Nickel-catalyzed C-P cross-coupling reactions of aryl iodides with H-phosphinates

Article abstract of DOI:10.1016/j.tet.2015.07.073

Synthesis of aryl phosphinates was achieved through cross-coupling reactions of aryl iodides with H-phosphinates catalyzed by nickel under mild conditions. The method was applicable to various aryl iodides and H-phosphinates having defined stereochemistry

Full text of DOI:10.1016/j.tet.2015.07.073

Tetrahedron xxx (2015) 1e6
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Nickel-catalyzed CeP cross-coupling reactions of aryl iodides
with H-phosphinates
*
Atsushi Kinbara, Momoko Ito, Tohru Abe, Takehiro Yamagishi
School of Pharmacy, Ohu University, 31-1 Misumido, Tomita-machi, Koriyama, Fukushima 963-8611, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthesis of aryl phosphinates was achieved through cross-coupling reactions of aryl iodides with
H-phosphinates catalyzed by nickel under mild conditions. The method was applicable to various aryl
iodides and H-phosphinates having defined stereochemistry at the phosphorus atom.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 18 June 2015
Received in revised form 27 July 2015
Accepted 28 July 2015
Available online xxx
Keywords:
Aryl phosphinates
CeP cross-coupling reactions
Ni catalyst
1. Introduction
reported the nickel-catalyzed inert CeO/PeH cross-coupling re-
action of H-phosphinate with 2-naphthyl pivalate in place of the
Phosphinic acid derivatives have attracted significant attention
due to their utility in the development of biologically active com-
pounds1 and organocatalysis.2 Some arylphosphinic acid de-
rivatives function as thrombin inhibitors,3 calpain inihibitors,4 HIV-
1 reverse transcriptase inihibitors,5 and mimetics of C-aryl-glyco-
sides, designated as phosphinosugars, which show antiproliferative
properties with respect to central nervous system cell lines.6
Arylphosphinic acid derivatives have been prepared via nucleo-
philic substitutions of the corresponding phosphorus chlorides
with Grignard reagents.7 Alternative synthesis has been achieved
by the CeP cross-coupling reactions of aryl halides or related
compounds with H-phosphinates catalyzed by transition metals,
which is a powerful and efficient method.8 In these reactions,
palladium9 and copper10 have frequently been utilized as the cat-
alyst to attain high turnover numbers and chemical yields. The
manganese-mediated arylation of H-phosphinates with arenes
have also been reported.11 Although nickel has the advantage of low
cost and easy separation from reaction products compared with
palladium, nickel-catalyzed CeP cross-coupling reactions have
rarely been studied. Tang and co-workers demonstrated that the
reaction of P-chiral H-phosphinate with 4-bromotoluene was suc-
cessfully catalyzed by NiCl2$6H2O/2,20-bipyridine with two equiv-
alents of zinc in aqueous solvent, proceeding with retention of the
phosphorus configuration.12 Quite recently, Han and co-workers
corresponding halide.13 However, the scope and limitation of these
reactions remained unclear because other H-phosphinates and
substrates have not been fully investigated. Thus, we have in-
dependently studied CeP cross-coupling reactions employing Ni
catalysts (Eq. 1), with anticipated applicability for various aryl-
phosphinic acid derivatives, as an extension of our previous work
on Pd-catalyzed CeP cross-coupling reactions of
a-amino-H-
phosphinates with enol triflates.14 In this paper, we will describe
our full experimental results.
ð1Þ
2. Results and discussion
At the outset, cross-coupling reactions of H-phosphinate 2a15
with phenyl iodide 1a were examined in the presence of nickel
complexes under several conditions (Table 1). Upon treatment of 1a
with 2a in the presence of NiCl2$6H2O (10 mol %), 2,20-bipyridine
(bipy) (20 mol %), and zinc (2 equiv) as an additive using water
solvent at 70 ꢀC, according to Tang’s conditions,12 the desired
product 3a was obtained in only 8% yield (entry 1). Employing
toluene or THF as the solvent with anhydrous NiCl2 at 50 ꢀC
resulted in no reaction, with the recovery of 1a (entries 2 and 3).
When the reaction was carried out in polar solvents such as DMSO
or DMF, the chemical yield was improved up to 64% and 75%,
* Corresponding author. Tel./fax: þ81 24 932 9212; e-mail address: t-yamagishi@
pha.ohu-u.ac.jp (T. Yamagishi).
http://dx.doi.org/10.1016/j.tet.2015.07.073
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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2
A. Kinbara et al. / Tetrahedron xxx (2015) 1e6
respectively (entries 4 and 5). In regard to the nickel source, the
reaction also proceeded by using Ni(COD)2 instead of NiCl2 (entry
6). The nickel catalyst was essential, as no formation of 3a occurred
in the absence of a nickel source (entry 7). It was speculated that
the role of zinc might be to reduce NiCl2 to generate a zero valent
nickel species, which suggested that decreasing the amount of zinc
from 2.0 equiv to 0.1 equiv would be possible. Although the re-
action using 0.1 equiv of zinc was investigated, no formation of 3a
took place (entry 8). However, when using 1.2 equiv of zinc, 3a was
formed in 73% yield (entry 9). Thus, the role of zinc might be as-
sociated with not only reducing NiCl2, but also another function in
(entry 6). It was possible to decrease the amount of Et3N from
3.7 equiv to 2.0 equiv while maintaining good yield (94%, entry 7).
Having established the optimum reaction conditions, we next
investigated the scope and limitations of aryl halides (Table 3). The
reaction of 2a with phenyl iodide bearing electron-donating
p-methoxy group 1b and m-methoxy group 1c gave the products
3b and 3c in 96% and 98% yields, respectively (entries 1 and 2). On
the other hand, a considerable decrease in chemical yield was
found in the reaction of 1d having an o-methoxy group (entry 3).
Substrates with electron-deficient methoxycarbonyl groups at
para- and meta-positions furnished products 3e and 3f in good
yields; however, 3g bearing the substituent at the ortho-position
gave a decreased yield (entries 4e6). These results implied that the
reactivity might be highly affected by the steric factors generated
by the neighboring CeI bond. The present reactions were limited to
phenyl iodide derivatives since using phenyl bromide 1h led to
a decrease in yield (entry 7). Although the reaction with 4-
iodopyridine as a substrate having aromatic heterocycle was ex-
amined, formation of the desired product was not detected because
of its decomposition.
the reaction.
A similar chemical yield (70%) was found by
employing 1.0 equiv of zinc (entry 10), which indicated at least
1.0 equiv of zinc would be necessary for the present reaction. In
regard to chemical yield, zinc was a superior reagent to manganese
(entry 11).
Screening of representative monodentate ligands (40 mol %) and
bidentate ligands (20 mol %) was performed next (Eq. 2). In most
cases, the product 3a was not obtained due to its decomposition,
while the desired reaction proceeded to give 3a when using 1,10-
bis(diphenylphosphino)ferrocene (dppf), N,N,N0,N0-tetramethyle-
thylenediamine (tmeda) or bathophenanthroline 4. Their chemical
yields were not improved in comparison with that of bipy (75%),
which showed bipy was the optimal ligand among those examined.
It was important to utilize 20 mol % of bipy because decreasing the
amount to 10 mol % brought about a slight deterioration in chem-
ical yield (67%). Although the exact reason for this remained un-
clear, it might be associated with stability of the Ni complex.
The CeP cross-coupling reactions were attempted using several
kinds of H-phosphinates under the optimized reaction conditions
(Table 4). The reaction of 1a with 2b16 and 2c17 having more bulky
phosphinate moieties in place of 2a proceeded smoothly to give the
products 5b and 5c in 77% and 81% yields, respectively (entries 1
and 2). Substrate 2d18 with a tert-butyl group also gave the product
5d, albeit in a slightly reduced yield (entry 3). Substrate 2e19
bearing a 1,1-diethoxyethyl group, which could be readily re-
moved under mild acidic conditions to give a PeH bond, reacted
with 1a to afford 5e in 72% yield (entry 4). The reaction of com-
mercially available P-chiral H-phosphinate 2f18,20 with 1i pro-
ceeded in a retentive manner, producing 5f in 83% yield as a single
diastereomer, which was analogous to the reported results (entry
5).12 The relative stereochemistry of 5f was confirmed by compar-
ison of the 1H NMR spectrum with that of the reported sample.12
The present reaction was also applicable to racemic diaster-
(2)
eomerically pure a
-amino-H-phoshinate 2g,21 serving as a useful
synthetic intermediate toward phosphinyl dipeptide isosteres,14,22
giving 5g in 62% yield without formation of any other di-
astereomers (entry 6). The relative configuration of 5g was esti-
mated analogously to 5f with the reaction proceeding with
retention of phosphorus configuration.
In order to better understand the present CeP cross-coupling
reactions, the following experiment was conducted. When 2,6-di-
tert-butyl-4-methylphenol (BHT), as a radical scavenger, was added
to the reaction system of 1a with 2a under the optimized condi-
tions, the product 3a was formed without a significant drop in yield
(73% yield). This result excluded the possibility of a radical reaction
mechanism. As shown in Table 1, the reaction proceeded by using
Ni(COD)2 instead of NiCl2, which suggested a zero valent nickel
species might be associated with the catalysis. Based upon the
above experimental results and literature information, a plausible
reaction mechanism is illustrated in Scheme 1. The Ni(0) species,
generated from NiCl2 and bipy in the presence of Zn, oxidatively
adds to aryl iodides to give A. The coordination of A with phos-
phonite 2a0, which is the P(III)-tautomer of H-phosphinate 2a, and
the subsequent HI elimination of B, affords C. Good results by
employing Et3N and Zn in the present reaction might be attributed
to their promoting the HI elimination in the conversion of B into C.
Finally, reductive elimination of C leads to the formation of the
cross-coupling product and regenerates the Ni (0) species.
In our previous study on Pd-catalyzed CeP cross-coupling re-
actions of
a-amino-H-phosphinates with enol triflates, both the
reactivity of H-phosphinates and yields of the products varied
depending upon the basic reagents employed.14 Based on this re-
sult, basic reagents were applied to the present Ni-catalyzed cross-
coupling reactions to improve chemical yields (Table 2). When 1a
was treated with 2a and NaHCO3 (3.7 equiv) in the presence of
NiCl2 (10 mol %), bipy (20 mol %), and zinc (1.2 equiv) in DMF at
50 ꢀC, the reaction proceeded smoothly to give 3a in 87% yield
(entry 1). It was obvious that chemical yield was increased com-
pared to the reaction without base (73%, Table 1, entry 9). An
analogous yield was observed by using Na2CO3 (entry 2), whereas
employing Cs2CO3 led to a significant drop in yield (entry 3). When
organic bases (DABCO, DIPEA, Et3N) were examined (entries 4e6),
we were pleased to find an improvement of yield to 99% with Et3N
3. Conclusion
In conclusion, we have developed a Ni-catalyzed PeC cross-
coupling reaction of aryl iodides with H-phosphinates under mild
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A. Kinbara et al. / Tetrahedron xxx (2015) 1e6
3
Table 1
Effect of solvent and additive
Entry
Ni source
Solvent
Additive (equiv)
Yield (%)a
1b
2
3
4
5
6
7
8
9
NiCl2$6H2O
NiCl2
NiCl2
NiCl2
NiCl2
Ni(COD)2
None
NiCl2
NiCl2
NiCl2
H2O
Toluene
THF
Zn (2.0)
Zn (2.0)
Zn (2.0)
Zn (2.0)
Zn (2.0)
Zn (1.2)
Zn (2.0)
Zn (0.1)
Zn (1.2)
Zn (1.0)
Mn (2.0)
8
0
0
64
75
49
0
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
DMF
0
73
70
57
10
11
NiCl2
a
Isolated yields.
Carried out at 70 ꢀC.
b
Table 2
Effect of base
Table 4
Substrate scope for H-phosphinates
Entry
Base (equiv)
Yield (%)a
1
2
3
4
5
6
7
NaHCO3 (3.7)
Na2CO3 (3.7)
Cs2CO3 (3.7)
DABCO (3.7)
DIPEA (3.7)
Et3N (3.7)
87
81
Trace
57
77
Entry
1
2
5
Yield (%)a
99
94
Et3N (2.0)
1
2
3
1a 2b: R0¼(CH2)9CH3
1a 2c: R0¼i-Pr
5b: R0¼(CH2)9CH3
5c: R0¼i-Pr
77
81
66
a
Isolated yields.
1a 2d: R0¼t-Bu
5d: R0¼t-Bu
Table 3
Substrate scope for aryl halides
4
1a
72
5
6
1i
83
62
1a
Entry
1
R
X
3
Yield (%)a
1
2
3
4
5
6
7
1b
1c
1d
1e
1f
p-MeO
m-MeO
o-MeO
p-CO2Me
m-CO2Me
o-CO2Me
H
I
I
I
I
I
I
Br
3b
3c
3d
3e
3f
96
98
32
89
84
48
28
a
Isolated yields.
1g
1h
3g
3a
4. Experimental
4.1. General
a
Isolated yields.
conditions, which affords arylphosphinates in good yields. The
present method was applicable to various p- and m-substituted aryl
iodides and H-phosphinates having bulky groups. The reactions of
P-chiral H-phosphinates were found to proceed with retention of
the phosphorus configuration. Investigations into a detailed re-
action mechanism and preparation of biologically active com-
pounds by this method are now in progress.
All melting points were obtained on a Yanagimoto micro-
melting point apparatus and are uncorrected. IR spectra were
recorded on a JASCO FTIR-4100 instrument. Optical rotations were
measured with a JASCO P-1020 polarimeter. Mass spectra were
measured on a JEOL JMS-MS700V instrument by FABþ. NMR spectra
were obtained on a JEOL JNM-AL300 instrument. The chemical shift
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4
A. Kinbara et al. / Tetrahedron xxx (2015) 1e6
(neat) cmꢁ1: 2980, 1591, 1577, 1476, 1439, 1223, 1025; 31P NMR
(121 MHz, CDCl3) : 7.85e7.78
: 31.9; 1H NMR (300 MHz, CDCl3)
d
d
(2H, m), 7.54e7.34 (6H, m), 7.04 (1H, m), 4.11 (2H, quin, J¼7.2 Hz),
3.82 (3H, s), 1.37 (3H, t, J¼7.2 Hz); 13C NMR (75 MHz, CDCl3)
d: 159.5
(d, JPC¼16.8 Hz), 133.1 (d, JPC¼97.5 Hz), 132.0 (d, JPC¼3.1 Hz), 131.5
(2C, d, JPC¼9.9 Hz), 131.3 (d, JPC¼99.4 Hz), 129.7 (d, JPC¼15.5 Hz),
128.4 (2C, d, JPC¼13.7 Hz), 123.7 (d, JPC¼9.9 Hz), 118.2 (d,
JPC¼2.5 Hz), 116.3 (d, JPC¼11.2 Hz), 61.0 (d, JPC¼6.2 Hz), 55.2, 16.2 (d,
JPC¼6.8 Hz); LRMS (FAB) m/z: 277, 231, 77; HRMS (FAB) m/z calcd for
C
15H18O3P ([MþH]þ) 277.0994, found 277.1006.
4.5. Ethyl (2-Methoxyphenyl)phenylphosphinate 3d
This compound (43.5 mg, 32%) was prepared from 1d (78.0 mL,
0.600 mmol) in an analogous manner to that for 3a. Pale yellow
solid; mp: 77e78 ꢀC; IR (neat) cmꢁ1: 2979, 1591, 1577, 1478, 1434,
1216, 1022; 31P NMR (121 MHz, CDCl3) : 30.2; 1H NMR (300 MHz,
d
CDCl3)
d
: 7.99 (1H, ddd, J¼13.2, 7.7, 1.7 Hz), 7.88e7.81 (2H, m),
7.52e7.38 (4H, m), 7.06 (1H, td, J¼7.3, 2.2 Hz), 6.87 (1H, m), 4.09
(2H, quin, J¼7.3 Hz), 3.70 (3H, s), 1.36 (3H, t, J¼7.2 Hz); 13C NMR
Scheme 1. Plausible reaction mechanism.
(75 MHz, CDCl3)
d
: 161.0 (d, JPC¼4.4 Hz), 134.7 (d, JPC¼6.2 Hz), 134.3
(d, JPC¼1.9 Hz), 133.5, 131.7 (2C, d, JPC¼10.6 Hz), 131.6, 127.9 (2C, d,
JPC¼13.7 Hz), 120.5 (d, JPC¼11.8 Hz), 119.4 (d, JPC¼9.9 Hz), 111.2 (d,
JPC¼8.1 Hz), 60.7 (d, JPC¼6.2 Hz), 55.3, 16.3 (d, JPC¼6.8 Hz); LRMS
(FAB) m/z: 277, 231, 199; HRMS (FAB) m/z calcd for C15H18O3P
([MþH]þ) 277.0994, found 277.0996.
data for each signal on 1H NMR are given in units of
d relative to
CHCl3
(d
¼7.26) for CDCl3 solution. For 13C NMR spectra, the
chemical shifts in CDCl3 are recorded relative to the CDCl3 reso-
nance (
external 85% H3PO4
d
¼77.0). The chemical shifts of 31P are recorded relative to
(
d
¼0) with broad-band 1H decoupling. Com-
mercial reagents were used as received with the following excep-
tions. Commercial zinc dust was stirred with 2% HCl for 1 min,
followed by filtration to remove the acid. This material was se-
quentially washed with 2% HCl, distilled H2O, EtOH, Et2O and then
dried under vacuum, which was utilized as zinc dust in the CeP
cross-coupling reactions.
4.6. Methyl 4-[ethoxy(phenyl)phosphoryl)benzoate 3e
This compound (139 mg, 89%) was prepared from 1e (157 mg,
0.600 mmol) in an analogous manner to that for 3a. White solid;
mp: 63e64 ꢀC; IR (neat) cmꢁ1: 2979, 2956, 1724, 1591, 1567, 1484,
1453; 31P NMR (121 MHz, CDCl3) : 30.6; 1H NMR (300 MHz, CDCl3)
d
d
: 8.10 (2H, dd, J¼8.3, 3.1 Hz), 7.93e7.78 (4H, m), 7.57e7.43 (3H, m),
4.13 (2H, quin, J¼7.2 Hz), 3.93 (3H, s), 1.38 (3H, t, J¼7.2 Hz); 13C NMR
4.2. Ethyl diphenylphosphinate 3a
(75 MHz, CDCl3)
d: 166.1, 136.6 (d, JPC¼134.2 Hz), 133.1 (d,
To an eggplant flask was added H-phosphinate 2a (86.5 mg,
JPC¼2.5 Hz), 132.3 (d, JPC¼3.1 Hz), 131.5 (2C, d, JPC¼10.6 Hz), 131.5
(2C, d, JPC¼9.9 Hz), 130.9 (d, JPC¼137.9 Hz), 129.3 (2C, d,
JPC¼13.1 Hz), 128.5 (2C, d, JPC¼13.1 Hz), 61.2 (d, JPC¼5.6 Hz), 52.2,
16.2 (d, JPC¼6.2 Hz); LRMS (FAB) m/z: 305, 135; HRMS (FAB) m/z
calcd for C16H18O4P ([MþH]þ) 305.0943, found 305.0948.
0.509 mmol), NiCl2 (7.7 mg, 0.0509 mmol), 2,20-bipyridine (17.1 mg,
0.109 mmol), triethylamine (142
mL, 1.02 mmol), zinc dust (43.2 mg,
0.610 mmol), iodobenzene 1a (68.0
mL, 0.610 mmol) and dry DMF
(1.0 mL) under Ar. Then the mixture was stirred at 50 ꢀC for 24 h.
After cooling to room temperature, the reaction mixture was con-
centrated under reduced pressure. The residue was purified by
silica gel column chromatography (hexane/EtOAc¼1:1) to give 3a
(118 mg, 94%). Colorless oil; IR (neat) cmꢁ1: 3060, 2981, 2901, 1592,
4.7. Methyl 3-[ethoxy(phenyl)phosphoryl)benzoate 3f
This compound (134 mg, 84%) was prepared from 1f (157 mg,
0.600 mmol) in an analogous manner to that for 3a. Pale yellow oil;
IR (neat) cmꢁ1: 2983, 1724, 1596, 1567, 1437; 31P NMR (121 MHz,
1484, 1439; 31P NMR (121 MHz, CDCl3) : 31.6; 1H NMR (300 MHz,
d
CDCl3) d: 7.85e7.78 (4H, m), 7.55e7.49 (2H, m), 7.48e7.40 (4H, m),
4.11 (2H, quint, J¼7.2 Hz), 1.37 (3H, t, J¼7.2 Hz); 13C NMR (75 MHz,
CDCl3)
d
: 30.3; 1H NMR (300 MHz, CDCl3)
d
: 8.48 (1H, d, J¼12.5 Hz),
CDCl3)
d
: 132.1 (2C, d, JPC¼2.5 Hz), 131.6 (2C, d, JPC¼136.7 Hz), 131.6
8.19 (1H, dd, J¼8.9, 1.1 Hz), 8.02 (1H, d, J¼11.7, 7.7 Hz), 7.86e7.79
(4C, d, JPC¼9.9 Hz), 128.5 (4C, d, JPC¼13.1 Hz), 61.0 (d, JPC¼5.6 Hz),
16.3 (d, JPC¼6.8 Hz); LRMS (FAB) m/z: 247, 201, 77; HRMS (FAB) m/z
calcd for C14H16O2P ([MþH]þ) 247.0888, found 247.0853.
(2H, m), 7.57e7.43 (4H, m), 4.13 (2H, quin, J¼7.2 Hz), 3.92 (3H, s),
1.39 (3H, t, J¼7.2 Hz); 13C NMR (75 MHz, CDCl3)
d: 166.1, 135.8 (d,
JPC¼10.6 Hz), 132.9 (d, JPC¼2.5 Hz), 132.6 (d, JPC¼136.7 Hz), 132.5 (d,
JPC¼11.2 Hz), 132.3 (d, JPC¼2.5 Hz), 131.5 (2C, d, JPC¼10.6 Hz), 131.0
(d, JPC¼137.9 Hz), 130.5 (d, JPC¼13.1 Hz),128.7 (d, JPC¼13.1 Hz), 128.6
(2C, d, JPC¼13.1 Hz), 61.2 (d, JPC¼6.2 Hz), 52.1, 16.2 (d, JPC¼6.2 Hz);
LRMS (FAB) m/z: 305; HRMS (FAB) m/z calcd for C16H18O4P
([MþH]þ) 305.0943, found 305.0931.
4.3. Ethyl (4-Methoxyphenyl)phenylphosphinate 3b
This compound (138 mg, 96%) was prepared from 1b (154 mg,
0.623 mmol) in an analogous manner to that for 3a. Colorless oil; 1H
NMR (300 MHz, CDCl3) d: 7.83e7.72 (4H, m), 7.50e7.43 (3H, m),
6.96 (3H, dd, J¼8.4, 2.3 Hz), 4.09 (2H, quint, J¼7.0 Hz), 3.83 (3H, s),
1.36 (3H, t, J¼7.0 Hz). The 1H NMR spectrum of 3b was identical
with that of this compound reported in the literature.23
4.8. Methyl 2-[ethoxy(phenyl)phosphoryl)benzoate 3g
This compound (73.3 mg, 48%) was prepared from 1g (87.0
0.600 mmol) in an analogous manner to that for 3a. Pale yellow oil;
IR (neat) cmꢁ1: 2980,1731, 1590, 1437; 31P NMR (121 MHz, CDCl3)
31.2; 1H NMR (300 MHz, CDCl3)
: 8.10 (1H, m), 7.81e7.74 (3H, m),
mL,
4.4. Ethyl (3-Methoxyphenyl)phenylphosphinate 3c
d:
d
This compound (134 mg, 98%) was prepared from 1c (71.0
0.600 mmol) in an analogous manner to that for 3a. Colorless oil; IR
m
L,
7.62e7.59 (2H, m), 7.54e7.41 (3H, m), 4.09 (2H, quind, J¼7.2, 1.6 Hz),
3.72 (3H, s), 1.34 (3H, t, J¼7.2 Hz); 13C NMR (75 MHz, CDCl3)
d: 166.2
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A. Kinbara et al. / Tetrahedron xxx (2015) 1e6
5
(d, JPC¼3.7 Hz), 136.2 (d, JPC¼8.7 Hz), 133.7 (d, JPC¼7.5 Hz), 132.4 (d,
JPC¼137.3 Hz), 131.9 (d, JPC¼12.4 Hz), 131.9 (d, JPC¼13.1 Hz), 131.3 (d,
JPC¼22.4 Hz), 131.2 (2C, d, JPC¼10.6 Hz), 130.8 (d, JPC¼11.8 Hz), 129.7
(d, JPC¼10.6 Hz), 128.2 (2C, d, JPC¼13.7 Hz), 61.1 (d, JPC¼5.6 Hz), 52.0,
16.2 (d, JPC¼6.8 Hz); LRMS (FAB) m/z: 305, 245; HRMS (FAB) m/z
calcd for C16H18O4P ([MþH]þ) 305.0943, found 305.0931.
131.8 (d, JPC¼3.1 Hz), 131.8 (2C, d, JPC¼10.6 Hz), 131.6 (2C, d,
JPC¼9.9 Hz), 130.1, 129.1 (2C, d, JPC¼13.7 Hz), 128.3 (2C, d,
JPC¼13.7 Hz), 128.3 (2C, d, JPC¼13.7 Hz), 77.1, 48.9 (d, JPC¼6.2 Hz),
43.5, 34.0, 31.5, 25.5, 22.6, 21.9, 21.5, 21.1, 15.3; [
a
]
25 ꢁ66.6 (c 0.98,
D
CHCl3); LRMS (FAB) m/z: 371; HRMS (FAB) m/z calcd for C23H32O2P
([MþH]þ) 371.2140, found 371.2110. The 1H NMR spectrum of 5f
was identical with that of this compound reported in the litera-
4.9. Decyl diphenylphosphinate 5b
ture.12 The optical rotation of 5f was quite similar to the corre-
20
sponding reported value ([
a
]
ꢁ67.2 (c 0.98, CHCl3)).12
D
This compound (132 mg, 77%) was prepared from 2b (136 mg,
0.482 mmol) in an analogous manner to that for 3a. Colorless oil; IR
4.14. Ethyl phenyl[2-phenyl-1-(toluene-4-sulfonylamino)
ethyl]phosphinate 5g
(neat) cmꢁ1: 2924, 1592, 1466, 1439; 31P NMR (121 MHz, CDCl3)
d:
31.4; 1H NMR (300 MHz, CDCl3)
d: 7.84e7.77 (4H, m), 7.54e7.41 (6H,
m), 4.02 (2H, q, J¼6.7 Hz), 1.76e1.67 (3H, m), 1.40e1.24 (13H, m),
This compound (109 mg, 62%) was prepared from 2g (145 mg,
0.396 mmol) in an analogous manner to that for 3a. Colorless oil; IR
(neat) cmꢁ1: 3061, 2981, 2887, 1671, 1598, 1496, 1455, 1438, 1332;
0.87 (3H, t, J¼6.6 Hz); 13C NMR (75 MHz, CDCl3)
d: 132.0 (2C, d,
JPC¼3.1 Hz), 131.7 (2C, d, JPC¼136.7 Hz), 131.6 (4C, d, JPC¼9.9 Hz),
128.4 (4C, d, JPC¼13.1 Hz), 64.9 (d, JPC¼6.2 Hz), 31.7, 30.4 (d,
JPC¼6.2 Hz), 29.3 (2C, d, JPC¼1.9 Hz), 29.1, 28.9, 25.4, 22.5, 13.9;
LRMS (FAB) m/z: 359, 201, 141, 77; HRMS (FAB) m/z calcd for
31P NMR (121 MHz, CDCl3) : 40.7; 1H NMR (300 MHz, CDCl3)
d d:
7.84e7.72 (2H, dd, J¼11.3, 7.5 Hz), 7.63 (1H, t, J¼7.5 Hz), 7.51e7.45
(2H, m), 7.35e7.32 (7H, m), 7.07 (2H, d, J¼8.1 Hz), 5.03 (1H, m),
4.27e4.07 (2H, m), 3.95 (1H, m), 3.41 (1H, ddd, J¼14.1, 11.2, 6.1 Hz),
3.03 (1H, ddd, J¼14.1, 11.7, 7.7 Hz), 2.43 (3H, s), 1.32 (3H, t, J¼7.2 Hz);
C
22H32O2P ([MþH]þ) 359.2140, found 359.2164.
13C NMR (75 MHz, CDCl3)
d
: 142.4, 138.3, 136.9 (d, JPC¼8.1 Hz), 132.8
4.10. Isopropyl diphenylphosphinate 5c
(2C, d, JPC¼9.9 Hz), 132.7, 129.8, 129.8, 129.3, 129.3, 128.5 (2C, d,
JPC¼12.4 Hz), 128.3, 128.3, 127.9 (d, JPC¼126.3 Hz), 126.6, 126.5,
126.5, 61.5 (d, JPC¼6.8 Hz), 54.1 (d, JPC¼114.9 Hz), 35.9, 21.3, 16.2 (d,
JPC¼6.2 Hz); LRMS (FAB) m/z: 444, 274, 155; HRMS (FAB) m/z calcd
for C23H27NO4P S ([MþH]þ) 444.1398, found 444.1368.
This compound (110 mg, 81%) was prepared from 2c (96.2 mg,
0.522 mmol) in an analogous manner to that for 3a. White solid;
mp: 99e100 ꢀC; IR (neat) cmꢁ1: 2973, 1591, 1440, 1247; 31P NMR
(121 MHz, CDCl3) d d: 7.85e7.78
: 30.4; 1H NMR (300 MHz, CDCl3)
(4H, m), 7.53e7.40 (6H, m), 4.68 (1H, m), 1.35 (6H, d, J¼6.2 Hz); 13
C
NMR (75 MHz, CDCl3)
d
: 133.3, 133.3, 131.9 (2C, d, JPC¼2.5 Hz), 131.6
Acknowledgements
(4C, d, JPC¼9.9 Hz), 128.4 (4C, d, JPC¼13.1 Hz), 70.0 (d, JPC¼5.6 Hz),
24.1 (2C, d, JPC¼4.4 Hz); LRMS (FAB) m/z: 261, 201, 183, 77; HRMS
(FAB) m/z calcd for C15H18O2P ([MþH]þ) 261.1044, found 261.1056.
We gratefully acknowledge the Foundation for Japanese
Chemical Research (440(R)) for financial support.
4.11. tert-Butyl diphenylphosphinate 5d
References and notes
This compound (86.6 mg, 66%) was prepared from 2d (95.4 mg,
0.481 mmol) in an analogous manner to that for 3a. White solid;
mp: 110e111 ꢀC; IR (neat) cmꢁ1: 2972, 1588, 1438, 1254; 31P NMR
ꢀ
ꢀ
1. For reviews, see: (a) Collinsova, M.; Jiracek, J. Curr. Med. Chem. 2000, 7, 629; (b)
Yiotakis, A.; Geogiadis, D.; Matziari, M.; Makaritis, A.; Dive, V. Curr. Org. Chem.
2004, 8, 1135; (c) Mucha, A.; Kafarski, P.; Berlicki, q. J. Med. Chem. 2011, 54, 5955.
2. For selected examples, see: (a) Liu, D.; Zhou, S.; Gao, J. Synth. Commun. 2014, 44,
1286; (b) Xia, L.; Li, S.; Chen, R.; Liu, K.; Chen, X. J. Org. Chem. 2013, 78, 3120; (c)
Alcalde, B.; Almendros, P.; Aragoncillo, C.; Callejo, R.; Ruiz, M. P. J. Org. Chem.
2013, 78, 10154; (d) Pan, C. S.; List, B. Angew. Chem., Int. Ed. 2008, 47, 3622.
3. Li, M.; Lin, Z.; Johnson, M. E. Bioorg. Med. Chem. Lett. 1999, 9, 1957.
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Poddesu, B.; Vargiu, L.; Liuzzi, M.; Roland, A.; Seifer, M.; Standring, D.; Storer, R.;
Dousson, C. B. J. Med. Chem. 2011, 54, 392.
(121 MHz, CDCl3)
d d: 7.82e7.75
: 26.4; 1H NMR (300 MHz, CDCl3)
(4H, m), 7.50e7.38 (6H, m), 1.51 (9H, s); 13C NMR (75 MHz, CDCl3)
d:
134.7 (2C, d, JPC¼138.5 Hz), 131.4 (2C, d, JPC¼2.5 Hz), 131.3 (4C, d,
JPC¼10.6 Hz), 128.2 (4C, d, JPC¼13.1 Hz), 83.5 (d, JPC¼8.1 Hz), 30.8
(3C, d, JPC¼4.4 Hz); LRMS (FAB) m/z: 275, 201, 77, 57; HRMS (FAB)
m/z calcd for C16H20O2P ([MþH]þ) 275.1201, found 275.1201.
6. Clarion, L.; Jacquard, C.; Sainte-Catherine, O.; Loiseau, S.; Filippini, D.; Hirle-
mann, M.; Volle, J.; Virieux, D.; Lecouvey, M.; Pirat, J.; Bakalara, N. J. Med. Chem.
2012, 55, 2196.
4.12. Ethyl phenyl(1,1-diethoxyethyl)phosphinate 5e
7. (a) Zhou, Y.; Wang, G.; Saga, Y.; Shen, R.; Goto, M.; Zhao, Y.; Han, L.-B. J. Org.
Chem. 2010, 75, 7924; (b) Gatineau, D.; Giordano, L.; Buono, G. J. Am. Chem. Soc.
2011, 133, 10728.
This compound (103 mg, 72%) was prepared from 2e (105 mg,
0.500 mmol) in an analogous manner to that for 3a. Colorless oil; 1H
NMR (300 MHz, CDCl3)
d
: 7.91e7.85 (2H, m), 7.57e7.40 (3H, m),
8. For reviews, see: (a) Tappe, F. M. J.; Trepohl, V. T.; Oestreich, M. Synthesis 2010,
3037; (b) Schwan, A. L. Chem. Soc. Rev. 2004, 33, 218.
4.27e4.08 (2H, m), 3.78e3.55 (4H, m), 1.44 (3H, d, J¼11.9 Hz), 1.35
(3H, t, J¼7.0 Hz), 1.21e1.15 (6H, m). The 1H NMR spectrum of 5e was
identical with that of this compound reported in the literature.9e
9. For selected examples of Pd-catalyzed C-P cross-couplings, see: (a) Deal, E. L.;
Petit, C.; Montchamp, J.-L. Org. Lett. 2011, 13, 3270; (b) Kalek, M.; Stawinski, J.
Tetrahedron 2009, 65, 10406; (c) Pirat, J.-L.; Monbrun, J.; Virieux, D.; Critau, H.-J.
Tetrahedron 2005, 61, 7029; (d) Bravo-Altamirano, K.; Huang, Z.; Montchamp, J.-
L. Tetrahedron 2005, 61, 6315; (e) Berger, O.; Petit, C.; Deal, E.; Montchamp, J.-L.
Adv. Synth. Catal. 2013, 355, 1361.
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Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2006, 71, 5020; (b) Rao, H.; Jin, Y.; Fu, H.;
Jiang, Y.; Zhao, Y. Chem.dEur. J. 2006, 12, 3636; (c) Zhuang, R.; Xu, J.; Cai, Z.;
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Zhou, Y.; Zhao, C.; Goto, M.; Yin, S.-F.; Han, L.-B. Adv. Synth. Catal. 2014, 356, 781.
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16. Afarinkia, K.; Yu, H. Tetrahedron Lett. 2003, 44, 781.
4.13. (SP)-(L)-Menthyl (4-methylphenyl)phenylphosphinate
5f
This compound (154 mg, 83%) was prepared from 1i (130 mg,
0.600 mmol) and 2f (140 mg, 0.500 mmol) in an analogous manner
to that for 3a. White solid; mp: 77e78 ꢀC; IR (neat) cmꢁ1: 2954,
2924, 2870, 1604, 1455, 1438; 31P NMR (121 MHz, CDCl3) : 30.3; 1H
d
NMR (300 MHz, CDCl3)
d
: 7.84e7.77 (2H, m), 7.66 (2H, dd, J¼12.1,
7.9 Hz), 7.52e7.40 (3H, m), 7.23 (2H, dd, J¼7.9, 3.0 Hz), 4.22 (1H, m),
2.37 (3H, s), 2.17e2.09 (2H, m), 1.64 (1H, m), 1.47e1.31 (2H, m), 1.20
(1H, m), 0.97e0.82 (7H, m), 0.54 (3H, d, J¼6.8 Hz); 13C NMR
17. Louis, Y. K.; Devon, C. B.; Adria, K. D.; Kristina, M. D. Organometallics 2013, 32,
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(75 MHz, CDCl3)
d: 142.4 (d, JPC¼3.1 Hz), 133.5 (d, JPC¼137.9 Hz),
Please cite this article in press as: Kinbara, A.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.07.073

6
A. Kinbara et al. / Tetrahedron xxx (2015) 1e6
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