Synthesis, characterization and first application of chiral C2-symmetric bis(phosphinite)-Pd(II) complexes as catalysts in asymmetric intermolecular Heck reactions

Article abstract of DOI:10.1002/aoc.3416

A series of new chiral C₂-symmetric bis(phosphinite) ligands and their palladium(II) complexes have been synthesized and for the first time used as catalysts in the palladium-catalysed asymmetric intermolecular Heck coupling reactions of 2,3-dihydrofuran with iodobenzene or aryl triflate. Under optimized conditions, products were obtained with high conversions and moderate to good enantioselectivities. The new C₂-symmetric bis(phosphinite) ligands and their palladium(II) complexes were characterized using multinuclear NMR and Fourier transform infrared spectroscopies and elemental analysis.

Full text of DOI:10.1002/aoc.3416

Full paper
Received: 17 September 2015
Revised: 2 November 2015
Accepted: 16 November 2015
Published online in Wiley Online Library: 28 December 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3416
Synthesis, characterization and first application
of chiral C2-symmetric bis(phosphinite)–Pd(II)
complexes as catalysts in asymmetric
intermolecular Heck reactions
Duygu Elma Karakaşa,b, Feyyaz Durapa,c*, Murat Aydemira,c and Akın Baysala
A series of new chiral C2-symmetric bis(phosphinite) ligands and their palladium(II) complexes have been synthesized and for the
first time used as catalysts in the palladium-catalysed asymmetric intermolecular Heck coupling reactions of 2,3-dihydrofuran with
iodobenzene or aryl triflate. Under optimized conditions, products were obtained with high conversions and moderate to good
enantioselectivities. The new C2-symmetric bis(phosphinite) ligands and their palladium(II) complexes were characterized using
multinuclear NMR and Fourier transform infrared spectroscopies and elemental analysis. Copyright © 2015 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: palladium(II); C2 symmetry; phosphinite; asymmetric Heck coupling
Introduction
obtained high enantioselectivity (96%).[9] In this regard, chiral
bidentate phosphorus-based ligands have been accepted to be
excellent ligands for such processes.[10] The C2 symmetry of BINAP
limits the possible number of diastereomeric transition states formed,
and the reactions performed using these ligands are therefore often
highly selective.[11]
Over the past few decades, transition-metal-catalysed reactions
have undergone substantial development and found widespread
applications in synthetic organic chemistry.[1] The noble metals of
group VIII, which are also known as platinum group metals, ruthe-
nium, osmium, rhodium, iridium, palladium and platinum, play
prominent roles in homogeneous catalysis.[2] Among the platinum
group metals, palladium has been successfully used as an efficient
catalyst in the formation of C–C, C–O, C–N bonds, etc., in modern
synthetic chemistry.[3]
In following years, Pfaltz and co-workers10a,b,12 and Hashimoto
et al.[13] reported phosphorus-containing oxazolines as efficient li-
gands in the same type of asymmetric intermolecular Heck reac-
tion. For the intermolecular Heck reaction, enantiomeric excess
higher than 96% has been reached.[14] Lee and Hartwig reported
rather low enantioselectivities using phosphoramidites as chiral li-
gands in asymmetric reactions.[15] Recently, phosphane oxazolines
have been found to be efficient ligands for intermolecular asym-
metric Heck reactions.[13] Peptide-derived phosphinite ligands
showed good catalytic activity and very high enantiomeric excesses
in intermolecular asymmetric Heck reactions. It is suggested that
phosphinite dissociation occurs and the observed high
stereocontrol is attributed to the inherent properties of the peptide
backbone in the ligand structure.[16] Partly because of their straight-
forward synthesis from readily available chiral diols, C2-symmetric
bis(phosphinite) ligands also retain a privileged position in asym-
metric transfer hydrogenation of ketones.[17–19]
The Mizoroki–Heck reaction, which was discovered in the 1970s by
Mizoroki and Heck, involves the palladium-catalysed coupling of aryl
or alkenyl halide or triflate to olefins. The reaction is often referred
to as the ‘Heck reaction’.[4] Chiral ligands bearing palladium(II)
complexes have received wide attention due to their exclusive appli-
cations in asymmetric catalysis, especially in asymmetric intermolec-
ular Heck coupling reactions.[5] Recently, research into the Heck
reaction has focused on obtaining enantioselectivity.[6] Since the first
reports in the late 1980s, various ligands have been developed for
the asymmetric Heck reaction. Phosphorus-containing chiral ligands
are of central importance for the asymmetric Heck reaction as well
as for other asymmetric catalytic transformations. The first asym-
metric variant of the Heck reaction was reported in 1989 by
Shibasaki and co-workers and Overman and co-workers in which
intramolecular cyclization of alkenyl iodide or triflate forms chiral
cyclic compounds of around 45% enantiomeric excess.[7] The
majority of the reported studies involve intramolecular reactions
due the fact that the alkene regiochemistry and geometry in the
product can be easily controlled.[8] In 1991, Hayashi and co-workers
reported the first enantioselective intermolecular Heck reaction
of 2,3-dihydrofuran and phenyl triflate, in which they used
Pd(OAc)2/2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP)/i-Pr2NEt
and several other bidentate chiral phosphine ligands as catalysts and
*
Correspondence to: Feyyaz Durap, Department of Chemistry, Faculty of Science,
Dicle University, 21280 Diyarbakır, Turkey. E-mail: fdurap@dicle.edu.tr
a Department of Chemistry, Faculty of Science, Dicle University, 21280, Diyarbakır,
Turkey
b Science and Technology Application and Research Center (SUBTAM), Siirt
University, 56000, Siirt, Turkey
c
Science and Technology Application and Research Center (DUBTAM), Dicle
University, 21280, Diyarbakir, Turkey
Appl. Organometal. Chem. 2016, 30, 193–198
Copyright © 2015 John Wiley & Sons, Ltd.

D. E. Karakaş et al.
Synthesis of 1
Herein we present the synthesis and characterization of new
chiral C2-symmetric bis(phosphinite) ligands and their palladium
(II) complexes. To the best of our knowledge, these C2-symmetric
bis(phosphinite)–Pd(II) complexes were used as catalysts for the
first time in the palladium-catalysed asymmetric intermolecular
Heck coupling reactions of 2,3-dihydrofuran with iodobenzene or
aryl triflate.
The crude product was purified by column chromatography over
silica gel using n-hexane–ethyl acetate (2:1) to afford 1 (7.0 g,
20
80%) as a colourless solid. M.p. 126.5–128C; ½αꢁD = ꢀ37.0° (c 1,
CH2Cl2). Anal. Calcd for C39H43O2N3 (%): C, 79.97; H, 7.40; N, 7.17.
Found (%): C, 79.83; H, 7.32; N, 7.04. 1H NMR (CD3CN, δ, ppm): 7.51
(t, 1H, J = 8.0 Hz, C5H3N), 7.17–7.30 (m, 20H, C6H5), 7.07 (d, 2H,
J = 8.0Hz C5H3N), 4.75 (broad, 2H, –CH2OH), 4.03–4.07 (m, 2H,
–CH2N (b)), 3.76–3.80 ( m, 6H, –;CH2Ph+ –;CH2N (a)), 3.60–3.75 (m,
2H, –CH2OH (b)), 3.34–3.36 (m, 2H –CH2OH (a)), 2.98–3.11 (m, 4H,
–CHCH2 (b) + –CHCH2), 2.57–2.60 (m, 2H, –CHCH2 (a)). 13C NMR
(CD3CN, δ, ppm): 159.77 (i-C5H3N), 140.44, 139.94 (i-C6H5), 137.05
(C5H3N), 129.18, 128.88, 128.33, 125.87, 128.03, 126.76 (C6H5),
121.39 (C5H3N), 63.50 (–CHCH2), 60.83 (–CH2OH), 54.78 (–CH2N),
54.14 (–CH2Ph), 32.65 (–CHCH2). FT-IR (KBr pellet, cmꢀ1): ν(OH),
3402; ν(CH), 3024, 2922, 2864; ν(C¼C), 1587, 1496, 1452.
Experimental
Materials and methods
All reactions were carried out under inert atmosphere of argon in
flame-dried glassware using conventional Schlenk techniques. Sol-
vents were dried using established procedures and distilled under
argon just prior to use. Analytical-grade and deuterated solvents
were purchased from Merck. The starting materials were purchased
from Sigma Aldrich or Merck and used as received. (2R)-2-[benzyl
({[6-({benzyl[(2R)-1-hydroxy-3-phenylpropan-2-yl]amino}methyl)
pyridine-2-yl]methyl})amino]-3-phenylpropan-1-ol (1), (2R)-2-[ben-
zyl({[3-({benzyl[(2R)-1-hydroxy-3-phenylpropan-2-yl]amino}methyl)
phenyl]methyl})amino]-3-phenylpropan-1-ol (2), (2R)-1-[benzyl({[6-
({benzyl[(2R)-2-hydroxypropyl]amino}methyl)pyridin-2-yl]methyl})
amino]propan-2-ol (3), (2R)-1-[benzyl({[3-({benzyl[(2R)-2-hydroxy-
Synthesis of 2
The crude product was purified by column chromatography over
silica gel using n-hexane–ethyl acetate (2.5:1) to afford 2 (6.0 g,
20
68%) as a colourless solid M.p. 121–123°C; ½αꢁD = ꢀ40.0° (c 1,
CH2Cl2). Anal. Calcd for C40H44O2N2 (%): C, 82.15; H, 7.60; N, 4.79.
Found (%): C, 82.00; H, 7.42; N, 4.54. 1H NMR (CDCl3, δ, ppm):
7.15–7.33 (m, 24H, C6H5), 3.95–3.99 (m, 4H, –NCH2), 3.54–3.59 (m,
2H, –CH2OH (a) + 4H, –NCH2Ph), 3.40–3.42 (m, 2H, –CH2OH (b)),
3.14–3.17 (m, 2H, –CHCH2Ph (b) + 2H, –NCH), 2.97 (broad, 2H,
–OH), 2.48–2.54 (m, 2H, –CHCH2Ph (a)). 13C NMR (CDCl3, δ, ppm):
139.14, 139.27, 139.59 (i-C6H5), 126.27, 127.34, 127.96, 128.60,
128.75, 129.01, 129.06, 129.50 (C6H5), 61.29 (–NCH), 60.58
(–CH2OH), 53.60 (–NCH2), 53.28 (–NCH2Ph), 31.96 (–CHCH2Ph).
FT-IR (KBr pellet, cmꢀ1): ν(OH), 3419; ν(CH), 3061, 3027, 2834;
ν(C¼C), 1493, 1480, 1451.
propyl]amino}methyl)phenyl] methyl})amino]propan-2-ol (4)[17]
[20]
and Pd(cod)Cl2
(cod= 1,5-cyclooctadiene) were prepared ac-
cording to literature procedures.
1H NMR (at 400.1 MHz), 13C NMR (at 100.6 MHz) and 31P-{1H} NMR
(at 162.0 MHz) spectra were recorded using a Bruker AV 400 spec-
trometer, with tetramethylsilane as an internal reference for 1H
NMR and 13C NMR or 85% H3PO4 as an external reference for 31P-
{1H} NMR. Attenuated total reflectance Fourier transform infrared
(FT-IR) spectra were recorded with a PerkinElmer Spectrum 100.
Specific rotations were obtained with a PerkinElmer 341 model po-
larimeter. Elemental analysis was carried out on with a Costech ECS
4010 instrument. Melting points were recorded with a Gallenkamp
model apparatus with open capillaries.
Synthesis of 3
The crude product was obtained as a yellow oil without further pu-
20
GC analyses were performed using a Shimadzu GC 2010 Plus in-
strument equipped with a Chiraldex G-TA (Supelco) capillary col-
umn (30 m × 0.25 mm inner diameter× 0.12 μm film thickness).
The GC parameters for asymmetric intermolecular Mizoroki–Heck
reactions of 2,3-dihydrofuran were as follows: initial temperature,
70°C; initial time, 5 min; solvent delay; temperature ramp,
rification (5.5g, 85%). ½αꢁD = ꢀ82.7° (c 1, CH2Cl2). Anal. Calcd for
C27H35O2N3 (%): C, 74.79; H, 8.15; N, 9.69. Found (%): C, 74.20; H,
8.03; N, 9.32. 1H NMR (CDCl3, δ, ppm): 7.56–7.05 (m, 13H, aromatic
protons), 3.99–3.87 (m, 2H, –CHCH3 + 4H, –NCH2), 3.71–3.61 (m,
4H, –CH2Ph), 2.64–2.51 (m, 4H, –CHCH2), 1.11 (d, 6H, J = 6.2Hz,
–CHCH3). 13C NMR (CDCl3, δ, ppm): 136.91 (i-C6H5), 121.40, 127.13,
128.30, 129.00 (aromatic carbons), 63.89 (–CHCH3), 62.77 (–CHCH2),
59.37, 59.61 (–CH2Ph + –CH2Py), 20.03 (–CHCH3). FT-IR (KBr pellet,
cmꢀ1): ν(OH), 3367; ν(CH), 3062, 3027, 2967, 2928; ν(N¼C), (1603);
ν(C¼C), 1592, 1576, 1453.
0.5°C minꢀ1; 90°C; initial time, 0 min; temperature ramp, 5°Cminꢀ1
;
final temperature, 120°C; initial time, 5 min; final time, 56 min; injec-
tor port temperature, 200°C; detector temperature, 200°C; injection
volume, 1.0 μl.
Synthesis of 4
General procedure for preparation of chiral C2-symmetric
aminoalcohols[17]
The crude product was obtained as a yellow oil without further pu-
20
rification (5.3g, 82%). ½αꢁD = ꢀ106.5° (c 1, CH2Cl2). Anal. Calcd for
Corresponding chiral aminoalcohol (30 mmol), 2,6-bis(bromo-
methyl)pyridine or 1,3-bis(bromomethyl)benzene (15mmol), so-
dium carbonate (46 mmol) and KI (50 mg) in EtOH (50ml) were
stirred at 100°C for 12 h under argon. Then the mixture was cooled
and CHCl3 (100 ml) was added to the mixture and refluxed for 2 h.
The solution was filtered, EtOH was removed in vacuo and CHCl3
(50 ml) was added to the residue. The solution was washed with wa-
ter and brine (50 ml) twice. The aqueous solution was extracted
with CHCl3 (2× 50 ml). The combined CHCl3 phases were dried over
anhydrous Na2SO4.
C28H36O2N2 (%): C, 77.74; H, 8.40; N, 6.48. Found (%): C, 77.40; H,
1
8.18; N, 6.19. H NMR (CDCl3, δ, ppm): 7.21–7.37 (m, 14H, C6H5),
3.83–3.89 (m, 2H, CHCH3 + 4H, –CH2Ph), 3.41–3.47 (m, 4H, –CH2Ph),
3.22 (broad, 2H, OH), 2.44 (d, 4H, J = 6.6 Hz, –CHCH2), 1.07 (d, 6H,
J = 6.1Hz, –CHCH3). 13C NMR (CDCl3, δ, ppm): 138.60, 138.87
(i-C6H5), 127.28, 128.01, 128.46, 128.54, 129.03, 129.70 (C6H5),
63.26 (–CHCH3), 61.55 (–CHCH2), 58.50, 58.71 (–CH2Ph, CH2Ph),
19.96 (–CHCH3). FT-IR (KBr pellet, cmꢀ1): ν(OH), 3434; ν(CH), 3028,
2968, 2930; ν(C¼C), 1495, 1451, 1408.
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Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 193–198

C2-symmetric phosphinites as catalysts in the asymmetric Heck reactions
General procedure for synthesis of chiral C2-symmetric Bis
(diphenylphosphinite) ligands (5–8)
ν(CH), 3055, 2966, 2926; ν(C¼N), 1589; ν(C¼C), 1494, 1479, 1453;
ν(O–P), 1070.
To a solution of aminoalcohol 1–4 (1.5 mol) in dry toluene (20 ml)
was added triethylamine (3.0mmol) and the mixture was stirred
for 10min under argon atmosphere. To this solution was added
dropwise monochlorodiphenylphosphine, Ph2PCl (3.0mmol). The
mixture was then stirred at room temperature for 1 h and the
triethylammonium chloride (Et3N.HCl) was removed by filtration
under argon.
Synthesis of (2R)-1-[benzyl({[3-({benzyl[(2R)-2-[(diphenylphosphanyl)oxy]propyl]
amino}methyl)phenyl]methyl})amino]propan-2-yl diphenylphosphinite (8)
White viscous oily product 8 (0.11 g, 92%). Anal. Calcd for
C52H54N2O2P2 (%): C, 77.98; H, 6.81; N, 3.50. Found (%): C, 77.73;
H, 6.61; N, 3.38. 1H NMR (CDCl3, δ, ppm): 7.25–7.52 (m, 34H,
aromatic protons), 4.21 (broad, 2H, –CHCH3), 3.56–3.61(m, 4H,
–NCH2Ph + –NCH2), 2.74–2.79 (m, 2H, –CHCH2 (b)), 2.53–2.56 (m,
2H, –CHCH2 (a)), 1.26–1.31 (m, 6H, –CHCH3). 13C NMR (CDCl3, δ,
ppm): 139.21, 139.44, 142.66 (ipso carbons), 126.81, 127.55,
128.16, 128.23, 128.34, 128.46, 128.94, 129.43, 130.05, 130.26,
130.37, 130.59 (aromatic carbons), 75.56 (d, J = 23.1 Hz, –CHCH3),
60.50 (–CHCH2), 59.07 (–NCH2Ph + –NCH2), 20.94 (–CHCH3).
31P-{1H} NMR (CDCl3, δ, ppm): 108.03 (s) (see supporting informa-
tion, Fig. S1). FT-IR (KBr pellet, cmꢀ1): ν(CH), 3054, 2926, 2904;
ν(C¼C), 1493, 1479, 1443; ν(O–P), 1071.
Synthesis of (2R)-2-[benzyl({[6-{[benzyl[(2R)-1-[(diphenylphosphanyl)oxy]-3-
phenylpropan-2-yl]amino}methyl)pyridin-2-yl]methyl})amino]-3-phenylpropyl-
diphenylphosphinite] (5)
White viscous oily product 5 (0.13 g, 91%). Anal. Calcd for
C63H61N3O2P2 (%): C, 79.31; H, 6.46; N, 4.40. Found (%): C, 79.04; H,
1
6.3; N, 4.21. H NMR (CDCl3, δ, ppm): 7.05–7.56 (m, 43H, aromatic
protons), 3.97–4.08 (m, 4H, –NCH2Py+ 4H, CH2OP), 3.79–3.85 (m,
4H, –NCH2Ph), 3.25 (broad, 2H, –NCH), 2.99–3.07 (m, 2H, –CHCH2Ph
(b)), 2.85–2.90 (m, 2H, –CHCH2Ph (a)). 13C NMR (CDCl3, δ, ppm):
137.29, 139.72, 141.80, 159.53 (i-carbons), 126.92, 127.41, 128.10,
128.22, 128.30, 128.81, 129.11, 129.19, 129.39, 130.20, 130.41,
130.51, 130.54, 130.73 (aromatic carbons), 69.33 (d, J = 18.1 Hz,
–CH2OP), 61.27 (d, J = 9.1Hz, –NCH), 56.15 (–NCH2Py), 55.11
(–NCH2Ph), 34.11 (–CHCH2Ph). 31P-{1H} NMR (CDCl3, δ, ppm):
114.14 (s, O–P(Ph)2) (see supporting information, Fig. S1). FT-IR
(KBr pellet, cmꢀ1): ν(CH), 3057, 3027, 2925; ν(C¼N), 1642; ν(C¼C),
1570, 1564, 1451; ν(O–P), 1021.
General procedure for synthesis of bis(phoshinite)–Pd(II) com-
plexes (9–12)
Pd(cod)Cl2 (1.5mmol) and bis(phosphinite) ligands 5–8 (1.5mol)
were dissolved in 30 ml of CH2Cl2 under an argon atmosphere
and stirred for 1 h at room temperature. The resulting yellow solu-
tion was concentrated to 2 ml under reduced pressure, and addi-
tion of petroleum ether (15 ml) caused the precipitation of a dark
yellow solid. The supernatant solution was decanted, the solid
was washed with hexane–diethyl ether (1:1) and dried by vacuum,
yielding palladium(II) complexes 9–12.
Synthesis of (2R)-2-[benzyl({[3-({benzyl[(2R)-1-[(diphenylphosphanyl)oxy]-3-
phenylpropan-2-yl]
diphenylphosphinite (6)
amino}methyl)phenyl]methyl})amino]-3-phenylpropyl
Synthesis of dichloro[(2R)-2-[benzyl({[6-{[benzyl[(2R)-1-[(diphenylphosphanyl)
oxy]-3-phenylpropan-2-yl]amino}methyl)pyridin-2-yl]methyl})amino]-3-phenyl-
propyldiphenyl phosphinite]palladium(II) (9)
White viscous oily product 6 (0.13 g, 91%). Anal. Calcd for
64H62N2O2P2 (%): C, 83.00; H, 6.77; N, 3.02. Found (%): C,
C
Yield 0.15g, 88%; m.p. 130–132°C; ½αꢁ2D0 = +12.9° (c: 1, CH2Cl2). Anal.
82.85; H, 6.53; N, 2.91. 1H NMR (CDCl3, δ, ppm): 7.02–7.55 (m,
44H, aromatic protons), 3.99 (broad, 4H, –CH2OP), 3.73–3.78
(m, 4H, –NCH2Ph + 4H, –NCH2), 3.24 (broad, 2H, –CHCH2Ph),
3.11–3.14 (m, 2H, –CHCH2Ph (a)), 2.86–2.92 (m, 2H, –CHCH2Ph
(b)). 13C NMR (CDCl3, δ, ppm): 139.92, 140.01, 140.23, 141.52,
142.10 (i-carbons), 125.88, 126.68, 127.12, 128.12, 128.18,
128.38, 128.43, 128.63, 129.05, 129.28, 129.42, 129.47, 130.26,
130.48, 130.62, 130.84 (aromatic carbons), 60.29 (d, J = 17.1 Hz,
–CH2OP), 60.13 (d, J = 10.7 Hz, –CHCH2Ph), 54.31, 54.53
(–NCH2Ph + NCH2), 34.58 (–CHCH2Ph). 31P-{1H} NMR (CDCl3, δ,
ppm): 114.58 (s, O–P(Ph)2) (see supporting information,
Fig. S1). FT-IR (KBr pellet, cmꢀ1): ν(CH), 3060, 3026, 2962;
ν(C¼C), 1434, 1453, 1437; ν(O–P), 1015.
Calcd for C63H61N3O2P2PdCl2 (%): C, 66.88; H, 5.43; N, 3.71. Found
1
(%): C, 66.45; H, 5.13; N, 3.51. H NMR (CDCl3, δ, ppm): 7.05–7.88
(m, 43H, aromatic protons), 4.26 (broad, 4H, –CH2OP), 3.81 (broad,
2H, –NCH2Py), 3.57–3.66 (m, 4H, –NCH2Ph (a) + –NCH2Py (b)),
3.38–3.42 (m, 2H, –NCH2Ph), 3.10 (broad, 2H, –NCH), 2.58–2.64
(m, 2H, –CHCH2Ph (a)), 2.38–2.42 (m, 2H, –CHCH2Ph (b)). 13C NMR
(CDCl3, δ, ppm): 136.40, 139.18, 139.49, 141.60, 159.43 (i-carbons),
126.10, 127.02, 127.40, 128.19, 128.33, 128.54, 129.10, 129.92,
130.93, 131.50, 131.82, 132.41, 132.47, 132.78 (aromatic carbons),
68.86 (–CH2OP), 61.35 (–NCH), 56.05, 55.07 (–NCH2Py + –NCH2Ph),
34.64 (–CHCH2Ph). 31P-{1H} NMR (CDCl3, δ, ppm): 110.45 (s, O–P
(Ph)2) (see supporting information, Fig. S2). FT-IR (KBr pellet,
cmꢀ1): ν(CH), 3067, 3020, 2915; ν(C¼N), 1640; ν(C¼C), 1560, 1554,
1441; ν(O–P), 1020. m/z: 1132.15 [M ꢀ H+] C63H61N3O2P2PdCl2
(MA: 1131.44).
Synthesis of (2R)-1-[benzyl({[6-({benzyl[(2R)-2-[(diphenylphosphanyl)oxy]propyl]
amino}methyl)pyridin-2-yl]methyl})amino]propan-2-yldiphenylphosphinite (7)
Synthesis of dichloro[(2R)-2-{benzyl[(3-{[benzyl-(2R)-1-[(diphenylphosphanyl)
oxy]-3-phenylpropan-2-yl)amino]methyl}phenyl]methy})amino]-3-phenylpropyl
diphenylphosphinite]palladium(II) (10)
White viscous oily product 7 (0.11 g, 92%). Anal. Calcd for
C51H53N3O2P2 (%): C, 76.38; H, 6.67; N, 5.24. Found (%): C, 76.21; H,
6.48; N, 5.16. 1H NMR (CDCl3, δ, ppm): 7.23–7.54 (m, 33H, aromatic
protons), 4.14–4.16 (m, 2H, –CHCH3), 3.61–3.75(m, 4H, –NCH2Ph
+ –NCH2), 2.83 (broad, 2H, –CHCH2 (a)), 2.58 (broad, 2H, –CHCH2
(b)), 1.26 (d, 2H, J = 6.20 Hz, –CHCH3). 13C NMR (CDCl3, δ, ppm):
136.51, 142.63, 158.93 (ipso carbons), 120.95, 126.89, 128.17,
128.23, 128.46, 128.99, 129.06, 130.01, 130.23, 130.50, 130.70 (aro-
matic carbons), 75.36 (–CHCH3), 60.85 (–CHCH2), 59.41 (–NCH2Ph
+ –NCH2Py), 20.87 (–CHCH3). 31P-{1H} NMR (CDCl3, δ, ppm): 106.84
(s) (see supporting information, Fig. S1). FT-IR (KBr pellet, cmꢀ1):
20
Yield 0.14g, 82%; m.p. 131–133°C; ½αꢁD = ꢀ59.9° (c: 1, CH2Cl2].
Anal. Calcd for C64H62N2O2P2PdCl2 (%): C, 68.00; H, 5.53; N,
2.48. Found (%): C, 67.75; H, 5.38; N, 2.15. 1H NMR (CDCl3, δ,
ppm): 6.72–7.74 (m, 44H, aromatic protons), 3.64–3.68 (m, 4H,
–NCH2Ph(a) + –NCH2(a)), 3.44–3.48 (m, 2H, NCH2Ph(b)), 3.15–3.22
(m, 4H, –NCH2(b) + –CH2OP(a)), 3.06–3.09 (m, 2H, –CH2OP (b)),
2,00 (broad, 2H, –CHCH2Ph), 1.57–1.70 (m, 4H, –CHCH2Ph). 13C
NMR (CDCl3, δ, ppm): 137.94, 138.68, 141.01 (i-carbons), 125.95,
Appl. Organometal. Chem. 2016, 30, 193–198
Copyright © 2015 John Wiley & Sons, Ltd.
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D. E. Karakaş et al.
126.14, 127.12, 127.37, 127.59, 128.17, 128.60, 128.67, 129.19,
129.66, 131.01, 132.43, 132.86, 133.64 (aromatic carbons), 64.96
(–CH2OP), 59.61 (CHCH2Ph), 52.18, 55.09 (–NCH2Ph+ NCH2), 35.39
(–CHCH2Ph). 31P-{1H} NMR (CDCl3, δ, ppm): 113.55 (s, O–P(Ph)2)
(see supporting information, Fig. S2). FT-IR (KBr pellet, cmꢀ1):
ν(CH), 3050, 3016, 2952; ν(C¼C), 1430, 1450, 1427; ν(O–P): 1025.
Synthesis of dichloro[(2R)-1-[benzyl({[6-({benzyl[(2R)-2-[(diphenylphosphanyl)
oxy]propyl]amino}methyl)pyridin-2-yl]methyl})amino]propan-2-yl diphenylphos-
phinite]palladium(II) (11)
C2-symmetric bis(phosphinite) ligands 5–8 (Fig. 2) were prepared
from the C2-symmetric aminoalcohols 1–4 by reaction with two
equivalents of Ph2PCl and triethylamine in freshly distilled toluene
under argon atmosphere. After 1 h stirring at room temperature,
the 31P NMR spectra of the reaction mixtures display the complete
disappearance of the signal corresponding to Ph2PCl (81.0 ppm)
and the appearance of a new signal for the expected bis(phos-
phinites). All ligands are obtained as white viscous oil in high yields.
A single resonance ranging from 106 to 114ppm is obtained for all
ligands (5–8) in the 31P-{1H} NMR spectra in line with the values pre-
viously observed for similar compounds (see supporting informa-
tion, Fig. S1).[17] It is well known that phosphinites are generally
unstable in the solid state and decompose rapidly on exposure to
air or moisture.[19] In contrast, we observe that our phosphinite
ligands are highly stable in the solid state and do not decompose
in the open-air atmosphere in two weeks. Additionally, structures
20
Yield 0.12 g, 82%; m.p. 122–124°C; ½αꢁD = ꢀ18.8° (c: 0.5, CH2Cl2).
Anal. Calcd for C51H53N3O2P2PdCl2 (%): C, 62.55; H, 5.46; N, 4.29.
Found (%): C, 62.38; H, 5.30; N, 4.09. 1H NMR (CDCl3, δ, ppm):
7.21–7.57 (m, 33H, aromatic protons), 4.12 (m, 2H, –CHCH3), 3.10–
3.84 (m, 8H, –NCH2Ph+ –NCH2), 2.55 (broad, 4H, –CHCH2), 1.26 (m,
6H, –CHCH3). 13C NMR (CDCl3, δ, ppm): 136.21, 140.63, 159.76 (ipso
carbons), 120.65, 126.70, 127.44, 127.44, 127.76, 128.46, 128.99,
131.76, 131.98, 132.47, 132.83, 133.39 (aromatic carbons), 74,95
(–CHCH3), 60.36 (–CHCH2), 59.54 (–NCH2Ph+ –NCH2Py), 19.86
(–CHCH3). 31P-{1H} NMR (CDCl3, δ, ppm): 108.20 (s) (see supporting
information, Fig. S2). FT-IR (KBr pellet, cmꢀ1): ν(CH), 3065, 2956,
2936; ν(C¼N), 1579; ν(C¼C), 1484, 1475, 1453; ν(O–P): 1065.
1
of 5–8 were investigated using H NMR, 13C NMR and FT-IR spec-
troscopies and elemental analysis, and all data are in agreement
with the structures (see Experimental section).
The complexes [LPdCl2], where L is 5–8, were prepared by the
addition of an equivalent of [Pd(cod)Cl2] to a dry CH2Cl2 solution
of each bis(phosphinite) ligand under argon atmosphere.
Synthesis of dichloro[(2R)-1-[benzyl({[3-({benzyl[(2R)-2-[(diphenylphosphanyl)
oxy]propyl]amino}methyl)phenyl]methyl})amino]propan-2-yl diphenylphosphinite]
palladium(II) (12)
20
Yield 0.13 g, 89%; m.p. 133–135°C; ½αꢁD = ꢀ20.5° (c: 0.5, CH2Cl2).
Anal. Calcd for C52H54N2O2P2PdCl2 (%): C, 63.84; H, 5.56; N, 2.86.
Found (%): C, 63.72; H, 5.42; N, 2.62. 1H NMR (CDCl3, δ, ppm):
7.20–7.58 (m, 34H, aromatic protons), 3.87 (broad, 2H, –CHCH3),
3.21–3.29 (m, 8H, –NCH2Ph+ –NCH2), 2.37–2.42 (m, 4H, –CHCH2),
0.84–0.90 (m, 6H, –CHCH3). 13C NMR (CDCl3, δ, ppm): 138.02,
138.25 (i-carbons), 127.24, 127.86, 128.37, 128.60, 128.73, 130.98,
131.69, 131.86, 132.07, 132.42, 132.72, 133.12 (aromatic carbons),
74.84 (–CHCH3), 59.51 (–CHCH2), 57.96 (–NCH2Ph+ –NCH2), 19.47
(–CHCH3). 31P-{1H} NMR (CDCl3, δ, ppm): 103.76 (s) (see supporting
information, Fig. S2). FT-IR (KBr pellet, cmꢀ1): ν(CH), 3064, 2936,
2924; ν(C¼C), 1483, 1469, 1453; ν(O–P), 1070.
Figure 1. Synthesis of chiral C2-symmetric amino alcohols: i, benzaldehyde,
NaBH4, CH3OH; ii, Na2CO3, KI, CH3CH2OH.
General procedure for asymmetric intermolecular Heck reac-
tions of 2,3-dihydrofuran
A solution of the chiral bis(phosphinite)Pd(II) complexes 9–12
(0.03mmol), organic base (3.0 mmol), phenyl triflate or iodo-
benzene (1.0 mmol) and 2,3-dihydrofuran (5.0mmol) in degassed
organic solvent (tetrahydrofuran (THF), benzene, toluene) (3ml)
were added to the catalyst solution. The solution was mixed until
the reaction completed. Periodically a sample taken from the reac-
tion medium was passed through an acetone silica gel column and
conversion rates were observed using GC. Conversion rates were
calculated based on unreacted phenyl triflate or iodobenzene.
Figure 2. Synthesis of chiral C2-symmetric bis(phosphinite) ligands.
Results and discussion
Synthesis of chiral C2-symmetric bis(phosphinite) ligands and
their Pd(II) complexes
To synthesize new chiral ligands with C2-symmetric backbones, we
were interested in chiral phosphinite ligands from chiral diols which
have C2-symmetric backbones. For this aim, initially C2-symmetric
chiral aminoalcohols 1–4 were synthesized according to a literature
procedure as shown in Fig. 1.
Figure 3. Synthesis of chiral C2-symmetric bis(phosphinite)–Pd(II)
complexes.
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Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 193–198

C2-symmetric phosphinites as catalysts in the asymmetric Heck reactions
Complexation reactions were simple, with coordination to palla-
dium(II) being carried out at room temperature, affording com-
pounds 9–12 as air-stable dark yellow powders in high yield as
shown in Fig. 3. The 31P NMR spectra of palladium(II) complexes
9–12 show singlets ranging from 108 to 113 ppm for all complexes
(see supporting information, Fig. S2). These spectra clearly indicate
that the cod moiety has been replaced by the chelating bis
(phosphinite) ligand and both phosphorus atoms are bonded to
the palladium(II). The 1H NMR, 13C NMR, FT-IR and elemental analy-
sis data for complexes 9–12 are consistent with the formulation of
[LPdCl2], and in line with the values previously observed for similar
complexes[21] as detailed in the Experimental section.
Table 1. Palladium-catalysed enantioselective phenylation of 2,3-
dihydrofuran using C2-symmetric chiral bis(phosphinite)–Pd(II) com-
plexes (9–12)
Catalyst
R
Base
Time Conversion 1a/ ee (%)b ee (%)c
(h)
(%)a
1b
(1a)
(1b)
9
I
DIPEA
240
240
240
240
240
<10
<10
<10
<10
<10
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
10
11
12
9
I
I
I
I
DIPEA
DIPEA
DIPEA
Proton
sponge
Proton
sponge
Proton
sponge
Proton
sponge
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Catalytic asymmetric intermolecular Heck reactions
The palladium-catalysed asymmetric intermolecular Heck reaction
has received increasing attention in the last decade, as it is a selec-
tive method for the formation of new chiral ligands in a single op-
erational step.[22,23] The reaction is appealing because of its
tolerance of nearly any solvent and functional group on the sub-
strates, its high selectivity and its moderate toxicity.[24,25] The activ-
ity of palladium(II) complexes bearing various chiral phosphorus
moieties is well known in this catalytic reaction.[26] To the best of
our knowledge, in this study the C2-symmetric chiral bis(phos-
phinite)–Pd(II) complexes were used for the first time in asymmetric
intermolecular Heck reactions. We report the use of C2-symmetric
chiral bis(phosphinite)–Pd(II) complexes 9–12 in the palladium-
catalysed asymmetric Heck reaction of 2,3-dihydrofuran using
iodobenzene or phenyl triflate. Generally, reaction of 2,3-
dihydrofuran and phenyl triflate has been used to study the asym-
metric intermolecular Heck reaction since the first report by Hayashi
and co-workers.[9]
A set of optimal catalytic conditions experiments was carried out
to discover a suitable reaction medium. The results are summarized
in Table 1. Initially, we studied the effect of various solvents includ-
ing polar (THF) and non-polar (benzene, toluene) media, organic
(N,N-diisopropylethylamine (DIPEA), proton sponge) and inorganic
(Ag2CO3) bases, and temperature (room temperature or reflux).
For instance, there is no conversion reaction of 2,3-dihydrofuran
with phenyl triflate when THF, benzene or toluene is used as sol-
vent and DIPEA or proton sponge is used as organic base at room
temperature or reflux conditions in 10 days. However, there is low
conversion (<10%) when Ag2CO3 is used as inorganic base in the
reaction of 2,3-dihydrofuran with phenyl triflate under reflux condi-
tions in 10 days when THF is used as the polar solvent. At room
temperature no appreciable formation of 1a or 1b is observed in
all reactions. The best activity and regio- or enantioselectivity are
achieved with iodobenzene as substrate, THF as polar solvent and
Ag2CO3 as inorganic base under reflux conditions. For these
optimized conditions conversion is high (<95%) but enan-
tioselectivities (<28%) and regioselectivities (<74%) are moderate
for the phenylation of 2,3-dihydrofuran. In another test reaction,
the use of THF as polar organic solvent and DIPEA or proton sponge
as organic base does not give improved conversion. Each catalytic
reaction was carried out three times to examine reproducibility.
Considering the number of reports that have dealt with the prep-
aration of efficient chiral palladium catalyst systems for the asym-
metric Heck reaction, they indicated that either activity or
selectivity is affected by the ligand structure.[8] In this study, ligand
structure was studied with C2-symmetric bis(phosphinites) 5–8. The
highest enantio- and regioselectivity is obtained from complex 12,
which bears ligand 8. The results clearly indicate that when the
10
11
12
I
I
I
240
240
240
<10
<10
<10
—
—
—
—
—
—
—
—
—
9
I
I
I
I
24
24
97
98
68/32
72/28
70/30
74/26
—
20(S)
23(S)
27(S)
28(S)
—
12(S)
10(S)
15(S)
13(S)
—
10
11
12
9
48
95
72
97
OTf Ag2CO3
OTf Ag2CO3
OTf Ag2CO3
OTf Ag2CO3
240
240
240
240
<10
<15
<10
<10
10
11
12
—
—
—
—
—
—
—
—
—
aCatalyst 9–12 (0.03 mmol), organic solvent (THF) (3 ml), base (3 mmol),
phenyl triflate or iodobenzene (1 mmol), 2,3-dihydrofuran (5 mmol).
bDetermined by GC (three independent catalytic experiments).
cRatios determined by GC with Chiraldex G-TA 30 M column at 70°C.
chiral centre is present near the metal centre, high enantio- and
regioselectivity is observed.
Acknowledgements
Analysis and research were supported by the Dicle University
Science and Technology Application and Research Center (DUBTAM)
which is gratefully acknowledged. Financial support from Dicle
University Research Fund DUBAP (project no. 13-FF-114) is grate-
fully acknowledged. The authors thank Prof. Dr Yılmaz Turgut
(Dicle University) for valuable contributions.
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sion of this article at the publisher’s web site.
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Appl. Organometal. Chem. 2016, 30, 193–198