Palladium-catalyzed asymmetric 1,4-addition of diarylphosphines to nitroalkenes for the synthesis of chiral P,N-compounds

Article abstract of DOI:10.1002/adsc.201200133

A highly stereoselective asymmetric 1,4-addition of diarylphosphines to nitroalkenes catalyzed by a bis(phosphine) pincer-palladium complex has been developed for the synthesis of chiral P,N compounds with good to excellent enantioselectivities (up to 94% ee) under mild conditions. Copyright

Full text of DOI:10.1002/adsc.201200133

UPDATES
DOI: 10.1002/adsc.201200133
Palladium-Catalyzed Asymmetric 1,4-Addition of
Diarylphosphines to Nitroalkenes for the Synthesis of Chiral
P,N-Compounds
Jian-Jun Feng,b Miao Huang,b Zi-Qi Lin,a and Wei-Liang Duana,*
a
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai 200032, Peopleꢀs Republic of China
Fax : (+86)-21-6416-6128; phone: (+86)-21-5492-5203; e-mail: wlduan@mail.sioc.ac.cn
School of Chemistry & Molecular Engineering, East China University of Science and Technology, 130 Meilong Road,
b
Shanghai 200237, Peopleꢀs Republic of China
Received: February 17, 2012; Revised: August 9, 2012; Published online: November 4, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200133.
Abstract: A highly stereoselective asymmetric 1,4-
addition of diarylphosphines to nitroalkenes cata-
lyzed by a bis(phosphine) pincer-palladium complex
has been developed for the synthesis of chiral P,N
compounds with good to excellent enantioselectivi-
ties (up to 94% ee) under mild conditions.
addition to nitroalkenes followed by a nitro group re-
duction step generates optically active P,N compounds
(Scheme 1), which are valuable chiral ligands in
metal-catalyzed asymmetric hydrogenation and enan-
tioselective organocatalyzed reactions.[6,7] This process
has been recently realized by Mechiolrre and his co-
workers through the use of Cinchona alkaloids as cat-
alysts for the reaction of diphenylphosphine with ni-
troalkenes, producing the 1,4-adduct with moderate
enantioselectivity.[8] Tan and his co-workers also re-
ported an asymmetric addition of diarylphosphine
oxides as nucleophiles to nitroalkenes in the presence
of a chiral biscyclic guanidine catalyst.[9] Typically,
when bis(2-naphthyl)phosphine oxide is used, the
product is isolated with 99% ee. However, the devel-
opment of new catalytic protocols still remains attrac-
Keywords: 1,4-addition; asymmetric hydrophosphi-
nation; diarylphosphines; nitroalkenes; pincer pal-
ladium catalysts
Introduction
Chiral phosphines play a very important role in asym- tive in term of the relatively narrow substrate scope
metric catalysis as ligands coordinated to transition (only for b-aryl nitroalkenes) and high catalyst load-
metal catalysts or organocatalysts.[1] Phosphorus-Mi- ing (10–20 mol%) of the reported catalytic systems.
chael addition reactions are well known processes for Recently, we have developed a highly efficient bi-
the synthesis of phosphine compounds; however their sphosphine (PCP) pincer-PdOAc catalyst for the
use in the formation of enantiopure phosphines has enantioselective hydrophosphination of electron-defi-
been scarely explored.[2,3] Some examples of catalytic cient alkenes.[4d,k,m] To continue our interest in the
asymmetric nucleophilic phosphorus addition to elec- synthesis of chiral phosphines, in the current report,
tron-deficient alkenes with good to excellent enantio- a PCP pincer palladium-catalyzed asymmetric 1,4-ad-
selectivities have been reported only very recently.[4]
dition of diarylphosphines to b-aryl and b-alkyl nitro-
Nitroalkenes are typical substrates in asymmetric alkenes with good to excellent enantioselectivty is de-
1,4-additon reactions.[5] They are frequently used to scribed as an alternative method for the synthesis of
react with various nucleophiles, and their nitro group chiral P,N compounds.
can be easily reduced to an amino moiety under mild
conditions. The asymmetric nucleophilic phosphorus
Results and Discussion
The current experiment began with the reaction of
trans-b-nitrostyrene with diphenylphosphine in the
presence of 2 mol% of PCP pincer-PdOAc (S,S)-
Scheme 1. Synthesis of chiral P,N compounds through asym-
metric hydrophosphination of nitroalkenes.
4a[4d,10,11] catalyst as the model reaction (Table 1),
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Palladium-Catalyzed Asymmetric 1,4-Addition of Diarylphosphines to Nitroalkenes
Table 1. Palladium-catalyzed asymmetric addition of diphenylphosphine to trans-b-nitrostyrene 1a.
Entry[a]
Temp. [8C]
Solvent
Time [h]
Yield [%][b]
ee [%][c]
1
2
3
4
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0
À10
À20
À30
À40
THF
2
2
2
2
2
2
2
5
5
5
5
5
41
64
55
50
59
63
68
72
80
69
70
64
83
73
64
54
60
87
39
89
91
91
91
91
CH2Cl2
CH3CN
t-BuOH
t-AmOH
toluene
toluene
toluene
toluene
toluene
toluene
toluene
5
6
7[d]
8
9
10
11
12
[a]
The reaction was quenched with 2.5 equiv. NaBH4/3.0 equiv. AcOH.
Isolated yields.
Determined by HPLC with hexane/2-propanol.
2 mol% of (S,S)-4b was used as the catalyst.
[b]
[c]
[d]
Given the oxygen sensitivity of the phosphine group also examined, given the capacity of the 1,4-adduct to
of the 1,4-adduct, NaBH4 and HOAc were added at be converted into a trans P,N bidentate phosphine
the work-up step to obtain a borane-phosphine com-
plex. The reaction proceeded well in various solvents
Table 2. Palladium-catalyzed asymmetric addition of diaryl-
at room temperature (entries 1–5). Toluene is the op-
timal solvent, producing the adduct 3a with 87% ee
(entry 6). The use of PCP PdCl complex (S,S)-4b only
afforded the product with 39% ee and 68% yield
(entry 7), which indicates the important role of ace-
tate anion on the palladium atom of 4a. Temperature
screening results show that À108C reaction tempera-
ture afforded the adduct with the best yield and ee
(80% yield and 91% ee; entry 9).
AHCTUNGTERGpNNUN hosphines to nitroalkenes.
Entry[a] R1
Ar
Ph
Yield [%][b] ee [%][c,d]
1
Ph
80
70
71
81
85
92
90
73
72
91
90
90
87
85
90
86
85
91
76
91
2
3
p-MeOC6H4 Ph
m-MeOC6H4 Ph
Under the optimized conditions with (S,S)-4a as the
catalyst, various nitroalkenes were reacted with
diarylACHTUNGTRENNUNGphosphines; the results are shown in Table 2.
4
5
6
7
8
9
10
11
p-BrC6H4
m-BrC6H4
2-naphthyl
2-furyl
cyclohexyl
i-propyl
Ph
Ph
Ph
Ph
Ph
Ph
Ph
The substrates bearing the electron-donating or elec-
tron-withdrawing groups on the aryl moiety all react-
ed with diphenylphosphine with high enantioselectivi-
ties and yields (70–90% yield, 87–91% ee; entries 1–
7). Moreover, alkyl-substituted substrates under the
current system also afforded adducts with good ste-
reoselectivities (72–73% yield, 85–91% ee; entries 8
and 9). For the nucleophilic component, phosphines
bearing electron-donating or electron-withdrawing
groups reacted smoothly with 1a, affording the phos-
phination products with high yields and enantioselec-
tivities (80% yield, 76–91% ee; entries 10 and 11).
The reaction of a,b-disubstituted nitroalkene sub-
strates such as 1-nitrocyclohexene (Scheme 2) was
p-MeOC6H4 80
p-ClC6H4 80
Ph
[a]
The reaction was quenched with 2.5 equiv. NaBH4/
3.0 equiv. AcOH.
Isolated yields.
Determined by HPLC with hexane/2-propanol.
The absolute configurations of products were determined
to be R by comparison of the specific optical rotation of
the adduct (entry 1) with the value reported in literature;
see the Supporting Information for details.
[b]
[c]
[d]
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Jian-Jun Feng et al.
UPDATES
Scheme 2. Palladium-catalyzed asymmetric addition of diphenylphosphine to 1-nitrocyclohexene.
amine ligand, which had been synthesized through the the phosphine product along with regeneration of the
optical resolution of its racemate with enantiopure catalyst.
tartaric acid.[12] The reaction of diphenylphosphine
with 1-nitrocyclohexene under the current conditions
proceeded smoothly to give cis and trans isomers with Conclusions
a ratio of 3:2. The cis-adduct can be converted in situ
to the more thermodynamically stable trans-isomer in In summary, we have developed a PCP pincer Pd-cat-
the presence of DBU as the base. After quenching alyzed highly stereoselective addition of diarylphos-
with a boron reagent, the trans-product, borane-phos- phines to nitroalkenes, producing phosphination prod-
phine complex 6, was isolated with 94% ee in 74% ucts with good to excellent enantioselectivities and
yield. Finally, the product 6 was converted to the yields. The application of the current method for the
highly useful P,N compound 7 in two steps, which has synthesis of a useful chiral P,N compound has also
been utilized as the chiral pool for the synthesis of been demonstrated.
various phosphine amine organocatalysts.[7]
A possible catalytic cycle of this reaction is shown
in Scheme 3.[4d] First pincer-PdOAc 4a reacts with di- Experimental Section
ACHTUNGTRENNUNGarylphosphine to generate a palladium phosphido
complex. Then, the nucleophilic attack of the diary- General Remarks
lphosphido group on palladium to the double bond of
All air- and moisture-sensitive manipulations were carried
out with standard Schlenk techniques under nitrogen or in
nitroalkenes, affords
a zwitterionic Pd-phosphine
complex with pendant anion,[3f,g] which may exist in
equilibrium with the neutral nitro-palladium inter-
mediate. Finally, the protonolysis of the formed Pd
species with the acetic acid in the system furnishes
1
a glove box under nitrogen. H, 13C and 31P NMR spectra
were recorded on a Varian instrument (400 MHz, 100 MHz
and 162 MHz, respectively). 1H and 13C NMR chemical
shifts are reported vs. tetramethylsilane signal or residual
protio solvent signals. Toluene and THF were distilled over
sodium benzophenone ketyl under nitrogen. Dichlorome-
thane was distilled over CaH2 under nitrogen. See the Sup-
porting Information for a general procedure and data for
the 1,4-adducts.
Typical Procedure for the Palladium-Catalyzed 1,4-
Addition Reaction of Diphenylphosphine to Nitro-
alkenes
Diphenylphosphine (41.0 mg, 0.22 mmol) was added to a so-
lution of (S,S)-4a (2.7 mg, 4 mmol Pd) in toluene (2.0 mL)
and the resulting solution was stirred for 4 min at À108C
(realized with a refrigerated bath circulator). After addition
of trans-b-nitrostyrene (29.8 mg, 0.20 mmol), the solution
was stirred for 2–24 h at À108C, then concentrated under
vacumm until 0.5 mL toluene was left. NaBH4 (18.9 mg,
0.50 mmol), HOAc (36.0 mg, 0.60 mmol) in THF (0.3 mL)
Scheme 3. The catalytic cycle in the palladium-catalyzed
asymmetric addition of diarylphosphines to nitroalkenes.
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Adv. Synth. Catal. 2012, 354, 3122 – 3126

Palladium-Catalyzed Asymmetric 1,4-Addition of Diarylphosphines to Nitroalkenes
wereadded and the resulting mixture was stirred for 1 h.
After addition of 2 mL saturated NaCl aqueous solution and
extraction with dichloromethane, the organic phase was
dried over anhydrous Na2SO4, filtered and concentrated
under vacuum. The residue was purified by silica gel chro-
matography with CH2Cl2/hexane=1/1 to afford the product
as a white solid (CAS 931411-28-8)[8]. The ee was deter-
mined on a Daicel ChiralPak AD-H column with hexane/2-
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3211.
propanol=80/20, flow=1.0 mLminÀ1
:
retention times:
5.6 min [(R)-enantiomer], 6.6 min [(S)-enantiomer]; 91% ee;
1
[a]2D0: À222 (c 1.00, CHCl3); H NMR (CDCl3): d=8.01–7.96
(m, 2H), 7.60–7.51 (m, 3H), 7.36–7.32 (m, 3H), 7.24–7.18
(m, 2H), 7.17–7.12 (m, 5H), 5.19–5.11 (m, 1H), 4.70–4.62
(m, 2H), 1.10 (br, 3H); 13C NMR (CDCl3): d=132.6 (d,
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JC,P =8.1 Hz), 132.5 (d, JC,P =9.6 Hz), 132.3 (d, JC,P =2.2 Hz),
131.6 (d, JC,P =2.2 Hz), 131.3 (d, JC,P =1.5 Hz), 129.4 (d,
J
C,P =9.6 Hz), 129.3 (d,
J
C,P =4.5 Hz), 128.4 (d, JC,P
=
11.9 Hz), 128.33, 128.30 (d, JC,P =3.7 Hz), 125.74 (d, JC,P
=
51.1 Hz), 125.72 (d, JC,P =55.8 Hz), 75.5 (d, JC,P =14.2 Hz),
41.5 (d, JC,P =30.5 Hz); 31P{1H} NMR (CDCl3): d=21.6 (m).
MS (ESI): m/z=348 [(MÀH)+].
Acknowledgements
We thank the NSFC (20902099, 21172238), National Basic
Research Program of China (973 Program 2010CB833300),
and SIOC for financial support.
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