was
quenched with SiO2 (5 g) and the solvent was evaporated. The
residue was purified by flash column chromatography on silica
gel to afford the pure chiral alcohol 6c (1.39 g, yield 92%). The
enantiomeric excess of 6c (90% ee) was determined by HPLC
analysis on a chiral stationary phase.
General Procedure for the Preparation of Complexes 1-4.
To a THF (5 mL) solution of proligand H3L1 (0.6388 g, 1 mmol),
a solution of RE[N(SiMe3)2]3 (1 mmol) in THF was added slowly.
The mixture was stirred at room temperature for 12 h. After THF
was removed under vacuum, the solid residue was washed with
hexane to remove HN(SiMe3)2. Crystals were obtained at room
temperature from a solution in a mixed solvent of DME and THF.
Characteristic Data of Complexes 1-4.
Complex Y2L1 (1): colorless crystals, 0.49 g, yield 67%; H
1
2
NMR (400 MHz, C6D6) δ 7.53 (d, J = 7.6 Hz, 8H), 7.18 (d, J =
6.7 Hz, 8H), 7.04 – 6.91 (m, 20H), 6.85 (t, J = 7.3 Hz, 4H), 6.69
(s, 4H), 3.86 – 3.65 (m, 8H), 3.20 – 3.11 (m, 4H), 2.58 (d, J =
Characteristic Data of Alcohols 6 and 8.
(S)-1-phenylethan-1-ol (6a): colorless oil, 36.3 mg, yield 99%;
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[]20D = -40.30 (c = 0.22 in CHCl3); 1H NMR (400 MHz, CDCl3)
δ 7.40-7.23 (m, 5H), 4.88 (q, J = 6.5 Hz, 1H), 1.99 (s, 1H), 1.49
(d, J = 6.5 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3): δ 145.8,
128.5, 127.5, 125.4, 70.4, 25.2; 92% ee, HPLC Daicel column IB,
yield 99%; []20 = -24.15 (c = 0.294 in CHCl3); H NMR (400
1
D
MHz, CDCl3) δ 7.33 (dd, J = 7.5, 1.6 Hz, 1H), 7.25 – 7.17 (m,
1H), 6.93 (td, J = 7.5, 0.9 Hz, 1H), 6.84 (dd, J = 8.2, 0.5 Hz, 1H),
5.07 (d, J = 5.8 Hz, 1H), 3.80 (s, 3H), 2.95 (s, 1H), 1.46 (d, J =
6.5 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 156.3, 133.5,
128.1, 125.9, 120.7, 110.3, 66.0, 55.1, 22.9; 83% ee, HPLC
i
98% hexanes, 2% PrOH, 1.0 mL/min, 9.7 min (minor), 10.7 min
(major); HRMS (ESI-MS) m/z [M+Na]+ calcd for C8H10ONa
145.0624, found 145.0633.
i
Daicel column IB, 98% hexanes, 2% PrOH, 1.0 mL/min, 11.9
(S)-1-(o-tolyl)ethan-1-ol (6b): colorless oil, 40.3 mg, yield 99%;
[]20D = -65.60 (c = 0.17 in CHCl3); 1H NMR (400 MHz, CDCl3)
δ 7.49 (d, J = 7.4 Hz, 1H), 7.31-7.02 (m, 3H), 5.10 (q, J = 6.4 Hz,
1H), 2.33 (s, 3H), 1.89 (s, 1H), 1.45 (d, J = 6.4 Hz, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 143.9, 134.2, 130.4, 127.2, 126.4,
124.5, 66.8, 23.9, 18.9; 90% ee, HPLC Daicel column IE, 99%
min (major), 12.6 min (minor); HRMS (ESI-MS) m/z [M+Na]+
calcd for C9H12O2Na 175.0730, found 175.0730.
9
(S)-1-(3-Methoxyphenyl)ethan-1-ol (6i): colorless oil, 44.5 mg,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
yield 98%; []20 = -37.15 (c = 0.253 in CHCl3); H NMR (400
1
D
MHz, CDCl3) δ 7.21 – 7.14 (m, 1H), 6.86 (dd, J = 4.4, 2.4 Hz,
2H), 6.73 (ddd, J = 8.3, 2.5, 0.8 Hz, 1H), 4.78 (q, J = 6.4 Hz, 1H),
3.73 (s, 3H), 1.87 (s, 1H), 1.40 (d, J = 6.5 Hz, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ 159.8, 147.6, 129.5, 117.7, 112.9, 110.9,
70.3, 55.2, 25.1; 84% ee, HPLC Daicel column IB, 98% hexanes,
i
hexanes, 1% PrOH, 1.0 mL/min, 11.3 min (minor), 12.3 min
(major); HRMS (ESI-MS) m/z [M+Na]+ calcd for C9H12ONa
159.0781, found 159.0781.
i
(S)-1-(2,6-dimethylphenyl)ethan-1-ol (6c): white powder, mp 71-
72 oC, 44.8 mg, yield 99%; []20D = -78.95 (c = 0.247 in CHCl3);
1H NMR (400 MHz, CDCl3) δ 6.99 (dt, J = 20.4, 6.7 Hz, 3H),
5.31 (q, J = 6.8 Hz, 1H), 2.40 (s, 6H), 2.08 (s, 1H), 1.48 (d, J =
6.8 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 140.6, 135.6,
129.3, 126.9, 67.5, 21.3, 20.6; 95% ee, HPLC Daicel column IB,
99% hexanes, 1% iPrOH, 1.0 mL/min, 11.2 min (major), 14.0 min
(minor); HRMS (ESI-MS) m/z [M+Na]+ calcd for C10H14ONa
173.0937, found 173.0937.
2% PrOH, 1.0 mL/min, 17.4 min (minor), 18.6 min (major);
HRMS (ESI-MS) m/z [M+Na]+ calcd for C9H12O2Na 175.0730,
found 175.0732.
(S)-1-(4-methoxyphenyl)ethan-1-ol (6j): colorless oil, 44.8 mg,
yield 98%; []20 = -58.50 (c = 0.174 in CHCl3); H NMR (400
1
D
MHz, CDCl3) δ 7.30 – 7.22 (m, 2H), 6.90 – 6.82 (m, 2H), 4.77 (q,
J = 6.4 Hz, 1H), 3.77 (s, 3H), 3.29 (s, 1H), 1.44 (d, J = 6.5 Hz,
3H); 13C{1H} NMR (101 MHz, CDCl3) δ 158.4, 138.0, 126.4,
113.4, 69.3, 54.9, 24.8; 87% ee, HPLC Daicel column IB, 98%
(S)-1-mesitylethan-1-ol (6d): white powder, mp 58-60 oC, 48.9
hexanes, 2% PrOH, 1.0 mL/min, 9.5 min (major), 10.2 min
i
(minor); HRMS (ESI-MS) m/z [M+Na]+ calcd for C9H12O2Na
175.0730, found 175.0730.
1
mg, yield 99%; []20 = -80.72 (c = 0.223 in CHCl3); H NMR
D
(400 MHz, CDCl3) δ 6.79 (s, 2H), 5.30 (q, J = 6.8 Hz, 1H), 2.38
(s, 6H), 2.23 (s, 3H), 1.98 (s, 1H), 1.48 (d, J = 6.8 Hz, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 137.7, 136.3, 135.6, 130.1,
67.4, 21.5, 20.6; 84% ee, HPLC Daicel column IE, 99% hexanes,
(S)-1-(2-fluorophenyl)ethan-1-ol (6k): colorless oil, 41.6 mg,
1
yield 99%; []20 = -48.38 (c = 0.184 in CHCl3); H NMR (400
D
i
MHz, CDCl3) δ 7.46 (td, J = 7.6, 1.7 Hz, 1H), 7.27 – 7.18 (m,
1H), 7.13 (td, J = 7.5, 0.9 Hz, 1H), 7.00 (ddd, J = 10.5, 8.2, 1.0
Hz, 1H), 5.17 (dd, J = 6.2, 2.7 Hz, 1H), 2.38 (d, J = 2.9 Hz, 1H),
1.49 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
159.7 (d, J = 245.3 Hz), 132.7 (d, J = 13.3 Hz), 128.7 (d, J = 8.2
Hz), 126.7 (d, J = 4.6 Hz), 124.3 (d, J = 3.3 Hz), 115.3 (d, J =
21.8 Hz), 64.5, 24.0; 19F NMR (376 MHz, CDCl3) δ -120.1; >99%
1% PrOH, 1.0 mL/min, 9.9 min (minor), 11.0 min (major);
HRMS (ESI-MS) m/z [M+Na]+ calcd for C11H16ONa 187.1094,
found 187.1096.
(S)-1-(m-tolyl)ethan-1-ol (6e): colorless oil, 40.2 mg, yield 99%;
[]20 = -44.21 (c = 0.216 in CHCl3); 1H NMR (400 MHz,
D
CDCl3) δ 7.28 – 7.04 (m, 4H), 4.85 (q, J = 6.4 Hz, 1H), 2.35 (s,
3H), 1.92 (s, 1H), 1.48 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ 145.8, 138.2, 128.4, 128.2, 126.1, 122.5, 70.4,
25.1, 21.5; 82% ee, HPLC Daicel column IB, 98% hexanes, 2%
iPrOH, 1.0 mL/min, 8.7 min (minor), 9.7 min (major); HRMS
(ESI-MS) m/z [M+Na]+ calcd for C9H12ONa 159.0781, found
159.0783.
i
ee, HPLC Daicel column OD-H, 98% hexanes, 2% PrOH, 1.0
mL/min, 10.6 min (major); HRMS (ESI-MS) m/z [M+Na]+ calcd
for C8H9FONa 163.0530, found 163.0526.
(S)-1-(4-fluorophenyl)ethan-1-ol (6l): colorless oil, 41.0 mg, yield
98%; []20 = -40.51 (c = 0.168 in CHCl3); H NMR (400 MHz,
CDCl3) δ 7.33 (dd, J = 8.4, 5.6 Hz, 2H), 7.02 (t, J = 8.7 Hz, 2H),
4.87 (q, J = 6.4 Hz, 1H), 2.01 (s, 1H), 1.47 (d, J = 6.5 Hz, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 162.1 (d, J = 245.1 Hz),
141.5 (d, J = 3.1 Hz), 127.1 (d, J = 8.1 Hz), 115.3 (d, J = 21.3
Hz), 69.8, 25.3; 19F NMR (377 MHz, CDCl3) δ -115.4; 90% ee,
1
D
(S)-1-(p-tolyl)ethan-1-ol (6f): colorless oil, 40.5 mg, yield 99%;
[]20 = -72.57 (c = 0.141 in CHCl3); 1H NMR (400 MHz,
D
CDCl3) δ 7.19 (d, J = 8.2 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 4.79
(q, J = 6.4 Hz, 1H), 2.27 (s, 3H), 1.72 (s, 1H), 1.41 (d, J = 6.4 Hz,
3H); 13C{1H} NMR (101 MHz, CDCl3) δ 142.84 (s), 137.1, 129.1,
125.3, 70.2, 25.1, 21.1; 90% ee, HPLC Daicel column IA, 98%
i
HPLC Daicel column IA, 98% hexanes, 2% PrOH, 1.0 mL/min,
i
16.5 min (major), 17.5 min (minor); HRMS (ESI-MS) m/z
hexanes, 2% PrOH, 1.0 mL/min, 13.6 min (minor), 14.5 min
[M+Na]+ calcd for C8H9FONa 163.0530, found 163.0523.
(major); HRMS (ESI-MS) m/z [M+Na]+ calcd for C9H12ONa
159.0781, found 159.0784.
(S)-1-(2-Chlorophenyl)ethan-1-ol (6m): colorless oil, 46.2 mg,
1
yield 98%; []20 = -38.55 (c = 0.189 in CHCl3); H NMR (400
(S)-1-(2-ethoxyphenyl)ethan-1-ol (6g): colorless oil, 49.3 mg,
D
1
yield 99%; []20 = -33.48 (c = 0.233 in CHCl3); H NMR (400
MHz, CDCl3) δ 7.58 (dd, J = 7.7, 1.7 Hz, 1H), 7.30 (ddd, J =
15.3, 7.7, 1.2 Hz, 2H), 7.19 (td, J = 7.6, 1.7 Hz, 1H), 5.28 (q, J =
6.3 Hz, 1H), 2.19 (s, 1H), 1.48 (d, J = 6.4 Hz, 3H); 13C{1H} NMR
(101 MHz, CDCl3) δ 143.1, 131.7, 129.4, 128.4, 127.2, 126.4,
67.0, 23.5; 93% ee, HPLC Daicel column IE, 99% hexanes, 1%
iPrOH, 1.0 mL/min, 10.3 min (minor), 12.1 min (major); HRMS
(ESI-MS) m/z [M+Na]+ calcd for C8H9ClONa 179.0234, found
179.0238.
D
MHz, CDCl3) δ 7.31 (dd, J = 7.5, 1.6 Hz, 1H), 7.24 – 7.15 (m,
1H), 6.92 (td, J = 7.5, 0.9 Hz, 1H), 6.84 (d, J = 8.2 Hz, 1H), 5.07
(q, J = 5.9 Hz, 1H), 4.05 (q, J = 7.0 Hz, 2H), 2.96 (s, 1H), 1.49 (d,
J = 6.5 Hz, 3H), 1.42 (t, J = 7.0 Hz, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ 155.8, 133.5, 128.1, 126.1, 120.6, 111.2, 66.6,
63.5, 22.9, 14.8; 93% ee, HPLC Daicel column OD-H, 98%
i
hexanes, 2% PrOH, 0.8 mL/min, 12.2 min (major), 13.6 min
(minor); HRMS (ESI-MS) m/z [M+Na]+ calcd for C10H14O2Na
189.0886, found 189.0886.
(S)-1-(3-chlorophenyl)ethan-1-ol (6n): colorless oil, 46.6 mg,
1
yield 99%; []20 = -52.53 (c = 0.211 in CHCl3); H NMR (400
D
MHz, CDCl3) δ 7.29 (d, J = 1.7 Hz, 1H), 7.22 – 7.13 (m, 3H),
(S)-1-(2-Methoxyphenyl)ethan-1-ol (6h): colorless oil, 45.0 mg,
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The Journal of Organic Chemistry
4.78 (q, J = 6.5 Hz, 1H), 1.95 (s, 1H), 1.39 (d, J = 6.5 Hz, 3H);
7.46 (t, J = 7.5 Hz, 1H), 7.35 – 7.31 (m, 1H), 5.55 (q, J = 6.6 Hz,
2
13C{1H} NMR (101 MHz, CDCl3) δ 147.9, 134.4, 129.8, 127.5,
125.7, 123.6, 69.8, 25.2; 88% ee, HPLC Daicel column OD-H,
99% hexanes, 1% iPrOH, 1.0 mL/min, 18.7 min (major), 20.0 min
(minor); HRMS (ESI-MS) m/z [M+Na]+ calcd for C8H9ClONa
179.0234, found 179.0237.
1H), 1.58 (d, J = 6.6 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
148.5, 132.1, 128.7, 121.2, 79.6, 20.9. 75% ee, HPLC Daicel
3
4
5
6
i
column IC, 95% hexanes, 5% PrOH, 1.0 mL/min, 15.7 min
(major), 18.9 min (minor); HRMS (ESI-MS) m/z [M+Na]+ calcd
for C9H9NONa 170.0576, found 170.0584.
7
8
9
(S)-1-(4-chlorophenyl)ethan-1-ol (6o): colorless oil, 46.1 mg,
Methyl (S)-4-(1-hydroxyethyl)benzoate (6v): colorless oil, 53.2
yield 98%; []20 = -50.89 (c = 0.226 in CHCl3); H NMR (400
mg, yield 99%; []20 = -38.52 (c = 0.257 in CHCl3); H NMR
1
1
D
D
MHz, CDCl3) δ 7.31 (s, 4H), 4.88 (q, J = 6.4 Hz, 1H), 1.86 (s,
(400 MHz, CDCl3) δ 7.99 – 7.91 (m, 2H), 7.40 (t, J = 7.8 Hz, 2H),
1H), 1.47 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
144.3, 133.1, 128.7, 126.8, 69.8, 25.3; 93% ee, HPLC Daicel
4.90 (q, J = 6.5 Hz, 1H), 3.88 (s, 3H), 3.07 (s, 1H), 1.46 (d, J =
6.5 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 167.0, 151.1,
129.6, 128.8, 125.2, 69.6, 52.0, 25.1; 86% ee, HPLC Daicel
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
i
column OD-H, 98% hexanes, 2% PrOH, 1.0 mL/min, 12.5 min
(major), 13.7 min (minor); HRMS (ESI-MS) m/z [M+Na]+ calcd
for C8H9ClONa 179.0235, found 179.0235.
column OD-H, 98% hexanes, 2% PrOH, 1.0 mL/min, 14.6 min
i
(minor), 15.6 min (major); HRMS (ESI-MS) m/z [M+Na]+ calcd
for C10H12O3Na 203.0679, found 203.0678.
(S)-1-(2,6-dichlorophenyl)ethan-1-ol (6p): colorless oil, 56.6 mg,
yield 99%; []20 = -27.10 (c = 0.059 in CHCl3); H NMR (400
1
(S)-1-(naphthalen-1-yl)ethan-1-ol (6w): colorless oil, 51.2 mg,
D
yield 99%; []20 = -54.33 (c = 0.343 in CHCl3); H NMR (400
1
MHz, CDCl3) δ 7.27 (d, J = 8.0 Hz, 2H), 7.11 (dd, J = 8.5, 7.6 Hz,
D
1H), 5.59 (dq, J = 10.0, 6.9 Hz, 1H), 3.07 (d, J = 10.0 Hz, 1H),
1.63 (d, J = 6.9 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ
138.6, 133.8, 129.3, 128.7, 68.2, 21.5; 74% ee, HPLC Daicel
MHz, CDCl3) δ 8.04 (d, J = 8.3 Hz, 1H), 7.83 (dd, J = 6.9, 2.6 Hz,
1H), 7.73 (d, J = 8.2 Hz, 1H), 7.61 (d, J = 7.1 Hz, 1H), 7.51 –
7.39 (m, 3H), 5.57 (q, J = 6.4 Hz, 1H), 2.21 (s, 1H), 1.60 (d, J =
6.5 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 141.4, 133.8,
130.3, 128.9, 127.9, 126.0, 125.5, 123.2, 122.0, 67.0, 24.3; 92%
ee, HPLC Daicel column IB, 98% hexanes, 2% iPrOH, 1.0
mL/min, 10.0 min (major), 13.2 min (minor); HRMS (ESI-MS)
m/z [M+Na]+ calcd for C12H12ONa 195.0780, found 195.0772.
(S)-1-(naphthalen-2-yl)ethan-1-ol (6x): white powder, mp 78-79
oC, 51.5 mg, yield 99%; []20D = -52.90 (c = 0.236 in CHCl3); 1H
NMR (400 MHz, CDCl3) δ 7.84 – 7.70 (m, 4H), 7.50 – 7.39 (m,
3H), 4.99 (q, J = 6.4 Hz, 1H), 2.21 (s, 1H), 1.53 (d, J = 6.5 Hz,
3H); 13C{1H} NMR (101 MHz, CDCl3) δ 143.2, 133.3, 132.9,
128.3, 127.9, 127.7, 126.1, 125.8, 123.8, 123.8, 70.5, 25.1; 83%
i
column OD-H, 99% hexanes, 1% PrOH, 1.0 mL/min, 10.7 min
(major), 11.7 min (minor); HRMS (ESI-MS) m/z [M+Na]+ calcd
for C8H8Cl2ONa 212.9844, found 212.9844.
(S)-1-(2-bromophenyl)ethan-1-ol (6q): colorless oil, 59.5 mg,
1
yield 99%; []20 = -44.45 (c = 0.432 in CHCl3); H NMR (400
D
MHz, CDCl3) δ 7.59 (d, J = 7.7 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H),
7.34 (t, J = 7.5 Hz, 1H), 7.12 (t, J = 6.9 Hz, 1H), 5.28 – 5.18 (m,
1H), 2.13 (s, 1H), 1.48 (d, J = 6.4 Hz, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ 144.7, 132.7, 128.8, 127.9, 126.7, 121.8, 69.2,
23.6; 91% ee, HPLC Daicel column IB, 99% hexanes, 1% iPrOH,
0.8 mL/min, 13.6 min (minor), 14.5 min (major); HRMS (ESI-
MS) m/z [M+Na]+ calcd for C8H9BrONa 222.9729, found
222.9723.
i
ee, HPLC Daicel column IA, 98% hexanes, 2% PrOH, 1.0
mL/min, 21.0 min (minor), 21.7 min (major); HRMS (ESI-MS)
(S)-1-(2-(trifluoromethyl)phenyl)ethan-1-ol (6r): colorless oil,
m/z [M+Na]+ calcd for C12H12ONa 195.0780, found 195.0776.
1
56.6 mg, yield 99%; []20 = -45.21 (c = 0.212 in CHCl3); H
(S)-1-(thiophen-2-yl)ethan-1-ol (6y): colorless oil, 38.0 mg, yield
D
1
NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.9 Hz, 1H), 7.57 (dd, J =
15.8, 7.8 Hz, 2H), 7.34 (t, J = 7.6 Hz, 1H), 5.30 (q, J = 5.8 Hz,
1H), 2.43 (s, 1H), 1.44 (d, J = 6.3 Hz, 3H); 13C{1H} NMR (101
MHz, CDCl3) δ 145.25 – 145.01 (m), 132.4, 127.2 (d, J = 19.6
Hz), 127.0, 126.5 (d, J = 30.1 Hz), 126.1, 125.8, 125.3 (q, J = 5.8
Hz), 65.7 (d, J = 2.3 Hz), 25.4; 19F NMR (377 MHz, CDCl3) δ -
58.4; 88% ee, HPLC Daicel column IA, 99% hexanes, 1% iPrOH,
1.0 mL/min, 8.7 min (minor), 10.5 min (major); HRMS (ESI-MS)
m/z [M+Na]+ calcd for C9H9F3ONa 213.0498, found 213.0503.
99%; []20 = -18.73 (c = 0.251 in CHCl3); H NMR (400 MHz,
D
CDCl3) δ 7.23 (dd, J = 4.8, 1.5 Hz, 1H), 7.00 – 6.93 (m, 2H), 5.13
(q, J = 6.4 Hz, 1H), 2.06 (s, 1H), 1.60 (d, J = 6.4 Hz, 3H);
13C{1H} NMR (101 MHz, CDCl3) δ 149.8, 126.6, 124.3, 123.1,
66.1, 25.1; 78% ee, HPLC Daicel column IC, 98% hexanes, 2%
iPrOH, 1.0 mL/min, 11.5 min (major), 12.6 min (minor); HRMS
(ESI-MS) m/z [M+Na]+ calcd for C6H8OSNa 151.0188, found
151.0192.
(S)-1-(pyridin-2-yl)ethan-1-ol (6z): colorless oil, 36.3 mg, yield
1
99%; []20 = -1.53 (c = 0.075 in CHCl3); H NMR (400 MHz,
(S)-1-(2-nitrophenyl)ethan-1-ol (6s): light yellow oil, 49.8 mg,
D
1
yield 99%; []20 = +21.37 (c = 0.323 in CHCl3); H NMR (400
CDCl3) δ 8.51 (d, J = 4.8 Hz, 1H), 7.68 (td, J = 7.7, 1.7 Hz, 1H),
7.33 – 7.10 (m, 2H), 4.88 (q, J = 6.5 Hz, 1H), 3.69 (s, 1H), 1.49 (d,
J = 6.6 Hz, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 163.0,
148.0, 136.9, 122.2, 119.8, 68.8, 24.2; 15% ee, HPLC Daicel
D
MHz, CDCl3) δ 7.85 (dd, J = 21.9, 8.0 Hz, 2H), 7.63 (t, J = 7.6
Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 5.39 (q, J = 6.4 Hz, 1H), 2.55 (s,
1H), 1.55 (d, J = 6.4 Hz, 3H);13C{1H} NMR (101 MHz, CDCl3) δ
147.8, 140.9, 133.6, 128.1, 127.5, 124.2, 65.5, 24.2; 82% ee,
i
column ID, 98% hexanes, 2% PrOH, 1.0 mL/min, 20.5 min
i
HPLC Daicel column IB, 99% hexanes, 1% PrOH, 1.0 mL/min,
(major), 25.6 min (minor); HRMS (ESI-MS) m/z [M+Na]+ calcd
for C7H9NONa 146.0576, found 146.0581.
20.0 min (minor), 21.1 min (major); HRMS (ESI-MS) m/z
[M+Na]+ calcd for C8H9NO3Na 190.0475, found 190.0475.
(S)-1,2,3,4-tetrahydronaphthalen-1-ol (8a): colorless oil, 41.5 mg,
1
yield 94%; []20 = -10.0 (c = 0.301 in CHCl3); H NMR (400
(S)-1-(4-nitrophenyl)ethan-1-ol (6t): yellow oil, 49.5 mg, yield
D
1
99%; []20 = -42.77 (c = 0.235 in CHCl3); H NMR (400 MHz,
MHz, CDCl3) δ 7.47 – 7.32 (m, 1H), 7.25 – 7.15 (m, 2H), 7.14 –
7.06 (m, 1H), 4.84 – 4.71 (m, 1H), 2.90 – 2.65 (m, 2H), 2.06 –
1.87 (m, 4H), 1.84 – 1.73 (m, 1H); 13C{1H} NMR (101 MHz,
CDCl3) δ 138.8, 137.1, 129.0, 128.7, 127.6, 126.2, 68.1, 32.3,
29.2, 18.8; 56% ee, HPLC Daicel column IB, 98% hexanes, 2%
iPrOH, 0.8 mL/min, 13.0 min (major), 13.9 min (minor); HRMS
(ESI-MS) m/z [M+Na]+ calcd for C10H12ONa 171.0780, found
171.0781.
D
CDCl3) δ 8.19 – 8.06 (m, 2H), 7.50 (t, J = 5.4 Hz, 2H), 4.98 (q, J
= 6.5 Hz, 1H), 2.72 (s, 1H), 1.47 (d, J = 6.5 Hz, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 153.2, 147.0, 126.1, 123.7, 69.4, 25.4;
i
89% ee, HPLC Daicel column IA, 98% hexanes, 2% PrOH, 1.0
mL/min, 31.9 min (minor), 32.9 min (major); HRMS (ESI-MS)
m/z [M+Na]+ calcd for C8H9NO3Na 190.0475, found 190.0475.
(S)-2-(1-hydroxyethyl)benzonitrile (6u): yellow oil, 42.5 mg, yield
1
96%; []20 = -42.53 (c = 0.325 in CHCl3); H NMR (400 MHz,
(S)-2,2-dimethyl-1-phenylpropan-1-ol (8b): colorless oil, 40.5 mg,
D
1
CDCl3) δ 7.84 (d, J = 7.5 Hz, 1H), 7.55 (td, J = 7.5, 1.0 Hz, 1H),
yield 82%; []20 = -4.32 (c = 0.125 in CHCl3); H NMR (400
D
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MHz, CDCl3) δ 7.32 – 7.21 (m, 5H), 4.34 (d, J = 2.1 Hz, 1H),
We gratefully acknowledge financial support from the National
2.05 (s, 1H), 0.90 (s, 9H); 13C{1H} NMR (101 MHz, CDCl3) δ
142.2, 127.6, 127.5, 127.2, 82.3, 35.5, 25.9; 16% ee, HPLC
Daicel column IB, 98% hexanes, 2% iPrOH, 1.0 mL/min, 6.5 min
(minor), 8.3 min (major); HRMS (ESI-MS) m/z [M+Na]+ calcd
for C11H16ONa 187.1093, found 187.1089.
Natural Science Foundation of China (Grant No. 21572151), the
Natural Science Foundation of the Jiangsu Higher Education
Institutions of China (Grant No. 19KJA320007), the project of
scientific and technologic infrastructure of Suzhou (SZS201708),
and PAPD.
(S)-phenyl(o-tolyl)methanol (8c): white powder, mp 92-93 oC,
51.8 mg, yield 87%; []20 = -14.84 (c = 0.291 in CHCl3); H
1
REFERENCES
D
NMR (400 MHz, CDCl3) δ 7.53 (dd, J = 7.5, 1.4 Hz, 1H), 7.37 –
(1) (a) Li, Z. Y.; Wang, M.; Bian, Q. H.; Zheng, B.; Mao, J. Y.; Li, S.
N.; Liu, S. Z.; Wang, M. A.; Zhong, J. C.; Guo, H. C. Highly
enantioselective addition of trimethylsilylacetylene to aldehydes
catalyzed by a zinc-amino-alcohol complex. Chem. Eur. J. 2011,
17, 5782-5786. (b) Periasamy, M.; Mohan, L.; Satyanarayana, I.;
Reddy, P. O. Enantioselective synthesis of -allenoates via
phosphine-catalyzed and ZnI2-promoted preparation of
oxazolidines and propargylamines using chiral amines, 1-alkynes,
and propiolates. J. Org. Chem. 2018, 83, 267-274.
9
7.14 (m, 8H), 5.99 (s, 1H), 2.35 (bs, 1H), 2.26 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 142.9, 141.5, 135.4, 130.5, 128.5,
127.6, 127.5, 127.1, 126.3, 126.1, 73.3, 19.4; 17% ee, HPLC
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
i
Daicel column IC, 98% hexanes, 2% PrOH, 1.0 mL/min, 12.1
min (major), 13.4 min (minor); HRMS (ESI-MS) m/z [M+Na]+
calcd for C14H14ONa 221.0937, found 221.0934.
(S)-1-phenylprop-2-yn-1-ol (8d): light yellow oil, 32.8 mg, yield
83%; []20 = 24.72 (c = 0.166 in CHCl3); H NMR (400 MHz,
1
(2) Quintard, A.; Constantieux, T.; Rodriguez, J. An Iron/amine-
D
catalyzed
cascade
process
for
the
enantioselective
CDCl3) δ 7.50 – 7.43 (m, 2H), 7.35 – 7.24 (m, 3H), 5.34 (dd, J =
functionalization of allylic alcohols. Angew. Chem. Int. Ed. 2013,
52, 12883-12887.
6.1, 2.1 Hz, 1H), 3.29 (s, 1H), 2.59 (d, J = 2.3 Hz, 1H); 13C{1H}
NMR (101 MHz, CDCl3) δ 139.9, 128.6, 128.4, 126.6, 83.5, 74.8,
64.2. 58% ee, HPLC Daicel column IA, 98% hexanes, 2% iPrOH,
1.0 mL/min, 15.5 min (major), 16.8 min (minor); HRMS (ESI-
MS) m/z [M+Na]+ calcd for C9H8ONa 155.0467, found 155.0477.
(3) Luo, K. X.; Zhao, Y. Q.; Zhang, J. W.; He, J.; Huang, R.; Yan,
S.J.; Lin, J.; Jin, Y. Enantioselective epoxypyrrolidines via a
tandem cycloaddition/autoxidation in air and mechanistic studies.
Org. Lett. 2019, 21, 423-427.
(4) Gao, E.; Li, M.; Duan, L. L.; Li, L.; Li, Y. M. Isosteric expansion
of the structural diversity of chiral ligands: design and application
of proline-based N, N’-dioxide ligands for coppercatalyzed
enantioselective Henry reactions. Tetrahedron 2019, 75, 130492-
130497.
(5) Qian, Q. Q.; Zhu, W. G.; Lu, C. R.; Zhao, B.; Yao, Y. M.
Asymmetric Michael addition of malonates to unsaturated
ketones catalyzed by rare earth metal complexes bearing phenoxy
functionalized chiral diphenylprolinolate ligands. Tetrahedron:
Asymmetry 2016, 27, 911-917.
(6) (a) Qian, Q. Q.; Tan, Y. F.; Zhao, B.; Feng, T.; Shen, Q.; Yao, Y.
M. Asymmetric epoxidation of unsaturated ketones catalyzed by
heterobimetallic rare earth-lithium complexes bearing phenoxy-
functionalized chiral diphenylprolinolate ligands. Org. Lett. 2014,
16, 4516-4519. (b) Zeng, C.; Yuan, D.; Zhao, B.; Yao, Y. M.
Highly enantioselective epoxidation of  -unsaturated ketones
catalyzed by rare-earth amides [(Me3Si)2N]3RE(-Cl)Li(THF)3
with phenoxy-functionalized chiral prolinols. Org. Lett. 2015, 17,
2242-2245.
(7) Fei, Z. H.; Zeng, C.; Lu, C. R.; Zhao, B.; Yao, Y. M. An efficient
asymmetric hydrophosphonylation of unsaturated amides
catalyzed by rare-earth metal amides [(Me3Si)2N]3RE(-
Cl)Li(THF)3 with phenoxyfunctionalized chiral prolinols. RSC
Adv. 2017, 7, 19306-19311.
(8) Song, P.; Lu, C. R.; Fei, Z. H.; Zhao, B.; Yao, Y. M.
Enantioselective reduction of ketones catalyzed by rare-earth
metals complexed with phenoxy modified chiral prolinols. J. Org.
Chem. 2018, 83, 6093-6100.
(9) (a) Trost, B. M.; Bartlett, M. ProPhenol-catalyzed asymmetric
aditions by spontaneously assembled dinuclear main group metal
complexes. Acc. Chem. Res. 2015, 48, 688-701. (b) Trost, B. M.;
Hung, C.-I.; Mata, G. Dinuclear metal-prophenol catalysts:
development and synthetic applications. Angew. Chem. Int. Ed.
2020, 59, 4240-4261, and references therein.
(10) (a) Li, H. J.; Tian, H. Y.; Wu, Y. C.; Chen, Y. J.; Liu, L.; Wang,
D.; Li, C. J. Aqueous asymmetric Mukaiyama Aldol reaction
catalyzed by chiral Gallium Lewis acid with Trost-type semi-
crown ligands. Adv. Synth. Catal. 2005, 347, 1247-1256. (b)
Baśand, S.; Mlynarski, J. Synthesis of 2-keto-D- and L-gluconic
acid via stereoselective direct Aldol reactions. J. Org. Chem.
2016, 81, 6112-6117.
(S,E)-1,3-diphenylprop-2-en-1-ol (8e): colorless oil, 62.7 mg,
1
yield 99%; []20 = -8.30 (c = 0.58 in CHCl3); H NMR (400
D
MHz, CDCl3) δ 7.44 – 7.31 (m, 6H), 7.30 – 7.25 (m, 3H), 7.24 –
7.18 (m, 1H), 6.65 (d, J = 15.8 Hz, 1H), 6.35 (dd, J = 15.8, 6.5
Hz, 1H), 5.33 (d, J = 6.5 Hz, 1H), 2.30 (s, 1H). 13C{1H} NMR
(101 MHz, CDCl3) δ 142.7, 136.5, 131.5, 130.5, 128.6, 128.5,
127.7, 126.6, 126.3, 75.0. 30% ee, HPLC Daicel column OD-H,
i
90% hexanes, 10% PrOH, 1.0 mL/min, 13.3 min (major), 16.8
min (minor); HRMS (ESI-MS) m/z [M+Na]+ calcd for
C15H14ONa 233.0937, found 233.0940.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: Experimental procedures, X-
ray data, and characterization data and HPLC chromatograms
(PDF)
Accession Codes
CCDC 1977347(1), 1977321(2), 1977340(3), 1977343(4), and
1977348(6c) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/data_request/cif,
or
by
emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
*E-mail: luchengrong@suda.edu.cn, zhaobei@suda.edu.cn.
Author Contributions
The manuscript was written through contributions of all authors. /
All authors have given approval to the final version of the
manuscript.
(11) (a) Zhao, D. P.; Wang, L. Q.; Yang, D. X.; Zhang, Y. X.; Wang,
ACKNOWLEDGMENT
R. Highly diastereo- and enantioselective synthesis of -alkyl
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Norstatine derivatives: catalytic asymmetric Mannich reactions of
Miller, Y. Development of non-C2-symmetric Prophenol ligands.
The asymmetric vinylation of N‑Boc imines. Org. Lett. 2015, 17,
3778-3781. (c) Huo, X. H.; He, R.; Zhang, X.; Zhang, W. B. An
Ir/Zn dual catalysis for enantio- and diastereodivergent -
allylation of -hydroxyketones. J. Am. Chem. Soc. 2016, 138,
11093-11096. (d) He, R.; Liu, P. L.; Huo, X. H.; Zhang, W. B.
Ir/Zn dual catalysis: enantioselective and diastereodivergent -
allylation of unprotected -hydroxy indanones. Org. Lett. 2017,
19, 5513-5516.
5H-Oxazol-4-ones. Angew. Chem. Int. Ed. 2012, 51, 7523-7527.
(b) Trost, B. M.; Hung, C.-I.; Gnanamani, E. Tuning the
reactivity of ketones through unsaturation: construction of cyclic
and acyclic quaternary stereocenters via Zn-ProPhenol catalyzed
Mannich reactions. ACS Catal. 2019, 9, 1549-1557. (c) Trost, B.
M.; Hung, C.-I.; Jiao, Z. W. Enantioselective divergent syntheses
of (+)-Bulleyanaline and related isoquinoline alkaloids from the
genus Corydalis. J. Am. Chem. Soc. 2019, 141, 16085-16092. (d)
Trost, B. M.; Gnanamani, E.; Hung, C.-I.; Kalnmals, C. A.
Synthesis of chiral, densely substituted pyrrolidones via
phosphine-catalyzed cycloisomerization. Org. Lett. 2019, 21,
1890-1894.
9
(19) (a) Xiao, Y. L.; Wang, Z.; Ding, K. L. Copolymerization of
cyclohexene oxide with CO2 by using intramolecular dinuclear
Zinc catalysts. Chem. Eur. J. 2005, 11, 3668-3678. (b) Xiao, Y.
L.; Wang, Z.; Ding, K. L. Intramolecularly dinuclear Magnesium
complex catalyzed copolymerization of cyclohexene oxide with
CO2 under ambient CO2 pressure: kinetics and mechanism.
Macromolecules 2006, 39, 128-137. (c) Netto, C. G. C. M.;
Toma, H. E. CO2 complexation and activation by a Trost-
bis(ProPhenol) Cobalt complex. Eur. J. Inorg. Chem. 2013, 5826-
5830. (d) Hua, Y. Z.; Lu, L. J.; Huang, P. J.; Wei, D. H.; Tang,
M. S.; Wang, M. C.; Chang, J. B. Highly enantioselective
catalytic system for asymmetric copolymerization of carbon
dioxide and cyclohexene oxide. Chem. Eur. J. 2014, 20, 12394-
12398. (e) Hua, Y. Z.; Yang, X. C.; Liu, M. M.; Song, X. X.;
Wang, M. C.; Chang, J. B. Asymmetric copolymerization of
cyclopentene oxide and CO2 using a dinuclear zinc−azephenol
catalyst: enlightened by DFT calculations. Macromolecules 2015,
48, 1651-1657.
(20) For recent papers, see: (a) Tsurugi, H.; Yamamoto, K.; Nagae,
H.; Kaneko, H.; Mashima, K. Direct functionalization of
unactivated C–H bonds catalyzed by group 3–5 metal alkyl
complexes. Dalton Trans. 2014, 43, 2331-2343. (b) Xiao, Y.;
Wang, Q. Y.; Zhao, B.; Yao, Y. M. C-N bond formation reaction
catalyzed by organo-rare-earth metal amides. Chin. J. Org. Chem.
2015, 35, 1598-1614. (c) Trifonov, A. A.; Basalovb, I. V.; Kissel,
A. A. Use of organolanthanides in the catalytic intermolecular
hydrophosphination and hydroamination of multiple C–C bonds.
Dalton Trans. 2016, 45, 19172–19193. (d) Gong, G.; Ding, H.;
Lu, C. R.; Zhao, B.; Yao, Y. M. An amidato divalent ytterbium
cluster: synthesis and molecular structure, its reactivity to
carbodiimides and application in the guanylation reaction. Dalton
Trans. 2017, 46, 6031-6038. (e) Lu, E.; Chu, J. X.; Chen, Y. F.
Scandium terminal imido chemistry. Acc. Chem. Res. 2018, 51,
557−566. (f) Lu, C. R.; Gong, C.; Zhao, B.; Hu, L. J.; Yao, Y. M.
RE[N(SiMe3)2]3-catalyzed guanylation/cyclization of amino acid
esters and carbodiimides. J. Org. Chem. 2018, 83, 1154-1159. (g)
Hu, L. J.; Lu, C. R.; Zhao, B.; Yao, Y. M. Intermolecular addition
of alcohols to carbodiimides catalyzed by rare-earth metal
amides. Org. Chem. Front. 2018, 5, 905-908. (h) Feng, Z. J.;
Huang, Z. M.; Wang, S. W.; Wei, Y.; Zhou, S. L.; Zhu, X. C.
Synthesis and characterization of 2-t-butyliminofunctionalized
indolyl rare-earth metal amido complexes for the catalytic
addition of terminal alkynes to carbodiimides: the dimeric
complexes with the alkynide species in the -1:2 bonding
modes. Dalton Trans. 2019, 48, 11094-11102. (i) Liu, X. J.;
Xiang, L.; Louyriac, E.; Maron, L.; Leng, X. B.; Chen, Y. F.
Divalent ytterbium complex-catalyzed homo- and cross-coupling
of primary arylsilanes. J. Am. Chem. Soc. 2019, 141, 138-142. (j)
Xie, Y. Q.; Lu, C. R.; Zhao, B.; Wang, Q. Y.; Yao, Y. M.
Cycloaddition of aziridine with CO2/CS2 catalyzed by amidato
divalent lanthanide complexes. J. Org. Chem. 2019, 84, 1951-
1958.
10
11
12
(12) (a) Trost, B. M.; Yeh, V. S. C.; Ito, H.; Bremeyer, N. Effect of
ligand structure on the Zinc-catalyzed Henry reaction.
Asymmetric syntheses of (-)-Denopamine and (-)-Arbutamine.
Org. Lett. 2002, 4, 2621-2623. (b) Trost, B. M.; Yeh, V. S. C. A
dinuclear Zn catalyst for the asymmetric Nitroaldol (Henry)
reaction. Angew. Chem. Int. Ed. 2002, 41, 861-863.
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(13) (a) Zhao, D. P.; Yuan, Y.; Chan, A. S.C.; Wang, R. Highly
enantioselective 1,4-addition of diethyl phosphite to enones using
a dinuclear Zn catalyst. Chem. Eur. J. 2009, 15, 2738-2741. (b)
Zhao, D. P.; Mao, L. J.; Wang, Y.; Yang, D. X.; Zhang, Q. L.;
Wang, R. Catalytic asymmetric hydrophosphinylation of  -
unsaturated N-acylpyrroles: application of dialkyl phosphine
oxides in enantioselective synthesis of chiral phosphine oxides or
phosphines. Org. Lett., 2010, 12, 1880-1882. (c) Zhao, D. P.;
Mao, L. J.; Wang, L. Q.; Yang, D. X.; Wang, R. Catalytic
asymmetric construction of tetrasubstituted carbon stereocenters
by conjugate addition of dialkyl phosphine oxides to  -
disubstituted  -unsaturated carbonyl compounds. Chem.
Commun. 2012, 48, 889-891. (d) Hua, Y. Z.; Han, X. W.; Yang,
X. C.; Song, X. X.; Wang, M. C.; Chang, J. B. Enantioselective
Friedel−Crafts alkylation of pyrrole with chalcones catalyzed by a
dinuclear Zinc catalyst. J. Org. Chem. 2014, 79, 11690-11699. (e)
Zhang, J. L.; Liu, X. H.; Wang, R. Magnesium complexes as
highly effective catalysts for conjugate cyanation of  -
unsaturated amides and ketons. Chem. Eur. J. 2014, 20, 4911-
4915. (f) Hua, Y. Z.; Liu, M. M.; Huang, P. J.; Song, X. X.;
Wang, M. C.; Chang, J. B. A new strategy for enantioselective
construction of multisubstituted five-membered oxygen
heterocycles via a Domino Michael/Hemiketalization reaction.
Chem. Eur. J. 2015, 21, 11994-11998.
(14) Trost, B. M.; Saget, T.; Hung, C.-I. Efficient access to chiral
trisubstituted aziridines via catalytic enantioselective Aza-
Darzens reactions. Angew. Chem. Int. Ed. 2017, 56, 2440-2444.
(15) (a) Smirnov, P.; Mathew, J.; Nijs, A.; Katan, E.; Karni, M.;
Bolm, C.; Apeloig, Y.; Marek, I. One-pot Zinc-promoted
asymmetric alkynylation/Brook-type rearrangement/ene-allene
cyclization: highly selective formation of three new bonds and
two stereocenters in acyclic systems. Angew. Chem. Int. Ed. 2013,
52, 13717-13721. (b) Cook, A. M.; Wolf, C. Efficient access to
multifunctional trifluoromethyl alcohols through base-free
catalytic asymmetric C-C bond formation with terminal
ynamides. Angew. Chem. Int. Ed. 2016, 55, 2929-2933.
(16) Bao, H. L.; Wang, Z.; You, T. P.; Ding, K. L. Enantioselective
ring opening of meso-epoxides with aromatic amines catalyzed by
dinuclear Magnesium complexes. Chin. J. Chem. 2013, 31, 67-71.
(17) (a) Wang, X. W.; Hua, Y. Z.; Wang, M. C. Synthesis of 3 ‑
indolylglycine derivatives via dinuclear Zinc catalytic asymmetric
Friedel−Crafts alkylation reaction. J. Org. Chem. 2016, 81, 9227-
9234. (b) Trost, B. M.; Gnanamani, E.; Hung, C.-I. Controlling
regioselectivity in the enantioselective N-alkylation of indole
analogues catalyzed by dinuclear Zinc-ProPhenol. Angew. Chem.
Int. Ed. 2017, 56, 10451-10456.
(21) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. Highly
enantioselective borane reduction of ketones catalyzed by chiral
oxazaborolidines: mechanism and synthetic implications. J. Am.
Chem. Soc. 1987, 109, 5551−5553. (b) Corey, E. J.; Bakshi, R. K.;
Shibata, S. A. Stable and easily prepared catalyst for the
enantioselective reduction of ketones: applications to multistep
syntheses. J. Am. Chem. Soc. 1987, 109, 7925-7926.
(18) (a) Li, Z. Y.; Plancq, B.; Ollevier, T. Bismuth triflate-catalyzed
asymmetric allylation of aromatic aldehydes. Chem. Eur. J. 2012,
18, 3144-3147. (b) Trost, B. M.; Hung, C.-I.; Koester, D. C.;
ACS Paragon Plus Environment

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Page 10 of 10
1
2
3
4
5
6
7
8
(22) (a) Corey, E. J.; Shibata, S.; Bakshi, R. K. An efficient and
nuclearity of neutral Titanium(IV)-based helicate assemblies.
Chem. Eur. J. 2014, 20, 5092-5101.
catalytically enantioselective route to (S)-(−)-phenyloxrane. J.
Org. Chem. 1988, 53, 2861−2863. (b) VanHeyst, M. D.; Oblak, E.
Z.; Wright, D. L. Stereodivergent resolution of oxabicyclic
ketones: preparation of key intermediates for platensimycin and
other natural products. J. Org. Chem. 2013, 78, 10555-10559. (c)
Kaldun, J.; Krimalowski, A.; Breuning, M. Enantioselective
borane reduction of ketones catalyzed by tricyclic 1,3,2-
oxazaborolidines. Tetrahedron Lett. 2016, 57, 2492-2495.
(26) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; et.
al. Gaussian 16, Revision B.01; Gaussian, Inc.: Wallingford CT,
2016.
(27) Yan, D. D.; Dai, P.; Chen, S. F.; Xue, M. Q.; Yao, Y. M.; Shen,
Q.; Bao, X. G. Highly efficient hydroboration of carbonyl
compounds catalyzed by tris(methylcyclopentadienyl)lanthanide
complexes. Org. Biomol. Chem. 2018, 16, 2787-2791.
9
(23) (a) Guo, J.; Chen, J. H.; Lu, Z. Cobalt-catalyzed asymmetric
hydroboration of aryl ketones with pinacolborane. Chem.
Commun. 2015, 51, 5725-5727. (b) Liu, W. B.; Guo, J.; Xing, S.
P.; Lu, Z. Org. Lett. 2020, 22, 2532-2536. (c) Vasilenko, V.;
Blasius, C. K.; Wadepohl, H.; Gade, L. H. Mechanism-based
enantiodivergence in manganese reduction catalysis: a chiral
pincer complex for the highly enantioselective hydroboration of
ketones. Angew. Chem. Int. Ed. 2017, 56, 8393-8397. (d)
Falconnet, A.; Magre, M.; Maity, B.; Cavallo, L.; Rueping, M.
Asymmetric magnesium-catalyzed hydroboration by metal-ligand
cooperative catalysis. Angew. Chem. Int. Ed. 2019, 58, 17567-
17571. (e) Lebedev, Y.; Polishchuk, I.; Maity, B.; Guerreiro, M.
D. V.; Cavallo, L.; Rueping, M. Asymmetric hydroboration of
heteroaryl ketones by aluminum catalysis. J. Am. Chem. Soc.
2019, 141, 19415-19423.
(24) (a) Farina, V.; Reeves, J. T.; Senanayake, C. H.; Song, J. J.
Asymmetric synthesis of active pharmaceutical ingredients. Chem.
Rev. 2006, 106, 2734-2793. (b) Klingler, F. D. Asymmetric
hydrogenation of prochiral amino ketones to amino alcohols for
pharmaceutical use. Acc. Chem. Res. 2007, 40, 1367-1376. (c) Li,
Y. Y.; Yu, S. L.; Shen, W. Y; Gao, J. X. Iron-, Cobalt-, and
Nickel-catalyzed asymmetric transfer hydrogenation and
asymmetric hydrogenation of ketones. Acc. Chem. Res. 2015, 48,
2587-2598. (d) Liu, H.; Liu, L.; Chen, B. S. The use of marine-
derived fungi for preparation of enantiomerically pure alcohols.
Appl. Microbiol. Biotechnol. 2018, 102, 1317-1330.
(28) (a) Umeda, R.; Studer, A. Ag-catalyzed stereoselective
cyclohexadienyl tansfer: a novel entry into arylphenylmethanols.
Org. Lett. 2008, 10, 993-996. (b) Guo, J.; Chen, J. H.; Lu, Z.
Cobalt-catalyzed asymmetric hydroboration of aryl ketones with
pinacolborane. Chem. Comm. 2015, 51, 5725-5727. (c) Wang, Y.
A.; Yang, G. Q.; Xie, F. Zhang, W. B. A ferrocene-based NH-free
phosphine-oxazoline ligand for iridium-catalyzed asymmetric
hydrogenation of ketones. Org. Lett. 2018, 20, 6135-6139. (d)
Zhou, G.; Aboo, A. H.; Robertson, C. M.; Liu, R. X.; Li, Z. H.;
Luzyanin, K.; Berry, N. G.; Chen, W. P.; Xiao, J. L. N,O- vs N,C-
chelation in half-sandwich Iridium complexes: a dramatic effect
on enantioselectivity in asymmetric transfer hydrogenation of
ketones. ACS Catal. 2018, 8, 8020-8026. (e) Zhang, L. L.; Tang,
Y. T.; Han, Z. B.; Ding, K. L. Lutidine-based chiral pincer
Manganese catalysts for enantioselective hydrogenation of
ketones. Angew. Chem. Int. Ed. 2019, 58, 4973-4977. (f)
Contente, M. L.; Serra, I.; Palazzolo, L.; Parravicini, C.;
Gianazza, E.; Eberini, I.; Pinto, A.; Guidi, B.; Molinari, F.;
Romano, D. Enzymatic reduction of acetophenone derivatives
with a benzil reductase from Pichia glucozyma (KRED1-Pglu):
electronic and steric effects on activity and enantioselectivity.
Org. Biomol. Chem. 2016, 14, 3404–3408. (g) Nakamura, S.;
Kusuda, S.; Kawamura, K.; Toru, T. Preparation of optically pure
propargylic and allylic alcohols from 2-(trimethylsilyl)vinyl
sulfoxides as a chiral ethynyl anion synthon: computational
studies on elimination reaction of 2-(trimethylsilyl)vinyl
sulfoxides. J. Org. Chem. 2002, 67, 640-647.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(25) Weekes, D. M.; Diebold, C.; Mobian, P.; Huguenard, C.;
Allouche, L.; Henry, M. A remarkable solvent effect on the
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