Palladium-catalyzed 1,4-addition of diarylphosphines to α,β-unsaturated N-acylpyrroles

Article abstract of DOI:10.1039/c1cc13785a

Highly stereoselective asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated N-acylpyrroles catalyzed by a PCP pincer-Pd complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (91-99% ee) under mild con

Full text of DOI:10.1039/c1cc13785a

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COMMUNICATION
Palladium-catalyzed 1,4-addition of diarylphosphines to a,b-unsaturated
N-acylpyrrolesw
Dan Dub and Wei-Liang Duan*a
Received 24th June 2011, Accepted 30th August 2011
DOI: 10.1039/c1cc13785a
Highly stereoselective asymmetric 1,4-addition of diarylphosphines
to a,b-unsaturated N-acylpyrroles catalyzed by a PCP pincer–Pd
complex has been developed for the synthesis of chiral phosphines
with excellent stereoselectivity (91–99% ee) under mild conditions.
The products obtained can be further converted into chiral
phosphine-oxazoline ligands.
Table
1
Palladium-catalyzed addition of diphenylphosphine to
a,b-unsaturated N-acylpyrrole 1a
Entry
Catalyst
Solvent
Time/h
Yielda (%)
eeb (%)
Chiral phosphines are some of the most important compounds
in asymmetric catalysis. These compounds have been used as
ligands coordinated to transition metals or organocatalysts in
various reactions to furnish optically active products with high
efficiency.1 However, the highly stereoselective preparation of
phosphine compounds through asymmetric catalysis is rare.2,3
Asymmetric 1,4-addition of substituted phosphines to a,b-
unsaturated compounds is a powerful tool for phosphorus–
carbon bond formation with simultaneous introduction of a new
stereogenic carbon center at the b-position.4 This process has been
realized very recently for the reactions of nitriles, enals, and enones
with substituted phosphines or phosphine oxides as nucleophiles
with high enantioselectivity.5–7 However, catalysis of highly
stereoselective asymmetric 1,4-addition of substituted phosphines
to a,b-unsaturated carboxylic acid derivatives has not been
reported to date. In this context, we describe a palladium-catalyzed
asymmetric addition of diarylphosphines to a,b-unsaturated
N-acylpyrroles,8 which produces chiral phosphine compounds in
high yields with excellent enantioselectivities (eqn (1)).
1
(S,S)-4
(S,S)-5
(S,S)-4
(S,S)-4
(S,S)-4
(S,S)-4
(S,S)-4
(S,S)-4
(S,S)-4
THF
2
15
2
2
2
2
2
2
2
95
20
92
87
95
88
91
99
98
99
0
2c
3
CH2Cl2
Hexane
CH2Cl2
Toluene
t-BuOH
THF
99
99
99
99
99
99
98
4
5
6
7d
8e
9f
THF
THF
a
b
Isolated yields. Determined by HPLC with hexane/2-propanol.
c
d
5 mol% K2CO3 was added. The adduct isolated without oxidation
e
was the trivalent phosphine. The reaction was quenched with 2 eq.
Me2SꢀBH3, and the product isolated was the borane–phosphine
f
complex. The reaction was quenched with 1 eq. S8, and the product
isolated was the phosphine sulfide.
PCP pincer–PdOAc (S,S)-47a as the catalyst. The reaction
proceeded well and generated products in 99% ee with 95%
yield (Table 1, entry 1).9 In contrast, use of the well-known chiral
NCN pincer–Pd complex (S,S)-510 in the presence of 5 mol%
K2CO3 as the catalyst affords only the racemic product in low
yield (entry 2). The solvents had little influence on the product
yield and ee (entries 3–6). Notably, other phosphination products
such as trivalent phosphines, borane–phosphine complexes, or
phosphine sulfides can also be isolated with a similarly high yield
and ee after different workup procedures (entries 7–9).
ð1Þ
Initially, addition of diphenylphosphine to a,b-unsaturated
N-acylpyrrole 1a was performed in the presence of 2 mol%
a State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032,
China. E-mail: wlduan@mail.sioc.ac.cn; Fax: +86-21-6416-6128;
Tel: +86-21-5492-5203
Under optimized conditions with (S,S)-4 as the catalyst,
various substrates 1 that bear electron-donating or -withdraw-
ing groups on the aromatic ring can be coupled with diphenyl-
phosphine, furnishing the chiral phosphine oxides uniformly
in high yields with excellent stereoselectivities (83–99% yield,
97–99% ee; Table 2, entries 1–8). In addition to the aromatic
b School of Chemistry & Molecular Engineering,
East China University of Science and Technology,
130 Meilong Road, Shanghai 200237, China
w Electronic supplementary information (ESI) available: Detailed
experimental procedures and analytical data for all new compounds.
See DOI: 10.1039/c1cc13785a
c
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Chem. Commun., 2011, 47, 11101–11103 11101

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Table 2 Palladium-catalyzed asymmetric addition of diarylpho-
sphines to a,b-unsaturated N-acylpyrroles
Entry
R1
Ar
Yielda (%)
eeb,c (%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
95
99
99
98
97
95
94
83
93
92
93
99
98
97
99
99
99
p-MeOC6H4
p-MeC6H4
p-ClC6H4
m-BrC6H4
2-Naphthyl
2-Furyl
b-(E)-Styryl
Methyl
i-Propyl
i-Butyl
Cyclohexyl
Ph
Ph
499
99
99
97
98
91
94
96
96
97
98
Scheme 2 Proposed catalytic cycle for the Pd-catalyzed addition of
diarylphosphines to a,b-unsaturated N-acylpyrroles.
9
10
11
12
13
14d
p-MeOC6H4
p-ClC6H4
a
b
Isolated yields. Determined by HPLC with hexane/2-propanol.
The absolute configurations of products were determined to be
c
S by comparison of the specific optical rotation of the hydrolyzed
product (entry 4) with the value reported in the literature; see ESIw for
details. 1.5 eq. diarylphosphine was used.
d
ring, other substituted groups at the b-position of the substrates
such as alkenyls and alkyls could also be tolerated under the
current conditions (92–99% yield, 91–96% ee; Table 2, entries
9–12). With regard to the nucleophilic component, phosphines
that have electron-donating or -withdrawing groups can be
effectively added to 1a with excellent yields and enantioselectivities
as well (97–98% yield, 97–98% ee; entries 13 and 14).
Scheme 3 Proposed stereochemical pathway (partial groups in
(S,S)-4 are omitted for clarity).
phosphido intermediate to the double bond of substrates 1
as the key steps (Scheme 2).7a The proposed stereochemical
pathway for the formation of (S)-product is shown in Scheme 3.
Due to the presence of chiral methyl groups at the benzylic
position of (S,S)-4, the different spatial orientation of phenyl
rings on the phosphorus atoms creates an efficient chiral
environment around the palladium atom. To minimize the
unfavorable steric repulsions between the substituent at the
b-position of substrates and the phenyl groups sticking out
from the phosphorus atom of the catalyst, a,b-unsaturated
N-acylpyrrole 1a approaches the palladium phosphido inter-
mediate with its Si-face preferentially; this facial selectivity
leads to the formation of (S)-isomers.
To demonstrate the utility of the current method, the
obtained phosphorus compound was converted into the chiral
phosphine-oxazoline ligand (Scheme 1). Thus, optically active
phosphine sulfide 3b (98% ee) was hydrolyzed to give an acid,
followed by amidation with (R)-valine, reduction of the carboxylic
ester group, cyclization, and desulfurization to produce
a
bidentate ligand 6, which was used in Pd-catalyzed asymmetric
allylic alkylation with high enantiomeric excess.11
The proposed catalytic cycle for this process involves the
transphosphination between the diarylphosphine and the
pincer–PdOAc, and the addition of the formed palladium
In summary, we have developed a palladium-catalyzed
asymmetric addition of diarylphosphines to a,b-unsaturated
N-acylpyrroles for the synthesis of chiral phosphine derivatives
under mild conditions. The transformation of the 1,4-adduct
into a chiral phosphine-oxazoline ligand for asymmetric
catalysis has also been described.
The NSFC (20902099), National Basic Research Program
of China (973 Program 2010CB833300), and SIOC are greatly
acknowledged for funding this work.
Notes and references
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¨
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´
Scheme 1 Synthesis of chiral phosphine-oxazoline ligand based on
the 1,4-adduct 3b.
c
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11102 Chem. Commun., 2011, 47, 11101–11103

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c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 11101–11103 11103