Asymmetric Hydrogenation of α-Boryl Enamides Enabled by Nonbonding Interactions

Article abstract of DOI:10.1021/acscatal.9b04543

The asymmetric hydrogenation of α-boryl enamides has been developed using a bisphosphine-rhodium catalyst. The chelate coordination of the amido group to rhodium and the nonbonding interactions between the substrate and the ligand play important roles to

Full text of DOI:10.1021/acscatal.9b04543

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Article
Asymmetric Hydrogenation of #-Boryl
Enamides Enabled by Nonbonding Interactions
Dongyang Fan, Jian Zhang, Yanhua Hu, Zhenfeng Zhang, Ilya D. Gridnev, and Wanbin Zhang
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b04543 • Publication Date (Web): 10 Feb 2020
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Asymmetric Hydrogenation of α-Boryl Enamides
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Enabled by Nonbonding Interactions
Dongyang Fan,† Jian Zhang,† Yanhua Hu,‡ Zhenfeng Zhang,*,† Ilya D. Gridnev,*,§ and Wanbin
Zhang*,†,‡
†Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy,
Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China
‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800
Dongchuan Road, Shanghai 200240, P. R. China
§Department of Chemistry, Graduate School of Science, Tohoku University, Aramaki 3-6, Aoba-
ku, Sendai 980-8578, Japan
ABSTRACT: The asymmetric hydrogenation of α-boryl enamides has been developed using a
bisphosphine-rhodium catalyst. The chelate coordination of the amido group to rhodium and the
nonbonding interactions between the substrate and ligand play important roles to afford chiral α-
amidoboronic esters with quantitative conversions, high chemoselectivity, and excellent
enantioselectivity (92-99% ee). Computation of the catalytic cycle revealed selectivity both in
the hydrogen activation and migratory insertion steps equally contributing to the high
enantioselectivity. In both cases the nonbonding interactions provided by the Bpin group
contributed significantly to the stabilization of the transition states in the lower energy pathway.
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KEYWORDS: asymmetric hydrogenation • rhodium • α-boryl enamides • α-aminoboronic acid •
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nonbonding interaction
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 INTRODUCTION
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Organoboron compounds are popular in the chemical and pharmaceutical fields owing to their
unique physical, chemical, and bioactive properties.[1] The Nobel Prize in chemistry has been
awarded to the development of boron-related reagents and reactions three times (1976, 1979,
2010). Recently, chiral organoboron compounds have attracted much attention due to their broad
utilization in drug discovery and synthetic applications.[2] Among them, chiral α-aminoboronic
acids, as mimics of chiral amino acids, are one of the most significant fragments in many
important pharmaceuticals, such as Bortezomib (marketed as Velcade®) and Ixazomib citrate
(marketed as Ninlaro®) (Figure 1).[3]
OH
Cl
O
O
O
H
H
H
N
N
N
N
Ph
N
N
N
N
N
H
H
H
O
B
O
B
O
B
HO
OH
HO
OH
HO
OH
Cl
Bortezomib
Ixazomib
Delanzomib
HN
O
O
NH2
O
H
N
H
N
N
N
COOH
N
H
N
H
O
O
B
B
B
HO
OH
HO
OH
HO
OH
Proteasome Inhibitor
Dutogliptin
-Lactamase Inhibitor
Figure 1. Pharmaceutically important compounds bearing chiral α-aminoboronic acid fragments.
The importance of chiral α-aminoboronic acid derivatives has promoted the development of
their asymmetric synthesis. The most common route is a diastereoselective method that utilizes
chiral auxiliaries to synthesize chiral α-aminoboronic esters.[4] A lithiation-borylation protocol
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has also been developed mediated by chiral sparteine or starting from chiral amines.[5] However,
such methods are unsatisfactory since they require stoichiometric amounts of chiral reagents. In
contrast, asymmetric catalytic routes for the synthesis of chiral α-aminoboronic acid derivatives
are supposed to be more economic but are not as widely reported. The asymmetric borylation of
imines or enamines is one of the most feasible approaches to furnish chiral α-aminoboronic
esters (Scheme 1a and 1b).[6] Another method to afford the target compounds is the asymmetric
amination of alkenylboronates (Scheme 1c).[7] However, high catalyst loadings and a large
dosage of boron-, silicon-, nitrogen-containing reagents reduces the practicality of the process
and increases problems in scale-up. Therefore, it is highly desirable to develop a more efficient
and green method for the construction of chiral α-aminoboronic acid derivatives.
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Transition-metal-catalyzed asymmetric hydrogenation is considered to be one of the most
efficient and green routes for the synthesis of chiral compounds.[8] It has shown extremely high
performance in the synthesis of chiral α-amino acid derivatives via asymmetric hydrogenation of
α-acyl enamides (Scheme 1d).[9] However, the enantioselective synthesis of their analogues,
chiral α-aminoboronic acid derivatives, has not yet been realized via the asymmetric
hydrogenation of α-boryl enamides, even though this method seems to be a natural and feasible
solution. The reason lies in the challenge with regards to high chemoselectivity between
hydrogenation and hydrodeboronation, as well as high stereoselectivity.[10] It was envisaged that
the presence of a chelating amido group at the α-position to the boryl group would be
advantageous for chemoselectivity. Additionally, one could expect that the Bpin group is capable
of several kinds of weak nonbonding interactions enabling it to act as a directing group to
provide high stereoselectivity.[11] Along with our continuing research on asymmetric
hydrogenation,[11,12] herein we report the chemo- and enantioselective synthesis of chiral α-
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aminoboronic acid derivatives via asymmetric hydrogenation using α-boryl enamides as the
substrates and BenzP*-Rh[13] as the catalyst (Scheme 1e).
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a: Asymmetric borylation of imines
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N
N
Pt, Cu, Rh, or metal-free
B2pin2
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*
R1 Bpin
R2
R1 R2
b: Asymmetric borylation of enamines
N
N
Rh or Cu
B2pin2
R1
R1
*
R2
Bpin
R2
c: Asymmetric amination of alkenylboronates
N
R2
Cu
R1
*
*
R1
Bdan
Nu + N-O
R2
Bdan
Nu
d: Asymmetric hydrogenation of -acyl enamides

Rh
NHCOR
COOR2
NHCOR
R1
R1
COOR2
H2
e: Asymmetric hydrogenation of -boryl enamides

O
O
BenzP*
-Rh
O
O
N
N
H2
R
R
Bpin
Bpin
Scheme 1. Catalytic Enantioselective Synthesis of Chiral α-Aminoboronic Acid Derivatives
 RESULTS AND DISCUSSION
Looking for appropriate substrates, we first considered 1a-NH as the one having a simple
structure. Unfortunately, our attempts to prepare 1a-NH were unsuccessful. This initiated the
search for alternative precursors and resulted in finding a substrate 1a with a five-membered
oxazolidinonyl group, which can be readily synthesized according to the procedure reported by
Zhu et al.[14] Actually, 1a may be a better substrate than 1a-NH, since the optimized structure of
1a shows a larger BC-NC twist angle of 37.5°, a larger N-C-O angle of 127.1°, and a longer
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O···B bond length of 2.85 Å compared to those computed for 1a-NH (Figure 2), which may be
advantageous for the coordination of the C=O and C=C bonds with the Rh atom. Indeed,
substrate 1a underwent smooth hydrogenation catalyzed by a BenzP*-Rh complex, affording the
desired product in 99% conversion and with 95% ee (Table 1, entry 1).
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O
B
O
B
O
O
2.71Å
2.85Å
31.0
37.5
O
O
N
H
N
124.5
127.1
O
O
1a-NH
1a
Figure 2. Representative substrates.
Table 1 shows the chiral diphosphine ligands that were tested in the Rh-catalyzed
hydrogenation of 1a carried out in dichloromethane (DCM) under 30 atm hydrogen pressure
(Table 1). Using the centrally chiral ligand NorPhos, the desired product was obtained with poor
chemoselectivity and moderate enantioselectivity. The hydrogenation in this case was
characterized by low conversion together with formation of some amount of the deboronated by-
products 2a' and 2a''. The axially chiral ligand BINAP exhibited moderate conversion, excellent
chemoselectivity, and poor enantioselectivity. The conversions and chemoselectivities were
dramatically improved by using the planarly chiral ligands PhanePhos and JosiPhos, although the
enantioselectivities were still poor. The ligand Me-FcPhos, bearing electron-rich phosphine
groups on a ferrocene skeleton, gave the desired product in quantitative conversion but with poor
enantioselectivity. Another typical electron-rich ligand Me-DuPhos, possessing the same
phosphine groups as Me-FcPhos, afforded a positive enantioselectivity but unsatisfactory
chemoselectivity. Both excellent chemoselectivity and enantioselectivity were only obtained by
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using the P-stereogenic ligand BenzP* possessing electron-rich tert-butylmethylphosphino
groups. The same excellent enantioselectivity of 95% was observed with another P-stereogenic
ligand QuinoxP* that demonstrates the importance of the t-Bu groups on the ligand for high
enantioselectivity in this reaction. Further optimization was focused on the screening of solvents
using the BenzP*-Rh catalyst. Another halogenated solvent, dichloroethane (DCE), gave a
higher enantioselectivity of 98% ee but lower conversion (entry 2 vs 1). Reaction in less polar
solvents such as tetrahydrofuran (THF), dimethyl ethyl diether (DME), and toluene also showed
high chemo- and enantioselectivity with incomplete conversion (entries 3-5). A better result was
obtained using ethyl acetate (EtOAc) as the solvent (entry 6). The desired product was obtained
without any loss of conversion and ee when the hydrogen pressure was reduced from 30 atm to 5
atm (entries 7-8). Further reduction of the hydrogen pressure to 1 atm gave incomplete
conversion with retention of enantioselectivity (entry 9). The hydrogenation of 1a was also
completed using 1 mol % catalyst, affording the desired product 2a in 99% conversion and 96%
ee (entry 10).
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With the optimized reaction conditions in hand, we set out to study the substrate scope of α-boryl
enamides in this hydrogenation (Scheme 2). It was found that the substituted positions and
electronic properties of the substituents had a great impact on reactivities as well as
enantioselectivities. Substrates bearing small substituents at the para-position showed higher
activity (2f, 2n, 2p, 2q, and 2t), while other substrates required a 2 mol % catalyst loading to
complete the hydrogenation (2b-d, 2g-k, 2o, 2r, and 2s), and the last three substrates needed a 4
mol % catalyst loading for complete hydrogenation (2e, 2l, and 2m). Generally, the electron-
withdrawing substituted substrates exhibited slightly better enantioselectivities compared with
the electron-donating substituted substrates. When a halogen was substituted on the phenyl ring,
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Table 1. Condition Optimization
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O
O
O
O
O
O
O
O
PP*-Rh (2 mol %)
H2 (30 atm)
N
Bpin
N
Bpin
N
N
*
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DCM, rt, 10 h
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1a
2a
2a'
2a''
PPh2
PPh2
Ph2P
PPh2
PPh2
Fe
PCy2
PPh2
PPh2
(R,R)-NorPhos
conv: 39/15/5
ee: 63%
(R)-BINAP
conv: 60/0/0
ee: 13%
(R)-PhanePhos
conv: 99/0/0
ee: 43%
(R,Sp)-JosiPhos
conv: 99/0/0
ee: 10%
P
P
P
P
P
N
N
P
P
Fe
P
(R,R)-Me-FcPhos
conv: 99/0/0
ee: 7%
(R,R)-Me-DuPhos
conv: 36/29/6
ee: 87%
(R,R)-BenzP*
conv: 99/0/0
ee: 95%
(R,R)-QuinoxP*
conv: 28/4/4
ee: 95%
entrya
solvent
H2 (atm)
conv 2a (%)b
ee (%)c
95
1
2
DCM
DCE
30
30
30
30
30
30
20
5
99
21
87
77
77
99
99
99
26
99
98
3
THF
94
4
DME
90
5
Toluene
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
98
6
96
7
96
8
96
9
1
96
10d
20
96
aConditions: 1a (0.1 mmol), PP*-Rh (2 mol %), H2, solvent (2 mL), rt, 10 h, unless otherwise
noted. bThe conversions were calculated from 1H-NMR spectra. cThe ee values were determined
by HPLC using chiral columns. d[Rh((R,R)-BenzP*)(nbd)]SbF6 (1 mol %).
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[Rh((R,R)-BenzP*)(nbd)]SbF6
(1 mol %)
O
B
O
B
H2 (20 atm)
O
O
O
O
Ar
Ar
N
N
EtOAc, 10 h, rt
O
O
2
1
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O
B
F
O
O
O
B
B
F
B
O
O
O
O
O
O
O
O
N
N
N
N
F
O
O
O
O
2ba
2ca
2da
2a
98% yield, 96% ee
97% yield, 96% ee
96% yield, 98% ee
97% yield, 98% ee
O
O
O
O
Cl
B
B
B
B
O
O
O
O
N
O
N
O
N
O
N
O
Cl
Br
F3C
O
O
O
O
2ec
2fb
2ga
2ha
97% yield, 96% ee
98% yield, 98% ee
96% yield, 98% ee
97% yield, 99% ee
O
B
O
O
B
OMe
O
B
B
O
O
O
O
O
O
N
N
O
N
N
O
MeOOC
Ph
O2N
O
O
2ja
O
O
2lc
2ia
2ka
95% yield, 99% ee
96% yield, 99% ee
96% yield, 97% ee
97% yield, 99% ee
O
B
O
B
O
O
MeO
Me
B
B
O
O
O
O
N
N
N
O
N
O
O
O
MeO
Me
O
O
O
O
2mc
2oa
2n
2p
96% yield, 92% ee
97% yield, 97% ee
98% yield, 97% ee
96% yield, 98% ee
O
O
O
O
B
B
B
B
O
O
O
O
N
O
N
O
N
O
N
O
Et
nPr
tBu
O
O
O
O
2qb
2ra
2sa
2tb
97% yield, 95% ee
95% yield, 97% ee
97% yield, 96% ee
95% yield, 95% ee
1
Conditions: (0.1 mmol), [Rh((R,R)-BenzP*)(nbd)]SbF6 (1 mol %), H2 (20 atm), EtOAc (2.0 mL), rt, 10 h, unless
otherwise noted. Isolated yields. The ee values were determined by HPLC using chiral columns. a[Rh((R,R)-
BenzP*)(nbd)]SbF6 (2 mol %), 24 h. b24 h. c[Rh((R,R)-BenzP*)(nbd)]SbF6 (4 mol %), 24 h.
Scheme 2. Substrate Scope.
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the ee values of the desired chiral products were no less than 96% (2b-g). The substrates with
trifluoromethyl, methoxy formyl, and phenyl groups at the para-position provided the products
with complete conversions and almost perfect enantioselectivities (99% ee for 2h-j), while
another product 2k with a nitro group at the para-position was obtained with 97% ee. When
electron-donating groups such as methoxy and methyl were present at the ortho-, meta-, and
para-positions, the activities increased while the enantioselectivities decreased gradually (2l-p).
The activities of the catalytic reaction were reduced significantly when the para-substituent was
changed from methyl to the relatively more bulky ethyl, n-propyl, and t-butyl groups, but the
enantioselectivities were almost identical (2q-s). The naphthyl-substituted product 2t can also be
obtained in high yield and excellent enantioselectivity. To demonstrate the potential utilities of
this protocol, the hydrogenation of 1a was carried out on a gram scale using DCM as the solvent
due to the solubility, affording the desired product in quantitative yield and with excellent
enantioselectivity (Scheme 3).
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[Rh((R,R)-BenzP*)(nbd)]SbF6
(1 mol %)
H2 (20 atm)
O
B
O
B
O
O
O
O
DCM, rt, 24 h
N
N
O
O
1a
1.00 g, 3.2 mol
2a
0.98 g, 98% yield, 96% ee
Scheme 3. Gram Scale Hydrogenation
To gain insight into the origin of activity and enantioselectivity, we have computed a catalytic
cycle of the reaction (Scheme 4 and 5, Figure 3). Similarly to the catalytic cycles of other
enamides, the amido group remains coordinated to the Rh atom throughout the whole catalytic
cycle – either in a chelating or non-chelating way. Scheme 4 summarizes computations of the
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hydrogen activation step. Although the solvate dihydrides E and F are reasonably stable, TS1
and TS2 have relatively high free energies, and the dihydride route for hydrogen activation is not
the lowest energy pathway in this case. On the other hand, the chelated catalyst-substrate
complexes I and M themselves are not capable of hydrogen activation. Molecular hydrogen
complex N formed from the chelated M, rearranges to the gauche-coordinated[13d] molecular
hydrogen complex P that can yield the monohydride Q with reasonably low barrier without
intermediate formation of a dihydride. Monohydride Q can directly produce the hydrogenated
product with the experimentally observed sense of enantioselection. However, the non-chelated
complex G, formed as a result of the approaching hydrogen to the Rh atom in the chelated
molecular hydrogen complex J, is significantly more reactive. Since the TS4 (hydrogen
activation via K and L) is also high in energy, apparently, all hydrogen activations proceed via G
formed either from J or from the non-chelated catalyst-substrate complex C, yielding selectively
the non-chelated dihydride intermediate H.
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As shown in Scheme 5, barrierless coordination of the double bond in H can give either α- or
β-dihydride R and S, respectively. The following migratory insertion and reductive elimination
proceed faster starting from S thus providing selective formation of the S-product. Therefore, the
S enantioselectivity is determined by the difference in stabilities of TS3 (-6.2 kcal/mol) and TS4
(-2.0 kcal/mol) which halves the number of possible pathways in the late reaction stages, as well
as between TS6 (-14.5 kcal/mol) and TS7 (-11.3 kcal/mol) that secures the formation of the S-
product.
Notably, in both cases the relative stability of TS3 or TS6 is caused by the pinacolylboryl
group being in close proximity to the t-Bu group, leading to the significant energy difference
(Figure 3). Thus, in TS3, the phenyl group is not participating in any intramolecular interactions.
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3
4
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tBu
Me
Me
tBu
(3.1)
TS1
E
F
(-0.3)
(3.2)
H
P
P
P
"dihydride"
Rh
H
tBu
Me
Me
tBu
(4.5)
TS2
tBu
Me
P
P
H
Me
tBu
Rh
H
P
Rh
H
H
B
(-4.9)
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tBu
Me
tBu
Me
Me
tBu
Me
tBu
H
"semi-dihydride"-1
P
P
P
P
H
(-6.2)
TS3
Rh
Ph
Rh
Ph
O
O
H
O
O
tBu
Me
H
Me
P
N
N
P
tBu
Rh
B
B
O
O
O
Ph
tBu
Me
O
O
Me
G
(-12.9)
H
(-7.8)
P
P
O
tBu
Rh
N
B
A + H + 1a
(0.0)
O
2
O
tBu
P
Me
Me
tBu
tBu
Me
Me
tBu
Ph
Rh
C
Ph
P
Rh
(-13.4)
P
P
O
O
H
N
H
"unsaturated"-R
O
O
B
N
O
B
O
O
O
I
J
(-25.9)
(-18.6)
tBu
Me
tBu
Me
tBu
Me
tBu
H
P
P
P
P
H
"semi-dihydride"-2
(-2.0)
TS4
Rh
Ph
Rh
Me
H
O
Ph
O
H
O
O
N
N
B
B
O
O
O
O
K
L
(-14.4)
(-6.7)
tBu
Me
P
tBu
tBu
Me
Me
P
P
P
Ph
Rh
P
Ph
Rh
P
tBu
O
Rh
Ph
Me
Me
tBu
Me
tBu
O
O
O
O
H
O
H
B
B
N
N
B
O
N
O
O
O
O
O
"unsaturated"-S
M
N
(-21.3)
(-26.9)
D
(-7.2)
tBu
Me
tBu
Me
Me
tBu
P
Ph
P
P
P
Me
tBu
Rh
Rh
Ph
O
O
H
H
O
O
"semi-unsaturated"-S
O
O
N
N
B
B
O
O
P
(-19.3)
O
(-28.1)
TS5
(-2.0)
tBu
Me
H
P
P
Me
Ph
tBu
Rh
O
O
O
N
B
O
Q
(-18.1)
Scheme 4. Calculated Free Energies for Hydrogen Activation via Various Pathways (A positive
charge on each Rh atom is omitted for clarity. The unit of energies is kcal/mol.)
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tBu
Me
H
P
P
H
tBu
Rh
Ph
Me
O
O
N
B
O
O
barrierless
barrierless
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H
(-7.8)
O
Me
tBu
Me
(-19.7)Ph
B
O
H
Rh
P
P
H
tBu
Me
tBu
O
H
Rh
P
P
t
Me
N
R
S
(-15.3)
Bu
B
H
O
N
O
O
Ph
O
O
TS7
TS6
(-11.3)
(-14.5)
O
tBu
O
tBu
Me
tBu
B
H
Rh
P
N
P
Me
H
Rh
Me
P
P
T
U
(-23.8)
(-18.5)
tBu
O
Me
Ph
B
N
O
O
O
O
Ph
O
TS9
TS8
(-0.6)
(-2.6)
O
O
R
S
B
B
tBu
tBu
Me
tBu
Ph
Ph
O
O
Me
P
P
P
P
N
N
tBu
Rh
Rh
Me
Me
O
O
O
O
V
W
(-31.5)
(-28.5)
Scheme 5. Calculated Free Energies for Hydrogen Transfer of Alternative Pathways (A positive
charge on each Rh atom is omitted for clarity. The unit of energies is kcal/mol.)
In the same fashion, in TS4, only the C-H…π interaction between the methyl group of the ligand
and the phenyl group of the substrate participates in the stabilization of the transition state.
Hence, the stabilizing free energy provided by the nonbonding interaction of t-Bu and
pinacoylboryl groups can be estimated to be over 4 kcal/mol. Comparing TS6 and TS7, it is
difficult to make any similar semi-quantitative estimation. It is only clear that the stabilizing
nonbonding interactions in TS6 are significantly greater in number than those in TS7, and that
the contribution from the t-Bu…Bpin interaction is likely to also be around 4 kcal/mol.[15] We are
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convinced that accumulation of the knowledge on the strength of the nonbonding interaction
between various groups provides useful information for the construction of potential substrates
and catalysts for asymmetric catalytic transformations.
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Figure 3. Optimized structures of TS3 and TS4 (up); TS6 and TS7 (down), their relative Gibbs
free energies and interatomic distances (Angstroms) for intramolecular interactions: C-H...H-C
(green), C-H...O (red), C-H... (violet), C-H...B (yellow), and C-H...N (blue).[16] Significant
relative stability of TS6 is secured by the whole network of 10 interactions against only 5 in
TS7.
 CONCLUSIONS
In summary, we have developed a highly efficient route for the synthesis of chiral α-
aminoboronates in high yield and excellent enantioselectivity via the rhodium-catalyzed
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asymmetric hydrogenation of α-boryl enamides. Computational studies showed that nonbonding
interactions of t-Bu…Bpin are important for both reactivity and selectivity. In addition, the
catalytic reaction can be carried out on a gram scale without any loss in enantioselectivity.
 EXPERIMENTAL SECTION
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[Rh((R,R)-BenzP*)(nbd)]SbF6 (0.001 mmol) and substrate (0.1 mmol) were placed in a
hydrogenation tube and then charged in an autoclave. The system was evacuated and filled with
hydrogen. After repeating this operation 3 times, degassed EtOAc (2 mL) was added and the
hydrogen pressure was adjusted to 20 atm. After vigorous stirring at room temperature for 10 h,
the vessel was vented and the reaction mixture was evaporated under reduced pressure. The
conversation was calculated from the 1H NMR spectrum of the crude product. After purification
by column chromatography, the enantiomeric excess of the product was determined by HPLC
using a chiral column.
 AUTHOR INFORMATION
Corresponding Author
*E-mail: wanbin@sjtu.edu.cn
*E-mail: gridnev.ilya.a6@tohoku.ac.jp
*E-mail: zhenfeng@sjtu.edu.cn
Notes
The authors declare no competing financial interest.
 ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
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Synthetic details for substrates, procedures for hydrogenation reactions, spectra of NMR
and HPLC data, computational details (PDF)
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Crystallographic data for 2h (CIF)
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 ACKNOWLEDGMENTS
This work was supported by National Key R&D Program of China (No. 2018YFE0126800),
National Natural Science Foundation of China (Nos. 21620102003, 21831005, 91856106, and
21572131), and Shanghai Municipal Education Commission (No. 201701070002E00030). We
thank the Instrumental Analysis Center of Shanghai Jiao Tong University. We acknowledge the
generous gifts of the P-stereogenic bisphosphine ligands from Nippon Chemical Industrial Co.
Ltd.
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(14) He, G.; Chen, S.; Wang, Q.; Huang, H.; Zhang, Q.; Zhang, D.; Zhang, R.; Zhu, H. Studies
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(15) A more accurate description of the interaction between the t-Bu and Bpin groups could be
possible via the NCIPLOT analysis [ref: Y. Cornaton, J.-P. Djukic, A Noncovalent Interaction
Insight onto the Concerted Metallation Deprotonation Mechanism. Phys. Chem. Chem. Phys.
2019, 21, 20486–20498]. The further investigations on the exact nature of the attractive
interaction between t-Bu and Bpin groups are underway and will be published in due course.
(16) The C-H...H-C interactions may be of minor significance for the stabilizing of these
molecules. Nevertheless, we have recently reported experimental evidence showing that C-
H...H-C interactions in the range of 2.3-2.7 Å are attractive and strong enough to control the
equilibrium between diastereomers of a Rh-diphosphine complex [ref: I. D. Gridnev, Attraction
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versus Repulsion in Rhodium-Catalyzed Asymmetric Hydrogenation. ChemCatChem 2016, 8,
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3463–3465].
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Table of Contents
Nonbonding Interaction
Me
O
B
O
B
(R,R)-BenzP*
[Rh(
)(nbd)]SbF6
P
P
O
O
O
O
Ar
Ar
N
N
H2
Me
O
O
20 examples
up to 99% ee
Chelate Coordination
(R,R)-BenzP*
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Figure 1
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Figure 2
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Figure 3
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