Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.
This journal is © The Royal Society of Chemistry 2015
Variable Mechanism of Nucleophilic Substitution of PStereogenic Phosphoryl Chloride with Alkynyl Metallic
Reagents
Lan Yao, Li-Juan Liu, Zhong-Yuan Xu, Shao-Zhen Nie, Xiao-Qing Xiao and
Chang-Qiu Zhao*
College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, Shandong
252059, China
Table of Contents
General.
S1. Procedure for reaction of phenylethynyl lithium 3a to (SP)-menthyl
phenylphosphonochloridate 1 under different conditions
S1-1. Typical procedure (for run 2 of Table 1)
S1-2. Reversed addition turn to S1-1 (procedure for run 1)
S1-3. Addition of 1 in one portion (typical procedure for run 3)
S1-4. To run the reaction initially at –80oC (procedure for run 5)
S1-5. Reaction mixture was warmed gradually to room temperature (run 6, typical procedure)
S1-6. Reaction was quenched with acetic acid (procedure of run 10)
S1-7. To run the reaction in dilute solution (procedure of run 12)
S1-8. To run the reaction with the ratio of 3a/1 was 1:2 (run 16, typical procedure)
S2. Determination of configuration of phosphorus atoms in 2
S3. Discussion about the apicalphilics of atoms on pentacoordinated phosphorus and reactivities
of P-heteroatom bonds
S4. Preparation of 2 via reaction of 1 to 3 and/or 8
Method A
Method B
S5. Selected 1H, 31P and 13C NMR spectroscopy of compound 2
1
General.
All reactions were carried out under high pure nitrogen using standard Schlenk techniques.
Syringes which were used to transfer anhydrous solvents or reagents were purged with nitrogen
prior to use. All solvents used in reactions were dried and purified according to standard procedure.
Unless otherwise noted, Grignard reagents were purchased from commercial suppliers or prepared
according standard method in ca. 1 mmol/ml solution in ether. Lithium reagents and other
materials were obtained from commercial suppliers and were used without further purification.
NMR spectroscopy were recorded on a Varian Mercury Plus 400 spectrometer. 1H, 13C NMR
spectra are referenced to SiMe4 or the residual solvent peak, 31P-NMR spectroscopy were
referenced externally to 85 % H3PO4 at 0 ppm. Chemical shifts were reported in δ ppm. All X-ray
crystallographic data were collected on a Bruker SMART CCD 1000 diffractometer with graphite
monochromated Mo-K radiation (=0.71073 Å ) at 298(2) K. HRMS mass spectra were obtained
on a Bruker Compass DataAnalysis 4.0.
S1. Procedure for reaction of phenylethynyl lithium 3a to (SP)-menthyl
phenylphosphonochloridate 1 under different conditions
S1-1. Typical procedure (for run 2 of Table 1):
The powder of 1 (0.046 g, 0.147 mmol) was added portionwise within 1 minute to the solution of
3a that was prepared in situ from addition of nBuLi (1.6 M solution in hexane, 0.092 ml, 0.147
mmol) to the solution of phenylethyne (0.016 ml, 0.147 mmol) in ether (1 ml) at 0°C. Then the
mixture was stirred for about 3 h while the temperature elevated to room temperature gradually.
Saturated ammonium chloride solution was added, and the mixture was extracted with
dichloromethane for three times. The combined organic layer was dried over sodium sulfate,
concentrated in vacuo. The residue was used for measurement of NMR. The yields and
diastereomeric ratio were estimated by 31P-NMR spectroscopy based on 1.
S1-2. Reversed addition turn to S1-1 (procedure for run 1):
The solution of 3a (0.735 M in ether, 0.20 ml, 0.147 mmol) was added dropwise to the solution of
1 (0.046 g, 0.147 mmol) in ether (1 ml) at 0°C. The mixture was stirred for 3 h while warmed to
room temperature gradually, then was processed as similar to S1-1.
S1-3. Addition of 1 in one portion (typical procedure for run 3):
The powder of 1 (0.046 g, 0.147 mmol) was added in one portion to the stirred solution of 3a
(0.735 M in ether, 0.20 ml, 0.147 mmol, diluted with 1 ml ether) at 0°C. The mixture was
gradually warmed to room temperature within 1 h, then was processed as similar to S1-1
S1-4. To run the reaction initially at –80oC (procedure for run 5):
The powder of 1 (0.046 g, 0.147 mmol) was added in one portion to the solution of 3a (0.735 M in
ether, 0.20 ml, 0.147 mmol, diluted with 1 ml ether) at –80°C. After 1 h, the mixture was
gradually warmed until to room temperature, and the stirring was continued to 16 h. The mixture
was processed as similar to S1-1.
S1-5. Reaction mixture was warmed gradually to room temperature (run 6, typical procedure):
The powder of 1 (0.046 g, 0.147 mmol) was added in one portion to the solution of 3a (0.735 M in
ether, 0.20 ml, 0.147 mmol, diluted with 1 ml ether) ether at –20°C. After 5 min the mixture was
gradually warmed until room temperature, and stirring was continued for 5 h. The mixture was
processed as similar to S1-1.
S1-6. Reaction was quenched with acetic acid (procedure of run 10):
2
The powder of 1 (0.046 g, 0.147 mmol) was added portionwise within 1 minute to the solution of
3a (0.735 M in ether, 0.20 ml, 0.147 mmol, diluted with 1 ml ether) at –20°C. After stirring
continued for 9 h, the mixture was quenched with acetic acid (0.016 ml, 0.294 mmol) at the same
temperature, then washed with water for three times. The organic layer was dried over sodium
sulfate. After removing solvents under reduced pressure, the residue was used for measurement of
NMR spectroscopy.
S1-7. To run the reaction in dilute solution (procedure of run 12):
The solution of 3a (0.0735 M in ether, 2.0 ml, 0.147 mmol) was added to the solution of 1 (0.046
g, 0.147 mmol, 2.0 ml, 0.0735 M in ether) dropwise at –15°C. Then the mixture was stirred for 2.5
h at –15°C. The upper clear solution in ether was used to run 31P-NMR spectroscopy at room
temperature.
S1-8. To run the reaction with the ratio of 3a/1 was 1:2 (run 16, typical procedure):
The powder of 1 (0.046 g, 0.147 mmol) was added portionwise within 1 minute to the solution of
3a (0.735 M in ether, 0.20 ml, 0.147 mmol, diluted with 1 ml ether) at –20°C. Then the mixture
was stirred for 3 h at –20°C. The upper clear solution in ether was used to measurement of 31PNMR spectroscopy at room temperature within about 5 min. The epimerization ratio of remaining
1 was estimated by 31P-NMR spectroscopy.
S2. Determination of configuration of phosphorus atoms in 2
Menthyl (Z)-2-(p-tolylthio)-2-phenylvinyl(phenyl)phosphinate 7, which was obtained from
reaction of 4-methylbenzenethiol to 2a under alkali condition, was proved to have SP
configuration by X-ray diffraction. Because the addition process didn’t involved in phosphorus
atom, it was believed that the phosphorus atom of 2a has RP configuration. The crude 7 was
recrystallized from dichloromethane, affording single crystal suitable for X-ray diffraction.
Ph
O
P OMen
Ph
S
7
Figure S1. The structure of X-ray diffraction for 7 (hydrogen atoms were removed for
clarity)
Crystals were mounted in lindemann capillaries under nitrogen. All X-ray crystallographic data
were collected on a Bruker SMART CCD 1000 diffractometer with graphite monochromated MoKα radiation (λ=0.71073 Å ) at 298(2) K. A semi-empirical absorption correction was applied to
the data. The structure was solved by direct methods using SHELXS-97 and refined against F2 by
3
full-matrix least squares using SHELXL-97.[S1] Hydrogen atoms were placed in calculated
positions. The absolute configurations were confirmed by evaluation of the Flack parameter. [S2]
The deposition number with the Cambridge Crystallographic Data Centre for 7 was
CCDC 878882 (as seen in Table S1 and Figure S1).
Table S1. Crystallographic Data of 7
Empirical formula
Formula weight
Wavelength (Å)
Crystal system
Space group
a (Å)
b (Å)
c (Å)
(º)
(º)
(º)
V (Å3)
Z
Dcalc (Mg/m3)
μ (mm-1)
F(000)
Crystal size (mm)
Reflections collected
Unique reflections [Rint]
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I>2σ (I)]
R indices (all data)
Flack parameter
CCDC number
C31H37O2PS
504.64
0.71073
Monoclinic
P2(1)
5.8682(4)
15.5218(14)
14.1795(13)
90
92.4450(10)
90
1290.36(19)
2
1.299
0.215
540
0.34 x 0.15 x 0.12
6407
3628 [R(int) = 0.1917]
3628 / 211 / 321
0.919
R1 = 0.1142
wR2 = 0.2511
R1 = 0.2086
wR2 =0.3049
-0.2(3)
CCDC 878882
S3. Discussion about the apicalphilics of atoms on pentacoordinated phosphorus and
reactivity of P-heteroatom bonds
According to Berry’s pseudorotation theory, pentacoordinated phosphorus species are formed and
the atoms having big electronegativity tend to occupy the apical position of trigonal bipyramide
structure. The apicalphilics of chloride is thought to be stronger than that of alkoxy group.
[S1]
G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112-122.
[S2]
H. D. Flack, Acta Crystallogr., Sect. A: Found. Crystallogr. 1983, 39, 876-881.
4
Attacking nucleophilic group and leaving group tend to locate at the apical position, too, since the
bonds at these two positions are relative weak.[S3] On the other hands, Akiba and coworkers have
reported the reaction selectivity of P-O over P-C bond in a pentacoordinated phosphoranes. The
phosphorus-oxygen bond had enhanced reactivity toward attack of nucleophlic reagents because
the presence of a lower-lying σ*P-O orbital as the reacting orbital, whereas the corresponding
orbital of phosphorus-carbon bond is a higher-lying σ*P-C. The assumption was supported by DFT
calculation. Similar results can be applied to explain the orientation when 1 was attacked by 3a.[S4]
[S3] (a) R. S. Berry, Chem. Physics, 1960, 32, 933-938. (b) J. Seckute, J. L. Menke, R. J. Emnett, E. V. Patterson,
C. J.Cramer, J. Org. Chem. 2005, 70, 8649−8660. (c) J. L. Menke, E. V. Patterson, THEOCHEM 2007, 811,
281−291.
[S4] S. Matsukawa, S. Kojima, K. Kajiyama, Y. Yamamoto, K.-y. Akiba, S. Re, S. Nagase, J. Am. Chem. Soc.
2002, 124, 13154-13170.
5
S4. Preparation of 2 via reaction of 1 to 3 and/or 8
Method A:
Typical procedure for preparation of 2b: The solution of 1 (0.046 g, 0.147 mmol, 0.294 M in dry
THF) was added dropwise at –20°C to the solution of 3b (0.147 mmol, 1 ml, 0.147 M in THF)
that was prepared in situ by addition of n-butyl lithium (1.6 M, in hexane) to 1-hexyne (0.147
mmol). After addition finished, the mixture was moved out from cold-bath and stirred for 5 h at
room temperature. The mixture was quenched with aqueous saturated ammonium chloride
solution, extracted with dichloromethane for three times. The combined organic layer was dried
over sodium sulfate. After removing solvents in vacuo, the residue was used for measurement of
NMR spectroscopy. The yields and dr were estimated by 31P-NMR spectroscopy based on 1.
As noted in Table 2, in the cases of run 1, 3 and 6, 2a, 2c and 2f were prepared by addition of 3 to
1 under cooling with ice-water followed with stirring till room temperature within 3 h. The
mixture was processed as others.
Method B:
Typical procedure for preparation of 2a: To a solution of phenylethynyl magnesium bromide 8a
(0.911 mmol, 2 ml, 0.456 M solution in ether, prepared in situ from ethyl magnesium bromide and
phenylethyne) in dry ethyl ether was added the powder of 1 (0.287 g, 0.911 mmol) at 0°C within 5
minutes, and the mixture was stirred for 5 h while the temperature elevated to rt gradually. Then
the mixture was quenched with saturated aqueous ammonium chloride solution, extracted with
dichloromethane for three times, and the combined organic layer was dried over sodium sulfate.
After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified
by preparative TLC on silica gel (hexane/ethyl acetate = 3/1 as eluent).
(RP)-(-)-Menthyl (phenylethynyl)phenylphosphinate (2a)
2a was obtained as colorless oil (dr=99:1, 92 %).
O
1H NMR (400 MHz, CDCl ) δ = 8.04 – 7.89 (m, 2H), 7.63 – 7.46 (m,
3
Ph
P OMen
5H), 7.46 – 7.31 (m, 3H), 4.44 (ddd, J=10.5, 4.4, 1H), 2.55 (d,
Ph
J=12.0, 1H), 2.21 – 2.03 (m, 1H), 1.68 (d, J=11.9, 2H), 1.59 – 1.21
(m, 3H), 1.16 – 1.00 (m, 1H), 0.95 (d, J=6.4, 3H), 0.88 (d, J=7.0, 4H), 0.71 (d, J=6.9, 3H). 31P
NMR (162 MHz, CDCl3) δ = 9.37 (s, 1 %), 7.78 (s, 99 %). 13C NMR (101 MHz, CDCl3) δ =
133.32 – 132.02 (m), 131.31 (t, J=14.6), 130.70 (d, J=8.4), 128.91 – 128.16 (m), 120.28 (s),
101.44 (s), 101.05 (s), 84.44 (d, J=20.6), 82.42 (s), 78.72 (d, J=6.9), 77.48 (d, J=32.0), 77.01 (s),
48.84 (t, J=6.7), 43.14 (s), 34.32 (s), 31.89 (s), 30.97 (s), 25.74 (d, J=6.0), 23.16 (d, J=11.4), 22.30
(d, J=8.0), 21.22 (d, J=6.7), 15.73 (d, J=5.8).
HRMS (FAB) calcd for C24H29O2P (M++H) 381.1983, found 381.1973.
(RP)-(-)-Menthyl 1-hexynylphenylphosphinate (2b)
2b was obtained as pale yellow oil (dr=98:2, 58 %).
1H NMR (400 MHz, CDCl ) δ = 7.95 – 7.80 (m, 2H), 7.60 – 7.51
O
3
n-Bu
P OMen
(m, 1H), 7.51 – 7.40 (m, 2H), 4.33 (ddd, J=20.5, 10.5, 4.5, 1H),
Ph
2.45 (d, J=12.0, 1H), 2.41 – 2.29 (m, 2H), 2.07 (dq, J=6.9, 4.6, 1H),
1.66 (dd, J=10.4, 2.7, 2H), 1.62 – 1.51 (m, 2H), 1.52 – 1.34 (m, 4H),
1.27 (dd, J=23.3, 12.0, 2H), 1.08 – 0.98 (m, 1H), 0.98 – 0.88 (m, 6H), 0.85 (d, J=7.0, 3H), 0.66 (d,
J=6.9, 3H). 31P NMR (162 MHz, CDCl3) δ = 9.12 (s, 2 %), 7.57 (s, 98 %). 13C NMR (101 MHz,
6
CDCl3) δ = 133.49 (s), 132.42 (t, J=6.2), 131.84 (s), 131.11 (d, J=11.1), 128.50 (dd, J=14.8, 7.3),
105.53 (s), 105.14 (s), 78.30 (d, J=7.4), 77.49 (d, J=11.6), 77.23 (s), 76.92 (s), 76.61 (s), 74.43 (s),
48.84 (d, J=6.2), 43.11 (s), 34.34 (s), 31.86 (s), 29.77 (d, J=18.4), 25.93 (s), 25.69 (s), 23.13 (d,
J=11.0), 22.18 (t, J=8.6), 21.19 (d, J=7.4), 19.34 (d, J=3.5), 15.69 (s), 13.64 (d, J=11.9).
HRMS (FAB) calcd for C22H33O2P (M++H) 361.2296, found 361.2302.
(RP)-(-)-Menthyl (3,3-dimethylbut-1-yn-1-yl)phenylphosphinate (2c)
2c was isolated in 87% yield (dr=99:1) as pale yellow oil.
O
1H NMR (400 MHz, CDCl ) δ = 7.87 (dd, J=14.0, 7.4, 2H), 7.59 –
3
t-Bu
P OMen
7.52
(m,
1H),
7.48
(dd,
J=8.0,
3.8, 2H), 4.35 (ddd, J=20.7, 10.2, 4.3,
Ph
1H), 2.48 (d, J=11.8, 1H), 2.16 – 2.01 (m, 1H), 1.76 – 1.61 (m, 3H),
1.40 (dd, J=29.4, 17.4, 2H), 1.34 – 1.19 (m, 9H), 1.13 – 0.97 (m, 1H), 0.94 (d, J=6.5, 3H), 0.87 (t,
J=8.6, 4H), 0.70 (d, J=6.9, 3H). 31P NMR (162 MHz, CDCl3) δ = 9.79 (s, 1 %), 7.96 (s, 99 %). 13C
NMR (101 MHz, CDCl3) δ = 133.52 (s), 132.35 (d, J=2.8), 131.86 (s), 131.09 (d, J=11.1), 128.46
(d, J=14.9), 112.44 (s), 112.07 (s), 78.31 (d, J=7.5), 77.51 (s), 77.19 (s), 76.88 (s), 74.86 (s), 72.70
(s), 48.83 (d, J=6.1), 43.02 (s), 34.36 (s), 31.89 (s), 29.97 (d, J=17.7), 28.37 (s), 25.72 (s), 23.25
(s), 22.21 (s), 21.17 (s), 15.76 (s).
HRMS (FAB) calcd for C22H33O2P (M++H) 361.2296, found 361.2267.
(RP)-(-)-Menthyl 1-heptynylphenylphosphinate (2d)
2d was isolated in 53 % yield (dr=98:2) as pale yellow oil.
O
n-Bu
1H NMR (400 MHz, CDCl ) δ = 7.84 (ddd, J=14.3, 8.2, 1.2, 2H),
3
P OMen
7.50
(ddd,
J=7.4,
6.0,
1.4,
1H), 7.47 – 7.38 (m, 2H), 4.30 (ddd,
Ph
J=20.5, 10.5, 4.4, 1H), 2.41 (d, J=12.1, 1H), 2.31 (td, J=6.9, 3.7,
2H), 2.11 – 1.95 (m, 1H), 1.62 (dd, J=10.3, 2.9, 2H), 1.59 – 1.49 (m, 2H), 1.49 – 1.39 (m, 1H),
1.39 – 1.16 (m, 6H), 1.05 – 0.94 (m, 1H), 0.90 (d, J=6.5, 3H), 0.89 – 0.73 (m, 7H), 0.62 (d, J=6.9,
3H). 31P NMR (162 MHz, CDCl3) δ = 9.13 (s, 2 %), 7.59 (s, 98 %). 13C NMR (101 MHz, CDCl3)
δ = 133.56 – 132.98 (m), 132.45 (dd, J=10.9, 2.8), 131.96 – 131.39 (m), 131.09 (d, J=11.1),
128.49 (dd, J=14.8, 6.1), 105.67 (d, J=9.9), 105.23 (s), 78.29 (d, J=7.4), 77.61 (s), 77.13 (d,
J=32.0), 76.72 – 76.22 (m), 74.50 – 73.99 (m), 48.80 (dd, J=8.9, 4.1), 43.08 (s), 34.32 (s), 31.85
(s), 31.13 (s), 29.85 (s), 27.32 (d, J=1.4), 25.64 (d, J=5.0), 23.32 – 22.86 (m), 22.24 (d, J=5.6),
21.18 (d, J=6.0), 19.61 (d, J=3.3), 16.28 (s), 15.65 (d, J=4.2), 14.24 – 13.83 (m).
HRMS (FAB) calcd for C23H35O2P (M++H) 375.2453, found 375.2430.
(RP)-(-)-Menthyl cyclopropylethynylphenylphosphinate (2e)
2e was isolated in 93 % yield (dr=97:3) as pale yellow oil.
O
1H NMR (400 MHz, CDCl ) δ = 7.93 – 7.81 (m, 2H), 7.59 – 7.51
3
P OMen
(m, 1H), 7.51 – 7.41 (m, 2H), 4.29 (ddd, J=20.5, 10.5, 4.4, 1H),
Ph
2.42 (d, J=12.1, 1H), 2.27 (d, J=13.9, 1H), 2.05 (tt, J=11.6, 3.5, 1H),
1.76 – 1.57 (m, 2H), 1.57 – 1.33 (m, 3H), 1.32 – 1.16 (m, 1H), 1.08 – 0.92 (m, 5H), 0.92 – 0.87 (m,
3H), 0.82 (dd, J=18.6, 8.2, 3H), 0.62 (d, J=6.9, 3H). 31P NMR (162 MHz, CDCl3) δ = 9.17 (s, 3
%), 7.77 (s, 97 %). 13C NMR (101 MHz, CDCl3) δ = 133.01 (s), 132.19 (d, J=2.9), 131.36 (s),
130.79 (dd, J=15.5, 11.2), 128.35 (t, J=19.2), 128.07 – 127.58 (m), 108.00 (s), 107.60 (s), 77.93 (d,
J=7.4), 77.32 (d, J=11.6), 77.06 (s), 76.75 (s), 70.95 (s), 68.74 (s), 48.76 – 47.81 (m), 43.60 (s),
7
42.82 (s), 34.02 (s), 31.49 (d, J=18.2), 29.63 (s), 25.72 – 25.20 (m), 23.75 – 22.16 (m), 21.93 (d,
J=17.8), 21.01 (d, J=13.5), 16.06 (s), 15.36 (s), 8.98 (d, J=1.2), -0.00 (d, J=4.5).
HRMS (FAB) calcd for C21H29O2P (M++H) 345.1983, found 345.1981.
(RP)-(-)-Menthyl (trimethylsilylethynyl)phenylphosphinate (2f)
To a solution of trimethylsilylethynyl magnesium bromide (0.750
O
mmol, 2 ml, 0.375 M) in dry toluene was added 1 (0.236 g, 0.750
TMS
P OMen
mmol) at 0°C portionwise within 5 minutes, and the mixture was
Ph
stirred overnight while the temperature elevated to r.t. gradually.
The reaction was quenched with saturated aqueous ammonium chloride solution, the mixture was
extracted with dichloromethane for three times, and the combined organic layer was dried over
sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The crude
product was purified with preparative TLC on silica gel (with hexane/ethyl acetate = 10/1,
containing 5 % acetic acid, as eluent ) to afford 2f as pale yellow oil (dr=96:4, 93 %).
1H NMR (400 MHz, CDCl ) δ 7.81 – 7.72 (m, 2H), 7.38 (ddd, J = 14.7, 12.3, 6.6 Hz, 4H), 4.28
3
(ddd, J = 16.1, 10.4, 5.4 Hz, 1H), 2.37 (d, J = 12.0 Hz, 1H), 1.95 (d, J = 7.1 Hz, 2H), 1.54 (d, J =
10.8 Hz, 2H), 1.42 – 1.22 (m, 2H), 1.22 – 1.07 (m, 2H), 0.84 (dd, J = 18.4, 9.6 Hz, 4H), 0.79 –
0.69 (m, 5H), 0.57 (d, J = 6.9 Hz, 3H), 0.14 – 0.03 (m, 9H). 31P NMR (162 MHz, CDCl3): δ 8.06
(s, 4 %), 6.11 (s, 96 %).
Elemental Analysis: calcd for C21H33O2PSi: C, 66.98; H, 8.83, found C, 66.88; H, 8.75.
(RP)-(-)-Menthyl (ethynyl)phenylphosphinate (2g)
The crude product obtained from 1 and trimethylsilylethynyl magnesium
O
bromide was purified by preparative TLC on silica gel (hexane/EtOAc =
P OMen
3/1) to afford 2g (dr=96:4，88 %) as white solid. Melting point 82-83oC
Ph
1H NMR (400 MHz, CDCl ) δ = 7.89 (dd, J=14.4, 7.2, 2H), 7.59 (t, J=7.4,
3
1H), 7.50 (td, J=7.5, 4.1, 2H), 4.41 (ddd, J=20.3, 10.5, 4.5, 1H), 3.08 (d, J=10.8, 1H), 2.46 (d,
J=12.1, 1H), 2.06 (dq, J=7.0, 4.6, 1H), 1.68 (d, J=12.1, 2H), 1.58 – 1.17 (m, 3H), 1.13 – 0.99 (m,
1H), 0.94 (t, J=8.2, 3H), 0.88 (dd, J=14.3, 4.7, 4H), 0.69 (d, J=6.9, 3H). 31P NMR (162 MHz,
CDCl3) δ = 8.12 (s, 4 %), 6.50 (s, 96 %). 13C NMR (101 MHz, CDCl3) δ = 133.00 (d, J=3.0),
132.09 (d, J=16.1), 131.20 (t, J=10.1), 130.51 (s), 128.72 (d, J=15.0), 90.17 (s), 89.80 (s), 80.17
(s), 79.86 (s), 79.13 (d, J=7.7), 78.14 (s), 77.52 (d, J=11.4), 77.26 (s), 76.94 (s), 48.79 (d, J=6.0),
43.84 (s), 42.83 (s), 34.25 (s), 31.86 (s), 29.91 (s), 25.77 (d, J=11.2), 23.10 (s), 22.16 (d, J=14.8),
21.26 (d, J=15.2), 16.42 (s), 15.67 (s).
HRMS (FAB) calcd for C18H25O2P (M++H) 305.1670, found 305.1653.
(RP)-(-)-Menthyl (5-chloro-1-pentyn-1-yl)phenylphosphinate (2h)
2h was isolated in 59 % yield (dr=97:3) as pale yellow oil.
O
1H NMR (400 MHz, CDCl ) δ = 7.88 (dd, J=14.0, 7.4, 2H),
3
P OMen
Cl(CH2)3
7.62
–
7.53
(m,
1H),
7.49
(dt, J=11.0, 5.7, 2H), 4.33 (ddd,
Ph
J=10.4, 4.5, 1H), 3.63 (t, J=6.2, 2H), 2.58 (td, J=6.8, 3.7, 2H),
2.43 (d, J=12.0, 1H), 2.17 – 1.88 (m, 3H), 1.67 (d, J=10.9, 2H), 1.58 – 1.17 (m, 3H), 1.15 – 0.93
(m, 4H), 0.93 – 0.76 (m, 4H), 0.64 (d, J=6.9, 3H). 31P NMR (162 MHz, CDCl3) δ = 8.76 (s, 3 %),
7.32 (s, 97 %). 13C NMR (101 MHz, CDCl3) δ = 133.15 (s), 132.86 – 132.32 (m), 131.50 (s),
8
131.14 (dd, J=11.2, 3.9), 128.60 (dd, J=14.8, 6.7), 103.00 (s), 102.67 (d, J=10.0), 78.50 (d, J=7.3),
77.89 – 77.42 (m), 77.26 (d, J=5.9), 76.95 (d, J=5.9), 75.63 (s), 48.79 (t, J=6.6), 43.56 – 42.93 (m),
34.31 (s), 31.87 (s), 30.37 (d, J=5.0), 29.87 (s), 25.69 (d, J=5.7), 23.11 (d, J=10.4), 22.26 (d,
J=7.3), 21.19 (d, J=6.7), 17.13 (d, J=3.5), 16.31 (s), 15.65 (d, J=5.3).
HRMS (FAB) calcd for C21H30ClO2P (M++H) 381.1750, found381.1756.
(RP)-(-)-Menthyl (3-methoxyprop-1-yn-1-yl)phenylphosphinate (2i)
2i was prepared in 95 % yield (dr=96:4) as pale yellow oil.
1H NMR (400 MHz, CDCl ) δ = 7.89 (dd, J=14.2, 7.4, 2H), 7.57
O
3
MeO
P OMen
(t, J=7.4, 1H), 7.49 (dt, J=10.9, 5.6, 2H), 4.37 (ddd, J=20.6, 10.6,
Ph
4.5, 1H), 4.22 (d, J=2.9, 2H), 3.51 – 3.30 (m, 3H), 2.46 (d,
J=12.4, 1H), 2.05 (dd, J=13.7, 6.9, 1H), 1.67 (d, J=10.8, 2H), 1.57 – 1.16 (m, 3H), 1.15 – 0.92 (m,
4H), 0.88 (dd, J=16.2, 6.6, 4H), 0.67 (d, J=6.9, 3H). 31P NMR (162 MHz, CDCl3) δ = 8.36 (s, 4
%), 6.82 (s, 96 %). 13C NMR (101 MHz, CDCl3) δ = 132.84 (d, J=3.0), 132.52 (s), 131.08 (dd,
J=26.6, 13.8), 128.59 (t, J=15.4), 98.64 (s), 98.27 (s), 82.40 (s), 80.32 (s), 79.53 (s), 78.79 (d,
J=7.5), 77.62 (s), 77.30 (s), 76.98 (s), 60.07 (d, J=3.4), 58.32 (s), 48.82 (t, J=9.5), 43.84 (s), 43.01
(s), 34.23 (s), 31.85 (s), 29.89 (s), 25.90 (s), 25.69 (s), 23.01 (d, J=17.2), 22.15 (d, J=14.8), 21.25
(d, J=14.8), 16.26 (s), 15.65 (s).
HRMS (FAB) calcd for C20H29O3P (M++H) 349.1933, found 349.1916.
(RP, RP) -Di(-)-menthyl octa-1,7-diyne-1,8-diylbis(phenylphosphinate) (2j)
To a solution of Grignard reagents of 1,7O
O
octadiyne, which was prepared from the addition
P
P
(CH
)
2 4
OMen
Ph
of ethyl magnesium bromide (0.2 ml, 3 M solution
Ph
MenO
in ether, 0.6 mmol) to the solution of 1,7octadiyne (0.038 ml, 0.3 mmol) in toluene (2 ml), was added 1 (0.189 g, 0.6 mmol) at 0°C within
5 minutes, and the mixture was stirred for 5 h while the temperature elevated to rt gradually. The
mixture was quenched with saturated aqueous ammonium chloride solution, extracted with
dichloromethane for three times, and the combined organic layer was dried over sodium sulfate.
After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified
by preparative TLC on silica gel (chloroform/ethyl acetate = 3/1 as eluent). 2j was isolated as pale
yellow oil (dr=95:5, 61 %)
1H NMR (400 MHz, CDCl ) δ 7.86 (dd, J = 14.3, 7.1 Hz, 4H), 7.54 (dd, J = 10.2, 4.3 Hz, 2H),
3
7.46 (td, J = 7.4, 3.9 Hz, 4H), 4.30 (qd, J = 10.5, 4.3 Hz, 2H), 2.40 (t, J = 11.9 Hz, 6H), 2.26 (s,
2H), 2.13 – 1.94 (m, 2H), 1.79 – 1.56 (m, 8H), 1.54 – 1.16 (m, 6H), 1.12 – 0.90 (m, 8H), 0.87 (dd,
J = 15.2, 6.6 Hz, 8H), 0.63 (t, J = 9.4 Hz, 6H). 31P NMR (162 MHz, CDCl3) δ = 8.85 (s, 5 %),
7.52 (s, 95 %). 13C NMR (101 MHz, CDCl3) δ = 133.21 (s), 132.58 (dd, J=11.2, 2.8), 131.57 (s),
131.37 – 130.69 (m), 128.57 (dd, J=14.8, 6.2), 104.08 (d, J=9.3), 103.69 (d, J=9.1), 78.99 (d,
J=7.8), 78.34 (d, J=7.3), 77.96 – 77.36 (m), 77.20 (dd, J=24.7, 13.0), 75.23 (s), 49.04 – 48.18 (m),
43.84 (s), 43.16 (s), 34.27 (s), 32.24 – 31.40 (m), 27.44 (s), 26.64 (d, J=1.5), 26.09 – 25.47 (m),
23.73 – 22.84 (m), 22.28 (d, J=6.8), 22.04 (s), 21.89 – 21.04 (m), 19.13 (d, J=3.5), 18.83 (s),
16.32 (s), 15.62 (d, J=6.0).
HRMS (FAB) calcd for C40H56O4P2 (M++H) 663.3732, found 663.3743.
9
(RP)-(-)-Menthyl octa-1,7-diyne-1-ylphenylphosphinate (2k)
2k was obtained together with 2j from the same reaction.
O
The crude product was purified by preparative TLC on
P OMen
(CH2)4
silica gel (hexane/ethyl acetate = 3/1 as eluent) to afford
Ph
2k as pale yellow oil (dr=92:8，32 %)
1H NMR (400 MHz, CDCl ) δ = 7.90 (dd, J=14.3, 8.0, 2H), 7.62 – 7.54 (m, 1H), 7.54 – 7.43 (m,
3
2H), 4.34 (qd, J=10.4, 4.3, 1H), 2.51 – 2.36 (m, 3H), 2.29 – 2.16 (m, 2H), 2.13 – 2.02 (m, 1H),
1.98 (d, J=2.6, 1H), 1.70 (ddd, J=34.0, 14.4, 6.9, 6H), 1.57 – 1.24 (m, 4H), 1.02 – 0.93 (m, 3H),
0.89 (dd, J=16.5, 7.3, 4H), 0.66 (d, J=6.9, 3H). 31P NMR (162 MHz, CDCl3) δ = 9.03 (s, 8 %),
7.57 (s, 92 %). 13C NMR (101 MHz, CDCl3) δ = 133.35 (s), 132.47 (d, J=2.9), 131.71 (s), 131.14
(d, J=11.2), 128.79 – 128.35 (m), 104.74 (s), 104.34 (s), 83.71 (s), 78.38 (d, J=7.4), 77.52 (s),
77.41 – 76.64 (m), 74.88 (s), 69.03 (s), 48.84 (d, J=6.2), 43.14 (s), 34.33 (s), 31.87 (s), 29.88 (s),
27.59 (s), 26.60 (s), 25.70 (s), 23.17 (s), 22.25 (s), 21.17 (s), 19.25 (d, J=3.5), 18.06 (s), 15.69 (s).
HRMS (FAB) calcd for C24H33O2P (M++H) 385.2296, found 385.2293.
10
S5. Selected 1H, 31P an 13C NMR spectroscopy of compounds 2
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28