Synthesis of meta-substituted monodentate phosphinite ligands and implication in hydroformylation ?

Article abstract of DOI:10.1007/s12039-017-1341-z

Abstract: Synthesis of meta-substituted phosphinite ligands 3,3^′-(methoxyphosphanediyl)bis(N,N- diethylaniline) (4a) and methoxybis(3-methoxyphenyl)phosphane (4b), in high yields, has been demonstrated. Typical phosphorus chemical shift between 110–120 ppm, appearance of methoxy protons and corresponding carbon, as well as ESI-MS spectra unambiguously confirmed the existence of phosphinite ligands 4a and 4b. To demonstrate the synthetic usefulness of 4a and 4b, these ligands were tested in the rhodium catalyzed hydroformylation of 1-octene. The diethylamine substituted ligand 4a was found to be highly active, whereas 4b was less reactive but revealed slightly better regioselectivity of 62% under optimized conditions. Additionally, 4a and 4b were found to catalyze the hydroformylation of styrene, 1-undecenol and 1,1-disubstituted functional olefin, methyl methacrylate. Both the ligands displayed excellent conversion of styrene, and 4b revealed an excellent branch selectivity of 75%. Although 1-undecenol proved to be amenable to hydroformylation (85–90% conversion to aldehyde), both the ligands failed to discriminate between the linear and branched products. Substrate methyl methacrylate proved to be highly challenging and reduced conversion (between 33–42%) was observed under optimized conditions. Ligand 4a was found to be highly selective towards linear aldehyde (81% linear selectivity). Graphical Abstract: Synopsis Two step synthetic protocol to access meta-substituted monodentate phosphinite ligands 3,3^′-(methoxyphosphanediyl)bis(N,N-diethylaniline) (4a) and methoxybis(3-methoxyphenyl)phosphane (4b) has been developed and the ligands have been fully characterized. Apart from catalyzing the hydroformylation of benchmark substrates 1-octene and styrene, 4a and 4b were found to catalyze the hydroformylation of 1-undecenol, a functional olefin and a highly challenging 1,1-disubstituted functional olefin methyl methacrylate. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s12039-017-1341-z

J. Chem. Sci.
© Indian Academy of Sciences
DOI 10.1007/s12039-017-1341-z
REGULAR ARTICLE
Synthesis of meta-substituted monodentate phosphinite ligands
†
and implication in hydroformylation
a
a
a
SATEJ S DESHMUKH , SHAHAJI R GAIKWAD , SWECHCHHA PANDEY ,
b
a,c,∗
PRAMOD S MALI and SAMIR H CHIKKALI
Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road,
Pune, Maharashtra 411 008, India
a
b
Central NMR facility, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune,
Maharashtra 411 008, India
c
Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg,
New Delhi 110 001, India
E-mail: s.chikkali@ncl.res.in
MS received 25 April 2017; revised 9 July 2017; accepted 9 July 2017
ꢀ
Abstract. Synthesis of meta-substituted phosphinite ligands 3,3 -(methoxyphosphanediyl)bis(N,N-
diethylaniline) (4a) and methoxybis(3-methoxyphenyl)phosphane (4b), in high yields, has been demonstrated.
Typical phosphorus chemical shift between 110–120 ppm, appearance of methoxy protons and corresponding
carbon, as well as ESI-MS spectra unambiguously confirmed the existence of phosphinite ligands 4a and 4b.
To demonstrate the synthetic usefulness of 4a and 4b, these ligands were tested in the rhodium catalyzed
hydroformylation of 1-octene. The diethylamine substituted ligand 4a was found to be highly active, whereas
4
4
b was less reactive but revealed slightly better regioselectivity of 62% under optimized conditions. Additionally,
a and 4b were found to catalyze the hydroformylation of styrene, 1-undecenol and 1,1-disubstituted functional
olefin, methyl methacrylate. Both the ligands displayed excellent conversion of styrene, and 4b revealed an
excellent branch selectivity of 75%. Although 1-undecenol proved to be amenable to hydroformylation (85–
90% conversion to aldehyde), both the ligands failed to discriminate between the linear and branched products.
Substrate methyl methacrylate proved to be highly challenging and reduced conversion (between 33–42%) was
observed under optimized conditions. Ligand 4a was found to be highly selective towards linear aldehyde (81%
linear selectivity).
Keywords. Phosphinite ligands; m-phosphinites; rhodium catalyst; hydroformylation.
1
. Introduction
these organo-phosphorus ligands, compounds bearing
two P-C and one P-O bond are named as phosphinite.
The electronic quantification measured in terms of χ-
Manipulating the reactivity of a metal center has been
central to the development of homogeneous catalysis
and a variety of ligands have been employed to tame
the metal. Among the wide array of ligands, applica-
tion of organo-phosphorus compounds in homogenous
catalysis has grown enormously in the recent past as they
offer control over reactivity, selectivity or both. Hence,
synthesis of organo-phosphorus ligands such as phos-
phine, phosphinite, phosphonite, phosphite, phos-
phoramidite, etc., has become indispensable. Among
9
parameter and steric crowding calculated by Tolman
10
cone angle ranks them between phosphine and phos-
phonite. Due to the characteristic electronic and steric
properties phosphinite offer, they have been popularly
employed in organic transformations such as Mitsunobu
reaction and Arbuzov reaction, to name a few.11 Apart
from organic synthesis, phosphinite ligands find appli-
cations in a variety of metal catalyzed transformations
as depicted in Figure 1. Notable among these are hydro-
genation, transfer hydrogenation, Suzuki-Miyaura cou-
pling, Mizoroki-Heck coupling, hydroformylation, and
1
2
3
4
5
6
7
8
*
For correspondence
†
Dedicated to Prof. K C Kumara Swamy on the occasion of his 60th
12
allylation. Recent surge in phosphinite derived pincer
birth anniversary.
Electronic supplementary material: The online version of this article (doi:10.1007/s12039-017-1341-z) contains supplementary material,
which is available to authorized users.

Satej S Deshmukh et al.
a synthetic methodology that can provide direct access
to meta-substituted phosphinites.
Herein, we report a synthetic method that provides
direct access to meta-substituted phosphinites with
electron donating substituents. Synthetic utility of the
meta-substituted phosphinites has been demonstrated
by evaluating the performance of these ligands in the
hydroformylation of 1-octene, styrene, 1-undecenol and
methyl methacrylate.
2
. Experimental
2.1 General
All experimental manipulations were performed under an
inert atmosphere of dry nitrogen or argon using standard
Schlenk techniques or glove box. Requisite solvents were
purified by conventional procedures and distilled prior to
usage. 1,1-dichloro-N, N-diethylphosphanamine was pre-
pared according to published procedure.21 The rhodium
Figure 1. Applications of phosphinite ligands in homoge-
neous catalysis.
precursor [Rh(acac)(CO) ] was procured from Acros Organ-
2
complexes has opened up new avenues and unexplored
territories.
Given the significance of phosphinites, there have
been consistent efforts to prepare them in minimum
steps. Literature survey suggests that two synthetic
protocols have been commonly utilized to synthe-
ics and used without further purification. Syngas (1:1 mixture
of CO:H2) was supplied by Ms. Vadilal Chemicals Ltd., Pune,
India. Common reagents were obtained from local suppliers
13
(Spectrochem Pvt. Ltd.; Avra Synthesis Pvt. Ltd.; Thomas
Baker Pvt. Ltd., etc.) and used after purification. Hydroformy-
lation was run in a high-pressure reactor (Amar Equipment
size phosphinites. In a very frequently used method, Pvt. Ltd.) equipped with pressure regulators and safety rup-
chlorophosphines have been treated with alcohols to ture valve. Solution NMR spectra were recorded on a Bruker
14
yield desired phosphinites. In a second method, Avance 200, 400 and 500 MHz instruments. Coupling con-
stants are given as absolute values. Multiplicities are given
Grignard reagent is reacted with methoxy chlorophos-
phines or substituted aryls are lithiated and treated
15
as follows; s: singlet, d: doublet, t: triplet, m: multiplet, dd:
doublet of doublet. Mass spectra were recorded on Thermo
scientific Q-Exactive (the column specification is Hypersil
gold C18 column diameter, 50 × 2.1 mm; particle size,
with aminodichlorophosphine in the first step, which
is then followed by methanolysis.16 Above two meth-
ods are very frequently used to synthesize ortho- and
para-substituted phosphinite ligands.17 However, syn-
thesis of meta-substituted phosphinite ligands is rarely
1.9 µm; mobile phase used, 90% methanol + 10% water +
0.1% formic acid) instrument. GC analysis for 1-octene was
carried out on an Agilent 7890B GC system using HP-05 col-
18
reported. This is most likely due to the classical
mesomeric effect, which imparts higher probability of
umn (30 m × 320 µm × 0.25 µm), split ratio 30:1, column
◦
flow 1.5 mL/min., injector temperature of 260 C, detector
◦
substitution/addition at ortho and para-position and temperature of 330 C, and argon carrier gas. Temperature
◦
disfavors substitution/addition at meta-position. In addi- program: Initial temperature 70 C, hold for 1 min; ramp
◦
◦
◦
◦
tion, effect of meta-substitution on catalytic activity or 1: 4 C/min to 120 C; ramp 2:10 C/min. to 250 C; ramp 3:
◦ ◦
0 C/min. to 320 C, hold for 2 min. Retention time for 1-
19
2
selectivity of a specific reaction is still in its infancy.
octene = 2.1 min; branched aldehydes = 6.0–7.1 min; linear
aldehyde = 8.1 min (Figure S28 in SI). GC analysis for styrene
wascarriedoutonanAgilent7890BGCsystemusingSupelco
β-dex column (30 m × 0.25 mm × 0.25 µm), split ratio 30:1,
In particular, phosphinites are the ligands of choice for
some reactions like hydroformylation due to their strong
π-accepting character and investigating the effect of
meta-substitution in this reaction will be of great sig-
nificance. The character and position of a substituent
on ligand backbone can substantially tailor the catalytic
properties and might alter the reactivity or selectivity of
a catalytic reaction. At times, it can completely shut
◦
inlet temperature of 220 C, and argon carrier gas. Tempera-
20
◦
ture program: Initial temperature 100 C, hold for 2 min.; ramp
1
◦
◦
◦
◦
: 2 C/min to 160 C; ramp 2: 20 C/min to 210 C, hold for
2
min Retention time for styrene = 7.3 min.; hydrogenated
product (ethyl benzene) = 6.3 min.; for branched aldehyde =
down one reaction pathway and improvise the other 17.0 min., linear aldehyde = 23.2 minute (Figures S30–S31
pathway. In this context, it is highly desirable to develop in SI).

m-Phosphinites: synthesis and hydroformylation
2.2 Synthesis of 3-bromo-N,N-diethylaniline (2a)
(d, JP−C = 6.82 Hz), 129.6 (d JC−H = 6.68 Hz), 120.4 (d,
JC−H = 19.07 Hz), 116.7 (d, JC−H = 23.8 Hz), 112.6, 45.3
3
1
(
d, JC−H = 15.26 Hz), 44.2, 15.3 (d, JC−H = 2 Hz), 13.1.
P
NMR (500 MHz, C6D6): δ = 64.64.
ꢀ
2
.4 Synthesis of 3,3 -(methoxyphosphanediyl)
bis(N,N-diethylaniline) (4a)
Precursor 2a was prepared by a modified literature proce-
dure.22 3-bromoaniline (5.0 g, 29.07 mmol) was added to a
suspension of sodium hydride (NaH) (1.5 g, 63.95 mmol)
◦
in tetrahydrofuran (THF) (50 mL) at 0 C under positive
argon flow and the reaction mixture was stirred for 2 h.
Next, ethyl iodide (9.97 g, 63.95 mmol) was added to the
above suspension and the violet coloured reaction mixture
was stirred at room temperature for 5 h. Finally, the reaction
was quenched with water, and organic layer was extracted
with ethyl acetate (three times). The combined extracts were
washed with brine and dried over sodium sulfate. Volatiles
were evaporated under vacuum and the resultant residue was
purified by column chromatography (using pet-ether) to pro-
Compound 3a (0.5 g, 1.25 mmol) was dissolved in 20 mL
methanol (MeOH) and stirred for 8 h at room temperature.
Volatiles were evaporated to obtain solid residue which was
extracted with hexane (2×10 mL). The resultant hexane was
evaporated under reduced pressure to obtain yellow coloured
compound in quantitative (>99%) yield (0.444 g), which
1
duce compound 2a in 40% isolated yield. H NMR (400 MHz,
CDCl3): δ = 7.08 (dd, J = 8.0, 7.6 Hz, 1H), 6.80 (m, 2H),
1
was identified as 4a. H NMR (500 MHz, C6D6): δ = 7.30
6
1
.60 (dd, J = 7.7, 1.83 Hz, 1H), 3.35 (q, J = 6.87 Hz, 4H),
.20 (t, J = 6.87 Hz, 6H).
(
m, 6H), 6.64 (dd, JH−H = 1.83, 8.24 Hz, 2H), 3.66 (d,
JH−H = 13.43 Hz, 3H), 3.07 (q, JH−H = 7.02 Hz, 8H), 0.96
1
3
(
t, JH−H = 7.02 Hz, 12H). C NMR (125 MHz, C6D6):
ꢀ
2
.3 Synthesis of 3,3 -((diethylamino)
δ = 148.2 (CNEt2, Ar), 143.8 (CPOMe, Ar), 129.9 (CH,
Ar), 118.7 (CH, Ar), 114.5 (CH, Ar), 113.5 (CH, Ar), 56.6
phosphanediyl)bis(N,N-diethylaniline) (3a)
(
(
OCH3), 44.8 (NCH2CH3), 13.0 (NCH2CH3). 31P NMR
500 MHz, CDCl3): δ = 120.4. ESI-MS (+ve mode) m/z =
+
3
59.22 [M+H] .
2.5 Synthesis of N,N-diethyl-1,1-bis
(
3-methoxyphenyl)phosphanamine (3b)
To a solution of N,N-diethyl-3-bromoaniline (2a) (5 g,
2
1.91 mmol) in diethyl ether (Et2O) was added n-butyl
◦
lithium (n-BuLi) (15.06 mL, 24.10 mmol) at 0 C. After com-
plete addition, reaction mixture was slowly warmed to room
temperature and was stirred for 3 h. Next, a solution of 1,1-
dichloro-N,N-diethylphosphanamine (1.90 g, 10.95 mmol)
in diethyl ether was added over 7 min to the above reaction A solution of 3-bromoanisole (5 g, 26.73 mmol) in diethyl
◦
mixture at 0 C with constant stirring. The reaction mixture ether (60 mL) was treated with n-BuLi (18.4 mL, 29.4 mmol)
◦
◦
was stirred for 12 h at 25 C. The resultant lithium bro- at 0 C. After complete addition, the reaction mixture was
mide was separated by cannula filtration and the filtrate was slowly warmed to room temperature and was stirred for next
evaporated under reduced pressure to yield yellow coloured 3 h. 1,1-dichloro-N,N-diethylphosphanamine (2.32 g, 13.3
residue. The residue was extracted in hexane to isolated yield mmol) was slowly (over 7 min) added to above reaction mix-
ꢀ ◦
2% (6.3 g) of 3,3 -((diethylamino)phosphanediyl)bis(N,N- ture at 0 C with constant stirring. The reaction was stirred
7
1
◦
diethylaniline) (3a). H NMR (500 MHz, C6D6): δ = 7.22 for 12 h at 25 C and lithium bromide salt was separated
t, JH−H = 8.77 Hz, 2H), 7.07 (m, 4H), 6.55 (dd, JH−H = 2 by cannula filtration. The resultant solution was evaporated
Hz, 2H), 3.23 (m, 4H), 3.01 (qd, JH−H = 2 Hz, 8H), 1.00 (t, under reduced pressure to yield a yellow coloured residue.
(
1
3
JH−H = 7.06 Hz, 6H), 0.90 (t, JH−H = 7.25 Hz, 12H).
C
The residue was extracted in hexane to isolate 3b in 56.6%
1
NMR (125 MHz, C6D6): δ = 148.2 (d, J = 6.82 Hz), 142.5 (3.94 g) yield. H NMR (500 MHz, CDCl3): δ = 7.22 (t, J

Satej S Deshmukh et al.
=
7.63 Hz, 2H), 6.97 (m, 4H), 6.82 (d, J= 8.39 Hz, 2H), 3. Results and Discussion
3.73 (s, 6H), 3.07 (q, J = 7.25 Hz, 4H), 0.95 (t, J = 7.25
1
3
Hz, 6H). C NMR (125 MHz, CDCl3): δ = 159.4 (d, J = 3.1 Ligand synthesis
6
1
4
.68 Hz), 141.9 (d, J= 15.26 Hz), 129.1 (d, J= 6.68 Hz),
24.3 (d, J= 20.03 Hz), 117.2 (d, J= 20.98 Hz), 113.8, 55.1, The precursor 2a was prepared by a modified literature
4.5 (d, J= 15.26 Hz), 14.5. 31P NMR (500 MHz, CDCl3): procedure. 3-bromoaniline (1a) was treated with ethyl
22
δ = 62.34.
iodide in presence of a base (NaH) and purification by
column chromatography produced 2a in 40% isolated
yield. After confirming the existence of 2a, it was treated
◦
withn-butyllithiumat0 C, whichwasfollowedbyaddi-
2
.6 Synthesis of methoxybis(3-methoxyphenyl)
tion of 1,1-dichloro-N,N-diethylphosphanamine (in
diethyl ether). The reaction mixture was stirred for 12
h, the by-product (LiBr) was separated by filtration
and the filtrate was concentrated under reduced pres-
sure to produce yellow viscous oily residue. Extraction
phosphane (4b)
ꢀ
of the residue with hexane produced anticipated 3,3 -
(
(diethylamino)phosphanediyl)bis(N,N-diethylaniline)
3
a in 72% isolated yield. Single resonance at 64.6 ppm
31
in P NMR (Figure S2 in SI) suggested formation of
a. The phosphorus NMR findings were corroborated
by proton NMR, which revealed characteristic triplet at
.0 ppm for the methyl protons and a multiplet at 3.23
ppm for the methylene protons. The P-C bond formation
3
1
13
Compound 3b (0.5 g, 15.75 mmol) was dissolved in 20 mL
MeOH and stirred for 8 h at room temperature. Volatiles
were evaporated and the resultant residue was extracted with
hexane (2 × 10 mL). The hexane solution was evaporated
under reduced pressure to obtain yellow coloured compound
in quantitative yield (97.5%), 0.424 g (15.36 mmol), which
was confirmed by C NMR, which displayed a peak at
42.5 ppm corresponding to the P-coupled carbon (SI
1
Figure S3–S5).
In the final step to phosphinite, isolated 3a was treated
with methanol and the progress of the reaction was
31
1
monitored by P NMR spectroscopy. The phosphorus
resonance at 64.6 ppm slowly disappears with a con-
comitant appearance of a new peak at 120.4 ppm (Figure
was identified as 4b. H NMR (500 MHz, CDCl3): δ = 7.28
(
2
d, J = 6.49 Hz, 2H), 7.04 (m, 4H), 6.86 (d, J = 7.25 Hz,
1
3
H), 3.76 (s, 6H), 3.64 (d, J = 14.11 Hz, 3H). C NMR (125
31
S6). Thus, P NMR indicated completion of the reac-
9.07 Hz), 129.6 (d, J = 7.6 Hz), 122.8 (d, J = 22.8 Hz), tion in 8 hours, after which volatiles were evaporated
MHz, CDCl3): δ = 159.6 (d, J = 7.63 Hz), 143.1 (d, J =
1
1
3
1
15.4, 115.3, 57.0 (d, J = 19.07 Hz), 55.3. P NMR (500 to produce the anticipated 4a in near quantitative yield
31
MHz, CDCl3): δ = 116.81. ESI-MS (+ve mode) m/z = 277.09 (>99%) (Scheme 1). A singlet in P NMR at 120.4
+
[
M+H] .
ppm indicated formation of P-OMe bond, whereas the
doublet at 3.67 in proton NMR further supported for-
mation of 4a. The existence of 4a was unambiguously
ascertained using combination of 1-2D NMR and mass
spectroscopy. The formation of P-OMe was illustrated
by recording a long range P-H correlation (HMBC)
NMR spectrum, which revealed a cross peak between a
phosphorus resonance at 120.4 and a proton resonance
2.7 General procedure for hydroformylation
In a typical hydroformylation experiment a stainless steel
autoclave (450 mL) equipped with pressure regulator and a
safety valve was used. Individual vials were charged with
metal precursor {[Rh(acac)(CO) ] (2 mg)}, ligand (as in at 3.67 ppm (Figure 2). The NMR findings were further
2
Tables 1 and 2), solvent (1 mL), substrate (100 equiv.) and corroborated by ESI-MS that revealed a molecular ion
+
stirring bars in a glove box. The vials were transferred to auto- peak at m/z = 359.22 [M+H] (Figure S12).
clave and the autoclave was purged three times with syngas
In our attempts to test the generality of the synthetic
protocol, we extended the scope to methoxy derivatives.
In this case, commercially available 3-bromoanisole
(CO: H2 = 1:1) before pressurizing it to the desired pressure.
Suitable temperature and pressure were maintained during
the reaction. After completion of the reaction, the autoclave
(
2b)waslithiatedusingn-BuLiandtheresultantsaltwas
◦
was cooled to 0 C, and excess gas was vented off in a well-
treated with 1,1-dichloro-N,N-diethylphosphanamine.
The reaction mixture was stirred for 12 h, solids were
separated by filtration and the filtrate was evaporated
ventilated fume-hood. The conversion and regio-selectivities
were determined by proton NMR spectroscopy and gas chro-
matography.

m-Phosphinites: synthesis and hydroformylation
Table 1. Rhodium catalyzed hydroformylation of 1-octene using 4a–b.a
◦
b
l:b selectivityb
Run
Ligand
L/M Ratio Temp. ( C) CO/H2 (bar) Time (hrs) Conversion (%)
1
2
3
4
5
6
7
8
9
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
4b
4b
4b
4b
5
2
4
6
4
4
4
4
2
4
6
4
4
4
4
5
2
100
100
100
100
100
120
80
100
100
100
100
100
120
80
10
10
10
5
20
10
10
10
10
10
5
20
10
10
20
30
16
16
16
16
16
16
16
16
16
16
16
16
16
16
4
92
94
97
60
97
37
70
36
33
24
15
87
56
53
96
98
44:56
51:49
55:45
39:61
49:51
50:50
15:85
44:56
47:53
49:51
52:48
54:46
62:38
30:70
67:33
69:31
10
11
12
13
14
15
16
c
c
100
60
6
6
a
b
Conditions: [Rh(acac)(CO) ] = 2 mg, Solvent: toluene (1 mL), Conversion and regioselectivity were determined
2
c
by GC, Comparision with literature reported ligands 5 and 6 (see Chart 1 for details). Note that the reaction
conditions reported in these runs may not be same as run 1–14. For report on ligand 5, see Ref. and for the report
on ligand 6, see Ref.24
1
9
under vacuum. The resultant residue was extracted 3.2 Rhodium catalyzed hydroformylation of 1-octene
with hexane and evaporation of hexane solution under
Hydroformylation of alkenes is arguably one of the
largest processes in industrial homogeneous cataly-
reduced pressure produced highly viscous material in
6.6% isolated yield, which was identified as N, N-
diethyl-1,1-bis(3-methoxyphenyl)phosphanamine (3b).
5
23
sis. Phosphorus ligands play prominent role in the
hydroformylation of variety of substrates. Among the
phosphorus ligands, phosphinites stand out as a good
σ-donor and strong π-acceptor ligands. Therefore,
rhodium catalyzed hydroformylation of 1-octene was
selected as a test reaction to evaluate the performance
of newly prepared meta-substituted phosphinite ligands.
After the successful synthesis of meta-phosphinites 4a–
b, we set out to evaluate their performance in the
hydroformylation of 1-octene and Table 1 summarizes
the most important results. It is anticipated that the nec-
essary catalyst for hydroformylation is generated in situ
31
Appearance of a P NMR resonance at 62.34 ppm along
with proton signals at 0.95 and 3.07 ppm for methyl
and methylene protons respectively confirmed the for-
mation of C-P bond. In a second step, suitable quantity
of methanol was added to 3b and the reaction solution
was stirred for 8 h. The resultant compound was puri-
fied by extraction with hexane to produce a semisolid
material, which was analysed by various techniques to
31
establish the identity. Thus, the P NMR spectrum of
isolated material revealed a new peak at 116.8 ppm,
which can be comfortably assigned to the anticipated
product methoxybis(3-methoxyphenyl)phosphane 4b.
Consistent with these results, the proton NMR of above
material disclosed decay of the diethyl amine signals
with simultaneous emergence of a new peak at 3.64 ppm
upon reaction of rhodium precursor [Rh(acac)(CO)2]
and the ligand (4a/4b), in presence of alkene under syn-
gas pressure. Preliminary screening of ligand to metal
ratio pointed to an optimal ligand to metal ratio of 4
with a competitive conversion of 94% (Table 1, run 1–
(
that can be easily assigned to methoxy protons directly
3
). Keeping the L/M ratio 4, we screened the effect of
located on phosphorus). The NMR findings were fur-
ther supported by ESI-MS (+ve mode) which revealed a
syngas pressure on conversion and regioselectivity. As
it is evident from Table 1, either reducing the pressure
to 5 bars or increasing it to 20 bars had negative impact
and led to reduced selectivity (Table 1, run 4–5). Thus,
syngas pressure of 10 bars seems to be the optimal pres-
+
molecular ion peak at m/z = 277.09 [M+H] (Figure 3).
The observed splitting pattern closely matches with the
simulated splitting pattern (Figure 3), authenticating the
existence of 4b.

Satej S Deshmukh et al.
Table 2. Rhodium catalyzed hydroformylation of styrene (S2), 1-undecenol (S3) and methyl methacrylate
a
(
S4).
Run Ligand (Substrate) Temp. ( C) CO/H2 (bar) Time (hrs) Conversion (%) l:b selectivityb
◦
b
1
2
3
4
5
6
4a (S2)
4b (S2)
4a (S3)
4b (S3)
4a (S4)
4b (S4)
100
100
100
100
100
120
10
10
10
10
10
10
16
16
16
16
16
16
99 (85)
99 (80)
99 (85)
96 (90)
62 (42)
33 (33)
34:66c
25:75
51:49
51:49
81:19
67:33
a
Conditions: [Rh(acac)(CO) ] = 2 mg, L/M = 4, Solvent: toluene (1 mL). S2: styrene, S3: 1-undecenol, S4:
2
methyl methacrylate; b Total conversion (conversion to aldehyde in parenthesis) & regioselectivity were
determined by proton NMR spectroscopy using CH2Br2 (equimolar to substrate) as an internal standard;
c
Regioselectivity was determined by GC.
Scheme 1. Synthesis of m-substituted phosphinites with electron donating functional groups.
sure. Next, the effect of temperature was investigated run 9), although the conversion and selectivity was con-
and it was found that the conversion as well as regios- siderably poor as compared to 4a. Reducing syngas
◦
electivity reduces at 80 C. Increasing the temperature pressure to 5 bars at a L/M ratio of 4 further reduced
◦
to 120 C showed similar trend with reduced conversion the conversion to 15% only, with 52% linear alde-
and selectivity. Thus, the best conversion of 94% could hyde (Table 1, run 11). Whereas, increasing the syngas
be obtained at a linear selectivity of 51% (Table 1, run 2). pressure led to the best conversion of 87%, without a
Along the same line, preliminary screening for 4b penalty on regioselectivity (which was 54:46). Increas-
◦
indicated an optimal ligand to metal ratio of 4 (Table 1, ing the temperature to 120 C led to a better linear

m-Phosphinites: synthesis and hydroformylation
Figure 2. A long range P-H correlation (HMBC) spectrum of 4a depicting the phosphorus-proton cross peak.
Figure 3. ESI-MS (+ve mode) spectrum of 4b, depicting the observed and simulated (inset) spectra.
selectivity of 62%, but at the cost of slightly reduced literature reported19,24 monodentate phosphinite ligands
conversion (Table 1, run 13). Overall, the monoden- 5, 6 presented in run 15 and 16 which are depicted in
tate meta-substituted ligands were found to catalyze Chart 1. These findings indicate that electron deficient
hydroformylation of 1-octene and the best linear regios- phosphinites will be better suited for higher activi-
electivity of 62% was obtained while employing 4b. ties, whereas, electron rich sterically demanding phos-
The thus obtained regioselectivity compares well with phinites will be more effective for (regio)selectivity.

Satej S Deshmukh et al.
(a)
(b)
Chart 1. Ligands employed in the hydroformylation of 1-octene; (a) this work (left) and
b) phosphinites reported in the literature (right).
(
In our attempts to broaden the substrate scope, to catalyze the hydroformylation of routine substrates
performance of 4a and 4b was evaluated in the hydro- such 1-octene; more importantly, these ligands are able
formylation of styrene (S2), 1-undecenol (S3) and a to catalyze hydroformylation of functional olefin, as
highly challenging 1,1-disubstituted electron deficient well as a highly challenging 1,1-disubstuted functional
1
olefin, methyl methacrylate (S4). Hydroformylation of olefins.
S2–S4 was performed under optimized conditions and
Table 2 presents the important results. As a representa-
4
. Conclusions
tive of aromatic substrate, hydroformylation of styrene
using 4a was attempted, that led to quantitative con-
version under optimized conditions (Table 2, run 1).
An enhanced branch selectivity of 75% was obtained
without compromising the activity when 4b was used
as ligand. Functional olefins are of great interest as
the resultant hydroformylation products can be used
as monomer for polycondensation reactions. However,
hydroformylation of functional olefins is more challeng-
ing, as the functional group can potentially poison the
catalyst. To evaluate the performance of 4a–b in func-
tional olefin hydroformylation, we choose 1-undecenol
Insummary, twostepprotocoltoaccessmeta-substituted
phosphinites 3,3 -(methoxyphosphanediyl)bis(N,N-di-
ꢀ
ethylaniline) (4a) and methoxybis(3-methoxyphenyl)
phosphane (4b) in high yields has been established.
Bromo-aniline and bromo-anisole were lithiated and
treated with 1,1-dichloro-N,N-diethylphosphanamine
ꢀ
to yield intermediate 3,3 -((diethylamino)phosphanediy
l)bis(N,N-diethylaniline) (3a) and N, N-diethyl-1,1
-
bis(3-methoxyphenyl)phosphanamine (3b), respectiv-
ely. Addition of methanol to 3a and 3b led to the
generation of new resonance between 110–120 ppm in a
(S3) (undec-10-en-1-ol). Hydroformylation of S3 under
31
P NMR spectrum, indicating the formation of desired
optimized conditions revealed 85% conversion to 12-
hydroxy dodecanal, without discriminating the linear
over branched (Table 2, run 3) product. Similar results
were obtained when 4b was employed as a ligand in
the hydroformylation of S3 (Table 2, run 4). The thus-
prepared 12-hydroxy dodecanal is key intermediate
to obtain a hydroxy-acid, which can be used as AB-
type monomer for polyester synthesis. 1,1-disubstituted
functional olefins are even more challenging for two rea-
sons: i) due to two substituents on the same carbon atom,
and they are sterically encumbered; ii) the functional
group can bite back to the metal, leading to catalyst
deactivation and loss of activity. Indeed, hydroformy-
lation of methyl methacrylate (S4) using 4a displayed
reduced formylation activity of 42%, while the linear
aldehyde product was obtained with 81% selectivity
phosphinites (4a and 4b). These findings were corrob-
orated by proton and carbon NMR. Thus, the existence
of 4a and 4b was unambiguously ascertained using a
combination of 1-2D NMR and mass spectroscopy. The
synthetic utility of the phosphinite ligands was demon-
strated by evaluating 4a and 4b in the rhodium catalyzed
hydroformylation of 1-octene. It was found that 4a is far
more active (with 94–97% conversion) than 4b under
identical conditions. Although 4b led to poor activ-
ity, it displayed slightly better selectivity of 62% linear
nonanal. In addition, 4a and 4b were found to catalyze
the hydroformylation of styrene (S2), a functional olefin
(S3) as well as a highly challenging 1,1-disubstituted
functional olefin (S4).
Supplementary Information (SI)
(
Table 2, run 5). Along the same line, 4b displayed
moderate performance with 33% conversion to alde-
hyde and 67% linear selective product (Table 2, run 6).
Thus, the phosphinite ligands 4a and 4b were found
1H, 13C, 31P, HSQC, HMBC, COSY, NOESY spectra of 3a,
3b, 4a and 4b, mass spectra of 4a and 4b are available at
www.ias.ac.in/chemsci.

m-Phosphinites: synthesis and hydroformylation
P-H bond addition reaction: A case study of hydrophos-
Acknowledgements
phination Coord. Chem. Rev. 265 52
. Tolman C A 1970 Electron donor-acceptor properties of
phosphorus ligands. Substituent additivity J. Am. Chem.
Soc. 92 2953
Financial support from SERB-DST (SR/S2/RJN-11/2012 and
EMR/2016/005120), India, is gratefully acknowledged. SSD,
SP and SRG would like to thank UGC and CSIR, respectively,
9
for the senior research fellowship. CSIR-National Chemical 10. Tolman C A 1977 Steric effects of phosphorus ligands
Laboratory is gratefully acknowledged for additional sup-
port. SHC is indebted to AvH foundation Bonn, Germany,
for equipment grant.
in organometallic chemistry and homogeneous catalysis
Chem. Rev. 77 313
1. (a) van den Goorbergh J A M and van der Gen A
1
1980 Ethyl 4-diphenylphosphinoyl-2-oxobutanoate: A
convenient reagent for the synthesis of γ -ketoesters
Tetrahedron Lett. 21 3621; (b) Bhattacharya A K and
Thyagarajan G 1981 The Michaelis-Arbuzov rearrange-
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