Synthesis of highly rigid phosphine-oxazoline ligands for palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1039/c8ob02265h

A highly rigid spiro phosphine-oxazoline ligand skeleton with a spirocarbon stereogenic center was developed from 7-bromo-1-indanone. The catalytic performance of the ligand was demonstrated in palladium-catalyzed asymmetric allylic alkylation. Under opti

Full text of DOI:10.1039/c8ob02265h

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Synthesis of highly rigid phosphine–oxazoline
ligands for palladium-catalyzed asymmetric allylic
alkylation†
Cite this: Org. Biomol. Chem., 2018,
16, 7717
Zhongxuan Qiu, Rui Sun and Dawei Teng
*
A highly rigid spiro phosphine–oxazoline ligand skeleton with a spirocarbon stereogenic center was
developed from 7-bromo-1-indanone. The catalytic performance of the ligand was demonstrated in pal-
ladium-catalyzed asymmetric allylic alkylation. Under optimized conditions, high yields (up to 99%) and
enantioselectivities (up to 99.9% ee) were obtained for reactions of 1,3-diphenylallyl acetates and sym-
metrical 1,3-dicarbonyl substrates.
Received 13th September 2018,
Accepted 1st October 2018
DOI: 10.1039/c8ob02265h
rsc.li/obc
(JM-Phos), which was successfully used in Pd-catalyzed allylic
alkylation reactions5a,b and Ir-catalyzed hydrogenation of
Introduction
Asymmetric catalysis utilizing transition-metal complexes is a several unfunctionalized olefins.5c The R group in the JM-Phos
powerful tool to prepare enantiopure compounds and is one of skeleton could be formed from the derivatives of carboxylic
the most important frontiers in chemical science.1 One impor- acid, giving more scope for diversity. This skeleton is fairly
tant and challenging task in the development of asymmetric conformationally flexible with an ethylene linker.
catalysis is to design and synthesize novel and efficient chiral
Noticeably, the spiro backbone has been recognized as a
ligands.2 The chiral phosphine–oxazoline (PHOX) ligand 1 privileged structure and shown impressive catalytic perform-
(Fig. 1) invented by Pfaltz/Helmchen/Williams,3 coordinates to ance in many cases because the rigid scaffold of the ligands
the metal center with a P and N atom, has proven to be a could reduce the conformational obscurity of the catalyst and
superior ligand in asymmetric catalysis.4 For the PHOX skel- create an effective asymmetric environment around the central
eton 1, the R group which is at C-4 of oxazoline is restricted to metal.6 In this context, Zhou6h and Ding6i have developed
those found in readily available amino alcohols. Many new SIPHOX (3, Fig. 1) and SpinPHOX (4, Fig. 1) respectively, which
phosphine–oxazoline ligands have been developed to improve demonstrated excellent asymmetric induction in Ir-catalyzed
the asymmetric performance and applicability of the ligands. asymmetric hydrogenation reactions. Despite these elegant
Burgess developed the phosphine–oxazoline ligand
2
contributions, developing a novel and practical backbone of
PHOX is still a highly valuable but challenging task.
By taking advantage of the synthetic diversity, the rigid
spiro backbone, and the chelating units of the phosphine–oxa-
zoline skeleton, we report a new type of rigid spiro indanyl
phosphine–oxazoline ligand (L, Fig. 1) synthesized facilely
from commercially available 7-bromo-1-indanone. To our
knowledge, this is the first phosphine–oxazoline skeleton that
bears a spirocarbon stereogenic center. The catalytic perform-
ance of the ligand in palladium-catalyzed asymmetric allylic
alkylation reactions was investigated.
Fig. 1 Chiral phosphine–oxazoline ligands.
Results and discussion
The new chiral phosphine–oxazoline ligands L1–L4 were syn-
thesized from commercially available 7-bromo-1-indanone.
The synthetic scheme is outlined in Scheme 1. (S)-Amino acid
hydrochloride 7 was synthesized by adapting the literature
College of Chemical Engineering, Qingdao University of Science and Technology,
Qingdao 266042, China. E-mail: dteng@qust.edu.cn
†Electronic supplementary information (ESI) available: NMR and HPLC spectra.
See DOI: 10.1039/c8ob02265h
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Table 1 Solvent and additive screeninga
Entry
Solvent
Additive
Time (h)
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
Toluene
CH2Cl2
THF
KOAc
KOAc
KOAc
KOAc
NaOAc
CsOAc
K2CO3
Cs2CO3
3
12
3
3
24
3
99
82
97
94
90
99
84
92
98.0
92.6
91.2
92.8
97.8
94.8
97.8
96.0
MeCN
Toluene
Toluene
Toluene
Toluene
24
24
a Unless otherwise noted, the reactions were performed with 10a
(0.3 mmol), 11a (0.9 mmol), [Pd(C3H5)Cl]2 (1 mol%), L1 (2 mol%), BSA
(0.9 mmol) and the additive (10 mol%) in a certain solvent (2 mL) at
room temperature. b Isolated yield. c Determined by HPLC using a
chiral AD-H column. d The absolute configurations were assigned R via
comparison of specific rotations with the literature data.10
Scheme 1 Synthesis of spiro phosphine–oxazoline ligands.
methods.7 The addition of (R)-phenylglycinol to 7-bromo-1-
indanone afforded the ketimine intermediate which sub-
sequently reacted with trimethylsilyl carbonitrile to obtain tri-
methylsilylated aminonitrile 5. Compound 5 was directly sub-
jected to hydrolysis with sulfuric acid to give hydroxyamino-
amide 6. Compound 6 was treated with lead(IV) acetate and
then was hydrolyzed with 6 N hydrochloric acid to afford 7.
Reduction of amino acid hydrochloride 7 by the borane
dimethyl sulfide complex gave enantiopure (S)-aminoalcohol 8.
The key intermediate 9 was obtained according to the litera-
ture methods.8 Lithium-halogen exchange of 9 with n-BuLi fol-
giving the desired product 12a in high yields and enantio-
selectivities (94–99% yields and 95.2–98.8% ee) (Table 2,
entries 1–4), indicating the high efficiency of the new spiro
phosphine–oxazoline ligands. Among them, ligand L2 pro-
vided superior results to others and was chosen for further
optimization. Subsequent optimization with respect to tem-
perature indicated that the reaction afforded low enantio-
selectivity at 40 °C and low reactivity at −10 °C. The best result
was given at 0 °C (Table 2, entries 7). A decrease of the catalyst
loading to 0.5 mol% led to a drop in yield even after extending
the reaction time to 24 h, without compromising on the
enantioselectivity (78% yield and 98.2% ee) (Table 2, entry 8).
lowed by the reaction with R2 PCl afforded the desired ligands
2
L1–L4.
The asymmetric allylic alkylation, which is one of the most
versatile methods for asymmetric C–C bond-forming reac-
tions,9 was employed to evaluate the catalytic performance of
the new chiral spiro phosphine–oxazoline ligands. The model
reaction between 1,3-diphenyl-2-propenyl acetate (10a) and
dimethyl malonate (11a) was initially performed in the pres-
ence of [Pd(C3H5)Cl]2 (1 mol%), L1 (2 mol%), N,O-bis(tri-
methylsilyl)acetamide (BSA, 3 equiv.) and a catalytic amount of
KOAc as the additive in toluene. Excellent enantioselectivity
and yield were achieved (98.0% ee and 99% yield) (Table 1,
entry 1).
Evaluation of solvents showed that dichloromethane, tetra-
hydrofuran and acetonitrile all gave good results with high
yields and enantioselectivities (Table 1, entries 2–4). Toluene
was the best solvent among them (entry 1). Different additives,
including NaOAc, CsOAc, K2CO3 and Cs2CO3 were tested
instead of KOAc to give lower reactivity or enantioselectivity
(Table 1, entries 5–8). Herein, KOAc was found to be the best
additive; up to 99% yield and 98.0% ee was obtained for the
allylic substitution reaction (Table 1, entry 1).
Table 2 Ligand and temperature screeninga
Entry
Ligand
T (°C)
Time (h)
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8e
L1
L2
L3
L4
L2
L2
L2
L2
25
25
25
25
40
0
3
3
12
3
1
5
99
99
94
99
99
99
85
78
98.0
98.8
95.2
97.4
96.4
99.4
99.1
98.2
−10
0
24
24
a Unless otherwise noted, the reactions were performed with 10a
(0.3 mmol), 11a (0.9 mmol), [Pd(C3H5)Cl]2 (1 mol%), ligand (2 mol%),
BSA (0.9 mmol) and KOAc (10 mol%) in toluene (2 mL) at a certain
temperature. b Isolated yield. c Determined by HPLC using a chiral
AD-H column. d The absolute configurations were assigned R via com-
parison of specific rotations with the literature data.10 e With [Pd(C3H5)Cl]2
(0.5 mol%) and L2 (1 mol%) for 24 h.
Having these results in hand, the other ligands (L2–L4)
with different R1 and R2 groups were investigated. To our
delight, all the ligands proved to be suitable for the reaction,
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Under the optimized conditions, the substrate scope of the
reaction was examined using the palladium-L2 catalyst
(Table 3). As shown in Table 3, a wide range of allylic acetates
10 and activated methylene carbonyl compounds 11 were used
for the Pd-catalyzed allylic alkylation. For symmetrical 1,3-
dicarbonyl substrates 11a–g, the desired products were
obtained in 98.0–99.9% ee (Table 3, 12a–12g). Notably, the use
of methyl, acetylamino, allyl, and phenyl-substituted dialkyl
malonates 11d–g as substrates in this reaction also resulted in
the same level of enantioselectivity. Besides, we found that the
reaction exhibited high tolerance of the 1,3-diphenylallyl
acetate components employing the new ligand. The substrates
bearing either electron-donating or electron-withdrawing sub-
stituents on the aromatic ring underwent the reaction
smoothly to give the corresponding products in good yield
with excellent ee values (98.2–99.4%) (Table 3, 12j–12o).
Table 3 Substrate scopea
Scheme 2 A plausible reaction mechanism.
Therefore, the ligand L2 exhibits superior catalytic perform-
ance for the allylic alkylation reaction of 1,3-diphenylallyl acet-
ates and symmetric 1,3-dicarbonyl substrates. Unfortunately,
for unsymmetrical dicarbonyl compounds 11h–i, the diastereo-
selectivity was not good (Table 3, 12h–12i). The allylic alkyl-
ation of unsymmetrical dicarbonyl compounds was still a chal-
lenging task.
The stereochemical course of the reaction can be rational-
ized by means of the model proposed in Scheme 2. It has been
reported that the most abundant isomer in the case of 1,3-
diphenyl substituted allyl systems corresponds to the exo-syn–
syn (A, W-type), followed by the endo-syn–syn one (B, M-type)
and the two isomers rapidly equilibrate.11 For the asymmetric
alkylation, it is known that, because the trans effect directs the
nucleophilic attack on the allylic terminus trans to the phos-
phorus atom,12 A is converted into Pd-olefin complex C that is
less sterically congested compared to complex D. As similar
steric interactions are already present in the transition states,
the reaction leading to C is faster than the nucleophilic
addition leading to D. The R configuration of the final product
12a for the 1,3-diphenyl-substituted starting material 11a
would be in agreement with this assumption.
Conclusions
In conclusion, we have designed and synthesized a new type of
rigid chiral phosphine–oxazoline ligand with a spirocarbon
stereogenic center. Notable features of the ligand are the rigid
and unique spiro core structure. The ligand exhibited excellent
catalytic performance in Pd-catalyzed asymmetric allylic alkyl-
ation reactions. High yields (up to 99%) and enantioselectivi-
a Unless otherwise noted, the reactions were performed with 10
(0.3 mmol), 11 (0.9 mmol), [Pd(C3H5)Cl]2 (1 mol%), L2 (2 mol%), BSA
(0.9 mmol) and KOAc (10 mol%) in toluene (2 mL) at 0 °C for 5 h.
b The dr was 51 : 49 as determined using chiral HPLC and 1H NMR.
c The dr was 70 : 30 as determined using chiral HPLC and 1H NMR.
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ties (up to 99.9% ee) were obtained for the reactions of 1,3- CDCl3): δ = 7.10–7.04 (m, 5H), 6.98 (s, 1H), 6.95–6.92 (m, 3H),
diphenylallyl acetates and symmetrical 1,3-dicarbonyl sub- 5.73 (s, 1H), 3.83 (s, 1H), 3.58–3.49 (m, 2H), 3.16 (s, 1H), 2.99
strates. Further application of these ligands in other asym- (t, J = 8.0 Hz, 2H), 2.94 (s, 1H), 2.57–2.50 (m, 1H), 2.38–2.33
metric transformations is currently under development.
(m, 1H); 13C NMR (125 MHz, CDCl3): δ = 178.2, 147.1, 142.7,
141.2, 131.0, 130.0, 128.2, 127.2, 126.4, 124.0, 119.9, 75.3, 67.5,
60.2, 36.7, 31.6. HRMS (ESI): calcd for C18H20N2O2Br [M + H]+:
375.0703, found 375.0705.
Synthesis of (S)-1-amino-7-bromo-indan-1-carboxylic acid
hydrochloride (7). A solution of hydroxyaminoamide 6 (3.7 g,
Experimental
General information
Unless stated otherwise, all reactions were performed under an 10 mmol) in dry CH2Cl2 (24 mL) and dry MeOH (12 mL) was
argon atmosphere using freshly distilled solvents, and the cooled to 0 °C under argon. Lead(IV) acetate (5.3 g, 12 mmol)
workups were carried out in air. Toluene, DCM, CH3CN and was added. The solution was stirred at 0 °C for 1 h and
THF were distilled over dehydrating reagents. Commercially quenched by the addition of phosphate buffer (0.2 M, pH 7,
available reagents were used without further purification. The 100 mL). After stirring at room temperature for 15 min, the
melting points were recorded on a RY-1 microscopic melting solution was diluted with CH2Cl2 (100 mL) and filtered
1
apparatus and uncorrected. H, 13C and 31P NMR spectra were through Celite. The organic layer was separated and the
recorded on a Bruker Avance 500 spectrometer. Chemical aqueous layer was extracted with CH2Cl2 (2 × 100 mL). The
shifts were reported in parts per million (δ) relative to tetra- combined organic layers were dried over magnesium sulfate,
methylsilane (TMS). HRMS measurements were performed on filtered and concentrated. The remaining yellowish oil was
an Ultima Global spectrometer or Thermo UltiMate 3000-Q taken up in HCl (6 N, 100 mL) and heated to reflux for 5 h.
Exactive Focus with an ESI source. High-performance liquid After cooling to room temperature, the solution was extracted
chromatography (HPLC) was performed with a Shimadzu with CH2Cl2 (3 × 100 mL) and concentrated to leave amino
LC-20 Liquid Chromatograph using Chiralcel OD-H, AD-H and acid hydrochloride 7 as a slightly yellowish solid (2.9 g, 99%
IC columns.
yield) without further purification for the next step.
Synthesis
of
(1S,1′R)-7-bromo-1-(1-phenyl-2-trimethyl-
Synthesis of (S)-(1-amino-7-bromo-indan-1-yl)-methanol (8).
silanyloxy-ethylamino)-indan-1-carbonitrile (5). To a stirred To a suspension of amino acid hydrochloride 7 (1.5 g,
solution of 7-bromo-1-indanone (12.6 g, 60 mmol) in toluene 5 mmol) in dry THF (10 mL) was added BH3-DMS-THF (2 M,
(240 mL) was added (R)-2-phenylglycinol (9.1 g, 66 mmol) and 7.5 mL) at room temperature via a syringe. The reaction
p-toluenesulfonic acid (51.6 mg, 0.3 mmol). The resulting mixture was then stirred under reflux for 8 h, then cooled to
mixture was heated to reflux with the azeotropic removal of 0 °C and quenched with NaOH (10%, 25 mL) and refluxed for
water until the starting material disappeared (monitored by 2 h. The solvent was evaporated, and the remaining aqueous
TLC). After the removal of the solvent at reduced pressure, the layers were extracted with CH2Cl2 (3 × 50 mL). The combined
residual oil was dissolved in 100 mL of dry CH2Cl2. The result- organic layers were washed with saturated aqueous solution of
ing solution was cooled to 0 °C, and to it was added trimethyl- NH4Cl, then brine and dried over MgSO4. The solvent was
siyl cyanide (11.9 g, 120 mmol) dropwise. The reaction mixture removed under reduced pressure and the residue was purified
was allowed to stir at 0 °C for 2 h and the solution was evapor- by flash chromatography on SiO2 (CH2Cl2/MeOH = 20/1) to
ated in vacuo to give aminonitrile 5 as an oil, which was dried give a white solid powder amino alcohol 8 (0.9 g), yield: 74%.
in vacuo and used for the next procedure without further m.p.: 123–125 °C, [α]2D5 = −4.62 (c = 0.25, CHCl3); 1H NMR
purification.
(500 MHz, CDCl3): δ = 7.34 (d, J = 7.8 Hz, 1H), 7.18 (d, J =
Synthesis of (1S,1′R)-7-bromo-1-(2-hydroxy-1-phenyl-ethyl- 7.3 Hz, 1H), 7.09 (t, J = 7.7 Hz, 1H), 3.79 (d, J = 10.7 Hz, 1H),
amino)-indan-1-carboxylic acid amide (6). Compound 5 was 3.48 (d, J = 10.7 Hz, 1H), 2.89–2.83 (m, 2H), 2.68–2.64 (m, 1H),
dissolved in n-hexane (100 mL) and cooled to −10 °C. Ice-cold 2.30 (s, 3H), 1.76 (dd, J = 22.0, 10.0 Hz, 1H); 13C NMR
conc. H2SO4 (100 mL) was slowly added to this reaction. The (125 MHz, CDCl3): δ = 147.1, 143.8, 131.5, 129.6, 124.5, 119.0,
resulting two-phase mixture was allowed to warm gradually to 68.5, 65.2, 37.3, 29.0. HRMS (ESI): calcd for C10H13NOBr
room temperature, and was stirred for 3 days. The n-hexane [M + H]+: 242.0175, found 242.0176.
layer was decanted, and the acidic layer was poured onto ice
Synthesis of (S)-7-bromo-2′-(tert-butyl)-2,3-dihydro-5′H-spiro
(100 g). This was then cooled in an ice bath, covered with ethyl [indene-1,4′-oxazole] (9a). To a mixture of amino alcohol 8
acetate (150 mL) and basified with NH3·H2O to pH 9–10. The (533 mg, 2.2 mmol) and triethylamine (1.2 mL, 8.8 mmol) in
organic phase was separated and the aqueous phase was dry CH2Cl2 (10 mL) was added a solution of pivaloyl chloride
extracted with ethyl acetate (3 × 100 mL). The combined (0.3 mL, 2.3 mmol) in dry CH2Cl2 (5 mL) at 0 °C. The reaction
organic layers were dried (MgSO4), filtered and evaporated mixture was stirred for 4 h at room temperature and then
in vacuo to give crude hydroxyaminoamide 6. The residue was cooled to 0 °C, followed by the addition of DIPEA (diisopropyl-
purified by flash silica gel column chromatography (petroleum ethylamine) (1.5 mL, 8.8 mmol), triethylamine (1.8 mL,
ether/ethyl acetate = 1/1) to give a white solid powder hydroxy- 13.2 mmol) and methanesulfonyl chloride (0.4 mL, 4.4 mmol).
aminoamide
6 (13.6 g), yield: 61% (two steps), m.p.: The resulting mixture was allowed to warm to room tempera-
1
175–177 °C, [α]2D5 = 12.98 (c = 0.5, CHCl3); H NMR (500 MHz, ture and stirred overnight. Compound 9a was isolated by
7720 | Org. Biomol. Chem., 2018, 16, 7717–7724
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column flash chromatography (petroleum ether/ethyl acetate = δ = −21.71. HRMS (ESI): calcd for C27H29NOP [M + H]+:
30/1) as a yellow oil (583 mg) after the removal of the solvent, 414.1981, found 414.1988.
the excessive diisopropylethylamine and triethylamine under
Synthesis of (S)-7-(diphenylphosphino)-2′-isopropyl-2,3-
reduced pressure. Yield: 86%. [α]2D5 = −13.7 (c = 0.2, CHCl3); dihydro-5′H-spiro[indene-1,4′-oxazole] (L2). Ligand L2 was pro-
1H NMR (500 MHz, CDCl3): δ = 7.35 (d, J = 7.9 Hz, 1H), 7.15 (d, duced from 9b by the same method used for L1 as a white
J = 7.4 Hz, 1H), 7.06 (t, J = 7.6 Hz, 1H), 4.57 (d, J = 8.6 Hz, 1H), solid (78%), m.p.: 85–86 °C, [α]2D5 = −40.5 (c = 0.3, CHCl3); H
1
4.19 (d, J = 8.7 Hz, 1H), 3.09–3.04 (m, 1H), 2.93–2.87 (m, 1H), NMR (500 MHz, CDCl3): δ = 7.30–7.18 (m, 11H), 7.15 (t, J =
2.43–2.37 (m, 1H), 2.18–2.13 (m, 1H), 1.29 (s, 3H); 13C NMR 7.5 Hz, 1H), 6.87 (t, J = 5.0 Hz, 1H), 4.75 (dd, J = 8.5, 3.0 Hz,
(125 MHz, CDCl3): δ = 173.7, 146.8, 142.6, 131.8, 129.8, 124.0, 1H), 4.34–4.26 (m, 1H), 3.10–3.04 (m, 1H), 2.96–2.90 (m, 1H),
120.4, 81.8, 76.7, 41.4, 33.2, 30.0, 27.8. HRMS (ESI): calcd for 2.47–2.36 (m, 2H), 2.17–2.12 (m, 1H), 1.11 (d, J = 7.0 Hz, 3H),
C15H19NOBr [M + H]+: 308.0645, found 308.0649.
1.01 (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ = 171.5,
Synthesis of (S)-7-bromo-2′-isopropyl-2,3-dihydro-5′H-spiro 150.5, 150.3, 144.2, 138.3, 138.2, 137.6, 137.5, 134.4, 134.0,
[indene-1,4′-oxazole] (9b). Compound 9b was produced from 8 133.8, 133.5, 133.3, 133.1, 128.4, 128.0, 125.6, 81.7, 78.8, 41.7,
and isobutyryl chloride by the same method used for 9a as a 29.9, 28.3, 19.2. 31P NMR (202 MHz, CDCl3): δ = −21.05. HRMS
yellow oil. Yield: 83%. [α]D25 = −9.6 (c = 0.3, CHCl3); 1H NMR (ESI): calcd for C26H27NOP [M
(500 MHz, CDCl3): δ = 7.35 (d, J = 7.8 Hz, 1H), 7.15 (d, J = 400.1830.
+
H]+: 400.1825, found
7.4 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 4.65 (d, J = 8.8 Hz, 1H),
Synthesis of (S)-7-(diphenylphosphino)-2′-phenyl-2,3-dihydro-
4.16 (d, J = 8.8 Hz, 1H),3.12–3.05 (m, 1H), 2.94–2.87 (m, 1H), 5′H-spiro[indene-1,4′-oxazole] (L3). Ligand L3 was produced
2.68–2.63 (m, 1H), 2.44–2.39 (m, 1H), 2.18–2.12 (m, 1H), 1.26 from 9c by the same method used for L1 as a white solid
1
(d, J = 7.0 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ = 171.8, (81%), m.p.: 125–127 °C, [α]D25 = 45.7 (c = 0.2, CHCl3); H NMR
146.8, 142.5, 131.8, 129.8, 124.0, 120.3, 81.7, 76.3, 41.4, 30.0, (500 MHz, CDCl3): δ = 7.61 (s, 2H), 7.42 (s, 1H), 7.33–7.12
28.3, 19.7. HRMS (ESI): calcd for C14H17NOBr [M + H]+: (m, 12H), 7.03 (t, J = 7.7 Hz, 2H), 6.85 (dd, J = 7.3, 4.8 Hz, 1H),
294.0488, found 294.0492.
4.97 (s, 1H), 4.53 (s, 1H), 3.09 (s, 1H), 3.02–2.95 (m, 1H), 2.49
Synthesis of (S)-7-bromo-2′-phenyl-2,3-dihydro-5′H-spiro (s, 1H), 2.25 (s, 1H); 13C NMR (125 MHz, CDCl3): δ = 164.0,
[indene-1,4′-oxazole] (9c). Compound 9c was produced from 8 150.3, 150.1, 144.1, 138.2, 138.1, 136.7, 134.2, 134.0, 133.8,
and benzoyl chloride by the same method used for 9a as a 133.6, 131.0, 128.6, 128.3, 128.1, 128.1, 128.0, 125.6, 82.3,
colorless oil. Yield: 77%. [α]2D5 = −13.3 (c = 0.5, CHCl3); 1H 78.8, 41.6, 30.0. 31P NMR (202 MHz, CDCl3): δ = −20.33.
NMR (500 MHz, CDCl3): δ = 8.02 (d, J = 7.5 Hz, 2H), 7.50 (t, J = HRMS (ESI): calcd for C29H25NOP [M + H]+: 436.1668, found
7.5 Hz, 1H), 7.43 (t, J = 7.5 Hz, 2H), 7.39 (d, J = 7.8 Hz, 1H), 434.1674.
7.21 (d, J = 7.5 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 4.83 (d, J =
8.7 Hz, 1H), 4.41 (d, J = 8.8 Hz, 1H), 3.19–3.13 (m, 1H), 2′-(tert-butyl)-2,3-dihydro-5′H-spiro[indene-1,4′-oxazole]
Synthesis of (S)-7-(bis(4-(trifluoromethyl)phenyl)phosphino)-
(L4).
3.01–2.95 (m, 1H), 2.61–2.55 (m, 1H), 2.31–2.26 (m, 1H); 13C Ligand L4 was produced from 9a and (4-CF3Ph)2PCl by the
NMR (125 MHz, CDCl3): δ = 164.1, 146.8, 142.6, 131.9, 131.5, same method used for L1 as a white solid (77%), m.p.:
130.0, 128.6, 128.4, 127.9, 124.0, 120.4, 82.3, 41.4, 30.1. HRMS 101–103 °C, [α]2D5 = 9.4 (c = 0.2, CHCl3); 1H NMR (500 MHz,
(ESI): calcd for C17H15NOBr [M + H]+: 328.0332, found 328.0335. CDCl3): δ = 7.56 (d, J = 7.8 Hz, 4H), 7.35–7.26 (m, 5H), 7.18 (t,
Synthesis of (S)-2′-(tert-butyl)-7-(diphenylphosphino)-2,3- J = 7.6 Hz, 1H), 6.78 (t, J = 6.1 Hz, 1H), 4.61 (d, J = 8.3 Hz, 1H),
dihydro-5′H-spiro[indene-1,4′-oxazole] (L1). To a solution of 9a 4.38 (d, J = 8.4 Hz, 1H), 3.08–3.03 (m, 1H), 2.98–2.91 (m, 1H),
(524 mg, 1.7 mmol) in dry THF (4 mL) n-BuLi (2.6 mmol, 2.5 2.38–2.32 (m, 1H), 2.18–2.14 (m, 1H); 13C NMR (125 MHz,
M in hexane) was added dropwise at −78 °C. After stirring at CDCl3): δ = 174.0, 150.8, 144.7, 142.7, 142.0, 134.4, 134.1,
the temperature for 1 h, Ph2PCl (751 mg, 3.4 mmol) was added 133.9, 133.4, 133.2, 131.3, 131.1, 130.9, 130.7, 130.5, 130.2,
dropwise at −78 °C. The mixture was stirred at −78 °C for 1 h 129.0, 126.5, 125.2, 123.0, 81.8, 79.2, 41.4, 33.1, 29.6, 27.3. 31P
and room temperature for 1 h. The reaction was terminated NMR (202 MHz, CDCl3): δ = −52.61. HRMS (ESI): calcd for
with a minimal amount of saturated NaHCO3 (aq.) and C29H27NOPF6 [M + H]+: 550.1729, found 550.1735.
extracted with CH2Cl2 (3 × 10 mL). The combined organic
General procedure for the Pd-catalyzed asymmetric allylic
alkylation
layers were washed with saturated aqueous solution of NH4Cl,
then brine and dried over MgSO4. The solvent was removed
under reduced pressure and the residue was purified by flash Ligand L2 (2.4 mg, 2 mol%) and [Pd(C3H5)Cl]2 (1.1 mg,
chromatography on SiO2 (petroleum ether/ethyl acetate = 40/1) 1 mol%) were dissolved in toluene (1.0 mL) in a Schlenk tube
to give a white solid L1 (545 mg), yield: 74%, m.p.: 71–73 °C, under an Ar atmosphere. After 1 h of stirring at room tempera-
1
[α]2D5 = −38.7 (c = 0.2, CHCl3); H NMR (500 MHz, CDCl3): δ = ture, allylic acetate 10 (0.3 mmol) dissolved in toluene (0.5 mL)
7.30–7.25 (m, 8H), 7.21–7.13 (m, 4H), 6.86 (t, J = 5.3 Hz, 1H), was added, followed by malonate 11 (0.9 mmol), N,O-bis(tri-
4.68 (s, 1H), 4.32 (s, 1H), 3.05 (s, 1H), 2.95–2.89 (m, 1H), 2.36 methylsilyl)acetamide (183 mg, 0.9 mmol), and KOAc (2.9 mg,
(s, 1H), 2.14 (d, J = 8.7 Hz, 1H), 1.12 (s, 9H); 13C NMR 10 mol%). The mixture was stirred at 0 °C for 5 h and then was
(125 MHz, CDCl3): δ = 173.6, 150.5, 144.3, 138.5, 137.7, 134.6, diluted with CH2Cl2 and washed with saturated NH4Cl (aq).
134.0, 133.9, 133.6, 133.3, 133.1, 128.4, 128.3, 127.9, 125.6, The organic layers were dried over MgSO4 and filtered, and the
81.9, 79.0, 41.5, 33.1, 29.8, 27.4. 31P NMR (202 MHz, CDCl3): solvents were evaporated in vacuo. The residue was purified by
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flash column chromatography, eluting with petroleum ether (m, 10H), 6.76 (dd, J = 15.9, 7.3 Hz, 1H), 6.58 (s, 1H), 6.30 (d,
and ethyl acetate to afford the corresponding product 12.
J = 15.9 Hz, 1H), 4.77 (d, J = 7.0 Hz, 1H), 4.32–4.24 (m, 2H),
4.17–4.10 (m, 1H), 4.07–4.00 (m, 1H), 1.96 (s, 3H), 1.25 (t, J =
7.1 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz,
Characterization of the compounds
(R,E)-Dimethyl 2-(1,3-diphenylallyl)malonate (12a). Colorless CDCl3): δ = 169.0, 167.5, 167.1, 138.4, 137.6, 132.4, 129.5,
oil. 99% yield and 99.4% ee, determined by chiral HPLC ana- 128.8, 128.4, 128.4, 127.6, 127.2, 126.4, 69.0, 62.7, 62.5, 53.1,
lysis (Chiralcel AD-H hexane/isopropanol, 90 : 10 v/v, 1.0 23.2, 14.1, 13.9.
mL min−1, 25 °C, UV 254 nm), retention times: tr = 12.358 min
(S,E)-Diethyl
2-allyl-2-(1,3-diphenylallyl)malonate
(12f).
for (R)-isomer (major), tr = 17.861 min for (S)-isomer (minor). Colorless oil. 94% yield and 98.7% ee, determined by chiral
1H NMR (500 MHz, CDCl3): δ = 7.32–7.25 (m, 8H), 7.23–7.18 HPLC analysis (Chiralcel AD-H hexane/isopropanol, 90 : 10 v/v,
(m, 2H), 6.47 (d, J = 15.8 Hz, 1H), 6.32 (dd, J = 15.8, 8.7 Hz, 0.5 mL min−1, 25 °C, UV 254 nm), retention times: tr
=
1H), 4.25 (dd, J = 10.7, 8.7 Hz, 1H), 3.94 (d, J = 10.9 Hz, 1H), 12.186 min for (S)-isomer (major), tr = 11.248 min for (R)-
1
3.69 (s, 3H), 3.51 (s, 3H); 13C NMR (125 MHz, CDCl3) δ = 168.3, isomer (minor). H NMR (500 MHz, CDCl3): δ = 7.32–7.30 (m,
167.9, 140.3, 136.9, 132.0, 129.2, 128.9, 128.6, 128.0, 127.7, 2H), 7.28–7.24 (m, 4H), 7.23–7.19 (m, 2H), 7.19–7.16 (m, 2H),
127.3, 126.5, 57.8, 52.8, 52.6, 49.3.
6.71 (dd, J = 15.7, 8.8 Hz, 1H), 6.35 (d, J = 15.7 Hz, 1H),
(R,E)-Diethyl 2-(1,3-diphenylallyl)malonate (12b). Colorless 5.77–5.71 (m, 1H), 5.04–4.99 (m, 2H), 4.15 (d, J = 8.8 Hz, 1H),
oil. 96% yield and 99.0% ee, determined by chiral HPLC ana- 3.72 (s, 3H), 3.62 (s, 3H), 2.61 (dd, J = 14.0, 6.5 Hz, 1H), 2.44
lysis (Chiralcel AD-H hexane/isopropanol, 95 : 5 v/v, 0.7 (dd, J = 14.5, 8.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ =
mL min−1, 25 °C, UV 254 nm), retention times: tr = 23.817 min 170.6, 170.5, 169.3, 139.1, 137.3, 133.9, 133.2, 132.2, 129.3,
for (R)-isomer (major), tr = 33.722 min for (S)-isomer (minor). 129.2, 128.4, 127.3, 126.3, 63.2, 53.7, 52.5, 52.1, 39.4.
1H NMR (500 MHz, CDCl3): δ = 7.26–7.24 (m, 6H), 7.23–7.20
(m, 2H), 7.19–7.15 (m, 2H), 6.43 (d, J = 16.0 Hz, 1H), 6.29 (dd, Colorless oil. 91% yield and 98.0% ee, determined by chiral
J = 16.0, 9.0 Hz, 1H), 4.21 (dd, J = 11.0, 9.0 Hz, 1H), 4.12 (q, J = HPLC analysis (Chiralcel AD-H hexane/isopropanol,
(S,E)-Diethyl 2-(1,3-diphenylallyl)-2-phenylmalonate (12g).
7.0 Hz, 2H), 3.95–3.90 (m, 2H), 3.87 (d, J = 11.0 Hz, 1H), 1.16 99.2 : 0.8 v/v, 0.5 mL min−1, 25 °C, UV 254 nm), retention
(t, J = 7.0 Hz, 3H), 0.96 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, times: tr = 37.084 min for (S)-isomer (major), tr = 39.304 min
CDCl3): δ = 167.9, 167.5, 140.4, 136.9, 131.7, 129.4, 128.7, for (R)-isomer (minor). 1H NMR (500 MHz, CDCl3): δ =
128.5, 128.1, 127.6, 127.1, 126.4, 61.6, 61.4, 57.8, 49.3, 14.2, 7.30–7.25 (m, 9H), 7.19–7.13 (m, 4H), 7.00–6.98 (m, 2H),
13.9.
6.50–6.40 (m, 2H), 4.64 (d, J = 8.8 Hz, 1H), 4.23–4.14 (m, 4H),
(R,E)-3-(1,3-Diphenylallyl)pentane-2,4-dione (12c). Colorless 1.20 (dt, J = 11.9, 7.2 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ =
oil. 96% yield and 98.6% ee, determined by chiral HPLC ana- 169.7, 169.6, 139.4, 137.4, 135.4, 132.5, 130.1, 129.5, 129.0,
lysis (Chiralcel AD-H hexane/isopropanol, 95 : 5 v/v, 0.7 mL 128.4, 127.5, 127.4, 127.2, 126.8, 126.3, 68.0, 61.5, 61.5, 55.2,
min−1, 25 °C, UV 254 nm), retention times: tr = 17.200 min for 53.4, 13.9.
(R)-isomer (major), tr = 18.908 min for (S)-isomer (minor). H
1
(E)-Ethyl 2-acetyl-3,5-diphenylpent-4-enoate (12h). Colorless
NMR (500 MHz, CDCl3): δ = 7.32–7.29 (m, 2H), 7.28–7.23 (m, oil. 87% yield, 51 : 49 dr and 97.0%/98.3% ee, determined by
6H), 7.21–7.17 (m, 2H), 6.41 (d, J = 15.8 Hz, 1H), 6.20–6.16 (m, chiral HPLC analysis (Chiralcel IC hexane/isopropanol, 98 : 2
1H), 4.35–4.32 (m, 2H), 2.24 (s, 3H), 1.91 (s, 3H); 13C NMR v/v, 0.5 mL min−1, 25 °C, UV 254 nm), diastereomer A: tr =
(125 MHz, CDCl3): δ = 202.9, 202.8, 140.2, 136.6, 131.7, 129.3, 22.813 min (major), tr = 26.087 min (minor); diastereomer B:
129.1, 128.6, 128.0, 127.8, 127.3, 126.4, 74.6, 49.2, 30.1, 29.8.
tr = 28.469 min (major), tr = 33.538 min (minor). 1H NMR
(S,E)-Diethyl 2-(1,3-diphenylallyl)-2-methylmalonate (12d). (500 MHz, CDCl3): δ = 7.33–7.25 (m, 16H), 7.24–7.18 (m, 4H),
Colorless oil. 93% yield and 98.2% ee, determined by chiral 6.44 (dd, J = 18.4, 15.9 Hz, 2H), 6.32–6.22 (m, 2H), 4.31–4.27
HPLC analysis (Chiralcel AD-H hexane/isopropanol, 95 : 5 v/v, (m, 2H), 4.16 (q, J = 7.0 Hz, 2H), 4.10 (t, J = 11.7 Hz, 2H), 3.94
0.5 mL min−1, 25 °C, UV 254 nm), retention times: tr
=
(q, J = 7.5 Hz, 2H), 2.30 (s, 3H), 2.04 (s, 3H), 1.21 (t, J = 7.2 Hz,
14.188 min for (S)-isomer (major), tr = 13.461 min for (R)- 3H), 0.98 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ =
1
isomer (minor). H NMR (500 MHz, CDCl3): δ = 7.35–7.32 (m, 201.7, 201.5, 167.9, 167.5, 140.3, 140.1, 136.8, 136.6, 131.8,
4H), 7.30–7.26 (m, 4H), 7.24–7.16 (m, 2H), 6.70 (dd, J = 15.7, 131.5, 129.5, 129.2, 128.9, 128.6, 128.5, 128.0, 127.9, 127.6,
9.0 Hz, 1H), 6.44 (d, J = 15.7 Hz, 1H), 4.30 (d, J = 8.9 Hz, 1H), 127.5, 127.1, 127.1, 126.3, 65.5, 65.2, 61.6, 61.4, 48.9, 48.7,
4.20–4.15 (m, 2H), 4.08 (q, J = 7.1 Hz, 2H), 1.48 (s, 3H), 1.23 (t, 29.8, 14.1, 13.7.
J = 7.1 Hz, 3H), 1.17 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz,
(E)-Ethyl
CDCl3): δ = 171.2, 170.9, 139.4, 137.3, 132.5, 129.6, 128.8, Colorless oil. 91% yield, 70 : 30 dr and 98.9%/98.8% ee, deter-
128.4, 128.2, 127.3, 127.1, 126.3, 61.3, 58.8, 53.7, 18.8, 14.0. mined by chiral HPLC analysis (Chiralcel AD-H hexane/isopro-
2-benzoyl-3,5-diphenylpent-4-enoate
(12i).
(S,E)-Diethyl 2-acetoamido-2-(1,3-diphenyl-2-propenyl)malo- panol, 98 : 2 v/v, 1.0 mL min−1, 25 °C, UV 254 nm), diastereo-
nate (12e). White powder. 98% yield and 99.9% ee, deter- mer A: tr = 34.726 min (major), tr = 40.447 min (minor); dia-
mined by chiral HPLC analysis (Chiralcel AD-H hexane/isopro- stereomer B: tr = 57.602 min (major), tr = 45.259 min (minor).
panol, 90 : 10 v/v, 1.5 mL min−1, 25 °C, UV 254 nm), retention 1H NMR (500 MHz, CDCl3): δ = 8.09 (d, J = 7.4 Hz, 2H), 7.93 (d,
times: tr = 11.555 min for (S)-isomer (major), tr = 8.282 min for J = 7.5 Hz, 4H), 7.59 (t, J = 7.5 Hz, 1H), 7.54 (t, J = 7.5 Hz, 2H),
1
(R)-isomer (minor). H NMR (500 MHz, CDCl3): δ = 7.31–7.15 7.49 (t, J = 7.5 Hz, 2H), 7.43–7.38 (m, 6H), 7.36–7.33 (m, 6H),
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7.31–7.29 (m, 8H), 7.24–7.20 (m, 8H), 7.18–7.11 (m, 6H), 6.53 HPLC analysis (Chiralcel AD-H hexane/isopropanol, 95 : 5 v/v,
(d, J = 15.5 Hz, 2H), 6.43–6.35 (m, 3H), 6.26–6.20 (m, 1H), 0.5 mL min−1, 25 °C, UV 254 nm), retention times: tr
=
5.03–4.98 (m, 3H), 4.63–4.55 (m, 3H), 4.16–4.08 (m, 4H), 27.531 min for (R)-isomer (major), tr = 40.658 min for (S)-
3.92–3.86 (m, 2H), 1.15 (t, J = 7.1 Hz, 6H), 0.92 (t, J = 7.1 Hz, isomer (minor). 1H NMR (500 MHz, CDCl3): δ = 7.46 (s, 1H),
3H); 13C NMR (125 MHz, CDCl3): δ = 193.2, 192.7, 168.1, 167.6, 7.42 (s, 1H), 7.38–7.33 (m, 2H), 7.22–7.13 (m, 4H), 6.40 (d, J =
140.9, 140.4, 137.0, 136.6, 133.7, 133.5, 131.8, 131.7, 129.9, 15.8 Hz, 1H), 6.27 (dd, J = 15.7, 8.6 Hz, 1H), 4.21 (t, J = 9.6 Hz,
129.8, 128.8, 128.7, 128.5, 128.4, 128.0, 127.5, 127.4, 127.2, 1H), 3.90 (d, J = 10.8 Hz, 1H), 3.71 (s, 3H), 3.56 (s, 3H); 13C
126.9, 126.4, 64.5, 61.8, 61.5, 59.9, 59.7, 49.0, 25.4, 14.2, 13.8.
NMR (125 MHz, CDCl3): δ = 167.8, 167.4, 142.2, 138.6, 131.0,
(R,E)-Dimethyl 2-(1,3-bis(4-fluorophenyl)allyl)malonate (12j). 130.9, 130.6, 130.4, 130.3, 130.0, 129.8, 129.1, 126.5, 125.1,
Colorless oil. 97% yield and 99.3% ee, determined by chiral 122.7, 57.2, 53.4, 52.7, 52.6, 48.6.
HPLC analysis (Chiralcel AD-H hexane/isopropanol, 80 : 20 v/v,
1.0 mL min−1, 25 °C, UV 254 nm), retention times: tr
9.629 min for (R)-isomer (major), tr = 14.870 min for (S)-isomer HPLC analysis (Chiralcel OD-H hexane/isopropanol, 95 : 5 v/v,
(minor). 1H NMR (500 MHz, CDCl3): δ = 7.29–7.24 (m, 4H), 0.8 mL min−1, 25 °C, UV 254 nm), retention times: tr
(R,E)-Dimethyl
2-(1,3-di-o-tolylallyl)malonate
(12o).
=
Colorless oil. 90% yield and 98.4% ee, determined by chiral
=
7.02 (t, J = 8.6 Hz, 2H), 6.97 (t, J = 8.6 Hz, 2H), 6.41 (d, J = 6.428 min for (R)-isomer (major), tr = 7.087 min for (S)-isomer
15.8 Hz, 1H), 6.22 (dd, J = 15.7, 8.6 Hz, 1H), 4.24 (t, J = 9.7 Hz, (minor). 1H NMR (500 MHz, CDCl3): δ = 7.30 (d, J = 7.1 Hz,
1H), 3.89 (d, J = 10.8 Hz, 1H), 3.71 (s, 3H), 3.54 (s, 3H); 13C 1H), 7.24–7.16 (m, 3H), 7.14–7.09 (m, 4H), 6.65 (d, J = 15.6 Hz,
NMR (125 MHz, CDCl3): δ = 168.1, 167.7, 163.4, 162.9, 161.5, 1H), 6.01 (dd, J = 15.6, 8.8 Hz, 1H), 4.56 (dd, J = 11.2, 9.1 Hz,
161.0, 135.9, 132.9, 130.9, 129.5, 129.5, 128.7, 128.0, 127.9, 1H), 4.07 (d, J = 11.4 Hz, 1H), 3.74 (s, 3H), 3.52 (s, 3H); 13C
115.8, 115.6, 115.4, 57.7, 52.7, 52.6, 48.3.
NMR (125 MHz, CDCl3): δ = 168.4, 167.8, 138.2, 136.4, 136.1,
(R,E)-Dimethyl 2-(1,3-bis(4-chlorophenyl)allyl)malonate (12k). 135.3, 130.8, 130.4, 130.1, 129.7, 127.4, 126.8, 126.3, 126.0,
Colorless oil. 93% yield and 98.2% ee, determined by chiral 125.8, 57.1, 53.4, 52.6, 52.4, 44.8, 19.7.
HPLC analysis (Chiralcel AD-H hexane/isopropanol, 80 : 20 v/v,
1.0 mL min−1, 25 °C, UV 254 nm), retention times: tr
=
12.863 min for (R)-isomer (major), tr = 19.394 min for (S)-
isomer (minor). 1H NMR (500 MHz, CDCl3): δ = 7.25 (d, J =
Conflicts of interest
8.4 Hz, 2H), 7.22–7.17 (m, 6H), 6.35 (d, J = 8.4 Hz, 2H), 6.22 There are no conflicts to declare.
(dd, J = 15.7, 8.5 Hz, 1H), 4.21–4.17 (m, 1H), 3.84 (d, J =
10.8 Hz, 1H), 3.66 (s, 3H), 3.50 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ = 168.0, 167.6, 138.5, 135.1, 133.5, 133.1, 131.1,
129.3, 129.0, 128.7, 127.6, 57.4, 52.8, 52.7, 48.4.
Notes and references
(R,E)-Dimethyl 2-(1,3-bis(4-bromophenyl)allyl)malonate (12l).
Colorless oil. 96% yield and 98.8% ee, determined by chiral
HPLC analysis (Chiralcel AD-H hexane/isopropanol, 80 : 20 v/v,
1 (a) B. P. Pritchett and B. M. Stoltz, Nat. Prod. Rep., 2018, 35,
559; (b) S. F. Zhu and Q. L. Zhou, Acc. Chem. Res., 2017, 50,
988; (c) G. Q. Yang and W. B. Zhang, Chem. Soc. Rev., 2018,
47, 1783.
1.0 mL min−1, 25 °C, UV 254 nm), retention times: tr
=
16.193 min for (R)-isomer (major), tr = 24.037 min for (S)-isomer
(minor). 1H NMR (500 MHz, CDCl3): δ = 7.44 (d, J = 8.3 Hz, 2H),
7.39 (d, J = 8.4 Hz, 2H), 7.17–7.15 (m, 4H), 6.38 (d, J = 15.7 Hz,
1H), 6.27 (dd, J = 15.7, 8.4 Hz, 1H), 4.22 (t, J = 9.6 Hz, 1H), 3.89
(d, J = 10.8 Hz, 1H), 3.70 (s, 3H), 3.55 (s, 3H); 13C NMR
(125 MHz, CDCl3): δ = 167.9, 167.5, 138.9, 135.4, 131.9, 131.6,
131.1, 129.6, 129.2, 127.9, 121.5, 121.2, 57.2, 52.7, 52.6, 48.4.
2 (a) M. P. Carroll and P. J. Guiry, Chem. Soc. Rev., 2014, 43,
819; (b) Y. Liu, W. Li and J. Zhang, Nat. Sci. Rev., 2017, 4,
326.
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1993, 32, 566; (b) J. Sprinz and G. Helmchen, Tetrahedron
Lett., 1993, 34, 1769; (c) G. J. Dawson, C. G. Frost,
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3149.
(R,E)-Dimethyl
2-(1,3-di-p-tolylallyl)malonate
(12m).
Colorless oil. 90% yield and 99.0% ee, determined by chiral
HPLC analysis (Chiralcel AD-H hexane/isopropanol, 80 : 20 v/v,
4 (a) G. Helmchen and A. Pfaltz, Acc. Chem. Res., 2000, 33,
336; (b) H. A. McManus and P. J. Guiry, Chem. Rev., 2004,
104, 4151; (c) Z. F. Zhang, N. A. Butt and W. B. Zhang,
Chem. Rev., 2016, 23, 14769; (d) H. Pellissier, Chem. Rev.,
2016, 116, 14868.
5 (a) D. R. Hou and K. Burgess, Org. Lett., 1999, 1, 1745;
(b) D. R. Hou, J. H. Reibenspies and K. Burgess, J. Org.
Chem., 2001, 66, 206; (c) D. Hou, J. Reibenspies,
T. J. Colacot and K. Burgess, Chem. – Eur. J., 2001, 7, 5391.
6 (a) Z. Mazloomi, M. Magre, E. D. Valle, M. A. Pericàs,
O. Pàmies, P. W. N. M. van Leeuwen and M. Diéguez, Adv.
Synth. Catal., 2018, 360, 1650; (b) W. Y. Sun, H. R. Gu and
X. F. Lin, J. Org. Chem., 2018, 83, 4034; (c) K. Meng,
1.0 mL min−1, 25 °C, UV 254 nm), retention times: tr
=
8.439 min for (R)-isomer (major), tr = 11.189 min for (S)-isomer
(minor). 1H NMR (500 MHz, CDCl3): δ = 7.16–7.12 (m, 4H),
7.06 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 6.38 (d, J =
15.8 Hz, 1H), 6.20 (dd, J = 15.7, 8.7 Hz, 1H), 4.16 (t, J = 9.8 Hz,
1H), 3.87 (d, J = 10.9 Hz, 1H), 3.64 (s, 3H), 3.48 (s, 3H), 2.25 (s,
6H); 13C NMR (125 MHz, CDCl3): δ = 168.3, 167.8, 137.2, 136.7,
134.1, 131.4, 129.4, 129.1, 128.2, 127.7, 126.3, 57.7, 52.5, 52.4,
48.8, 21.1, 21.0.
(R,E)-Dimethyl 2-(1,3-bis(3-bromophenyl)allyl)malonate (12n).
Colorless oil. 95% yield and 99.0% ee, determined by chiral
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Paper
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