Asymmetric 1,4-Conjugate Addition of Diarylphosphines to α,β,γ,δ-Unsaturated Ketones Catalyzed by Transition-Metal Pincer Complexes

Article abstract of DOI:10.1021/acs.organomet.5b00787

An enantioselective asymmetric 1,4-addition of diarylphosphines to linear α,β,γ,δ-unsaturated dienones was developed. A series of chiral PCP- and PCN-transition-metal (Pd, Pt and Ni) pincers, themselves prepared catalytically via asymmetric hydrophosphination, were sequentially screened to reveal the roles of backbone architecture and metal ion in catalyst design. The selected ester-functionalized PCP-palladium pincer afforded the chiral 1,4-phosphine adducts in excellent yields with up to >99% ee. The same catalyst when utilized for the hydrophosphination of an α,β,γ,δ-unsaturated malonate ester also revealed the critical role played by the ester functionality on the ligand backbone in dictating the enantioselectivity of the 1,6-adduct.

Full text of DOI:10.1021/acs.organomet.5b00787

Article
pubs.acs.org/Organometallics
Asymmetric 1,4-Conjugate Addition of Diarylphosphines to α,β,γ,δ-
Unsaturated Ketones Catalyzed by Transition-Metal Pincer
Complexes
Xiang-Yuan Yang, Wee Shan Tay, Yongxin Li, Sumod A. Pullarkat,* and Pak-Hing Leung*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371
S
* Supporting Information
ABSTRACT: An enantioselective asymmetric 1,4-addition of diarylphos-
phines to linear α,β,γ,δ-unsaturated dienones was developed. A series of
chiral PCP- and PCN-transition-metal (Pd, Pt and Ni) pincers, themselves
prepared catalytically via asymmetric hydrophosphination, were sequentially
screened to reveal the roles of backbone architecture and metal ion in
catalyst design. The selected ester-functionalized PCP-palladium pincer
afforded the chiral 1,4-phosphine adducts in excellent yields with up to >99% ee. The same catalyst when utilized for the
hydrophosphination of an α,β,γ,δ-unsaturated malonate ester also revealed the critical role played by the ester functionality on
the ligand backbone in dictating the enantioselectivity of the 1,6-adduct.
Scheme 1. Examples of Regioselective C−P Bond Formation
INTRODUCTION
■
The enantioselective formation of carbon−carbon bonds
through conjugate addition (CA) is a practical and attractive
strategy toward generating highly functionalized molecular
synthons.1 However, the simultaneous control of both regio-
and stereoselectivity is a significant challenge in asymmetric
CA, especially in the case of linear α,β,γ,δ-unsaturated Michael
acceptors. Because of the presence of three potentially
accessible electrophilic sites, the selective formation of 1,2-,
1,4-, or 1,6-adducts becomes inherently difficult. Nevertheless,
significant progress has been achieved by the groups of Hayashi,
Fillion, Feringa, and Alexakis2 in the highly regioselective
construction of C−C bonds in an enantioselective manner in
such scenarios. In contrast, the asymmetric formation of
carbon-heteroatom bonds (such as C−Si, C−P, C−N, and C−
S) involving linear α,β,γ,δ-unsaturated substrates are relatively
rare in the literature.3 In the case of asymmetric C−P bond
formation involving α,β,γ,δ-unsaturated substrates, this is in fact
limited to just two literature reports.3d,4 Because of the well-
established role of chiral phosphines in many areas of science
such as pharmaceuticals, agrochemicals, fine chemicals,
transition-metal catalysis, and organocatalysis,5 compounding
interest has been generated recently in the asymmetric
formation of C−P bonds via the metal-catalyzed hydro-
phosphination reaction on α,β-unsaturated substrates.6 This
method is able to produce enantiopure tertiary phosphines in
arguably the most economical, practical, and straightforward
manner.
α,β,γ,δ-unsaturated sulfonic esters, which proceeded with 1,6-
regioselectivity at −60 °C, while in the latter, when employing
an α,β,γ,δ-unsaturated malonate ester, viz., diethyl 2-cinnamy-
lidenemalonate, the addition of diphenylphosphine yielded the
1,6-adduct as the major product at −80 °C. Interestingly, in the
latter study, when a phosphapalladacycle was employed in the
same reaction, the regioselectivity could be switched to favor
the traditional 1,4-addition product, thus indicating the need to
further investigate the role of catalyst design in this synthetically
useful methodology.
The two reports of chiral phosphines produced via
regioselective CA (Scheme 1) utilizing the hydrophosphination
protocol, which have been reported recently by Duan et al.3d
and by us,4 both conspicuously employed chiral PCP pincer
catalysts (albeit generated via differing methodologies). The
former report focused on the addition of diarylphosphines to
Received: September 14, 2015
© XXXX American Chemical Society
A
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a
Herein, we report the development of an efficient protocol
for the asymmetric CA of diarylphosphines to linear α,β,γ,δ-
unsaturated dienones. The aim was to establish an efficient
methodology toward the asymmetric hydrophosphination
(AHP) of activated diunsaturated enones, which could also
provide further insights into the role of transition-metal pincer
based catalyst design in the control of regio- and stereo-
selectivity control in this relatively under-developed asymmetric
CA.
Table 1. Screening of Catalysts in the AHP Reaction
b
c
entry
cat.
t (h)
ee (%)
yield (%)
d
1
2
3
4
5
6
7
8
9
(S)-1
3
3
24
5
80
80
73
79
89
86
71
85
69
(R,R)-2a
(R,R)-2b
(R,R)-2c
(R,R)-3a
(R,R)-3b
(R,R)-3c
(R)-4a
24
4
2
21
69
16
4
RESULTS AND DISCUSSION
■
20
24
48
24
24
From the point of view of catalyst design, a major obstacle to
accessing chiral variants of the pincer complexes lies in their
syntheses.7 Existing methods are highly dependent on the chiral
pool of starting materials such as amino acids8 and BINOL- and
TADDOL-derivatives.9 For instance, the catalyst used in the
aforementioned study by Duan et al.3d was prepared from an
optically pure diol and required extensive protection−
deprotection protocols,10 which are known to adversely affect
optical purity and yield.11 The multistep synthesis ultimately
afforded the PCP-pincer in a low overall yield of 32%.
Leveraging on a recently developed synthetic methodology,12
we have successfully bypassed these traditional impediments to
produce catalytically a series of optically pure PCP- and PCN-
pincer complexes in an efficient and diastereoselective manner
from cheap and easily accessible achiral substrates (Figure 1,
10
3
(R)-4b
a
Conditions: compound 5a (0.05 mmol), catalyst (R,R)-3a (2.5 μmol,
5 mol %), and HPPh2 (0.06 mmol) in 3 mL of solvent stirred at RT.
Determined by chiral HPLC. Isolated yield. Addition of NEt3 (1.2
b
c
d
equiv) as an external base was necessary.
entries 2−9 in Table 1 allowed three main inferences to be
made: (1) palladium is by far a better metal ion than both
platinum and nickel in terms of reactivity, (2) the PCN pincers
were inferior to their PCP counterparts in having lower
reactivity along with diminished ee/yields, and (3) the ester-
functionalized PCP-pincer 3 clearly outperforms the keto-
functionalized pincers 2 and 4 in controlling the stereo-
selectivity of the AHP reaction.
Comparing the same general ligand backbone with different
transition metals thus sheds light on the contrasting reactivity
between Pd, Pt, and Ni for this hydrophosphination reaction. It
also shows the differing ability between the complexes to
efficiently transmit the stereocontrol to the reaction site on the
metal (Table 1, entries 2−3, 5−7). Another point to note is
that the modification of the terminal R groups in the keto-
functionalized catalyst 2 (Table 1, entries 2, 4) had only
marginal impact on both yields and enantioselectivity, possibly
due to the remoteness of these groups from the metal center. It
is noteworthy that, in all cases, only the 1,4-adduct 6a was
formed exclusively. The pincer (R,R)-3a surpassed all other
catalysts in providing the optimum balance between reactivity,
ee, and yield and, hence, was shortlisted as the catalyst of choice
for further optimization studies (Table 2).
Figure 1. Cyclometalated complexes employed.
We were delighted to find out that, in the majority of the
cases, the reaction gave high ee with moderate to excellent
yields under mild conditions, albeit with varying reaction times.
Acetone was selected as the solvent of choice due to the short
reaction time, high ee, and excellent yield (Table 2, entry 5). To
further improve enantioselectivity, the reaction was completed
in 6 h at 0 °C (Table 2, entry 10), and 99% ee was achieved. In
terms of both ee and reactivity, this outperformed a previously
reported methyl-substituted PCP-pincer catalyzed AHP of
substrate 5a to form adduct 6a (in 93% ee and 93% yield at RT
over 24 h).3d In an attempt to determine if the steric bulkiness
of the ester groups at the terminal ends of the PCP pincer
(R,R)-3a has a direct influence on the stereochemical outcome,
pincer (R,R)-3d was prepared and employed in the same
catalytic scenario. The data (Table 2, entry 11) obtained
suggest that modification of the steric bulk has negligible effects
on stereoselectivity.
complexes 2, 3, and 4) in isolated yields of up to 75%.
Furthermore, this new catalytic preparation of optically pure
pincer ligands allows the flexibility for the facile incorporation
of various backbone functionalities. In the context of AHP, it
also allows us to diversify from the traditional catalyst design
based on the palladacycle (S)-1 and its analogues (Figure 1),
which have proven potential as efficient catalysts in the AHP of
α,β-unsaturated substrates. However, such protocols are
routinely conducted at −80 °C, and a higher reaction
temperature such as RT results in lower ee values.6f−k
We initiated our current study by screening the PCP- and
PCN-pincer complexes presented in Figure 1 as well as the
phosphapalladacycle (S)-1 for the AHP of α,β,γ,δ-unsaturated
dienone 5a with diphenylphosphine (Table 1). The reaction
catalyzed by palladacycle (S)-1 (Table 1, entry 1) was
encouraging in terms of reactivity and yield, but the ee achieved
was substantially low when compared to the best performing
pincer (Table 1, entry 5) at room temperature. As far as the
pincer type catalysts were concerned, a preliminary analysis of
With the optimal conditions established, a range of linear
α,β,γ,δ-unsaturated dienones were screened (Table 3). This is
the first instance in the literature wherein an AHP has been
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a
proceeded smoothly to afford the desired products without any
visible changes in reactivity. The sterically bulkier phosphine
(HP(o-tolyl)2) (Table 3, entry 21) was also successful in
generating the 1,4-adduct in 97% ee.
Table 2. Optimization of the Reaction Conditions
b
c
entry
solvent
t (h)
ee (%)
yield (%)
1
2
toluene
MTBE
MeOH
THF
15
8
92
93
16
80
97
94
92
91
90
99
95
88
83
51
62
84
81
81
76
82
92
88
As aforementioned, Duan et al.3d had reported the
regioselective addition of phosphines to α,β,γ,δ-unsaturated
sulfonic esters to afford the 1,6-adduct as the only products.
Subsequently, our group had published an article investigating
the control of regioselectivity by the appropriate choice of
palladium catalyst for α,β- and α,β,γ,δ-unsaturated malonate
esters. However, when the keto-based pincer (R,R)-2a was
employed as catalyst, 1,6-adducts were obtained regioselectively
but with low ee’s (22−70%).4
d
3
24
24
5
d
4
5
6
7
8
9
acetone
MeCN
DEE
22
4
EA
4
benzene
acetone
acetone
12
6
e
10
f
11
6
Encouraged by the excellent results obtained in the current
study where 1,4-adducts were regioselectively generated with
the ester-based pincer (R,R)-3a, we decided to further
investigate the underlying factors which caused the dramatic
regioselectivity reversal observed. We, therefore, set up a model
reaction involving the AHP of diethyl-2-cinnamylidenemalo-
nate 7, but this time employing both pincers (R,R)-2a and
(R,R)-3a for comparison (Table 4).
a
Conditions: compound 5a (0.05 mmol), catalyst (R,R)-3a (2.5 μmol,
5 mol %), and HPPh2 (0.06 mmol) in 3 mL of solvent stirred at RT.
b
d
f
c
Determined by chiral HPLC. Isolated yield of adduct 6a.
e
Incomplete conversion of HPPh2. Reaction was done at 0 °C.
Catalyst (R,R)-3d was used.
a
Table 3. Substrate Scope of the AHP Reaction
a
Table 4. Catalytic AHP of Substrate 7
b
c
entry
R
R1
T (°C)
6
ee (%)
yield (%)
1
2
3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Et
4-PhC6H4
4-PhC6H4
3-NO2C6H4
3-NO2C6H4
3-NO2C6H4
4-CF3C6H4
3,4-ClC6H3
2-naphthyl
2-furyl
RT
0
6b
6b
6c
6c
6c
6d
6e
6f
90
81
86
84
89
92
86
88
85
78
90
89
86
90
91
82
85
88
88
89
91
84
94
b
c
entry
cat.
8a:8a′
0:100
0:100
ee (%)
yield (%)
RT
RT
0
95
d
4
94
1
2
(R,R)-2a
(R,R)-3a
37
79
81
5
6
>99
>99
>99
>99
99
>99
a
0
Conditions: compound 7 (0.05 mmol), catalyst (2.5 μmol, 5 mol %),
b
7
0
and HPPh2 (0.06 mmol) in DCM (3 mL). Determined by chiral
c
8
0
HPLC. Isolated yield.
9
0
6g
6h
6h
6h
6i
10
4-pyrenyl
4-pyrenyl
4-pyrenyl
4-BrC6H4
4-FC6H4
RT
RT
0
93
It was noted that both the keto-functionalized (R,R)-2a
(Table 1, entry 2) and ester-functionalized (R,R)-3a (Table 1,
entry 5) afforded the 1,4-adduct 6a with ee values of 5% and
69% respectively.When extended to the bulkier substrate 7,
pincer (R,R)-2a yielded the 1,6-adduct 8a′ in a highly
regioselective manner, but with moderate ee (Table 4, entry
1). The pincer (R,R)-3a, however, yielded the same 1,6-adduct
regioselectively with >99% ee (Table 4, entry 2). Modifying the
substrate bulk predictably resulted in the exclusive formation of
the 1,6-adduct 8a′, whereas the ketone 5a selectively formed
the traditionally favored (in terms of activation toward
nucleophilic attack) 1,4-adduct 6a. This is in agreement with
earlier reports which explained that the regioselectivity is
controlled by the sterically unfavorable interaction of the pincer
with the bulkier ester functionalities on substrate 7 during the
course of the catalytic reaction.4 In addition, an analogous
methyl-substituted analogue of pincer (R,R)-2a could only
afford the adducts 8a and 8a′ in a 1:9 ratio with 43% ee.3d From
the viewpoint of the PCP pincers, we could infer that the
methyl-substituted pincer experienced less steric interactions
with substrate 7 compared with pincers (R,R)-2a and (R,R)-3a,
which contributes to better regioselective control.
d
11
96
12
13
14
15
16
17
18
19
20
97
e
0
>99(S)
97
0
6j
2-NH2C6H4
4-OMeC6H4
2,5-ClC6H3
2-pyridinyl
2-thionyl
Ph
0
6k
6l
98
0
>99
96
0
6m
6n
6o
6p
6q
0
>99
97
0
0
97
f
21
Ph
Ph
RT
97
a
Conditions: compound 5 (0.05 mmol), catalyst (R,R)-3a (2.5 μmol,
5 mol %), and HPAr2 (0.06 mmol) in 3 mL of solvent. Determined
by chiral HPLC. Isolated yield of product. Catalyst (R,R)-3d was
used. Absolute configuration determined by X-ray analysis; see the
b
c
d
e
f
Supporting Information. HP(o-tolyl)2 (0.06 mmol) was used.
attempted on such a wide range of functionalized conjugated
dienones. The pincer (R,R)-3a was found to exhibit appreciable
substrate tolerance, furnishing only the 1,4-adduct 6 in high ee’s
(90−99%) and isolated yields of 78−92% across a broad
spectrum of functional groups at the position adjacent to the
keto moiety such as substituted aryls and heterocyclic rings.
Notably present were both electron-donating groups such as
amino (Table 3, entry 15) or methoxy (Table 3, entry 16)
groups and an electron-withdrawing moiety such as nitro
(Table 3, entries 3−5). In all of these instances, the reaction
Notably, we have observed that pincer (R,R)-3a achieves
higher enantio-discrimination than its analogous complex
(R,R)-2a with both substrates 5a and 7. Pincer (R,R)-3a gave
ee values of 69% for ketone 5a and >99% for substrate 7 (Table
1, entry 5 and Table 4, entry 2), while pincer (R,R)-2a gave 5%
(ketone 5a, Table 1, entry 2) and 37% (substrate 7, Table 4,
C
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entry 1) under the same reaction conditions. To investigate the
origin for the superior stereochemical control exhibited by
pincer (R,R)-3a as compared to complex (R,R)-2a, their steric
properties were first conveniently analyzed from the perspective
of their characteristic twist angle, θ (Figure 2).13
Figure 2. Diagrammatic representation of the twist angle θ.
For a particular pincer system, a larger θ with a smaller P→
M←P angle will reflect a more compact conformation, which
potentially limits the access of a reactant to the metal center in
the direction trans to the M−C bond axis.14 A comparison of
the single-crystal X-ray structures12 of the chloro derivatives
(R,R)-2a′ and (R,R)-3a′ revealed that both solid-state
structures have identical θ (19.64°) and similar P→Pd←P
angles ((R,R)-2a′ = 162.24(4)° and (R,R)-3a′ = 161.05(2)°).
Bond lengths, bond angles, and geometry of the atoms around
the metal centers of both pincers are also identical, therefore,
suggesting that the contrasting stereoselectivity of the pincer
complexes might be directly related to the substituents on the
C-stereogenic centers.
1
Figure 4. 2D H−1H NOESY NMR spectrum of complex 3a′.
assigned to their respective protons based on their chemical
shifts, multiplicities, and integral ratios (Table 5 and Figure 5).
1
Table 5. Essential H NMR Assignments of Complex 3a′
δ (ppm)
multiplicity
doublet
integral
assignment
The X-ray crystal structure of complex (R,R)-3a′ (Figure 3)
shows two five-membered chelate rings, each bearing a C-
7.09
2
1
2
2
6
6
H(4)
H(3)
H(1)
H(2)
Me(2)
Me(1)
6.94
triplet
4.84−4.80
3.84
multiplet
doublet of doublet
singlet
3.18
a
2.68
singlet
a
Assignment is supported by the ring-shielding effect,15 in which
protons on C(10) and C(28) will be shielded by the central aryl ring.
Figure 3. Single-crystal X-ray structure of complex (R,R)-3a′.4
stereogenic center. The bulky −CO2Me groups are located on
the axial plane, and the stereogenic protons are found at the
equatorial position. This arrangement will avoid major steric
repulsions between the −CO2Me groups and the adjacent
central aryl ring as well as the −PPh2 groups. It was noted that
the two phenyl substituents on each P atoms are nonequivalent.
In order to investigate if the structural features of the pincer
complex in the solid state is retained in solution, a two-
Figure 5. Representative numbering scheme of complex 3a′.
1
From the H−1H NOESY NMR spectrum, crystal structure,
and model studies of complex (R,R)-3a′, the presence of the
signals A−I are noted in Table 6. In particular, signals F−I
suggest the existence of unique structural features in the
complex. First, if the chelate ring undergoes δ and λ conversion
in solution, NOE interactions of Me(2) with both H(5) and
H(6) as well as H(2) with both H(5) and H(6) will be
detected.
1
dimensional H−1H nuclear Overhauser effect spectroscopy
(NOESY) experiment was conducted on the chloro derivative
(R,R)-3a′ of pincer (R,R)-3a (Figure 4). Special attention was
directed to the study on the rotation of the −CO2Me groups
along the C(25)−C(26) and C(7)−C(8) bond axes, as well as
the rigidity of the ring conformation in solution. Prior to the
analysis of the 2D 1H−1H NOESY NMR spectrum, it is
However, the absence of NOE interactions corresponding to
Me(2)−H(5) and H(2)−H(5) indicate that the two five-
membered chelate rings adopt a fixed δ conformation in
solution (Figure 6).
A model study revealed that the rotations of the CH-
(CO2Me)2 groups along the C(25)−C(26) and C(7)−C(8)
1
essential to assign the key H NMR signals of the complex
(R,R)-3a′. Six of the 1H NMR signals are unambiguously
D
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tolerate a wide range of functionalities on the ketone substrate.
A comparative study conducted subsequently revealed how the
combination of substrate selection in conjunction with catalyst
choice can provide excellent control on enantio- and
regioselectivity (1,4- vs 1,6-addition) in the case of AHP. The
origin of the enhanced stereoselectivity exhibited by pincer
(R,R)-3a was also revealed.
Table 6. Important NOE Interactions in Complex 3a′
signal
NOE interaction
A
B
C
D
E
F
H(1)−H(4)
H(1)−H(5)
H(1)−H(6)
H(5)−H(6)
H(1)−H(2)
H(2)−H(6)
Me(1)−H(5)
Me(1)−H(4)
Me(2)−H(6)
EXPERIMENTAL SECTION
G
H
I
■
General Information. All reactions were carried out under a
positive pressure of nitrogen using a standard Schlenk technique.
Solvents were purchased from their respective companies and used as
supplied. Where necessary, solvents were degassed prior to use. A Low
Temp Pairstirrer PSL-1800 was used for controlling low-temperature
reactions. Column chromatography was done on Silica gel 60 (Merck).
Melting points were measured using an SRS Optimelt Automated
Point System SRS MPA100. Optical rotation were measured with a
JASCO P-1030 polarimeter in the specified solvent in a 0.1 dm cell at
21.0 °C. NMR spectra were recorded on Bruker AV 300, AV 400, and
AV 500 spectrometers. Chemical shifts were reported in ppm and
referenced to an internal SiMe4 standard (0 ppm) for 1H NMR,
chloroform-d (77.23 ppm) for 13C NMR, and an external 85% H3PO4
for 31P{1H} NMR. HPLC analysis was done with an Agilent
Technologies 1200 Series HPLC machine. The palladacycle (S)-1,6g
(R,R)-2a−c, (R,R)-3a−d, and (R)-4a−b12 were prepared according to
literature methods. All other reactants and reagents were used as
supplied.
Figure 6. Conformation of chelate ring in complex 3a′.
bond axes are sterically hindered by the equatorial Ph moieties
on the P atoms. The NOESY NMR spectrum shows long-range
NOE interactions of Me(1) with H(5) (signal G), but not with
H(6). In contrast, Me(2) has an NOE interaction with H(6)
(signal I), but not with H(5). The absence of Me(2)−H(4)
NOE interaction suggests the possibility of restricted rotation
of the CH(CO2Me)2 groups. If the chiral functionalities are
rotatable along the C(25)−C(26) and C(7)−C(8) bond axes,
both Me(1) and Me(2) should exhibit NOE interactions with
H(4), H(5), and H(6).
Overall, all the data collated is indicative of a favorable
disposition of the pendant arms bearing the ester moieties
around the active site of complex (R,R)-3a′, which is not
observed for pincer (R,R)-2a′. The unique arrangement of the
carboxylate groups together with the nonequivalent Ph
substituents on each P atom serves to regulate the approach
of the reactants during the course of the catalytic cycle. NOE
signals corresponding to the protons on the terminal
carboxylate groups and the aromatic protons on the −PPh2
groups suggest a close spatial proximity of the ester groups to
the P atoms of the P→Pd←P moiety. In addition, restricted
rotation of the groups in the pendant arms of pincer (R,R)-3a′
due to the sterically bulkier ester moieties may exert more
stereocontrol over the accessibility of the substrate to the active
site, which translates into enantio-discrimination.
General Procedure for Preparation of Wittig Reagents. Aryl-
substituted 2-bromoethanone (5.00 mmol, 1.0 equiv) and PPh3 (1.44
g, 5.50 mmol, 1.1 equiv) were refluxed in THF (10 mL) for 4 h. Upon
cooling, volatiles were removed, and the solids were redissolved in
DCM, extracted with aq. NaOH (20% w/w in H2O, 1 × 20 mL),
washed with water (1 × 20 mL), dried over MgSO4, filtered, and
evaporated to dryness. The crude product was purified by silica gel
chromatography (2 EA:1 n-hexane) to afford the pure product.
General Procedure for Preparation of αβγδ-Unsaturated
Substrates. Method A: Wittig Reaction. A solution of aldehyde
(7.57 mmol, 1.0 equiv) and Wittig reagent (8.32 mmol, 1.1 equiv) in
toluene (30 mL) was refluxed for 24 h. The mixture was cooled and
extracted with EA (3 × 40 mL), washed with H2O (1 × 40 mL), dried
over MgSO4, filtered, and evaporated to dryness. The crude product
was purified by silica gel chromatography (2 n-hexane:1 DCM) to
afford the pure product. Method B: Aldol Condensation. To a
solution of NaOH (0.11 g, 2.75 mmol, 1.2 equiv) in H2O (20 mL) and
aromatic ketone (2.29 mmol, 1.0 equiv) in ethanol (12 mL) at 0 °C
was gradually added aromatic aldehyde (0.30 g, 0.29 mL, 2.29 mmol,
1.0 equiv). The mixture was allowed to warm to room temperature
and stirred for 4 h, after which the precipitate of the product was
collected by suction filtration on a Buchner funnel and washed
repeatedly with cold water. The residue was redissolved in DCM and
extracted, washed with H2O (1 × 40 mL), dried over MgSO4, filtered,
and evaporated to dryness. The crude product was purified by silica gel
chromatography (2 n-hexane:1 DCM) to afford the pure product.
General Procedure for Catalytic AHP Reaction. The catalyst
(2.25 mg, 2.5 umol, 5 mol %) was added to a solution of
diarylphosphine (0.06 mmol, 1.2 equiv) in the stated solvent (3
mL) and brought to the desired temperature. The substrate (0.05
mmol, 1.0 equiv) was subsequently added and stirred at the stated
temperature. Completion of the reaction was determined by the
disappearance of the phosphorus signal attributed to diphenylphos-
phine (−40 ppm) or di(o-tolyl)phosphine (−60 ppm) in the 31P{1H}
NMR spectrum. Upon completion of the reaction, aq. H2O2 (0.1 mL,
31% v/v) was added to form the respective product. The volatiles were
removed under reduced pressure and the crude product was directly
loaded onto a silica gel column (ethyl acetate:n-hexane = 3:2) to afford
the pure product.
CONCLUSIONS
■
In summary, we have screened a series of enantiopure PCP-
and PCN-pincer complexes (themselves generated via an
efficient catalytic methodology)12 in the asymmetric P-H
addition of diarylphosphines to linear α,β,γ,δ-unsaturated
dienones. It should be reiterated that the new methodology
developed provides substantial improvement in reactivity while
allowing the AHP to be conducted on a wide range of
functionalized conjugated ketones. The study provided key
insights into the molecular structure required in terms of metal
ion and backbone functionalities for an efficient catalyst design.
A straightforward preparation of synthetically useful chiral
allylic phosphines was achieved in high yields (81−92%) with
excellent enantioselectivity (94% to >99%) under mild reaction
conditions catalyzed by pincer (R,R)-3a. The protocol could
E
DOI: 10.1021/acs.organomet.5b00787
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.5b00787.
■
S
Detailed experimental procedures for the syntheses of
substrates and products; crystal and refinement data for
1
complex (S)-6i; and H, 13C, 31P{1H} NMR spectra and
HPLC spectra (PDF)
Crystallographic data for (S)-6i (CIF)
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AUTHOR INFORMATION
Corresponding Authors
*E-mail: sumod@ntu.edu.sg (S.A.P.).
*E-mail: pakhing@ntu.edu.sg (P.-H.L.).
Notes
■
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
We wish to acknowledge the funding support for this project
from Nanyang Technological University (NTU). X.-Y.Y thanks
NTU for the award of a scholarship, and W.S.T. thanks the
NTU Undergraduate Research Experience on CAmpus
(URECA) program for the support.
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DOI: 10.1021/acs.organomet.5b00787
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