Variable Mechanism of Nucleophilic Substitution of P-

Stereogenic 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 ContentsGeneral.S1. Procedure for reaction of phenylethynyl lithium 3a to (SP)-menthyl

phenylphosphonochloridate 1 under different conditionsS1-1. 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 2S3. Discussion about the apicalphilics of atoms on pentacoordinated phosphorus and reactivities

of P-heteroatom bondsS4. Preparation of 2 via reaction of 1 to 3 and/or 8

Method AMethod B

S5. Selected 1H, 31P and 13C NMR spectroscopy of compound 2

1

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2015

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 S1-1S1-4. 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 31P-NMR 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

S P OMenPh

O

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 Mo-Kα 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 C31H37O2PSFormula weight 504.64Wavelength (Å) 0.71073Crystal system MonoclinicSpace group P2(1)

a (Å) 5.8682(4)b (Å) 15.5218(14)c (Å) 14.1795(13)(º) 90(º) 92.4450(10)(º) 90

V (Å3) 1290.36(19)Z 2

Dcalc (Mg/m3) 1.299μ (mm-1) 0.215F(000) 540

Crystal size (mm) 0.34 x 0.15 x 0.12Reflections collected 6407

Unique reflections [Rint] 3628 [R(int) = 0.1917]Data/restraints/parameters 3628 / 211 / 321

Goodness-of-fit on F2 0.919Final R indices [I>2σ (I)] R1 = 0.1142

wR2 = 0.2511R indices (all data) R1 = 0.2086

wR2 =0.3049Flack parameter -0.2(3)CCDC number 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 8Method 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 %). 1H NMR (400 MHz, CDCl3) δ = 8.04 – 7.89 (m, 2H), 7.63 – 7.46 (m, 5H), 7.46 – 7.31 (m, 3H), 4.44 (ddd, J=10.5, 4.4, 1H), 2.55 (d, 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, CDCl3) δ = 7.95 – 7.80 (m, 2H), 7.60 – 7.51 (m, 1H), 7.51 – 7.40 (m, 2H), 4.33 (ddd, J=20.5, 10.5, 4.5, 1H), 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

Ph P OMenPh

O

n-Bu P OMenPh

O

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.1H NMR (400 MHz, CDCl3) δ = 7.87 (dd, J=14.0, 7.4, 2H), 7.59 – 7.52 (m, 1H), 7.48 (dd, J=8.0, 3.8, 2H), 4.35 (ddd, J=20.7, 10.2, 4.3, 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.1H NMR (400 MHz, CDCl3) δ = 7.84 (ddd, J=14.3, 8.2, 1.2, 2H), 7.50 (ddd, J=7.4, 6.0, 1.4, 1H), 7.47 – 7.38 (m, 2H), 4.30 (ddd, 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.1H NMR (400 MHz, CDCl3) δ = 7.93 – 7.81 (m, 2H), 7.59 – 7.51 (m, 1H), 7.51 – 7.41 (m, 2H), 4.29 (ddd, J=20.5, 10.5, 4.4, 1H), 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

t-Bu P OMenPh

O

n-BuP OMenPh

O

P OMenPh

O

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 mmol, 2 ml, 0.375 M) in dry toluene was added 1 (0.236 g, 0.750 mmol) at 0°C portionwise within 5 minutes, and the mixture was 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, CDCl3) δ 7.81 – 7.72 (m, 2H), 7.38 (ddd, J = 14.7, 12.3, 6.6 Hz, 4H), 4.28 (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 bromide was purified by preparative TLC on silica gel (hexane/EtOAc = 3/1) to afford 2g (dr=96:4，88 %) as white solid. Melting point 82-83oC1H NMR (400 MHz, CDCl3) δ = 7.89 (dd, J=14.4, 7.2, 2H), 7.59 (t, J=7.4,

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.1H NMR (400 MHz, CDCl3) δ = 7.88 (dd, J=14.0, 7.4, 2H), 7.62 – 7.53 (m, 1H), 7.49 (dt, J=11.0, 5.7, 2H), 4.33 (ddd, 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

P OMenPh

O

Cl(CH2)3 P OMenPh

O

P OMenPh

OTMS

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, CDCl3) δ = 7.89 (dd, J=14.2, 7.4, 2H), 7.57 (t, J=7.4, 1H), 7.49 (dt, J=10.9, 5.6, 2H), 4.37 (ddd, J=20.6, 10.6, 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 1,7-octadiyne, which was prepared from the addition of ethyl magnesium bromide (0.2 ml, 3 M solution in ether, 0.6 mmol) to the solution of 1,7-

octadiyne (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, CDCl3) δ 7.86 (dd, J = 14.3, 7.1 Hz, 4H), 7.54 (dd, J = 10.2, 4.3 Hz, 2H), 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

MeOP OMenPh

O

PPhMenO

O(CH2)4 P OMen

Ph

O

(RP)-(-)-Menthyl octa-1,7-diyne-1-ylphenylphosphinate (2k)2k was obtained together with 2j from the same reaction. The crude product was purified by preparative TLC on silica gel (hexane/ethyl acetate = 3/1 as eluent) to afford 2k as pale yellow oil (dr=92:8，32 %)

1H NMR (400 MHz, CDCl3) δ = 7.90 (dd, J=14.3, 8.0, 2H), 7.62 – 7.54 (m, 1H), 7.54 – 7.43 (m, 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

(CH2)4 P OMenPh

O

S5. Selected 1H, 31P an 13C NMR spectroscopy of compounds 2

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14

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