Diastereoselective Synthesis of P-Chirogenic and Atropisomeric 2,2′-Bisphosphino-1,1′-binaphthyls Enabled by Internal Phosphine Oxide Directing Groups

Article abstract of DOI:10.1002/anie.202001561

Diphosphine ligands that merge both axial and P-centered chirality may exhibit superior or unique properties. Herein we report the diastereoselective introduction of P-centered chirality at the 2-position of the axially chiral 2′-(phosphine oxide)-1,1′-binaphthyl scaffold. A lithium–bromide exchange reaction of a 2-bromo-2′-(phosphine oxide)-1,1′-binaphthyl and treatment with dichlorophosphines followed by a nucleophilic organometallic reagent afforded unsymmetrical 2-phosphino-2′-(phosphine oxide)-1,1′-binaphthyls with binaphthyl axial chirality and one or two phosphorus stereocenters with a variety of P substituents. The final diastereomerically pure 2,2′-bisphosphino-1,1′-binaphthyls were obtained by reduction of the phosphine oxide directing group. Preliminary results demonstrated that a ligand with this hybrid chirality could induce higher stereoselectivity in the metal-complex-catalyzed asymmetric hydrogenation of a dialkyl ketone.

Full text of DOI:10.1002/anie.202001561

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Accepted Article
Title: Diastereoselective Synthesis of P-Chirogenic and Atropoisomeric
2,2'-bis(phosphino)-1,1'-binaphthyls Enabled by Internal
Phosphine Oxide Directing Groups
Authors: Qingquan Xue, Shangfei Huo, Tingyi Wang, Zeming Wang,
Jianli Li, Meifang Zhu, and Weiwei Zuo
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202001561
Angew. Chem. 10.1002/ange.202001561
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10.1002/anie.202001561
Angewandte Chemie International Edition
RESEARCH ARTICLE
Diastereoselective Synthesis of P-Chirogenic and Atropoisomeric
2,2'-bis(phosphino)-1,1'-binaphthyls Enabled by Internal
Phosphine Oxide Directing Groups
Qingquan Xue,a Shangfei Huo,a Tingyi Wang,a Zeming Wang,a Jianli Li,b Meifang Zhu*,a and Weiwei
Zuo*,a
Abstract: The diphosphine ligand family that merges both axial and
P-centered chirality may exhibit superior or unique properties. Here,
we report a phosphine oxide (chiral or achiral) group-directed
reaction for diastereoselectively introducing P-centered chirality into
the 2-position of the axially chiral 2’-phosphine-oxide-1,1’-binaphthyl
scaffold. This process proceeds through a lithium-bromide exchange
phosphorus centers. First, there has been no efficient method
that can produce a 1,1’-binaphthyl-based C-P bond in a highly
diastereoselective manner. The biaryl-lithium intermediate
generated by a lithium-halide exchange reaction and the
subsequent electrophilic quenching with chlorophosphine
derivatives utilized by Cereghetti[5] and Buchwald[6] in the
production of corresponding P-chirogenic atroposiomeric mono
or diphosphines ligands resulted in moderated diastereoisomeric
purities. This approach required further purification such as
recrystallization, which usually led to low yields of the
diastereomerically pure products. Transition metal complex-
reaction
of
2-bromo-2’-phosphine-oxide-1,1’-binaphthyl
and
electrophilic reaction with dichlorophosphines followed by treatment
with a nucleophilic organometallic reagent, to afford unsymmetrical
2-phosphino-2’-phosphine-oxide-1,1’-binaphthyls
with
the
combination of one binaphthyl axial chirality and one or two tunable
P-chirogenic phosphorus center(s) having a variety of P-substituents.
catalyzed coupling of
a secondary phosphine oxide with
The
final
diastereomerically
pure
2,2’-bis(phosphino)-1,1’-
binaphthyl electrophiles and related C-P cross-coupling
reactions were also attempted to synthesize P-chirogenic
binaphthyl monophosphines.[7] This method is limited not only by
the low efficiency of C-P bond formation but also by the
availability of the chiral secondary phosphine oxide starting
precursors. In addition, the products are prone to racemization
at the phosphorus center due to the high temperatures required
to achieve high conversion and therefore generally result in
diastereomeric mixtures.[7a,c,e] Also the racemisation of the P-
chirogenic phosphine-oxide moieties in all subsequent reduction
attempts was another problem that hampered the high
diastereoselectivity. Second, the introduction of P-chirality with a
predictable and variable P-configuration has never been
reported, largely due to the abovementioned racemization
process and the limited availability of the starting precursors.
Our initial results indicated that the ephedrine method,[8] which is
usually very efficient in constructing P-centered chirality, also
proved to be ineffective and led to the formation of a
diastereomeric mixture.
Inspired by Chen’s work[9] on the highly stereoselective
synthesis of ferrocene-based P-chirogenic phosphine ligands,
we developed a new method to diastereoselectively introduce
stereogenic phosphorus moieties into the axially chiral 1,1’-
binaphthyl backbone with controllable P-configuration and
excellent stereoselectivity, thus allowing the synthesis of
unsymmetrical 2,2’-bis(phosphino)-1,1’-binaphthyl ligands that
incorporate both axial and P-centered chiralities.
binaphthyls were obtained by quantitative and regiospecific
reduction of the phosphine oxide directing groups. The preliminary
catalytic results using the hybrid-chirality ligand demonstrated its
capability to induce higher stereoselectivity in the metal complex-
catalyzed asymmetric hydrogenation of alkyl-alkyl ketone.
Introduction
Transition metal complexes of axially chiral 2,2’-substituted-
1,1’-binaphthyl-based diphosphine ligands, represented by the
iconic 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl (BINAP), have
been shown to display excellent stereoselectivity in a variety of
catalytic reactions.[1] Additionally, since the pioneering work of
Knowles,[2] P-chirogenic phosphines have constituted an
important category of chiral ligands for a wide range of catalytic
applications.[3] We envisaged that merging the structural
characteristics of both atropisomerism and chirality at the P-
center would create a new family of chiral phosphine ligands that
would allow further fine-tuning of the enantioinduction of the
resulting chiral ligands, by a chiral cooperativity between these
two types of asymmetric elements.[4]
However, due to some challenges there are currently no
synthetic methods available for the reliable access to
diastereomerically pure 2,2’-substituted-1,1’-binaphthyl-based
diphosphine ligands that are also chirogenic at one or both
[a]
Q. Xue, S. Huo, T. Wang, Z. Wang, Prof. Dr. M. Zhu, Prof. Dr. W.
Zuo
State Key Laboratory for Modification of Chemical Fibers and
Polymer Materials, College of Materials Science and Engineering
Donghua University
Results and Discussion
The key to the success of this strategy was the utilization of
a 2’-position phosphine oxide group, in either stereogenic or
achiral form, as the directing group for the subsequent
introduction of the second chiral phosphine group and its regio-
and stereospecific deoxygenation (Scheme 1).[10]
Shanghai 201620, P. R. China
E-mail: zhumf@dhu.edu.cn, zuoweiwei@dhu.edu.cn
Prof. Dr. J. Li
Department Key Laboratory of Synthetic and Natural Functional
Molecule Chemistry of the Ministry of Education, Shaanxi Key
Laboratory of Physico-Inorganic Chemistry, College of Chemistry
and Materials Science
[b]
Specifically,
(RA)-2-bromo-2’-phosphine-oxide-1,1’-
Northwest University
binaphthyl (1) undergoes a lithium-bromide exchange and
Xi'an 710127, P. R. China
further reacts with dichlorophosphine (R3PCl2) to afford
Supporting information for this article is given via a link at the end of
the document
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10.1002/anie.202001561
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RESEARCH ARTICLE
Scheme 1. Strategies for the synthesis of unsymmetrical (RA)-2,2’-diphosphino-1,1’-binaphthyls that comprise both axial and P-
centered chiralities. a) The synthesis of unsymmetrical (RA)-2,2’-diphosphino-1,1’-binaphthyls (3 a-q) that possess one stereogenic
phosphorus center by employing phosphine oxide induced P-chirality-recognition protocol and the regioselective deoxygenation of
the phosphine oxide directing groups. b) The synthesis of unsymmetrical (RA)-2,2’-bis(phosphino)-1,1’-binaphthyls that bear two P-
chirogenic centers by similar strategies.
a P-chiral monochlorophosphine intermediate (D). Treatment of
such monochloro-substituted intermediate with another
organometallic reagent (R4M, M= Li, MgBr) results in a highly
bis(phosphino)-1,1’-binaphthyls
with
two
P-chirogenic
a
phosphorus atoms, through the first installation of a P-chirogenic
phosphine oxide group on the 2’-position of the binaphthyl
backbone in an epimeric mixture (Scheme 1b). The individual
diastereomerically pure isomers of (RA)-2-bromo-2’-phosphine-
oxide-1,1’-binaphthyls were isolated and then subjected to the
above phosphine oxide-directed P-chirality recognition
processes to independently afford the phosphine oxide-
phosphine ligands that incorporate three adjacent stereocenters.
Same reduction of the phosphine oxide directing groups afford
all four possible stereoisomers, which are inaccessible via
alternative methods.
diastereoselective nucleophilic substitution process that favors
formation
of
(RA)-2-phosphino-2’-phosphine-oxide-1,1’-
binaphthyls (2) possessing one axial binaphthyl chirality and a
P-stereogenic center, with only one single diastereomer being
formed for all P-substituents except 1'-bromo-ferrocen-1-yl
(Scheme 1a). The high diastereoselectivity in this nucleophilic
substitution step is rationalized by an internal assistance of the
phosphine oxide in the organometallic attack, particularly
Grignard, in the anti-position of the P-Cl bond. It is possible that
one chlorophosphine epimer reacts, when the second quickly
epimerizes in the presence of lithium halide salt.[11]
The stereoselective synthesis starts with the preparation of
(RA)-2-bromo-2’-phosphine-oxide-1,1’-binaphthyls (1) (Table 1).
(RA)-2,2’-Dibromo-1,1’-binaphthyl was first lithiated at -90 °C in a
glovebox for 5 min and then successfully quenched with
chlorophosphine to give (RA)-2-bromo-2’-phosphine-oxide-1,1’-
binaphthyl (1) in moderate to good yields after oxidation with
H2O2. No binaphthyl axial chirality racemization under such low
reaction temperature and short reaction period was observed, as
revealed by chiral high-performance liquid chromatography
(HPLC) analysis (see Supporting Information, Figure S2).[12]
The diastereomerically pure epimer having an opposite
configuration at the phosphorus center can be easily made
simply by reversing the introduction order of the P-substituents
(R3 and R4), e.g., by first engaging R4PCl2 and then treating with
R3M. More importantly, when combined with the borane
protection strategy, the CeCl3/NaBH4/LiAlH4 mixture was found
to be an efficient reducing system to deoxygenate the directing
phosphine oxide group cleanly, while leaving the chiral
phosphino group intact, to allow the stereoselective synthesis of
the target P-chirogenic BINAP derivatives (3 a-q).
The effectiveness of this methodology was further illustrated
in the efficient synthesis of unsymmetrical (RA)-2,2’-
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RESEARCH ARTICLE
various substituents, including alkyl, cyclic alkyls, aryls and
naphthyl, were stereoselectively prepared by employing different
dichlorophosphines and using the appropriate organometallic
reagents for the nucleophilic substitution step. Replacement of
1a with 1b and 1c results in a similar reaction pattern to afford
the corresponding products (RA)-2p-2s possessing methyl and
phenyl P-substituents and predictable configurations, also in
acceptable yields and high diastereomeric purities (de> 99%).
Table 2: The synthesis of (RA)-2-phosphino-2’-phosphine-oxide-1,1’-
binaphthyls that bear one P-stereogenic center.
Table 1: The synthesis of (RA)-2-bromo-2’-phosphine-oxide-1,1’-
binaphthyls.[a]
[a] Isolated yields.
Similar to the ferrocenyl analogous procedure,[9] the
diastereoselective installation of a second P-chiral phosphino
group involves the following: first, a lithium-bromide exchange
process at the (RA)-2-bromo-2’-phosphine-oxide-1,1’-binaphthyl,
second, a reaction with alkyl- or arylchlorophosphines (R3PCl2)
to yield a monochloro-phosphine intermediate, and third, a
nucleophilic substitution reaction by an organometallic reagent
R4M (Table 2). For example, the binaphthyl monoanion
generated from (RA)-1a and n-butyl lithium sequentially reacts
with dichlorophenylphosphine and methyl magnesium bromide
to afford (RA, SP)-2a in a 63% NMR yield, with only one
diastereomer being observed. Similar to the installation step of
the first phosphine oxide group, the reactions proceed without
epimerization of the binaphtyl moiety (checked by chiral HPLC,
see Supporting Information section for details).
Interestingly, the epimer (RA, RP)-2b with an opposite
configuration at the chiral P center was readily accessible simply
by reversing the introduction sequence of the phenyl and methyl
groups. More importantly, this epimer was also formed as a
single diastereomer in high yield based on the 31P NMR analysis.
The absolute configurations of the chiral phosphorus center of
(RA, SP)-2a and (RA, RP)-2b were determined by single-crystal X-
ray diffraction analysis of the bis(phosphine oxide) analog (RA,
SP)-4b,obtained by H2O2 oxidation of 2b (see Supporting
Information, Figure S168), and further confirmed by the
stereochemistry of the deoxygenated products (RA, SP)-3a and
(RA, RP)-3b (vide infra). The 31P{1H} NMR analysis of these two
epimers shows a distinct difference between the chemical shifts
of the centrally chiral phosphorus nucleus. The (RA, SP) isomer
2a presents resonances at -37.81 and 27.47 ppm, while the
opposite epimer (RA, RP)-2b shows signals at -35.45 and 27.98
ppm, respectively (see Supporting Information, Figure S33 and
Figure S36).
[a]
[b]
Isolated yield.
Two epimers separated by column chromatography.
Br-Fc = 1'-bromo-ferrocen-1-yl.
The (RA)-2-phosphino-2’-phosphine-oxide-1,1’-binaphthyls
were subjected to deoxygenation by various reducing agents to
synthesize free P-chirogenic diphosphine BINAP derivatives.
The combination of trichlorosilane/triethylamine at 60-80 °C can
reduce all of the tested substrates from (RA)-2a to (RA)-2s, but
for many substrates, obvious P-chirality epimerization was
observed (Table 3). A further search for efficient reducing agents
that regioselectively deoxygenate the phosphine oxide group
while leaving the P-chiral center intact led to the finding of a
combination of CeCl3/NaBH4/LiAlH4 in a ratio of 5:5:3, which was
first reported by Imamoto.[13] With a slight modification of
Imamoto’s procedure, the chiral phosphorus center was first
The high diastereoselectivity in the synthesis of (RA)-2a-2o
from (RA)-1a was found to be general for most substituents
except 1'-bromo-ferrocen-1-yl (Table 2). A series of (RA)-2-
phosphino-2’-phosphine-oxide-1,1’-binaphthyls having
a
P-
centered chirality on the 2-position phosphorus atom with
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protected by a borane group prior to the deoxygenation process
by reacting the (RA)-2-phosphino-2’-phosphine-oxide-1,1’-
binaphthyls with one equivalent of BH3-THF, and the
deoxygenation then proceeded regioselectively on the
phosphine oxide group with negligible racemization at the
protected P-chirogenic phosphine moiety, affording only one
major diastereomer in >90% NMR analysis yield. The borane
group could be easily removed by reacting with diethylamine at
Figure 1. The 31P{1H} NMR spectrum (243 MHz, CDCl3) of (RA, SP)-3a
and (RA, RP)-3b. Top, (RA, SP)-3a, δ: -15.20, -37.93, d, JPP = 14.6 Hz;
bottom, (RA, RP)-3b, δ: -15.71, -35.42, d, JPP = 11.7 Hz.
room
temperature.
The
31P{1H}
NMR
spectra
of
diastereomerically pure (RA, SP)-3a and (RA, RP)-3b prepared by
this reduction process are shown in Figure 1, which indicates no
epimerization of the P-chirogenic center for both substrates.
Single crystals suitable for X-ray diffraction of the epimers (RA,
SP)-3a and (RA, RP)-3b were both obtained, and the molecular
structures are shown in Figure 2. Overall, for other substrates of
(RA)-2c-2s, the reductions using this mixture offered
straightforward transformations within 2 h.
Table 3: The synthesis of unsymmetrical (RA)-2,2’-bis(phosphino)-1,1’-
binaphthyls that bear one P-stereogenic center.
Figure 2. The molecular structures of (RA, SP)-3a and (RA, RP)-3b. The
hydrogen atoms are omitted for clarity and the thermal ellipsoids are
depicted at a 30% probability level.
The above method was extended to the synthesis of a
range of modified BINAP ligands possessing two P-chirogenic
centers, a task that is very challenging if the other existing
procedures are employed (Table 4). This process commences
with the installation of a chiral isopropylphenylphosphine oxide
directing group at the 2’-position of the 1,1’-binaphthyl backbone
in a diastereomeric mixture in a 1.4:1 ratio (Scheme 1 and Table
4). The phosphine oxide diastereomeric mixtures were
separated by column chromatography to independently afford
the
diastereomerically
pure
(RA)-2-bromo-2’-
isopropylphenylphosphine-oxide-1,1’-binaphthyls (SP, RA)-1t and
(RP, RA)-1u in 20% and 14% yields, respectively. The
stereochemistry of (RP, RA)-1u was also determined by single-
crystal X-ray diffraction (see Supporting Information, Figure
S172).
Further
sequential
treatment
pure
of
the
individual
diastereomerically
(RA)-2-bromo-2’-
isopropylphenylphosphine-oxide-1,1’-binaphthyl [(SP, RA)-1t or
(RP, RA)-1u] with n-butyl lithium, methyl dichlorophosphine and
phenylmagnesium bromide afforded new diastereomerically
pure
2-methylphenylphosphino-2’-isopropylphenylphosphine-
oxide-1,1’-binaphthyls [(SP, RA, RP)-2t and (RP, RA, RP)-2u], each
of which bears two P-chirogenic centers and a binaphtyl axial
chirality, in 63% and 65% yield, respectively. The molecular
structure of (SP, RA, RP)-2t is shown in the Supporting
Information, Figure S173.
[a]
Comparable diastereoselectivities can be obtained with
trichlorosilane/triethylamine. For all substrates, the NMR yields are higher
[b]
than 90%.
Br-Fc = 1'-bromo-ferrocen-1-yl. The crude and isolated
products have same de %.
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Table 4: The synthesis of (RA)-2-bromo-2’-phosphine-oxide-1,1’-binaphthyls that bear a chirogenic phosphine oxide directing group and their
syntheses of unsymmetrical (RA)-2,2’-bis(phosphino)-1,1’-binaphthyls that are stereogenic at both phosphorus atoms. [a]
[a] All the yields are isolated yields.
Figure 3. Ruthenium complexes for asymmetric hydrogenation of ketone (See Supporting Information for the detailed synthetic procedures).
Similar to the above cases, the initial borane protection of
(SP, RA, RP)-2t and the subsequent deoxygenation of the
boronato adduct with CeCl3/NaBH4/LiAlH4 at low temperature (-
90 °C ) proceeded regiospecifically and stereoselectively at the
phosphine oxide group with inversion of configuration at the
phosphorus center to afford new unsymmetrical (SP, RA, RP)-
2,2’-diphosphino-1,1’-binaphthyls (3t) that bear two P-chirogenic
phosphine moieties on each side of the 1,1’-binaphthyl
backbone, with only one diastereomer being formed (see
Supporting Information section for inversion of the P-chirality).
(RP, RA, RP)-2u, which has (RP)-configurations at the phosphine-
oxide and phosphine moieties, gives rise to the corresponding
diastereomerically pure diphosphine product (RP, RA, RP)-3u.
The other two diastereomers of (SP, RA, SP)-2v and (RP, RA, SP)-
2w with opposite configurations to those of 2t and 2u at the
second installed chiral phosphorus atoms are also easily
accessible simply by reversing the introduction sequence of the
methyl and phenyl groups, and the corresponding free
diphosphines (SP, RA, SP)-3v and (RP, RA, SP)-3w were easily
obtained by employing the same deoxygenation and purification
diastereomers can be independently and stereoselectively
prepared with good yields.
Preliminary catalytic results revealed the advantage of
hybrid-chirality ligands in inducing higher stereoselectivities in its
ruthenium complexes for the asymmetric hydrogenation of
ketones. A challenging substrate, 3-methyl-2-butanone, was
used because it was usually reduced with very low
enantioselectivities.[14] The results are shown in Table 5. While
the traditional Noyori catalysts (RA, SS)-I and (RA, SS)-II (Figure
3) containing only one axial chirality of the binaphthyl group
show 32% and 50% enantiomeric excess, respectively, the
hybrid-chlirality analogue (RA, SP, SS)-III (Figure 3) exhibited an
obviously increased enantio-purity of 63% under otherwise the
identical conditions. Interestingly, the unsymmetrical but not P-
chirogenic analogues (RA, SS)-IV and (RA, SS)-V also show
lower enantioselectivities than (RA, SP, SS)-III. This 63%
enantio-purity, although slightly inferior to the highest value that
was obtained in the Rh-PennPhos complex,[14a] clearly
demonstrated the merit of using a hybrid-chirality diphosphine
ligand to achieve higher enantioselectivity.
procedures.
Therefore, all four
structurally possible
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Keywords: Asymmetric synthesis • Phosphane ligands • P-
chirogenic • Atropisomeric • Axial to point chirality transfer
Table 5: Ruthenium complex-catalyzed asymmetric hydrogenation of 3-
methyl-2-butanone. [a]
[1] a) A. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, T. Souchi, R.
Noyori, J. Am. Chem. Soc. 1980, 102, 7932-7934; b) R. Noyori, Angew.
Chem. Int. Ed. 2002, 41, 2008-2022; c) M. Berthod, G. Mignani, G.
Woodward, M. Lemaire, Chem. Rev. (Washington, DC, U. S.) 2005, 105,
1801-1836.
[2] a) W. S. Knowles, M. J. Sabacky, B. D. Vineyard, D. J. Weinkauff, J. Am.
Chem. Soc. 1975, 97, 2567-2568; b) B. D. Vineyard, W. S. Knowles, M. J.
Sabacky, G. L. Bachman, D. J. Weinkauff, J. Am. Chem. Soc. 1977, 99,
5946-5952; c) W. S. Knowles, Angew. Chem. Int. Ed. 2002, 41, 1998-
2007.
[3] a) K. Dziuba, A. Flis, A. Szmigielska, K. M. Pietrusiewicz, Tetrahedron:
Asymmetry 2010, 21, 1401-1405; b) O. I. Kolodiazhnyi, Tetrahedron:
Asymmetry 2012, 23, 1-46; c) M. Dutartre, J. Bayardon, S. Juge, Chem.
Soc. Rev. 2016, 45, 5771-5794; d) T. Imamoto, Chem. Rec. 2016, 16,
2655-2669; e) J. Jia, Z. Ling, Z. Zhang, K. Tamura, I. D. Gridnev, T.
Imamoto, W. Zhang, Adv. Synth. Catal. 2018, 360, 738-743; f) C. F.
Czauderna, A. M. Z. Slawin, D. B. Cordes, J. I. van der Vlugt, P. C. J.
Kamer, Tetrahedron 2019, 75, 47-56;.
[4] a) K. Burgess, M. J.Ohlmeyer, K. H. Whitmire, Organometallics 1992, 11,
3588-3600; b) G. J. H. Buisman, L. A. van der Veen, A. Klootwijk, W. G. J.
de Lange, P. C. J. Kamer, P. W. N. M. van Leeuwen, D. Vogt,
Organometallics 1997, 16, 2929-2939; c) L. Qiu, J. Qi, C.-C. Pai, S. Chan,
Z. Zhou, M. C. K. Choi, A. S. C. Chan, Org. Lett. 2002, 4, 4599-4602; d) D.
Chen, N. Lu, G. Zhang, S. Mi, Tetrahedron: Asymmetry 2009, 20, 1365-
1368; e) Y.-S. Jang, M. Dieckmann, N. Cramer, Angew. Chem. Int. Ed.
2017, 56, 15088-15092.
Precatalyst
(RA, SS)-I
Yield (%)[b]
10
ee (%)[b]
32
Config.[c]
S
S
S
S
S
(RA, SS)-II
(RA, SP, SS)-III
(RA, SS)-IV
(RA, SS)-V
100
50
100
63
100
40
100
55
[a]
Reactions conditions: reaction temperature 25 °C , 10 atm of H2,
reaction time 3 h, [catalyst] = 1.2 × 10-2 M, [substrate] = 2.4 M, [KOtBu] =
[b]
1.1
×
10-2 M, isopropanol as solvent.
Determined by gas
[c]
chromatography (GC).
The absolute configurations were obtained by
GC by comparison to known standards.
Conclusion
[5] M. Cereghetti, W. Arnold, E. A. Broger, A. Rageot, Tetrahedron Lett. 1996,
37, 5347-5350.
In summary, a series of unsymmetrical 2,2’-bis(phosphino)-1,1’-
binaphthyls with one or two P-chirogenic centers were prepared
for the first time by virtue of phosphine oxide directing groups
and their regioselective and stereoselective reductions. The
phosphine oxide directing group was advantageous in achieving
high diastereoselectivity, while the reduction reaction that
proceeded at low temperature by the combination of
CeCl3/NaBH4/LiAlH4, assisted by the borane protection strategy,
allowed overcoming the frequently encountered but yet unsolved
problem of P-chirality racemization. The hybrid-chirality ligand
has demonstrated its unique property in inducing higher
stereoselectivity of the corresponding ruthenium catalyst in the
asymmetric hydrogenation of 3-methyl-2-butanone.
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Acknowledgements
Dr. Zuo thanks Prof. P. Braunstein at University of Strasbourg,
France and Prof. R. H. Morris at University of Toronto, Canada
for their comments on the manuscript preparation. This work
was supported by Natural Science Foundation of China
(21772021),
the
“Shanghai
Rising-Star
Program”
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Higher Learning (TP2014035), National Key Research Program
of China (Nos. 2016YFA0201702 of 2016YFA0201700), and
International Joint Laboratory for Advanced Fiber and Low-
dimension Materials (18520750400).
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Conflicts of interest
Donghua University has issued a patent titled “Diphosphine
chiral compound having both phosphorus central chirality and
dinaphthalene axial chirality and preparation method thereof”
(CN108690074A).
This article is protected by copyright. All rights reserved.

10.1002/anie.202001561
Angewandte Chemie International Edition
RESEARCH ARTICLE
Qingquan Xue,a Shangfei Huo,a Tingyi
Wang,a Zeming Wang,a Jianli Li,b
Meifang Zhu*,a and Weiwei Zuo*,a
Page No. – Page No.
Diastereoselective Synthesis of P-
Chirogenic and Atropoisomeric 2,2'-
bis(phosphino)-1,1'-binaphthyls
Enabled by Internal Phosphine Oxide
Directing Groups
Atropisomeric and P-chirogenic 2,2’-bis(phosphino)-1,1’-binaphthyls with
configurationally controllable chiral phosphorus center(s) were synthesized with
excellent diastereoselectivity, enabled by 2’-phosphine oxide directing groups and
their regio- and stereospecific reductions.
This article is protected by copyright. All rights reserved.