Development of Axially Chiral Cyclo-Biaryldiol Ligands with Adjustable Dihedral Angles

Article abstract of DOI:10.1002/chem.201603706

A new type of axially chiral cyclo-[1,1′-biphenyl]-2,2′-diol (CYCNOL) ligands with adjustable dihedral angles have been developed by varying the bridge chain length. Eight-, nine- and ten-membered cyclo-ligands were prepared and evaluated by using two representative examples: enantioselective additions of diethylzinc to aldehydes and organometallic reagents to enones. The results revealed that the fine regulation of dihedral angles through variation of the bridge chain length was effective in the asymmetric synthesis.

Full text of DOI:10.1002/chem.201603706

DOI: 10.1002/chem.201603706
Full Paper
&
Ligand Design
Development of Axially Chiral Cyclo-Biaryldiol Ligands with
Adjustable Dihedral Angles
Pengxiang Zhang, Jipan Yu, Fei Peng, Xudong Wu, Jiyang Jie, Can Liu, Hua Tian,
Haijun Yang, and Hua Fu*[a]
Abstract: A new type of axially chiral cyclo-[1,1’-biphenyl]-
2,2’-diol (CYCNOL) ligands with adjustable dihedral angles
have been developed by varying the bridge chain length.
Eight-, nine- and ten-membered cyclo-ligands were prepared
and evaluated by using two representative examples: enan-
tioselective additions of diethylzinc to aldehydes and organ-
ometallic reagents to enones. The results revealed that the
fine regulation of dihedral angles through variation of the
bridge chain length was effective in the asymmetric synthe-
sis.
Introduction
identified that can in deal with the many challenging transi-
tion-metal-catalyzed asymmetric transformations because
subtle variations in geometric, steric, and/or electronic proper-
ties of chiral ligands can cause dramatic changes of reactivity
and enantioselectivity. Conformationally rigid and adjustable
chiral ligands can improve the enantioselectivity of a reaction.
It is noted that the introduction of a chiral or achiral bridge
with variable chain length can provide additional handles for
fine-tuning the axially chiral ligand rigidity and the dihedral
angles (and bite angles).[10] Unfortunately, previous bridges
have been constructed through linkage of alkylaryl ethers,
which does not favor further modification of ligands, so the di-
versity and application of tunable ligands has thus far been
very limited. We realized that the introduction of a full-carbon
bridge chain to biaryl diols may help to overcome such difficul-
ties. In this paper, we report a new type of axially chiral cyclo-
[1,1’-biphenyl]-2,2’-diol (CYCNOL) ligands with adjustable dihe-
dral angles by varying the chain length of the full-carbon 6,6’-
tether, and eight-, nine-, and ten-membered cyclo-ligands (Fig-
ure 1b) were prepared and evaluated in asymmetric transfor-
mations.
Optically active compounds are widely found in biomolecules,
natural products and drugs.[1] Preparation of high optical
purity molecules is mainly through enzyme-promoted organic
reactions,[2] organocatalysis,[3] and transition-metal-catalyzed
asymmetric synthesis,[4] and their efficiency depends highly on
the chiral inducers such as amino acid residues in enzymes,
chiral organocatalysts, and chiral ligands of transition metals.
In previous asymmetric organic syntheses, transition-metal-cat-
alyzed asymmetric reactions and organocatalysis have been
most commonly used. Therefore, the development of chiral li-
gands and organocatalysts has been a key issue for obtaining
high reactivity and enantioselectivity. In the past decades,
thousands of chiral ligands have been developed and success-
fully applied in academic research and industrial production,[5]
and axially chiral ligands have found widespread applications
in transition-metal-catalyzed asymmetric synthesis. It is well
known that axially chiral biaryldiols constitute a key type of
cores and their modification has provided a diverse range of
excellent supporting ligands. The most prominent axially chiral
ligand cores are [1,1’-naphenyl]-2,2’-diol (BINOL)[6] and 1,1’-spi-
robiindane-7,7’-diol (SPINOL; Figure 1a).[7] BINOL[8] and
SPINOL[9] derivatives such as mono- and diphosphine com- Results and Discussion
pounds have been extensively evaluated as versatile chiral li-
Synthesis of axially chiral (R)-CYC-8-NOL and (S)-CYC-8-NOL
gands and catalysts in asymmetric transformations. However,
the catalytic reactivity and enantioselectivity are generally sub-
strate dependent, and no omnipotent ligand has yet been
Racemic 6,6’-dimethoxybiphenyl-2,2’-dicarbaldehyde (rac-1)
was prepared according to the previous procedures.[11] As
shown in Scheme 1, reduction of rac-1 in tetrahydrofuran
(THF) with NaBH4 provided the corresponding diol 2 in 99%
yield, and bromination of 2 with triphenylphosphine dibro-
mide (Ph3PBr2) in anhydrous dichloromethane (CH2Cl2) led to 3
in 96% yield in the presence of imidazole at 08C. Copper-cata-
lyzed coupling of 3 with vinyl magnesium bromide in anhy-
drous THF afforded diallylbiphenyl 4 in 41% yield, and an in-
tramolecular ring-closing metathesis using Grubbs’ catalyst
generated 5 in 86% yield.[12] Subsequently, hydrogenation with
[a] P. Zhang, Dr. J. Yu, F. Peng, X. Wu, J. Jie, C. Liu, H. Tian, Dr. H. Yang,
Prof. Dr. H. Fu
Key Laboratory of Bioorganic Phosphorus Chemistry and
Chemical Biology (Ministry of Education), Department of Chemistry
Tsinghua University, Beijing 100084 (P.R. China)
E-mail: fuhua@mail.tsinghua.edu.cn
Homepage: http://chem.tsinghua.edu.cn
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201603706.
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Figure 1. Axially chiral biaryldiol ligand cores. a) Typical supporting ligand cores; b) Our cyclo-ligand cores.
Pd/C at atmospheric pressure produced the hydrogenated
butyl-bridged biaryl ether (6) in almost quantitative yield. De-
methylation of diethers with BBr3 in CH2Cl2 followed by hydrol-
ysis afforded rac-CYC-8-NOL in 95% yield. Treatment of rac-
CYC-8-NOL with l-menthyl chloroformate (7) in the presence
of NEt3 and 4-(N,N-dimethylamino)pyridine (DMAP) gave 8, and
separation of 8 by silica gel column chromatography provided
(Ra)-8 and (Sa)-8. Pure enantiomers, (R)-CYC-8-NOL and (S)-CYC-
8-NOL, were obtained by hydrazinolysis of (Ra)-8 and (Sa)-8, re-
spectively. Their enantiomeric purity was determined by chiral
HPLC (see the Supporting Information for details). The polarim-
eter analysis confirmed that the compounds were (R)-(À)-CYC-
8-NOL and (S)-(+)-CYC-8-NOL. To ascertain absolute configura-
tion of the newly synthesized (R)-(À)-CYC-8-NOL and (S)-
(+)-CYC-8-NOL, a single crystal of (S)-(+)-CYC-8-NOL obtained
from mixed solvent of hexane and dichloromethane was pre-
pared, and its structure was unambiguously confirmed by X-
Figure 2. Crystal structure of (S)-CYC-8-NOL. CCDC 1493466 contains the
supplementary crystallographic data for this paper. These data are provided
free of charge by The Cambridge Crystallographic Data Centre.
ray diffraction analysis (Figure 2; see the Supporting Informa-
tion for details).
Synthesis of axially chiral (R)-CYC-9-NOL, (S)-CYC-9-NOL, (R)-
CYC-10-NOL, and (S)-CYC-10-NOL
details). Here, the synthesis of (R)-CYC-9-NOL and (R)-CYC-10-
NOL is reported as an example. Wittig coupling of (R)-1 with
Ph3P=CHCH2CH=PPh3 (from treatment of propane-1,3-diylbis-
(triphenylphosphonium) bromide with nBuLi) in anhydrous THF
led to (R)-10 in 30% yield, and reduction with hydrogen under
catalysis of Pd/C provided (R)-11 in 98% yield. Finally, deme-
thylation of (R)-11 followed by hydrolysis generated the de-
sired axially chiral (R)-(À)-CYC-9-NOL (Scheme 2b). (S)-(+)-CYC-
9-NOL was prepared by using the same procedures (see the
Supporting Information for details). Their enantiomeric purity
was determined by chiral HPLC (see the Supporting Informa-
We investigated the preparation of (R)-CYC-9-NOL, (S)-CYC-9-
NOL, (R)-CYC-10-NOL, and (S)-CYC-10-NOL. As shown in
Scheme 2a, optical resolution of racemic 6,6’-dimethoxybi-
phenyl-2,2’-dicarbaldehyde (rac-1) performed well using enan-
tiomeric tert-butanesulfinamide as the resolving agent accord-
ing to the previous reference.[13] We prepared single crystals of
(R)-1 and (S)-1 from mixed solvent of hexane and dichlorome-
thane, and their structures were unambiguously confirmed by
X-ray diffraction analysis (see the Supporting Information for
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Scheme 1. Synthesis and separation of axially chiral (R)-CYC-8-NOL and (S)-CYC-8-NOL.
tion for details). Optical rotations of (R)-(À)-CYC-9-NOL and (S)-
(+)-CYC-9-NOL were determined, and the corresponding abso-
lute configurations were unambiguously indentified by X-ray
diffraction analysis (Figure 3; see the Supporting Information
for details). Similarly, preparation of (R)-CYC-10-NOL and (S)-
CYC-10-NOL were also investigated. Fortunately, (R)-(+)-CYC-
10-NOL and (S)-(À)-CYC-10-NOL were obtained (Scheme 2c),
and their structures were confirmed by X-ray diffraction analy-
sis (Figure 3; see the Supporting Information for details).
with variation of the ring sizes (Table 1). It is well known that
the dihedral angles for the axially chiral ligands are a key
factor for reactivity and enantioselectivity in asymmetric syn-
thesis.
Enantioselective addition of diethylzinc to aldehydes using
biaryldiol ligands
Applications of the obtained axially chiral cyclo-biaryldiols in
asymmetric synthesis were investigated. It is known that the
enantioselective addition of diethylzinc to aldehydes using
biaryldiol ligands is one of the most reliable protocols for syn-
thesis of chiral sec-alcohols and also a standard reaction to test
the reactivity and enantioselectivity of newly developed chiral
ligands.[14] As shown in Table 2, enantioselective addition of di-
ethylzinc to 2-naphthaldehyde (14m) was chosen as the
Dihedral angles of axially chiral (S)-CYC-8-NOL, (S)-CYC-9-
NOL, and (S)-CYC-10-NOL
According to data from X-ray diffraction analysis of (S)-CYC-8-
NOL, (S)-CYC-9-NOL, and (S)-CYC-10-NOL, dihedral angles of
the axially chiral cyclo-biaryldiols show remarkable difference
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Scheme 2. Synthesis of axially chiral (R)-1, (S)-1, (R)-CYC-9-NOL, (S)-CYC-9-NOL, (R)-CYC-10-NOL, and (S)-CYC-10-NOL. a) Separation of axially chiral (R)-1 and (S)-
1. b) Synthesis of axially chiral (R)-CYC-9-NOL. c) Synthesis of axially chiral (R)-CYC-10-NOL.
Figure 3. Crystal structures of (R)-CYC-9-NOL, (S)-CYC-9-NOL, (R)-CYC-10-NOL and (S)-CYC-10-NOL. CCDC 1476688 ((R)-CYC-9-NOL), 1475886 ((S)-CYC-9-NOL),
1475890 ((R)-CYC-10-NOL), and 1475888 ((S)-CYC-10-NOL) contain the supplementary crystallographic data for this paper. These data are provided free of
charge by The Cambridge Crystallographic Data Centre.
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Table 1. Dihedral angles of axially chiral cyclo-biaryldiols determined
from X-ray diffraction analysis.
Table 2. Enantioselective addition of diethylzinc to 2-naphthaldehyde
(14m).[a]
Ligand
(S)-CYC-8-NOL
(S)-CYC-9-NOL
(S)-CYC-10-NOL
dihedral angle [8]
61.4
82.9
100.8
model to screen ligands including known (S)-BINOL, (S)-
SPINOL, and our newly developed (S)-CYC-8-NOL, (S)-CYC-9-
NOL, and (S)-CYC-10-NOL; the reaction was performed in anhy-
drous CH2Cl2 at À208C using titanium tetraisopropoxide as the
Lewis acid. All ligands exhibited high reactivity, but the enan-
tioselectivity showed remarkable difference (entries 1–5). (S)-
CYC-8-NOL and (S)-CYC-10-NOL afforded similar enantioselec-
tivity as (S)-BINOL, and (S)-CYC-9-NOL gave an excellent ee
value (94% ee). The results indicated that the fine regulation of
dihedral angles by varying bridge chain length was effective in
asymmetric synthesis. When the amount of (S)-CYC-9-NOL was
changed from 10 to 5 mol%, a 90% ee was recorded (entry 6).
Further reduction of the amount of (S)-CYC-9-NOL led to re-
duction in enantioselectivity (entries 7 and 8). After obtaining
the optimal ligand, (S)-CYC-9-NOL, we investigated the sub-
strate scope for the enantioselective addition of diethylzinc to
aldehydes 14, and found that the examined aldehydes all pro-
vided excellent yields and high to excellent ee values (Table 3).
Aryl aldehydes containing ortho-halogens exhibited slightly
lower enantioselectivity (see (S)-15 f, (S)-15g, and (S)-15k in
Table 3), and aliphatic aldehyde (see (S)-15o in Table 3) provid-
ed lower ee value than aromatic aldehydes. The reaction can
tolerate various functional groups including ether, CÀF bond,
CÀCl bond, CÀBr bond, and S-heterocycle. The results confirm
that the axially chiral cyclo-biaryldiol ligands are very useful in
asymmetric synthesis.
Entry
Ligand
Product[b]
Yield [%][c]
ee [%][d]
1
2
3
4
(S)-BINOL
(S)-SPINOL
(S)-15m
(R)-15m
(S)-15m
(S)-15m
(S)-15m
(S)-15m
(S)-15m
(S)-15m
97
94
97
97
95
96
93
88
86
75
84
94
86
90
81
62
(S)-CYC-8-NOL
(S)-CYC-9-NOL
(S)-CYC-10-NOL
(S)-CYC-9-NOL
(S)-CYC-9-NOL
(S)-CYC-9-NOL
5
6[e]
7[f]
8[g]
[a] Reaction conditions: 14m/ligand/Ti(OiPr)4/Et2Zn=1:0.1:1.4:3 (molar
ratio), 14m (0.125 mmol), ligand (12.5 mmol), Ti(OiPr)4 (0.175 mmol), Et2Zn
(0.375 mmol), CH2Cl2 (1.0 mL), À208C, 4 h, 1N NH4Cl (2.0 mL). [b] Absolute
configurations known, determined or assigned by analogy (see the Sup-
porting Information). [c] Isolated yield. [d] The ee values were determined
by HPLC analysis using
a
chiral stationary phase (ChiralpakꢁOD-H).
[e] Using 6.25 mmol of (S)-CYC-9-NOL as the ligand. [f] Using 2.5 mmol of
(S)-CYC-9-NOL as the ligand. [g] Using 1.25 mmol of (S)-CYC-9-NOL as the
ligand.
Table 3. Enantioselective addition of diethylzinc to aldehydes 14 leading
to 15.[a–d]
Enantioselective addition of organometallic reagents 17 to
enones 18 using phosphoramidite ligands
We surveyed derivatization of our axially chiral cyclo-biaryl-
diols. Given that phosphoramidites of axially chiral biaryldiols
are privileged ligands in asymmetric catalysis,[15] we prepared
twenty phosphoramidite ligands (Table 4) according to the pre-
vious procedures (see the Supporting Information for de-
tails).[16] An interesting reaction, copper-catalyzed asymmetric
carbon–carbon bond formation using alkenes as alkylmetal
equivalents, developed by Fletcher and co-workers[16] was se-
lected as the model to evaluate the effects of the known li-
gands and our newly developed biaryldiol phosphoramidites.
As shown in Table 4, treatment of phosphoramidite ligand
with (CuOTf)2PhH led to the formation of their respective com-
plex (ligand-Cu) at room temperature under argon atmos-
phere; meanwhile, reaction of alkene 16a with Cp2ZrHCl gave
addition product 17a in another flask under the similar condi-
tions. The reaction of 17a with 18a was then performed
under catalysis of ligand-Cu at room temperature under argon
atmosphere. Here, some representative phosphoramidite li-
gands were selected as examples to evaluate their reactivity
(Table 4; see the Supporting Information for more data). Phos-
[a] Reaction
conditions:
aldehyde/ligand/Ti(OiPr)4/Et2Zn=1:0.1:1.4:3
(molar ratio), aldehyde 14 (0.125 mmol), (S)-CYC-9-NOL (12.5 mmol),
Ti(OiPr)4 (0.175 mmol), Et2Zn (0.375 mmol), CH2Cl2 (1.0 mL), À208C, 4 h,
1N NH4Cl (2.0 mL). [b] Absolute configurations known, determined or as-
signed by analogy (see the Supporting Information). [c] Isolated yield.
[d] The ee values were determined by HPLC analysis using a chiral station-
ary phase (see the Supporting Information).
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phoramidites of (S)-CYC-8-NOL (entries 5 and 6) displayed simi-
lar reactivity and enantioselectivity to those of known ligands
(entries 1–4). Interestingly, ligands (Sa,R,R)-P, with nine-mem-
bered ring (entry 8), and (Sa,R,R)-T, with ten-membered ring
(entry 10), exhibited excellent enantioselectivity. The results
showed that the fine regulation of dihedral angles by varying
the bridge chain length could change the level of enantiose-
lectivity. The reactivity and enantioselectivity decreased when
amount of ligand-Cu was reduced (entries 11 and 12).
Table 4. Ligand screening for enantioselective addition of organometallic
reagent 17a to 4,4-dimethylcyclohex-2-enone (18a).[a]
In the enantioselective addition of organometallic reagent
17a to 4,4-dimethylcyclohex-2-enone (18a) above, the phos-
phoramidite ligands (Sa,R,R)-P, with nine-membered ring, and
(Sa,R,R)-T, with ten-membered ring, provided higher enantiose-
lectivity than that of (Sa,R,R)-L, with eight-membered ring, as
shown in Table 4. However, the catalytic reactivity and enantio-
selectivity are generally substrate-dependent. To further deter-
mine the effect of ligands with different dihedral angles in the
asymmetric synthesis, alkenes 16b and 16c were used as the
partner of 18a. Interestingly, (Ra,S,S)-I and (Sa,R,R)-L, with eight-
membered ring, and (Ra,S,S)-M and (Sa,R,R)-P, with nine-mem-
bered ring, afforded higher enantioselectivity than (Ra,S,S)-Q
and (Sa,R,R)-T, with ten-membered ring (Table 5, entries 1–6).
According to the results above, (Ra,S,S)-M and (Sa,R,R)-P, with
nine-membered ring, are optimal ligands. Subsequently, we
used (Sa,R,R)-P as the ligand to investigate the substrate scope
on the enantioselective addition of organometallic reagents 17
to enones 18 leading to 19; the examined alkenes 16 and
enones 18 afforded moderate yields and high to excellent ee
values (Table 5). For alkenes 16, aliphatic terminal alkenes gave
higher ee values than aromatic alkenes. For enones 18, 4,4-di-
methylcyclohex-2-enone (18a) provided higher enantioselec-
tivity than cyclohex-2-enone (18b) and cyclopent-2-enone
(18c), and cyclohept-2-enone also was a good Michael accept-
or. Interestingly, the reaction could tolerate the presence of
a CÀCl bond, which is usually difficult for reactions of other or-
ganometallic reagents. The method exhibits some advantages
including the ready availability of alkenes and enones as the
starting materials, application of alkylmetal agents generated
in situ from alkenes, room temperature conditions, and high
levels of enantioselectivity. The results show that our newly de-
veloped axially chiral cyclo-biaryldiols have significant potential
in asymmetric synthesis.
Entry
Ligand
Product[b]
Yield [%][c]
ee [%][d]
1
2
3
4
5
6
7
8
(Sa,S,S)-C
(Sa,R,R)-D
(Sa,S,S)-G
(Sa,R,R)-H
(Sa,S,S)- K
(Sa,R,R)- L
(Sa,S,S)-O
(Sa,R,R)-P
(Sa,S,S)-S
(Sa,R,R)-T
(Sa,R,R)-P
(Sa,R,R)-P
(R)-19a
(R)-19a
(S)-19a
(S)-19a
(R)-19a
(R)-19a
(R)-19a
(R)-19a
(R)-19a
(R)-19a
(R)-19a
(R)-19a
68
64
66
65
73
72
70
75
60
77
53
40
85
85
82
86
81
88
86
92
67
91
79
27
9
10
11[e]
12[f]
Conclusions
[a] Reaction conditions: alkene 16a (1.0 mmol, 2.5 equiv), Cp2ZrHCl
(0.80 mmol, 2 equiv), enone 18a (0.40 mmol, 1 equiv), ligand (0.04 mmol,
0.1 equiv), (CuOTf)2PhH (0.02 mmol, 0.05 equiv), trimethylsilylchloride
(TMSCl; 2.0 mmol, 0.25 mL, 5.0 equiv), ether (2.0 mL), CH2Cl2 (1.0 mL).
[b] Absolute configurations known, determined or assigned by analogy
(see the Supporting Information). [c] Isolated yield. [d] The ee values were
determined by HPLC using a chiral stationary phase (ChiralpakꢁAY-H).
[e] (CuOTf)2PhH (0.01 mmol, 0.025 equiv), ligand (0.02 mmol, 0.05 equiv).
[f] (CuOTf)2PhH (0.004 mmol, 0.01 equiv), ligand (0.008 mmol, 0.02 equiv).
We have developed a new type of axially chiral cyclo-[1,1’-bi-
phenyl]-2,2’-diol (CYCNOL) ligands with dihedral angles that
can be adjusted by varying the chain length of the full-carbon
6,6’-tether, and eight-, nine-, and ten-membered cyclo-ligands
were obtained. The enantioselective addition of diethylzinc to
aldehydes was conducted in the presence of the axially chiral
cyclo-ligands, and the systems provided good to excellent re-
activity and enantioselectivity, in which the ligands with differ-
ent dihedral angles exhibited remarkable differences. Further-
more, the phosphoramidites of the axially chiral biaryldiols
were used as ligands in the enantioselective addition of organ-
ometallic reagents to enones. The results showed that fine reg-
ulation of the dihedral angles by varying the bridge chain
length was effective in the asymmetric synthesis. We believe
that our newly developed axially chiral biaryldiols will find
wide applications in synthesis of chiral molecules.
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Table 5. Substrate scope for enantioselective addition of organometallic
reagents 17 to enones 18 leading to 19.[a]
Table 5. (Continued)
Entry
17
Ligand
Product[b]
Yield [%][c]
74
ee [%][d]
Entry
1
Ligand
Product[b]
Yield [%][c]
ee [%][d]
(Sa,R,R)-P
84
(Ra,S,S)-I
51
92
[a] Reaction conditions: alkene 16 (1.0 mmol, 2.5 equiv), Cp2ZrHCl
(0.80 mmol, 2 equiv), enone 18 (0.40 mmol, 1 equiv), ligand (0.04 mmol,
0.1 equiv), (CuOTf)2PhH (0.02 mmol, 0.05 equiv), trimethylsilylchloride
(TMSCl; 2.0 mmol, 0.25 mL, 5.0 equiv), ether (2.0 mL), CH2Cl2 (1.0 mL).
[b] Absolute configurations known, determined or assigned by analogy
(see the Supporting Information). [c] Isolated yield. [d] The ee values were
determined by HPLC (see the Supporting Information).
2
3
(Ra,S,S)-M
(Ra,S,S)-Q
(S)-19b
(S)-19b
63
56
93
86
4
(Sa,R,R)-L
57
91
5
6
(Sa,R,R)-P
(Sa,R,R)-T
(R)-19c
(R)-19c
56
50
93
88
Acknowledgements
7
(Sa,R,R)-P
66
84
Financial support for this work was provided by the National
Natural Science Foundation of China (Grant Nos. 21372139 and
8
(Sa,R,R)-P
69
90
21221062),
and
Shenzhen
Sci
&
Tech
Bureau
(CXB201104210014A).
9
(Sa,R,R)-P
(Sa,R,R)-P
(Sa,R,R)-P
80
79
75
86
92
82
Keywords: asymmetric catalysis
enantioselectivity · ligand design · ligand effects
· asymmetric synthesis ·
10
11
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Received: August 2, 2016
Published online on && &&, 0000
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FULL PAPER
Adjustable ligands: A new type of ax-
ially chiral cyclo-[1,1’-biphenyl]-2,2’-diol
(CYCNOL) ligands with adjustable dihe-
dral angles were developed (see figure).
Eight-, nine-, and ten-membered cyclo-
ligands were prepared and evaluated by
using two representative examples:
enantioselective additions of diethylzinc
to aldehydes and organometallic re-
agents to enones. The results revealed
that the fine regulation of dihedral
angles through variation of the bridge
chain length was effective in the asym-
metric synthesis.
&
Ligand Design
P. Zhang, J. Yu, F. Peng, X. Wu, J. Jie,
C. Liu, H. Tian, H. Yang, H. Fu*
&& – &&
Development of Axially Chiral Cyclo-
Biaryldiol Ligands with Adjustable
Dihedral Angles
Chem. Eur. J. 2016, 22, 1 – 9
www.chemeurj.org
9
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
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These are not the final page numbers! ÞÞ