Azetidine-derived dinuclear zinc catalyzed asymmetric phospha-Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1039/c7ob02222k

The asymmetric phospha-Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl compounds by using an azetidine-derived dinuclear zinc catalyst was described. The catalyst was proved to be general and efficient for a broad spectrum of enones and α,β-unsaturated N-acylpyrroles. A series of phosphonate-containing compounds were generated with excellent enantioselectivities (up to 99% ee) and chemical yields (up to 99%) under mild conditions without using additives. The products were obtained with more than 95% ee for 23 examples of α,β-unsaturated carbonyl compounds. A positive nonlinear effect was observed and the possible mechanism was proposed.

Full text of DOI:10.1039/c7ob02222k

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: S. Liu, N. Shao, F.
Li, X. Yang and M. Wang, Org. Biomol. Chem., 2017, DOI: 10.1039/C7OB02222K.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Page 1 of 9
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C7OB02222K
Organic & Biomolecular Chemistry
PAPER
Azetidines-derived dinuclear zinc catalyzed asymmetric phospha-
Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl
compounds
Received 00th January 20xx,
Accepted 00th January 20xx
Shanshan Liu,a Na Shao,b Feng-Zhen Li,b Xiao-Chao Yang,b and Min-Can Wang*b
DOI: 10.1039/x0xx00000x
The asymmetric phospha-Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl compounds by using
azetidines-derived dinuclear zinc catalyst was described. The catalyst was proved to be general and efficient for a broad
spectrum of enones and α,β-unsaturated N-acylpyrroles. A series of phosphonate-containing compounds were generated
with excellent enantioselectivities (up to 99% ee) and chemical yields (up to 99%) under mild conditions without using
additives. The products were obtained with more than 95% ee for 23 examples of α,β-unsaturated carbonyl compounds. A
positive nonlinear effect was observed and the possible mechanism was proposed.
www.rsc.org/
wide range of enones or α,β-unsaturated N-acylpyrroles. The
Introduction
proline-derived dinuclear zinc catalyst has proven effectively to
afford products with good enantiomeric excess.12–16 In this protocol,
The formation of C–P bonds is one of the most important
transformations in the field of organic synthesis due to the wide
application of organophosphorus compounds in the ligands
synthesis1 and pharmaceuticals.2 The catalytic asymmetric
phosphonylation of carbonyl compounds is one of the most useful
methods to provide these kinds of compounds, mainly through the
phospha-aldol reaction, phospha-Mannich reaction, as well as
phospha-Michael reaction.3 Asymmetric phospha-Michael addition
is considered distinct not only because of its significant atom
economy for asymmetric synthesis but also the adducts which are
relevant chiral scaffolds for further conversion into β- or γ-
substituted phosphonates.4 Wang and co-workers has described the
first enantioselective 1,4-addition of diphenyl phosphite to
nitroalkenes in the presence of cinchona alkaloid catalyst.5
Subsequently, the phospha-Michael addition of nitroalkenes has
been also reported by using chiral guanidine catalyst6 or chiral Al–
Li–BINOL complex.7 Jogensen8a and Melchiorre8b–c has
demonstrated respectively phospha-Michael addition by employing
α,β-unsaturated aldehydes as electrophiles. Ye presented an
organocatalytic phospha-Michael reaction of cyclic α,β-unsaturated
however, additives such as 4Å MS12–13 or pyridine14–16 are necessary
to improve the reactivity and enantioselectivity. Pyridine has been
found essential to prevent the deactivation of catalyst by inhabiting
unfavorable binding between potential product and catalyst.14 It is
still highly desired to develop an effective and straightforward
catalytic strategy for this transformation.
Based on our previous work, the azetidines-derived dinuclear zinc
catalyst system has shown excellent performance on a number of
efficient, catalytic, enantioselective transformations, including
asymmetric domino Michael/Hemiketalization reaction,17 Friedel–
Crafts alkylation,18 methylation,19 alkynylation,19 as well as
enantioselective co-polymerization.20 It is noteworthy that much
higher enantioselectivity has been achieved by using our novel
chiral catalyst than that of Trost’s dinuclear zinc-ProPhenol catalyst
in the asymmetric co-polymerization of cyclohexene oxide with
carbon dioxide, which may attribute to the lower flexibility
azetidine ring skeleton and appropriate sterically hindered
microenvironment compared with that of pyrrolidine. We postulate
that our azetidines-derived dinuclear zinc catalyst may be a well
suitable catalytic system for the phospha-Michael reaction. Dialkyl
phosphites, secondary phosphine oxides, and secondary
phosphines are commonly used phosphorus nucleophiles towards
this transformation. In view of the lowest pKa of dialkyl phosphites
among the phosphorus nucleophiles,2b therefore they are very
prone to deprotonate and activate. Dialkyl phosphites are ideal
substrates to be employed due to their readily available and more
enones.3b
A
pincer-palladium
complex
catalyzed
hydrophosphonylation of enones has been disclosed by Duan9 and
Leung,10 respectively. An asymmetric hydrophosphonylation of
chalcones has been described with high enantioselectivity in the
presence of a chiral ytterbium silylamide.11 Recently, the Wang
group has achieved a dinuclear zinc catalyzed phosphonylation of a
a. College of Chemistry and Chemical Engineering, Shaanxi University of Science and
Technology, 6 Xuefu Road, Weiyang District, Xi’an, Shaanxi 710021, P. R. China
b. The College of Chemistry and Molecular Engineering, Zhengzhou University, No.
75 Daxue Road, Zhengzhou, Henan 450052, P. R. China. E-mail:
reactive toward
a wide range of α,β-unsaturated carbonyl
compounds. Herein, we elaborate an azetidines-derived dinuclear
zinc catalyzed phospha-Michael addition of dialkyl phosphite to
enones and α,β-unsaturated N-acylpyrroles.
wangmincan@zzu.edu.cn
Electronic Supplementary Information (ESI) available: All chiral HPLC
chromatograms data and spectra for phospha-Michael addition products and
copies of NMR spectra for all products. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 2017
Org. Biomol. Chem., 2017, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 9
PAPER
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C7OB02222K
Table 1 Identification of the catalyst system for the catalytic asymmetric addition of dialkyl phosphite to chalcone derivatives.
Entry
1c
L*
R
Et2Zn
Solvent
Tactivation (oC)
Treaction (oC)
Yield (%)a
ee (%)b
L1
L2
L3
L4
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
40
40
40
40
40
40
20
80
40
40
40
40
40
40
40
40
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
30
30
30
30
30
30
30
30
30
30
30
25
30
30
30
30
25
25
25
25
25
25
25
25
25
25
25
25
45
17
17
25
76
67
0
2
trace
99
3
0
4
5d
65
90
0
77
82
0
6
99
62
7
8
9
99
78
trace
81
95
99
99
85
19
51
0
62
74
25
99
80
53
10
11
12
13
14
15e
16
DCM
EtO2
Toluene
Toluene
Toluene
Toluene
Toluene
Me
b
65
a
Isolated yield reported. The ee values were determined by HPLC analysis. In all cases, the product chromatograms were
c
compared against a known racemic mixture. The absolute configurations were assigned by comparison to literature values.
mol% of ligand was loaded. d 10 mol% of ligand was loaded. e 100 mg 4Å MS was introduced as additive.
5
the presence of 20 mol% of our ligand. We found that the racemic
product was delivered when 20 mol% of Et2Zn was used.
Comparatively, up to 82% ee was obtained by the employment of
40 mol% of Et2Zn (Table 1, entry 6). However, very poor ee was
observed when the loading increased to 0.8 equivalent (Table 1,
entry 8). The results indicated diethylzinc in combination with chiral
ligands with a ratio of 2:1 might lead to the best asymmetric
induction for the current transformation, 20 mol% of ligand and 40
mol% of Et2Zn was found out optimal. A survey of various solvents
revealed that toluene was the choice of solvent to provide product
with 99% yield and 82% ee. With these results in hand, we further
investigated the influence of dialkyl phosphites nucleophiles (Table
1, entries 6 and 16), a comparatively better reactivity and
enantioselectivity was obtained when diethyl phosphite (2a) was
Scheme 1 Different kinds of chiral ligands involved.
Results and discussion
Preliminary studies began with several chiral ligands and their used. We found out the reactivity and enantioselectivity was
loading screening in the model reaction between enone 1a and sensitive to both the activation temperature and reaction
diethyl phosphite 2a (Table 1, entries 1–5). A trace amount of temperature. A decrease in activation temperature resulted in
product 3aa was isolated when chiral ligand L2 was used. Chiral β- reduction of ee (Table 1, entry 12), while an increase in reaction
amino alcohols L3–L4 gave desired products without showing temperature led to a diminishment of the enantioselectivity (Table
enantioselectivity. Fortunately, our azetidines-derived ligand L1 1, entry 13). A 99% yield and 99% ee was achieved when diethyl
restored high enantioselectivity. In addition, an enhancement in phosphite (2a) was activated at 30oC and the reaction was carried
enantioselectivity was observed with the increasing ligand loading out at 17oC (Table 1, entry 14). However, an obvious decrease in the
(Table 1, entry 5). Dialkyl phosphite presented a tautomerism with enantiomeric excess was observed when 4Å MS was added (Table 1,
the nucleophilic phosphinous acid tautomer, the equilibrium could entry 15). This result was contrary to the report of Wang,12–13 in
shift towards the reactive phosphinous acid form under an which the 4Å MS was necessary to significantly enhance the
appropriate basic environment.14 An Et2Zn was employed as a base conversion and enantioselectivity, suggesting the superior of our
to activate the phosphite, and its loading was investigated as well in catalytic system.
2 | Org. Biomol. Chem., 2017, 00, 1-3
This journal is © The Royal Society of Chemistry 2017
Please do not adjust margins

Please do not adjust margins
Page 3 of 9
Organic & Biomolecular Chemistry
Organic & Biomolecular Chemistry
PAPER
View Article Online
DOI: 10.1039/C7OB02222K
Scheme 2 Substrate scope for the catalytic asymmetric addition of
diethyl phosphite to chalcone derivatives. Reaction conditions: 1b–
1r (0.5 mmol), 2a (2.0 equiv), L1 (20 mol%), Et2Zn (40 mol%),
activation temperature (30oC), reaction temperature 17oC) in
toluene. Unless otherwise noted, all reactions were processed
under argon for indicated reaction time. Isolated yield reported.
The ee values were determined by HPLC analysis. In all cases, the
product chromatograms were compared against a known racemic
mixture. The absolute configuration of 3aa was assigned by
comparison of optical rotation and chiral HPLC traces with the
literature.12 The other products were tentatively assigned by
analogy.
Scheme 3 Substrate scope for the catalytic asymmetric addition of
diethyl phosphite to α,β-unsaturated N-acylpyrroles. Reaction
conditions: 4a–4n (0.5 mmol), 2a (2.0 equiv), L1 (20 mol%), Et2Zn
(40 mol%), activation temperature (35oC), reaction temperature
(20oC) in toluene. Unless otherwise noted, all reactions were
processed under argon for indicated reaction time. Isolated yield
reported. The ee values were determined by HPLC analysis. In all
cases, the product chromatograms were compared against a known
racemic mixture. The absolute configurations were assigned by
analogy.
Therefore, the optimal reaction conditions were finally identified as
follows: 20 mol% of L1, 40 mol% of Et2Zn, and diethyl phosphite (2a)
in toluene, the mixture was activated at 30oC for 0.5 h and then the
subsequent reaction was performed at 17oC for 16 h.
3ba, 1i → 3ia). The enone 1i with substituents on the 2,6-positions
of the phenyl ring afforded the corresponding product 3ia with poor
ee probably due to the bilateral steric hinderance. 2-Naphthyl 1o, 2-
piperonyl 1p and ferrocenoyl substituted enone 1q were
undergoing hydrophosphonylation with high enantioselectivity.
However, the products with poor yield and relatively low
enantiomeric excess was obtained when the enones bearing a
pyridyl on the α position was introduced (1r → 3ra) because the
catalyst might be poisoned by pyridine ring binding to the catalyst.
It is worthy to mention that when the reaction was scaled up to 4
mmol of chalcone substrate 1o, product (S)-3oa was obtained in
A series of substituted enones 1b–1r were examined under the
optimized conditions, excellent yields and enantioselectivities were
achieved by employing
a broad range of aromatic and
heteroaromatic substrates (Scheme 2). The electronic properties of
the substituents on the both aryls had no obvious effect on the
enantioselectivities of the products (1c–1h → 3ca–3ha). In addition,
the enones with substitutions on the different positions of phenyl
ring showed similar reactivity and enatioselectivity. Notably, the
steric effect was crucial with respect to the enantioselectivity (1b →
This journal is © The Royal Society of Chemistry 2017
Org. Biomol. Chem., 2017, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 9
PAPER
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C7OB02222K
Scheme 4 Proposed catalytic cycle of the phospha-Michael addition.
82% yield without losing enantioselectivit, demonstrating the utility N-acylpyrroles. Either electron donating methoxyl substituent or
on a preparative scale (1o → 3oa, gram scal). electron withdrawing nitro group led to high enantiomeric excess
It is still highly demanded to improve the synthetic utility by (5ia vs 5ja). The ortho, meta or para methoxyl substituted N-
extension the substrate scope of the α,β-unsaturated carbonyl acylpyrroles gave the corresponding products in comparable yield
compounds. α,β-Unsaturated N-acylpyrroles are desired substrates and enantioselectivity (5ca, 5da, and 5ia). We were pleased to find
because they are highly reactive, monodentate ester surrogates and that the phosphonylation of N-acylpyrroles bearing furyl, thienyl, or
their adducts can be readily converted into alcohols, naphthyl substituents on the
β position were also highly
aldehydes/ketones, and carboxylic acid derivatives.21 To our delight, enantioselective (4k–4n → 5ka–5na). However, a bulkyl bromo
a broad spectrum of aromatic α,β-unsaturated N-acylpyrroles 4a– substituent in the ortho position of the phenyl ring reduced both
4n irrespective of electronic nature or positions of substituents on yield and enantioselectivity (4b → 5ba).
the phenyl ring were well applicable to the present catalyst with To shed some light on reaction mechanism, a non-linear effect (NLE)
excellent enantioselectivity (Scheme 3). However, a relative lower was identified by measuring the correlation of the enantiomeric
yields were obtained compared to the enones due to the less excess between product and chiral ligand.22–26 The variation of ee
reactivity of α,β-unsaturated
values of the ligand generated asymmetric phosphonylation. A
4 | Org. Biomol. Chem., 2017, 00, 1-3
This journal is © The Royal Society of Chemistry 2017
Please do not adjust margins

Please do not adjust margins
Page 5 of 9
Organic & Biomolecular Chemistry
Organic & Biomolecular Chemistry
PAPER
positive non-linear effect was observed in the reaction of diethyl
phosphite (2a) and α,β-unsaturated N-acylpyrrole 4a catalyzed by
azetidines-derived dinuclear zinc (Figure 1). The result suggested
that the homochiral and heterochiral aggregates or dimeric form of
the catalyst (Zn2EtL)n would be involved in the catalytic cycle. The
homochiral polymeric complex composed of the optically pure
ligands dissociates more readily than the corresponding
heterochiral one containing both (S,S) and (R,R) ligands to give
monomeric enantiopure catalyst Zn2EtL1, hence leading to a (+)-NLE.
Experimental
View Article Online
DOI: 10.1039/C7OB02222K
General remarks: All reactions were performed in flame-dried
glassware using conventional Schlenk techniques under a static
pressure of argon. Liquids and solutions were transferred with
(micro)syringes. Solvents were purified and dried following
standard procedures. Technical grade solvents for extraction and
chromatography were distilled prior to use. Analytical thin-layer
chromatography (TLC) and flash column chromatography were
performed on silica gel using the indicated solvents. Infrared (IR)
spectra were recorded on a Nicolet IR 200 spectrophotometer in
KBr pellets and are reported (br = broad, vw = very weak, w = weak,
Based on the above results and the previous reports,12,18 the
catalytic cycle would involve the formation of inactive species
(Zn2EtL)n by the coordination of chiral ligand to 2 equiv of Et2Zn, the
complex (Zn2EtL)n is decomposed to the catalytically active species
Zn2EtL simultaneously. Subsequently, the diethyl phosphite (2a) is
deprotonated by the catalyst to generate a zinc phosphonate
intermediate A. Then the coordinating of α,β-unsaturated carbonyl
compound to the other zinc atom from the most sterically
accessible site leads to the formation of complexes B followed by
undergoing the phospho-transfer (B → C). The catalytic cycle is
regenerated by a proton exchange with another diethyl phosphite
(2a) to release the product (Scheme 4).
m = medium, s = strong) in wavenumbers (cm–1). H and 13C NMR
1
spectra were recorded in CDCl3 on Bruker DPX 400 (400 MHz).
Chemical shifts are reported in parts per million (ppm) downfield
from tetramethylsilane and are referenced to the residual solvent
1
resonance as the internal standard (δ = 7.26 ppm for H and δ =
77.16 ppm for 13C). Data are reported as follows: chemical shift,
multiplicity (br s = broad singlet, s = singlet, d = doublet, t = triplet, q
= quartet, m = multiplet), coupling constants (Hz) and integration.
Optical rotations were recorded on a Perkin-Elmer 341 polarimeter.
Mass spectra were recorded on VG-FAB mass spectrometer. The ee
value determination was carried out using chiral HPLC on a Chiralcel
AD, OD, or OD-H Column (for all the columns: 4.6 mmφ × 250 mm,
Daicel Chemical Ind., LTD, Japan) combined with a JASCO model PU-
1580 intelligent HPLC pump and a JASCO model UV-1575 intelligent
UV-vis detector.
Conclusions
In conclusion, we achieved an azetidines-derived dinuclear zinc
catalyzed conjugate addition of dialkyl phosphite to α,β-
unsaturated carbonyl compounds in the absence of additives. Our
catalytic system was proved to be effective and general to provide
the corresponding products in good yields with excellent
enantioselectivity. Diethyl phosphite was found to be a highly
reactive nucleophils, the phosphonylation of various α,β-
unsaturated carbonyl compounds were highly enantioselective. a
positive nonlinear effect was observed. On the basis of the
experimental results and previous reports, a possible mechanism
was proposed. Detailed reaction mechanism and applications of the
phospha-Michael adducts are investigated in our ongoing studies.
General procedure for the catalytic asymmetric addition of diethyl
phosphite to enones: In a flame-dried Schlenk tube equipped with
a magnetic stir bar, a solution of the chiral ligand L1 (15.3 mg, 0.025
mmol, 20 mol%) in dry toluene (1.0 mL, 0.125 M) under nitrogen at
0 oC. Then diethylzinc (0.05 mL, 1.0 mol/L in hexane, 0.05 mmol, 40
mol%) and diethyl phosphite (2a, 0.19 mmol, 1.5 equiv) were added
into the mixture successively. The system is stirred at 30oC for 30
min before cooled to 0oC. Then enone substrates (1a─1r, 0.125
mmol, 1.0 equiv) is added by a micro syringe to the mixture. The
solution is stirred at 17oC for 16–20 h. After complete consumption
of the starting material, as monitored by TLC analysis, the reaction
mixture is allowed to cool to room temperature, quenched with 1M
HCl (1.0 mL), and extracted with dichloromethane (3 × 5 mL). The
combined organic phases are washed with brine (5.0 mL) and dried
over anhydrous Na2SO4. After evaporation of the solvent under
reduced pressure, purification of the residue by column
chromatography on silica gel using mixtures of petroleum ether and
ethyl acetate as eluents (ethyl acetate: petroleum ether = 1:4 → 1:2)
affords the analytically pure compounds 3aa─3ra.
100
80
60
40
20
0
(S)-Diethyl 3-oxo-1,3-diphenylpropylphosphonate (3aa):12
A
20
colorless oil, 42.9 mg, 99% yield, 99% ee; [α]D = –17.8 (C = 1.0,
CHCl3); determined by HPLC on a Chiralcel OD column (hexane/2-
propanol = 90/10, flow rate = 0.3 mL/min, UV detection at 254 nm);
retention time: tR(S) = 20.67 min, tR(R) = 22.46 min.
0
20
40
60
80
100
(S)-Diethyl
1-(2-methoxyphenyl)-3-oxo-3-phenylpropylphospho-
ee of ligand (%)
nate (3ba):12 A colorless oil, 41.9 mg, 89% yield, 87% ee;
determined by HPLC on a Chiralcel AD column (hexane/2-propanol
= 90/10, flow rate = 1.0 mL/min, UV detection at 254 nm); retention
time: tR(S) = 15.94 min, tR(R) = 22.75 min.
Figure 1 Correlation between the ee values of the ligand (S,S)-L1
and the ee of product.
This journal is © The Royal Society of Chemistry 2017
Org. Biomol. Chem., 2017, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 9
PAPER
(S)-Diethyl 1-(3-chlorophenyl)-3-oxo-3-phenylpropylphosphonate (S)-Diethyl
Organic & Biomolecular Chemistry
3-(4-methoxyphenyl)-3-oxo-1-phenylpropylphospho-
View Article Online
(3ca):12 A colorless oil, 46.6 mg, 98% yield, 99% ee; determined by nate (3ja):12 A white solid, 45.2 mg, 96% yield, 98% ee; determined
HPLC on a Chiralcel AD column (hexane/2-propanol = 90/10, flow by HPLC on a Chiralcel OD column (hexane/2-propanol = 90/10,
rate = 0.3 mL/min, UV detection at 254 nm); retention time: tR(S) = flow rate = 0.5 mL/min, UV detection at 254 nm); retention time:
DOI: 10.1039/C7OB02222K
50.74 min, tR(R) = 44.85 min.
tR(S) = 20.21 min, tR(R) = 19.30 min.
(S)-Diethyl 1-(4-chlorophenyl)-3-oxo-3-phenylpropylphosphonate (S)-Diethyl
1-(2-chlorophenyl)-3-(4-chlorophenyl)-3-oxopropyl-
(3da):12 A colorless oil, 45.2 mg, 95% yield, 97% ee; determined by phosphonate (3ka): A yellow solid, 45.2 mg, 87% yield, 93% ee;
HPLC on a Chiralcel AD column (hexane/2-propanol = 90/10, flow determined by HPLC on a Chiralcel AD column (hexane/2-propanol
rate = 1.0 mL/min, UV detection at 254 nm); retention time: tR(S) = = 90/10, flow rate = 1.0 mL/min, UV detection at 254 nm); retention
20
19.76 min, tR(R) = 23.39 min.
(S)-Diethyl 1-(4-bromophenyl)-3-oxo-3-phenylpropylphosphonate CHCl3); m.p. = 77.1‒77.6 C; IR (KBr): nu(tilde)/cm–1 = 2982, 2928,
time: tR(S) = 24.59 min, tR(R) = 22.13 min; [α]D = –27.2 (C = 0.4,
o
1
(3ea):12 A colorless oil, 52.6 mg, 99% yield, 95% ee; determined by 1690, 1589, 1477, 1246, 1093, 967, 748, 566; H NMR (400 MHz,
HPLC on a Chiralcel AD column (hexane/2-propanol = 90/10, flow CDCl3) δ (major + minor) = 8.86 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 7.6 Hz,
rate = 1.0 mL/min, UV detection at 254 nm); retention time: tR(S) = 1H), 7.40‒7.37 (m, 3H), 7.18‒7.11 (m, 2H), 4.61‒4.54 (m, 1H),
21.99 min, tR(R) = 27.58 min.
(S)-Diethyl 3-oxo-3-phenyl-1-p-tolylpropylphosphonate (3fa):12
4.14‒4.09 (m, 2H), 3.89‒3.86 (m, 1H), 3.78‒3.69 (m, 3H), 1.29 (t, J =
7.0 Hz, 3H), 1.08 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ
A
colorless oil, 41.9 mg, 93% yield, 97% ee; determined by HPLC on a (major + minor) = 194.7 (d, J = 15.1 Hz), 139.7, 135.1 (d, J = 8.6 Hz),
Chiralcel OD column (hexane/2-propanol = 50/1, flow rate = 1.0 134.5, 133.8 (d, J = 6.4 Hz), 129.6 (d, J = 2.3 Hz), 129.4, 128.9 (d, J =
mL/min, UV detection at 254 nm); retention time: tR(S) = 16.54 min, 4.5 Hz), 128.8, 128.2 (d, J = 3.1 Hz), 126.8 (d, J = 3.0 Hz), 62.9 (d, J =
tR(R) = 25.23 min.
7.0 Hz), 62.2 (d, J = 7.0 Hz), 34.5 (d, J = 140.0 Hz), 29.5, 16.2 (d, J =
(S)-Diethyl 1-(4-methoxyphenyl)-3-oxo-3-phenylpropylphospho- 6.1 Hz), 16.0 (d, J = 5.7 Hz) ppm; HRMS m/z: calcd. for C19H22Cl2O4P
nate (3ga):12 A colorless oil, 43.8 mg, 93% yield, 99% ee; determined [M+H]+ 415.0627, found 415.0624.
by HPLC on a Chiralcel OD-H column (hexane/2-propanol = 20/1, (S)-Diethyl 1-(2-chlorophenyl)-3-(4-methoxyphenyl)-3-oxopropyl-
flow rate = 1.0 mL/min, UV detection at 254 nm); retention time: phosphonate (3la): A colorless oil, 50.3 mg, 98% yield, 99% ee;
tR(S) = 17.49 min, tR(R) = 21.88 min.
determined by HPLC on a Chiralcel OD-H column (hexane/2-
(S)-Diethyl 1-(4-dimethylamino)-3-oxo-3-phenylpropylphospho- propanol = 90/10, flow rate = 0.15 mL/min, UV detection at 254
20
nate (3ha): A colorless oil, 48.2 mg, 99% yield, 99% ee; determined nm); retention time: tR(S) = 99.78 min, tR(R) = 96.19 min; [α]D = –
by HPLC on a Chiralcel AD column (hexane/2-propanol = 90/10, flow 25.2 (C = 0.7, CHCl3); IR (KBr): nu(tilde)/cm–1 = 2981, 2926, 1680,
rate = 1.0 mL/min, UV detection at 254 nm); retention time: tR(S) = 1597, 1511, 1394, 1246, 1172, 968, 757, 547;1H NMR (400 MHz,
29.43 min, tR(R) = 23.48 min; [α]D20 = –35.2 (C = 0.7, CHCl3); IR (KBr): CDCl3) δ (major + minor) = 7.93 (d, J = 8.7 Hz, 2H), 7.51 (d, J = 7.6 Hz,
nu(tilde)/cm–1 = 3004, 2921, 1706, 1557, 1507, 1217, 897, 744, 524; 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.20‒7.14 (m, 2H), 6.90 (d, J = 8.8 Hz,
1H NMR (400 MHz, CDCl3) δ (major + minor) = 7.94 (d, J = 7.2 Hz, 2H), 2H), 4.66‒4.60 (m, 1H), 4.17‒4.11 (m, 2H), 3.90‒3.84 (m, 1H), 3.84
7.52 (dd, J = 7.2 Hz, J = 7.4 Hz, 1H), 7.42 (dd, J = 7.2 Hz, J = 7.4 Hz, (s, 3H), 3.75‒3.68 (m, 3H), 1.30 (t, J = 6.6 Hz, 3H), 1.09 (t, J = 6.6 Hz,
2H), 7.30‒7.27 (m, 2H), 6.65 (d, J = 7.2 Hz, 2H), 4.08‒4.06 (m, 2H), 3H) ppm; 13C NMR (100 MHz, CDCl3) δ (major + minor) = 194.4 (d, J
3.91‒3.89 (m, 2H), 3.71‒3.62 (m, 3H), 2.88 (s, 6H), 1.26 (t, J = 6.6 Hz, = 15.3 Hz), 163.6, 135.2 (d, J = 8.7 Hz), 134.1 (d, J = 6.5 Hz), 130.3,
3H), 1.13 (t, J = 6.6 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ (major 129.7 (d, J = 2.5 Hz), 129.4, 129.1 (d, J = 4.6 Hz), 128.1 (d, J = 3.2 Hz),
+ minor) = 196.6 (d, J = 5.2 Hz), 149.6 (d, J = 2.4 Hz), 136.5, 133.0, 126.8 (d, J = 3.2 Hz), 113.7, 62.9 (d, J = 7.0 Hz), 62.2 (d, J = 7.0 Hz),
129.7 (d, J = 6.6 Hz), 128.4, 128.0, 123.1 (d, J = 7.2 Hz), 112.5 (d, J = 55.4, 34.6 (d, J = 139.7 Hz), 29.6, 16.3 (d, J = 6.2 Hz), 16.1 (d, J = 5.8
2.0 Hz), 62.8 (d, J = 7.0 Hz), 61.7 (d, J = 7.3 Hz), 40.4, 39.9 (d, J = Hz) ppm; HRMS m/z: calcd. for C20H25ClO5P [M+H]+ 411.1123, found
139.0 Hz), 29.6, 16.3 (d, J = 6.0 Hz), 16.2 (d, J = 5.8 Hz) ppm; HRMS 411.1118.
m/z: calcd. for C21H29NO4P [M+H]+ 390.1829, found 390.1826.
(S)-Diethyl 3-(4-chlorophenyl)-1-(2-methoxyphenyl)-3-oxopropyl-
(S)-Diethyl 1-(2,6-dimethoxyphenyl)-3-oxo-3-phenylpropylphos- phosphonate (3ma): A colorless oil, 47.2 mg, 92% yield, 96% ee;
phonate (3ia): A colorless oil, 49.3 mg, 97% yield, 46% ee; determined by HPLC on a Chiralcel AD column (hexane/2-propanol
determined by HPLC on a Chiralcel OD-H column (hexane/2- = 90/10, flow rate = 1.0 mL/min, UV detection at 254 nm); retention
20
propanol = 90/10, flow rate = 1.0 mL/min, UV detection at 254 nm); time: tR(S) = 23.08 min, tR(R) = 32.42 min; [α]D = –18.9 (C = 0.47,
retention time: tR(S) = 11.53 min, tR(R) = 13.39 min; [α]D20 = –9.2 (C = CHCl3); IR (KBr): nu(tilde)/cm–1 = 2923, 2850, 1688, 1589, 1511,
0.2, CHCl3); IR (KBr): nu(tilde)/cm–1 = 2924, 2850, 1687, 1594, 1398, 1394, 1246, 1172, 968, 757, 571; 1H NMR (400 MHz, CDCl3) δ (major
1163, 957, 781, 568; 1H NMR (400 MHz, CDCl3) δ (major + minor) = + minor) = 7.87 (d, J = 8.2 Hz, 2H), 7.41‒7.38 (m, 3H), 7.19 (dd, J =
7.95 (d, J = 7.4 Hz, 2H), 7.53 (dd, J = 7.3 Hz, J = 7.3 Hz, 1H), 7.42 (dd, 7.5 Hz, J = 7.5 Hz, 1H), 6.88 (dd, J = 7.6 Hz, J = 8.2 Hz, 2H), 4.61‒4.54
J = 7.5 Hz, J = 7.5 Hz, 2H), 7.15 (m, 1H), 6.52 (d, J = 7.8 Hz, 2H), 4.86– (m, 1H), 4.10‒4.07 (m, 2H), 3.93‒3.88 (m, 1H), 3.87 (s, 3H),
4.77 (m, 1H), 4.12–4.08 (m, 3H), 4.17–4.05 (m, 2H), 3.90 (s, 6H), 3.78‒3.72 (m, 1H), 3.68‒3.64 (m, 2H), 1.36‒1.25 (m, 6H) ppm; 13C
3.83–3.72 (m, 1H), 1.30 (t, J = 6.5 Hz, 3H), 1.13 (t, J = 6.5 Hz, 3H) NMR (100 MHz, CDCl3) δ (major + minor) = 195.5 (d, J = 14.9 Hz),
ppm; 13C NMR (100 MHz, CDCl3) δ (major + minor) = 198.0 (d, J = 157.3 (d, J = 7.0 Hz), 139.4, 134.9, 129.5, 128.8, 128.6 (d, J = 4.9 Hz),
13.5 Hz), 158.4, 137.0, 132.7, 129.3, 128.2, 112.7, 112.6, 104.3, 62.0 128.2 (d, J = 3.2 Hz), 124.3 (d, J = 6.9 Hz), 120.6 (d, J = 3.0 Hz), 110.9
(d, J = 6.8 Hz), 61.7 (d, J = 6.7 Hz), 55.9, 29.3, 22.7, 16.4 (d, J = 6.3 (d, J = 2.2 Hz), 62.6 (d, J = 7.0 Hz), 61.9 (d, J = 7.0 Hz), 55.8, 30.5 (d, J
Hz), 16.2 (d, J = 6.3 Hz) ppm; HRMS m/z: calcd. for C21H28O6P [M+H]+ = 140.5 Hz), 29.6, 16.3 (d, J = 6.2 Hz), 16.1 (d, J = 6.0 Hz) ppm; HRMS
407.1618, found 407.1620.
m/z: calcd. for C20H25ClO5P [M+H]+ 411.1123, found 411.1120.
6 | Org. Biomol. Chem., 2017, 00, 1-3
This journal is © The Royal Society of Chemistry 2017
Please do not adjust margins

Please do not adjust margins
Page 7 of 9
Organic & Biomolecular Chemistry
Organic & Biomolecular Chemistry
PAPER
(S)-Diethyl 1,3-bis(3-chlorophenyl)-3-oxopropylphosphonate (3na): HRMS m/z: calcd. for C24H30FeO5P [M+H]+ 485V.i1ew16A4rti,clefOonulinned
DOI: 10.1039/C7OB02222K
A colorless oil, 50.4 mg, 97% yield, 95% ee; determined by HPLC on 485.1162.
a Chiralcel AD column (hexane/2-propanol = 90/10, flow rate = 0.8 (S)-Diethyl 3-(ferrocene)-1-(2-pyridinyl)-3-oxopropylphosphonate
mL/min, UV detection at 254 nm); retention time: tR(S) = 18.15 min, (3ra): A brown oil, 27.3 mg, 48% yield, 80% ee; determined by HPLC
20
tR(R) = 16.60 min; [α]D = –35.2 (C = 0.47, CHCl3); IR (KBr): on a Chiralcel AD column (hexane/2-propanol = 90/10, flow rate =
nu(tilde)/cm–1 = 2980, 2925, 1689, 1596, 1246, 1163, 965, 755, 585; 1.0 mL/min, UV detection at 254 nm); retention time: tR(S) = 27.73
1H NMR (400 MHz, CDCl3) δ (major + minor) = 7.95 (d, J = 7.5 Hz, 2H), min, tR(R) = 16.71 min; [α]D = –27.2 (C = 0.3, CHCl3); IR (KBr):
20
7.46 (d, J = 7.4 Hz, 1H), 7.44 (d, J = 7.8 Hz, 2H), 7.35‒7.33 (m, 1H), nu(tilde)/cm–1 = 2924, 1688, 1633, 1542, 1509, 1398, 1399, 1256,
7.31‒7.21 (m, 2H), 4.11‒4.07 (m, 2H), 3.99‒3.94 (m, 2H), 3.82‒3.78 1161, 1025, 968, 561; 1H NMR (400 MHz, CDCl3) δ (major + minor) =
(m, 1H), 3.72‒3.67 (m, 2H), 1.29 (t, J = 7.1 Hz, 3H), 1.13 (t, J = 7.2 Hz, 8.52 (s, 1H), 7.58‒7.53 (m, 1H), 7.47‒7.41 (m, 1H), 7.20‒7.09 (m,
3H) ppm; 13C NMR (100 MHz, CDCl3) δ (major + minor) = 195.9 (d, J 1H), 4.75‒4.70 (m, 2H), 4.42‒4.37(m, 2H), 4.09‒4.00 (m, 11H),
= 14.9 Hz), 138.1 (d, J = 6.7 Hz), 136.3, 134.2 (d, J = 2.9 Hz), 133.4, 3.27‒3.25 (m, 1H), 1.24 (t, 3H), 0.84 (t, 3H) ppm; 13C NMR (100 MHz,
129.6 (d, J = 2.4 Hz), 129.2, 129.2, 128.6, 128.0, 127.4, 127.4, 127.4, CDCl3) δ (major + minor) = 200.8 (d, J = 16.2 Hz), 155.9 (d, J = 7.4 Hz),
62.9 (d, J = 6.9 Hz), 62.1 (d, J = 7.1 Hz), 38.9, 29.6, 16.3 (d, J = 6.0 Hz), 149.0, 136.3, 125.4, 122.0, 78.4, 72.2, 69.8, 69.4, 69.0, 62.5 (d, J =
16.1 (d, J = 5.7 Hz) ppm; HRMS m/z: calcd. for C19H22Cl2O4P [M+H]+ 6.9 Hz), 62.3 (d, J = 6.5 Hz), 40.4 (d, J = 137.1 Hz), 29.6, 16.4 (d, J =
415.0627, found 415.0622.
5.8 Hz), 16.2 (d, J = 5.7 Hz) ppm; HRMS m/z: calcd. for C22H27FeNO4P
(S)-Diethyl 1-(naphthalen-3-yl)-3-oxo-3-phenylpropylphosphonate [M+H]+ 456.1022, found 456.1018.
(3oa):12 A white solid, 43.6 mg, 88% yield, 99% ee; determined by General procedure for the catalytic asymmetric addition of diethyl
HPLC on a Chiralcel OD-H column (hexane/2-propanol = 90/10, flow phosphite to α,β-unsaturated N-acylpyrroles: In a flame-dried
rate = 1.0 mL/min, UV detection at 254 nm); retention time: tR(S) = Schlenk tube equipped with a magnetic stir bar, a solution of the
9.29 min, tR(R) = 10.82 min.
chiral ligand L1 (15.3 mg, 0.025 mmol, 20 mol%) in dry toluene (1.0
o
(S)-Diethyl 1-(benzo[d][1,3]dioxol-6-yl)-3-oxo-3-phenylpropylphos- mL, 0.125 M) under nitrogen at 0 C. Then diethylzinc (0.05 mL, 1.0
phonate (3pa): A white solid, 48.3 mg, 99% yield, 99% ee; mol/L in hexane, 0.05 mmol, 40 mol%) and diethyl phosphite (2a,
determined by HPLC on a Chiralcel AD column (hexane/2-propanol 0.19 mmol, 1.5 equiv) were added into the mixture successively.
= 90/10, flow rate = 1.0 mL/min, UV detection at 254 nm); retention The system is stirred at 35oC for 30 min before cooled to 0oC. Then
20
time: tR(S) = 38.91 min, tR(R) = 35.08 min; [α]D = –16.7 (C = 0.4, α,β-unsaturated N-acylpyrrole substrate (4a─4n, 0.125 mmol, 1.0
CHCl3); IR (KBr): nu(tilde)/cm–1 = 2981, 1688, 1597, 1489, 1245, equiv) is added by a micro syringe to the mixture. The solution is
1
1163, 1099, 964, 755, 572; H NMR (400 MHz, CDCl3) δ (major + stirred at 20oC for 30 h. After complete consumption of the starting
minor) = δ 7.94 (d, J = 7.4 Hz, 2H), 7.55 (t, J = 7.3 Hz, 1H), 7.44 (t, J = material, as monitored by TLC analysis, the reaction mixture is
7.6 Hz, 2H), 6.98 – 6.82 (m, 2H), 6.72 (d, J = 8.0 Hz, 1H), 5.91 (s, 2H), allowed to cool to room temperature, quenched with 1M HCl (1.0
4.19 – 4.03 (m, 2H), 4.02 – 3.75 (m, 3H), 3.73 – 3.54 (m, 2H), 1.29 (t, mL), and extracted with dichloromethane (3 × 5 mL). The combined
J = 7.1 Hz, 3H), 1.15 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz, organic phases are washed with brine (5.0 mL) and dried over
CDCl3) δ (major + minor) = 196.4 (d, J = 15.2 Hz), 147.6 (d, J = 2.6 Hz), anhydrous Na2SO4. After evaporation of the solvent under reduced
146.8 (d, J = 3.0 Hz), 136.6, 133.3, 130.0 (d, J = 7.2 Hz), 128.6, 128.1, pressure, purification of the residue by column chromatography on
122.7(d, J = 7.8 Hz), 109.9 (d, J = 6.1 Hz), 108.0 (d, J = 2.1 Hz), 101.0, silica gel using mixtures of petroleum ether and ethyl acetate as
62.9(d, J = 7.1 Hz), 61.9(d, J = 7.3 Hz), 39.2, 37.8, 29.6, 16.4 (d, J = eluents (ethyl acetate: petroleum ether = 1:4 → 1:2) affords the
5.9 Hz) 16.3 (d, J = 5.7 Hz) ppm; HRMS m/z: calcd. for C20H23O6P analytically pure compounds 5aa─5ma.
[M+H]+ 391.1305, found 391.1307.
(S)-Diethyl
1-phenyl-3-oxo-3-pyrrol-1-yl-propylphosphonate
(S)-Diethyl 3-(ferrocene)-1-(2-methoxyphenyl)-3-oxopropylphos- (5aa):13 A colorless oil, 41.3 mg, 63% yield, 96% ee; determined by
phonate (3qa): A brown solid, 53.9 mg, 89% yield, 97% ee; HPLC on a Chiralcel OD-H column (hexane/2-propanol = 97/3, flow
determined by HPLC on a Chiralcel AD column (hexane/2-propanol rate = 0.5 mL/min, UV detection at 254 nm); retention time: tR(S) =
= 90/10, flow rate = 1.0 mL/min, UV detection at 254 nm); retention 25.83 min, tR(R) = 29.04 min.
20
time: tR(S) = 22.35 min, tR(R) = 17.59 min; [α]D = –35.2 (C = 0.35, (S)-Diethyl
o
1-(2-bromophenyl)-3-oxo-3-pyrrol-1-yl-propylphos-
CHCl3); m.p. = 102.1 ‒103 C; IR (KBr): nu(tilde)/cm–1 = 2921, 2850, phonate (5ba):13 A colorless oil, 17.1 mg, 33% yield, 57% ee;
1
1677, 1494, 1451, 1398, 1250, 1106, 964, 755, 571; H NMR (400 determined by HPLC on a Chiralcel OD-H column (hexane/2-
MHz, CDCl3) δ (major + minor) = 7.45 (d, J = 7.6 Hz, 1H), 7.17 (dd, J = propanol = 97/3, flow rate = 1.0 mL/min, UV detection at 254 nm);
7.8 Hz, J = 7.8 Hz, 1H), 6.91 (dd, J = 7.5 Hz, J = 7.5 Hz, 1H), 6.86 (d, J retention time: tR(S) = 15.03 min, tR(R) = 18.01 min.
= 8.2 Hz, 1H), 4.74 (s, 2H), 4.63‒4.55 (m, 1H), 4.43 (s, 2H), 4.11‒4.06 (S)-Diethyl 1-(2-methoxyphenyl)-3-oxo-3-pyrrol-1-yl-propylphos-
(m, 2H), 3.99 (s, 5H), 3.89‒3.85 (m, 3H), 3.85‒3.83 (m, 1H), phonate (5ca):13 A colorless oil, 29.8 mg, 65% yield, 99% ee;
3.71‒3.69 (m, 1H), 3.50‒3.47(m, 1H), 3.36‒3.33 (m, 1H), 1.26 (t, J = determined by HPLC on a Chiralcel OD-H column (hexane/2-
7.0 Hz, 3H), 0.85 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ propanol = 97/3, flow rate = 1.0 mL/min, UV detection at 254 nm);
(major + minor) = 200.2 (d, J = 16.3 Hz), 157.5 (d, J = 7.1 Hz), 128.7 retention time: tR(S) = 19.76 min, tR(R) = 22.38 min.
(d, J = 5.0 Hz), 128.1 (d, J = 3.2 Hz), 124.6 (d, J = 6.6 Hz), 120.5 (d, J = (S)-Diethyl 1-(3-methoxyphenyl)-3-oxo-3-pyrrol-1-yl-propylphos-
3.1 Hz), 111.0 (d, J = 3.2 Hz), 78.4, 72.1 (d, J = 5.1 Hz), 69.5 (d, J = 4.9 phonate (5da):13 A colorless oil, 27.8 mg, 61% yield, 98% ee;
Hz), 69.1, 69.0, 62.5 (d, J = 6.9 Hz), 61.6 (d, J = 7.0 Hz), 55.9, 39.9, determined by HPLC on a Chiralcel OD-H column (hexane/2-
29.5 (d, J = 140.4 Hz), 16.3 (d, J = 6.2 Hz), 16.0 (d, J = 5.9 Hz) ppm; propanol = 97/3, flow rate = 1.0 mL/min, UV detection at 254 nm);
retention time: tR(S) = 19.24 min, tR(R) = 22.83 min.
This journal is © The Royal Society of Chemistry 2017
Org. Biomol. Chem., 2017, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 8 of 9
PAPER
Organic & Biomolecular Chemistry
(S)-Diethyl 1-(4-fluorophenyl)-3-oxo-3-pyrrol-1-yl-propylphospho- We are grateful to the National Natural Sciences Foundation of
View Article Online
nate (5ea):13 A white solid, 28.7 mg, 65% yield, 93% ee; determined China (NNSFC: 21272216, 20972140), and the Department of
DOI: 10.1039/C7OB02222K
by HPLC on a Chiralcel OD-H column (hexane/2-propanol = 97/3, Science and Technology of Henan Province for financial support.
flow rate = 1.0 mL/min, UV detection at 254 nm); retention time:
tR(S) = 13.46 min, tR(R) = 20.10 min.
Notes and references
(S)-Diethyl 1-(4-chlorophenyl)-3-oxo-3-pyrrol-1-yl-propylphospho-
nate (5fa):13 A white solid, 26.3 mg, 57% yield, 91% ee; determined
1
(a) W. Tang, X. Zhang, Chem. Rev., 2003, 103, 3029; (b) V. V.
Grushin, Chem. Rev., 2004, 104, 1629; (c) R. Martin, S. L.
Buchwald, Acc. Chem. Res., 2008, 41, 1461.
by HPLC on a Chiralcel AD column (hexane/2-propanol = 97/3, flow
rate = 1.0 mL/min, UV detection at 254 nm); retention time: tR(S) =
47.81 min, tR(R) = 64.54 min.
2
(a) V. D. Romanenko, V. P. Kukhar, Chem. Rev., 2006, 106, 3868;
(b) D. Zhao, R. Wang, Chem. Soc. Rev., 2012, 41, 2095; (c) U.
Pradere, E. C. Garnier-Amblard, S. J. Coats, F. Amblard, R. F.
Schinazi, Chem. Rev., 2014, 114, 9154.
(S)-Diethyl 1-(4-bromophenyl)-3-oxo-3-pyrrol-1-yl-propylphospho-
nate (5ga):13 A white solid, 32.6 mg, 63% yield, 99% ee; determined
by HPLC on a Chiralcel OD-H column (hexane/2-propanol = 97/3,
flow rate = 1.0 mL/min, UV detection at 254 nm); retention time:
tR(S) = 17.48 min, tR(R) = 20.73 min.
3
(a) S. Greenberg, D. W. Stephan, Chem. Soc. Rev., 2008, 37,
1482; (b) S. Wen, P. Li, H. Wu, F. Yu, X. Liang, J. Ye, Chem.
Commun., 2010, 46, 4806; (c) O. I. Kolodiazhnyi, V. P. Kukhar, A.
O. Kolodiazhna, Tetrahedron: Asymmetry, 2014, 25, 865; (d) A. Y.
Rulev, RSC Adv., 2014, 4, 26002.
(S)-Diethyl 1-(4-methylphenyl)-3-oxo-3-pyrrol-1-yl-propylphospho-
nate (5ha):13 A colorless oil, 25.3 mg, 58% yield, 97% ee;
determined by HPLC on a Chiralcel OD-H column (hexane/2-
propanol = 97/3, flow rate = 1.0 mL/min, UV detection at 254 nm);
retention time: tR(S) = 12.09 min, tR(R) = 17.02 min.
4
5
G. Desimoni, G. Faita, P. Quadrelli, Chem. Rev., 2015, 115, 9922.
J. Wang, L. D. Heikkinen, H. Li, L. Zu, W. Jiang, H. Xie, W. Wang,
Adv. Synth. Catal., 2007, 349, 1052.
6
7
8
M. Terada, T. Ikehara, H. Ube, J. Am. Chem. Soc., 2007, 129,
14112.
V. Rai, I. N. N. Namboothiri, Tetrahedron: Asymmetry, 2008, 19,
2335.
(a) E. Maerten, S. Cabrera, A. Kjarsgaard, K. A. Jørgensen, J. Org.
Chem., 2007, 72, 8893; (b) A. Carlone, G. Bartoli, M. Bosco, L.
Sambri, Paolo Melchiorre, Angew. Chem., Int. Ed., 2007, 46,
4504; (c) G. Bartoli, M. Bosco, A. Carlone, M. Locatelli, A.
Mazzanti, L. Sambri, P. Melchiorre; Chem. Commun., 2007, 722.
J. Feng, X. Chen, M. Shi, W. Duan, J. Am. Chem. Soc., 2010, 132,
5562.
(S)-Diethyl 1-(4-methyoxylphenyl)-3-oxo-3-pyrrol-1-yl-propylphos-
phonate (5ia):13 A colorless oil, 31.5 mg, 69% yield, 97% ee;
determined by HPLC on a Chiralcel OD-H column (hexane/2-
propanol = 97/3, flow rate = 1.0 mL/min, UV detection at 254 nm);
retention time: tR(S) = 20.45 min, tR(R) = 24.67 min.
(S)-Diethyl 1-(4-nitrophenyl)-3-oxo-3-pyrrol-1-yl-propylphospho-
nate (5ja):13 A pale yellow solid, 28.1 mg, 59% yield, 99% ee;
determined by HPLC on a Chiralcel OD-H column (hexane/2-
propanol = 97/3, flow rate = 1.0 mL/min, UV detection at 254 nm);
retention time: tR(S) = 7.45 min, tR(R) = 8.55 min.
9
10 Y. Huang, S. A. Pullarkat, Y. Li, P. Leung, Chem. Commun., 2010,
46, 6950.
11 G. Li, L. Wang, Z. Yao, F. Xu, Tetrahedron: Asymmetry, 2014, 25,
989.
12 D. Zhao, Y. Yuan, A. S. C. Chan, R. Wang, Chem.–Eur. J., 2009, 15,
2738.
13 D. Zhao, Y. Yuan, A. S. C. Chan, R. Wang, Chem.–Eur. J., 2009, 15,
10983.
14 D. Zhao, L. Mao, Y. Wang, D. Yang, Q. Zhang, R. Wang, Org. Lett.,
2010, 12, 1880.
15 D. Zhao, L. Mao, D. Yang, R. Wang, J. Org. Chem., 2010, 75, 6756.
16 D. Zhao, L. Mao, L. Wang, D. Yang, R. Wang, Chem. Commun.,
2012, 48, 889.
(S)-Diethyl 1-(furan-2-yl)-3-oxo-3-pyrrol-1-yl-propylphosphonate
(5ka):13 A colorless oil, 20.7 mg, 51% yield, 97% ee; determined by
HPLC on a Chiralcel OD-H column (hexane/2-propanol = 97/3, flow
rate = 0.5 mL/min, UV detection at 254 nm); retention time: tR(S) =
42.68 min, tR(R) = 45.48 min.
(S)-Diethyl 1-(thiophen-2-yl)-3-oxo-3-pyrrol-1-yl-propylphospho-
nate (5la):13 A colorless oil, 20.5 mg, 48% yield, 98% ee; determined
by HPLC on a Chiralcel OD-H column (hexane/2-propanol = 97/3,
flow rate = 0.5 mL/min, UV detection at 254 nm); retention time:
tR(S) = 18.60 min, tR(R) = 20.56 min.
17 Y.-Z. Hua, M.-M. Liu, P.-J. Huang, X. Song, M.-C. Wang, J.-B.
Chang, Chem.–Eur. J., 2015, 21, 11994.
(S)-Diethyl 1-(1-naphthyl)-3-oxo-3-pyrrol-1-yl-propylphosphonate
(5ma):13 A colorless oil, 25.5 mg, 53% yield, 97% ee; determined by
HPLC on a Chiralcel OD-H column (hexane/2-propanol = 97/3, flow
rate = 1.0 mL/min, UV detection at 254 nm); retention time: tR(S) =
18.98 min, tR(R) = 21.43 min.
18 Y.-Z. Hua, X.-W. Han, X.-C. Yang, X. Song, M.-C. Wang, J.-B.
Chang, J. Org. Chem., 2014, 79, 11690.
19 S. Liu, G.-W. Li, X.-C. Yang, D.-Y. Zhang, M.-C. Wang, Org. Biomol.
Chem., 2017, 15, 7147.
20 (a) Y.-Z. Hua, L.-J. Lu, P.-J. Huang, D.-H. Wei, M.-S. Tang, M.-C.
Wang, J.-B. Chang, Chem.–Eur. J., 2014, 20, 12394; (b) Y.-Z. Hua,
X.-C. Yang, M.-M. Liu, X. Song, M.-C. Wang, J.-B. Chang,
Macromolecules, 2015, 48, 1651.
21 (a) S. D. Lee, M. A. Brook, T. H. Chan, Tetrahedron Lett., 1983,
24, 1569; (b) D. A. Evans, G. Borg, K. A. Scheidt, Angew. Chem.,
Int. Ed., 2002, 41, 3188.
(S)-Diethyl 1-(2-naphthyl)-3-oxo-3-pyrrol-1-yl-propylphosphonate
(5na):13 A colorless oil, 18.8 mg, 39% yield, 99% ee; determined by
HPLC on a Chiralcel OD-H column (hexane/2-propanol = 97/3, flow
rate = 1.0 mL/min, UV detection at 254 nm); retention time: tR(S) =
8.20 min, tR(R) = 13.98 min.
22 C. Girard, H. B. Kagan, Angew. Chem., Int. Ed., 1998, 37, 2922.
23 D. G. Blackmond, Acc. Chem. Res., 2000, 33, 402.
24 C. Puchot, O. Samuel, E. Duñach, S. Zhao, C. Agami, H. B. Kagan,
J. Am. Chem. Soc., 1986, 108, 2353.
Conflicts of interest
25 T. Satyanarayana, S. Abraham, H. B. Kagan, Angew. Chem., Int.
Ed., 2009, 48, 456.
There are no conflicts of interest to declare.
26 Y. Yuan, X. Li, J. Sun, K. Ding, J. Am. Chem. Soc., 2002, 124,
14866.
Acknowledgements
8 | Org. Biomol. Chem., 2017, 00, 1-3
This journal is © The Royal Society of Chemistry 2017
Please do not adjust margins

Page 9 of 9
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C7OB02222K