Electronic Supplementary Information

for

Mn(III)-Mediated Phosphonation-Azidation of Alkenes: A Facile Synthesis of β-Azidophosphonates

Jian Xu,a Xueqin Li,a Yuzhen Gao,a Liangliang Zhang,a Weizhu Chen,ab Hua Fang,b Guo Tang,*a and Yufen Zhaoa

Table of Contents 1. General and typical procedures for the synthesis of β-azidophosphonates and

5a-5d............................................................................................................................... S2 2. Control experiments for the possible reaction pathways.......................................... S4 3. Compounds list...............................................................................................................S5 4. Spectral data...................................................................................................................S6 5. 1H and 13C NMR spectra........................................................................................... ...S15

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

2

General and Experimental Section General All reactions were carried out under nitrogen. Unless otherwise noted, materials were obtained from commercial suppliers and used without further purification. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were measured on Bruker AVⅢ 400M spectrometers with CDCl3 as solvent and tetramethylsilane (TMS) as internal standard or 85% H3PO4 as external standard for 31P NMR (162 MHz). Chemical shifts were reported in units (ppm) by assigning TMS resonance in the 1H spectrum as 0.00 ppm and CDCl3 resonance in the 13C spectrum as 77.23 ppm. All coupling constants (J values) were reported in Hertz (Hz). Column chromatography was performed on silica gel 300-400 mesh. The CAS number of the known compound was listed. The unknown products were further characterized by HRMS(FT-ICR-MS). Typical procedure for the synthesis of β-azidophosphonates: An oven-dried Schlenk tube containing Mn(OAc)3·2H2O (1.0 mmol) were evacuated and purged with nitrogen three times. Alkene (0.40 mmol), P(O)H (0.6 mmol), and TMSN3 (0.8 mmol) all were dissolved in NMP (3.0 mL) and added to the system at room temperature. The reaction mixture was heated with stirring at 55 oC for 12 hours. The reaction solution was concentrated in vacuo and then added 10 mL of saturated sodium bicarbonate solution and extracted with EtOAc (3×10 mL). The combined organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography using petroleum ether–AcOEt (15:1-5:1, v/v) as the eluent to give the corresponding products. Synthesis of diethyl 2-(4-tert-butylbenzylamino)-2-phenylethylphosphonate (5b)

PPh3 (58 mg, 0.22 mmol) and 4a (56.6 mg, 0.2 mmol in THF:H2O (3:1, 1 mL) was stirred for 12 h at room temperature. The mixture was extracted with ethyl acetate (3×5 mL), and the combined organic layers were washed with brine, dried over MgSO4. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane/methanol (5:1, v/v) as the eluent to give the corresponding product 5a(44 mg, 85%). Synthesis of diethyl 2-(4-tert-butylbenzylamino)-2-phenylethylphosphonate (5b)

PPh3 (58 mg, 0.22 mmol) and 4a (56.6 mg, 0.2 mmol in THF (1 mL) was stirred for 2 h at room

3

temperature. 4-(tert-butyl)benzaldehyde (0.26 mmol) was added and the mixture was heated at 60 °C for 10 h. The mixture was cooled to room temperature and MeOH (0.5 mL) was added followed by NaBH4 (15 mg, 0.4 mmol). After stirring for 1 h at room temperature, water (1 mL, mixed with 100 mL of AcOH) was added and stirred for 15 min. The mixture was extracted with ethyl acetate (3×5 mL), and the combined organic layers were washed with brine, dried over MgSO4. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether–AcOEt (5:1, v/v) as the eluent to give the corresponding product 5b (57 mg, 70%). Synthesis of dimethyl 2-(diethoxyphosphoryl)-1-phenylethyl(methyl)phosphoramidate(5c)

In an oven-dried, two-necked round bottom flask, 4a was dissolved in dry benzene (0.6 mmol/mL) and 1.0 equivalents of trimethyl phosphite was added. The reaction mixture was refluxed for 2 h at 80 °C. After cooling to room temperature, 1 mol% of BF3•EtO2 dissolved in 1 mL of dry benzene, was added to the reaction mixture and the rearrangement was allowed to proceed for 2 h at 80 °C. The solvent was removed under reduced pressure to give the crude product. The residue was purified by silica gel column chromatography using petroleum ether–AcOEt (5:1, v/v) as the eluent to give the corresponding product 5c (52%). Synthesis of diethyl 2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethylphosphonate (5d)

To a solution of azide 4a (56.6 mg, 0.2 mmol) in t-BuOH:H2O (1:1, 1 mL) at room temperature was added CuSO4﹒5H2O (1.5 mg, 0.01 mmol) and sodium carbonate (4 mg, 0.02 mmol) and ethynylbenzene (24.5 mg, 0.24 mmol). The reaction mixture was stirred for 12 h at room temperature and the solvents were removed under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether–AcOEt (5:1, v/v) as the eluent to give the corresponding product 5c (65 mg, 84%).

4

Control experiments for the possible reaction pathways

PR2

R1O

H

A

PR2

R1O

R

BR

PO R1

R2

CR

PO R1

R2

R

TMSN3

RPO

R1

R2

N3++ TMSN3

oxidation

oxidation

N3path a

path b

1) No desired product 4a was obtained when 2.0 equiv of TEMPO was added in the reaction under the optimal conditions. This result suggests that the radical was intercepted by TEMPO. However, no TEMPO-N3 was separated.

2) When N,N-diallyl-4-methylbenzenesulfonamide reacted with TMSN3 under the optimal

conditions, no substituted pyrrolidine was obtained, and N,N-diallyl-4-methylbenzenesulfonamide was recovered quantitatively.

NTs N

Ts

N3

+ TMSN3

not detected

0.2 mmol 0.4 mmolNMP(3 mL),55 oC, 12 h

Mn(OAc)3 2H2O(0.5 mmol )

3) TMSCN and TMCN easily produced anions of SCN and CN. When TMSN3 was replaced

with TMSCN or TMCN, no 6a or 8a was obtained under our condition.

0.6 mmol 0.8 mmol0.4 mmol

Ph TMSSCNH PO OEt

OEt PhPO OEt

OEt

SCN++

1a 2a 5a 6anot detected

NMP(3 mL),55 oC, 12 h

Mn(OAc)3 2H2O(1.0 mmol )

According to the above four control experiments, trapping the N3 radical was failed. However, we couldn’t exclude that N3 radical finishes the reaction. So we proposed two pathways (path a and path b) for this reaction. Path a was reported in many literatures (RSC Adv. 2014, 4, 51776–51779; Chem. Commun. 2015, 51, 1605–1607).

5

Compounds list No. compound page No. compound page 4a

S14 4p

329

4b

S15 4q

S30

4c

S16 4r

S31

4d

S17 4s

S32

4e

S18 4t

S33

4f

S19 4u

S34

4g

S20 4v

S35

4h

S21 4w

S36

4i

S22 4x

S37

4j P

N3 OOEt

OEtBr

S23 4y P

N3 OPh

OEt

S38

4k

S24 4z P

N3 OPh

Ph

S39

4l

S25 5a

S40

4m

S26 5b

S41

4n

S27 5c

S42

4o

S28 5d

S43

6

Spectral data Diethyl (2-azido-2-phenylethyl)phosphonate (4a)

1H NMR (400 MHz, CDCl3, ppm) δ 7.41 – 7.34 (m, 5 H), 4.90 – 4.84 (m, 1 H), 4.15 – 3.90 (m, 4 H), 2.41 – 2.30 (m, 1 H), 2.27 – 2.17 (m, 1 H), 1.31 – 1.21 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 139.1 (d, J = 10.9 Hz), 129.0, 128.8, 126.9, 62.1 (d, J = 6.4 Hz), 61.9 (d, J = 6.5 Hz), 61.0 (d, J = 1.7 Hz), 33.3 (d, J = 141.6 Hz), 16.3 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 26.08; HRMS-ESI: m/z 306.0982 ([M+Na]+, C12H18N3NaO3P +

calcd. 306.0983). Diethyl (2-azido-2-o-tolyl)ethyl)phosphonate (4b)

1H NMR (400 MHz, CDCl3, ppm) δ 7.27 (t, J = 6.9 Hz, 1 H), 7.15 (s, 3 H), 4.82 (d, J = 7.5 Hz, 1 H), 4.11 – 3.95 (m, 4 H), 2.36 – 2.15 (m, 5 H), 1.31 – 1.21 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 139.0 (d, J = 11.1 Hz), 138.6 , 129.4 , 128.8 , 127.4 , 123.8 , 61.9 (d, J = 6.4 Hz), 61.7 (d, J = 6.5 Hz), 60.9 , 33.2 (d, J = 141.6 Hz), 21.3 , 16.2 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 26.07; HRMS-ESI: m/z 320.1143 ([M+Na]+, C13H20N3NaO3P +

calcd. 320.1140). Diethyl (2-azido-2-(m-tolyl)ethyl)phosphonate (4c)

1H NMR (400 MHz, CDCl3, ppm) δ 7.27 (t, J = 7.9 Hz, 1 H), 7.15 (t, J = 7.5 Hz, 3 H), 4.86 – 4.80 (m, 1 H), 4.13 – 3.93 (m, 4 H), 2.37 – 2.19 (m, 5 H), 1.31 – 1.21 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 139.0 (d, J = 11.1 Hz), 138.8 , 129.5 , 128.9 , 127.5 , 123.9 , 62.0 (d, J = 6.4 Hz), 61.8 (d, J = 6.5 Hz), 61.0 (d, J = 1.8 Hz), 33.3 (d, J = 140.3 Hz), 21.4 , 16.3 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 26.14; HRMS-ESI: m/z 320.1141 ([M+Na]+, C13H20N3NaO3P +

calcd. 320.1140). Diethyl (2-azido-2-(p-tolyl)ethyl)phosphonate (4d)

1H NMR (400 MHz, CDCl3, ppm) δ 7.24 – 7.18 (m, 4 H), 4.86 – 4.80 (m, 1 H), 4.13 – 3.92 (m, 4 H), 2.37 – 2.29 (m, 4 H), 2.25 – 2.15 (m, 1 H), 1.31 – 1.22 (m, 6 H); 13C NMR (100 MHz, CDCl3,

7

ppm) δ 138.5, 135.9 (d, J = 11.3 Hz), 129.5, 126.7, 61.9 (d, J = 6.5 Hz), 61.7 (d, J = 6.5 Hz), 60.6 (d, J = 1.9 Hz), 33.1 (d, J = 141.1 Hz), 21.1, 16.2 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 26.16; HRMS-ESI: m/z 320.1136 ([M+Na]+, C13H20N3NaO3P +

calcd. 320.1140). Diethyl (2-azido-2-(4-(tert-butyl)phenyl)ethyl)phosphonate (4e)

N3PO

OEt

OEt

1H NMR (400 MHz, CDCl3, ppm) δ 7.40 (d, J = 8.3 Hz, 2 H), 7.27 (d, J = 8.3 Hz, 2 H), 4.87 – 4.81 (m, 1 H), 4.13 – 4.05 (m, 2 H), 4.02 – 3.89 (m, 2 H), 2.40 – 2.30 (m, 1 H), 2.27 – 2.17 (m, 1H), 1.32 – 1.19 (m, 15 H); 13C NMR (100 MHz, CDCl3, ppm) δ 151.8, 136.1 (d, J = 10.9 Hz), 126.6, 125.8, 62.0 (d, J = 6.5 Hz), 61.8 (d, J = 6.6 Hz), 60.7, 34.7, 33.2 (d, J = 141.1 Hz), 31.3, 16.3 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 26.17; HRMS-ESI: m/z 340.1787 ([M+H]+, C16H27N3O3P +

calcd. 340.1790). Diethyl (2-azido-2-(4-methoxyphenyl)ethyl)phosphonate (4f)

PN3 O

OEtOEt

MeO 1H NMR (400 MHz, CDCl3, ppm) δ 7.27 (d, J = 8.6 Hz, 2 H), 6.91 (d, J = 8.7 Hz, 2 H), 4.86 – 4.80 (m, 1 H), 4.15 – 3.88 (m, 4 H), 3.81 (s, 3 H), 2.39 – 2.29 (m, 1 H), 2.23 – 2.15 (m, 1 H), 1.31 – 1.22 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 159.9, 131.1 (d, J = 10.1 Hz), 128.2, 114.3, 62.1 (d, J = 6.5 Hz), 61.9 (d, J = 6.5 Hz), 60.6 , 55.4, 33.2 (d, J = 139.2 Hz), 16.4 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 26.18; HRMS-ESI: m/z 336.1086 ([M+Na]+, C13H20N3NaO4P +

calcd. 336.1089). Diethyl (2-azido-2-(3-nitrophenyl)ethyl)phosphonate (4g)

1H NMR (400 MHz, CDCl3, ppm) δ 8.25 – 8.22 (m, 2 H), 7.72 (d, J = 7.8 Hz, 1 H), 7.61 (d, J = 7.8 Hz, 1 H), 5.04 – 4.99 (m, 1 H), 4.15 – 3.98 (m, 4 H), 2.41 – 2.33 (m, 1 H), 2.25 – 2.18 (m, 1 H), 1.32 – 1.23 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 148.6, 141.5 (d, J = 10.3 Hz), 133.1, 130.1, 123.7, 122.0, 62.4 (d, J = 6.3 Hz), 62.1 (d, J = 6.6 Hz), 60.4, 33.5 (d, J = 141.9 Hz), 16.4 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 24.71; HRMS-ESI: m/z 351.0835 ([M+Na]+, C12H17N4NaO5P +

calcd. 351.0834). 4-(1-Azido-2-(diethoxyphosphoryl)ethyl)phenyl acetate (4h)

8

1H NMR (400 MHz, CDCl3, ppm) δ 7.36 (d, J = 8.5 Hz, 2 H), 7.12 (d, J = 8.5 Hz, 2 H), 4.91 – 4.85 (m, 1 H), 4.15 – 3.90 (m, 4 H), 2.38 – 2.28 (m, 4 H), 2.23 – 2.14 (m, 1 H), 1.31 – 1.22 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 169.2 , 150.8 , 136.7 (d, J = 10.7 Hz), 127.9, 122.1, 62.0 (d, J = 6.4 Hz), 61.9 (d, J = 6.5 Hz), 60.5, 33.4 (d, J = 142.6 Hz), 21.1, 16.3 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 25.62 ; HRMS-ESI: m/z 342.1216 ([M+H]+, C14H21N3O5P +

calcd. 342.1219). Diethyl (2-azido-2-(4-chlorophenyl)ethyl)phosphonate (4i)

1H NMR (400 MHz, CDCl3, ppm) δ 7.29 (d, J = 8.5 Hz, 2 H), 7.22 (d, J = 8.5 Hz, 2 H), 4.81 – 4.75 (m, 1 H), 4.08 – 3.84 (m, 4 H), 2.29 – 2.23 (m, 1 H), 2.15 – 2.05 (m, 1 H), 1.24 – 1.14 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 137.6 (d, J = 10.6 Hz), 134.6, 129.1, 128.3, 62.1 (d, J = 6.3 Hz), 61.9 (d, J = 6.5 Hz), 60.3 (d, J = 1.4 Hz), 33.3 (d, J = 141.5 Hz), 16.3 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 25.48; HRMS-ESI: m/z 318.0779 ([M+H]+, C12H18ClN3O3P+

calcd. 318.0774). Diethyl (2-azido-2-(4-bromophenyl)ethyl)phosphonate (4j)

1H NMR (400 MHz, CDCl3, ppm) δ 7.53 (d, J = 8.4 Hz, 2 H), 7.23 (d, J = 8.4 Hz, 2 H), 4.87 – 4.81 (m, 1 H), 4.15 – 3.92 (m, 4 H), 2.36 – 2.26 (m, 1 H), 2.22 – 2.13 (m, 1 H), 1.31 – 1.22 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 138.2 (d, J = 10.6 Hz), 132.2, 128.6, 122.8, 62.2 (d, J = 6.5 Hz), 61.9 (d, J = 6.6 Hz), 60.5 (d, J = 1.3 Hz), 33.3 (d, J = 141.3Hz), 16.4 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 25.45; HRMS-ESI: m/z 362.0270 ([M+H]+, C12H18BrN3O3P +

calcd. 362.0269). Diethyl (2-azido-2-(2-bromophenyl)ethyl)phosphonate (4k)

PN3 O

OEtOEt

Br 1H NMR (400 MHz, CDCl3, ppm) δ 7.60 – 7.58 (m, 1 H), 7.47 – 7.45 (m, 1 H), 7.37 (t, J = 7.8 Hz, 1 H), 7.21 – 7.17 (d, J = 7.7 Hz, 1 H), 5.40 – 5.34 (m, 1 H), 4.17 – 4.08 (m, 4 H), 2.34 – 2.27 (m, 1 H), 2.25 – 2.21 (m, 1 H), 1.34 – 1.30 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 138.7 (d, J = 13.1 Hz), 133.3, 129.9, 128.1, 127.9, 122.8, 62.1 (d, J = 6.4 Hz), 61.9 (d, J = 6.5 Hz), 59.8 (d, J = 3.2 Hz), 33.4 (d, J = 142.1 Hz), 16.4 (d, J = 6.2 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 25.35; HRMS-ESI: m/z 362.0270 ([M+H]+, C12H18BrN3O3P +

calcd. 362.0269).

9

Diethyl (2-azido-2-(4-fluorophenyl)ethyl)phosphonate (4l)

1H NMR (400 MHz, CDCl3, ppm) δ 7.28 – 7.25 (m, 2 H), 7.01 (t, J = 8.7 Hz, 2 H), 4.82 – 4.76 (m, 1 H), 4.07 – 3.83 (m, 4 H), 2.31 – 2.20 (m, 1 H), 2.16 – 2.06 (m, 1 H), 1.23 – 1.13 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 162.7 (d, J = 248.7 Hz), 134.9 (d, J = 3.1 Hz), 134.8 (d, J = 3.2 Hz), 128.7 (d, J = 8.3 Hz), 115.7 (d, J = 21.6 Hz), 62.0 (d, J = 6.5 Hz), 61.8 (d, J = 6.5 Hz), 60.2 , 33.2 (d, J = 141.3 Hz), 16.2 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 25.6; HRMS-ESI: m/z 324.0886 ([M+Na]+, C12H17FN3NaO3P +

calcd. 324.0889). Diethyl (2-azido-2-(3-fluorophenyl)ethyl)phosphonate (4m)

1H NMR (400 MHz, CDCl3, ppm) δ 7.40 – 7.32 (m, 1 H), 7.14 (d, J = 7.7 Hz, 1 H), 7.09 – 7.03 (m, 2 H), 4.91 – 4.85 (m, 1 H), 4.14 – 3.94 (m, 4 H), 2.37 – 2.27 (m, 1 H), 2.24 – 2.14 (m, 1 H), 1.32 – 1.23 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 162.9 (d, J = 248.0 Hz), 141.7 (d, J = 6.7 Hz), 141.6 (d, J = 6.7 Hz), 130.6 (d, J = 8.3 Hz), 122.5 (d, J = 2.8 Hz), 115.6 (d, J = 21.0 Hz), 113.8 (d, J = 22.4 Hz), 62.1 (d, J = 6.5 Hz), 61.8 (d, J = 6.5 Hz), 60.4 , 33.3 (d, J = 140.4 Hz), 16.3 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 25.47; HRMS-ESI: m/z 302.1069 ([M+H]+, C12H18FN3O3P+

calcd. 302.1070). Diethyl (2-azido-2-(naphthalene-2-yl)ethyl)phosphonate (4n)

1H NMR (400 MHz, CDCl3, ppm) δ 7.89 – 7.81 (m, 4 H), 7.53 – 7.44 (m, 3 H), 5.09 – 5.03 (m, 1 H), 4.14 – 3.89 (m, 4 H), 2.45 – 2.39 (m, 1 H), 2.35 – 2.25 (m, 1 H), 1.29 – 1.15 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 136.3 (d, J = 11.1 Hz), 133.3, 133.1, 129.1, 128.1, 127.7, 126.6, 126.6, 126.2, 124.0, 62.1 (d, J = 6.4 Hz), 61.8 (d, J = 6.4 Hz), 61.2 (d, J = 1.7 Hz), 33.2 (d, J = 141.2 Hz), 16.3 (d, J = 6.1 Hz), 16.2 (d, J = 6.2 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 25.86; HRMS-ESI: m/z 356.1142 ([M+Na]+, C16H20N3NaO3P +

calcd. 356.1140). Diethyl (2-azido-1,1-diphenylethyl)phosphonate (4o)

10

1H NMR (400 MHz, CDCl3, ppm) δ 7.29 – 7.23 (m, 8 H), 7.20 – 7.17 (m, 2 H), 3.89 – 3.77 (m, 2 H), 3.75 – 3.62 (m, 2 H), 2.99 (s, 1 H), 2.95 (s, 1 H), 1.08 – 1.05 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 142.8 (d, J = 8.8 Hz), 128.4, 127.8, 126.7, 69.0 (d, J = 4.6 Hz), 61.7 (d, J = 6.5 Hz), 36.6 (d, J = 145.6 Hz), 16.2 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 24.26; HRMS-ESI: m/z 382.1295 ([M+Na]+, C18H22N3NaO3P +

calcd. 382.1296). Diethyl (2-azido-2-phenylpropyl)phosphonate (4p)

1H NMR (400 MHz, CDCl3, ppm) δ 7.47 (d, J = 7.2 Hz, 2 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.30 (d, J = 7.2 Hz, 1 H), 4.04 – 3.75 (m, 4 H), 2.41 (s, 1 H), 2.36 (s, 1 H), 1.94 (s, 3 H), 1.25 (t, J = 6.8 Hz, 3 H), 1.14 (t, J = 6.8 Hz, 3 H); 13C NMR (100 MHz, CDCl3, ppm) δ 143.1 (d, J = 7.9 Hz), 128.5, 127.8, 125.6, 63.8, 61.7 (d, J = 6.5 Hz), 61.4 (d, J = 6.5 Hz), 39.2 (d, J = 141.2 Hz), 25.4 (d, J = 3.8 Hz), 16.3 (d, J = 6.3 Hz), 16.1(d, J = 6.3 Hz);31P NMR (162 MHz, CDCl3, ppm) δ 24.52; HRMS-ESI: m/z 320.1139 ([M+Na]+, C13H20N3NaO3P +

calcd. 320.1140). Diethyl (2-azido-2-cyclopropyl-2-phenylethyl)phosphonate (4q)

N3

PO

EtOEtO

1H NMR (400 MHz, CDCl3, ppm) δ 7.52 (d, J = 7.7 Hz, 2 H), 7.38 (t, J = 7.9 Hz, 2 H), 7.30 (t, J = 7.5 Hz, 1 H), 4.05 – 3.83 (m, 3 H), 3.78 – 3.66 (m, 1 H), 2.70 – 2.61 (m, 1 H), 2.53 – 2.44 (m, 1 H), 1.86 – 1.79 (m, 1 H), 1.23 – 1.11 (m, 6 H), 0.67 – 0.57 (m, 2 H), 0.52 – 0.38 (m, 1 H); 13C NMR (100 MHz, CDCl3, ppm) δ 140.4 (d, J = 5.7 Hz), 128.3, 128.0, 126.9, 61.7 (d, J = 6.5 Hz), 61.6 (d, J = 6.6 Hz), 37.1 (d, J = 142.7 Hz), 20.3 (d, J = 6.9 Hz), 16.3 (m), 2.0 (d, J = 65.7 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 24.48; HRMS-ESI: m/z 346.1294 ([M+Na]+, C15H22N3NaO3P+

calcd. 346.1296). Diethyl (1-azido-2,3-dihydro-1H-inden-2-yl)phosphonate (4r)

1H NMR (400 MHz, CDCl3, ppm) δ 7.31 – 7.29 (m, 1 H), 7.22 – 7.15 (m, 3 H), 5.12 – 5.07 (m, 1 H), 4.12 – 4.04 (m, 4 H), 3.24 – 3.09 (m, 2 H), 2.67 – 2.61 (m, 1 H), 1.28 – 1.21 (m, 6 H); 13C

11

NMR (100 MHz, CDCl3, ppm) δ 140.8 (d, J = 10.4 Hz), 139.8 (d, J = 11.0 Hz), 129.1, 127.4, 124.8, 124.5, 66.8, 62.3 (m), 42.8 (d, J = 148.1 Hz), 32.0 , 16.5 (d, J = 3.4 Hz), 16.4 (d, J = 3.3 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 29.65; HRMS-ESI: m/z 318.0985 ([M+Na]+, C13H18N3NaO3P +

calcd. 318.0983). Diethyl (2-azido-2-(thiophen-2-yl)ethyl)phosphonate (4s)

1H NMR (400 MHz, CDCl3, ppm) δ 7.33 – 7.32 (m, 1 H), 7.08 (d, J = 2.9 Hz, 1 H), 7.01 – 6.99 (m, 1 H), 5.16 – 5.10 (m, 1 H), 4.15 – 4.3.97 (m, 4 H), 2.42 – 2.32 (m, 2 H), 1.33 – 1.25 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 142.0 (d, J = 13.3 Hz), 126.8, 126.0 (d, J = 3.5 Hz), 62.1 (d, J = 6.4 Hz), 61.9 (d, J = 6.4 Hz), 56.4, 33.8 (d, J = 142.0 Hz), 16.3(m); 31P NMR (162 MHz, CDCl3, ppm) δ 25.09; HRMS-ESI: m/z 312.0545 ([M+Na]+, C10H16N3NaO3PS +

calcd. 312.0548). Diethyl (2-azido-3-phenylpropyl)phosphonate (4t)

1H NMR (400 MHz, CDCl3, ppm) δ 7.33 (t, J = 7.5 Hz, 2 H), 7.28 – 7.26 (m, 1 H), 7.24 – 7.22 (m, 2 H), 4.17 – 4.07 (m, 4 H), 3.98 – 3.89 (m, 1 H), 3.00 – 2.95 (m, 1 H), 2.91 – 2.86 (m, 1 H), 2.02 – 2.00 (m, 1 H), 1.98 – 1.96 (m, 1 H), 1.35 – 1.31 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 136.8, 129.5, 128.8, 127.2, 62.1 (d, J = 6.6 Hz), 62.0 (d, J = 6.5 Hz), 59.0 (d, J = 3.3 Hz), 41.0 (d, J = 11.9 Hz), 30.9 (d, J = 141.9 Hz), 16.5 (d, J = 6.0 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 27.00; HRMS-ESI: m/z 320.1142 ([M+Na]+, C13H20N3NaO3P +

calcd. 320.1140). Diethyl (2-azidocyclohexyl)phosphonate (4u)

1H NMR (400 MHz, CDCl3, ppm) δ 4.20 – 4.10 (m, 4 H), 4.47 – 3.39 (m, 1 H), 2.16 – 1.75 (m, 7 H), 1.43 – 1.40 (m, 1 H), 1.37 – 1.33 (m, 6 H), 1.26 (s, 1 H); 13C NMR (100 MHz, CDCl3, ppm) δ 62.0 (d, J = 6.9 Hz), 60.0 (d, J = 5.9 Hz), 41.0 (d, J = 143.6 Hz), 32.1 (d, J = 12.5 Hz), 25.7 (d, J = 4.8 Hz), 24.8 (d, J = 14.1 Hz), 24.4, 16.6 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 29.36; HRMS-ESI: m/z 284.1137 ([M+Na]+, C10H20N3NaO3P +

calcd. 284.1140). Diisopropyl (2-azido-2-phenylethyl)phosphonate (4v)

1H NMR (400 MHz, CDCl3, ppm) δ 7.36 – 7.34 (m, 5 H), 4.85 – 4.83 (m, 1 H), 4.71 – 4.61 (m, 2

12

H), 2.34 – 2.25 (m, 1 H), 2.23 – 2.13 (m, 1 H), 1.28 – 1.20 (m, 12 H); 13C NMR (100 MHz, CDCl3, ppm) δ 139.3 (d, J = 10.7 Hz), 128.9, 128.6, 126.9, 70.7 (d, J = 6.6 Hz), 70.5 (d, J = 6.7 Hz), 61.3, 34.5 (d, J = 142.0 Hz), 24.0 (m), 23.8 (m); 1P NMR (162 MHz, CDCl3, ppm) δ 23.77; HRMS-ESI: m/z 334.1296 ([M+Na]+, C14H22N3NaO3P +

calcd. 334.1296). Diisopropyl (2-azido-2-(4-fluorophenyl)ethyl)phosphonate (4w)

PN3 O

O

O

F 1H NMR (400 MHz, CDCl3, ppm) δ 7.27 – 7.24 (m, 2 H), 7.00 (t, J = 8.0 Hz, 2 H), 4.80 – 4.74 (m, 1 H), 4.68 – 4.48(m, 2 H), 2.26 – 2.18 (m, 1 H), 2.13 – 2.03 (m, 1 H), 1.23 – 1.19 (m, 9 H), 1.12 (d, J = 6.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3, ppm) δ 162.8 (d, J = 247.4 Hz), 135.2 (d, J = 9.9 Hz), 128.8 (d, J = 8.3 Hz), 115.8 (d, J = 21.7 Hz), 70.8 (d, J = 6.6 Hz), 70.6 (d, J = 6.7 Hz), 60.6, 34.7 (d, J = 124.5 Hz), 24.0 (m), 23.9 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 23.45; HRMS-ESI: m/z 352.1201 ([M+Na]+, C14H21FN3NaO3P +

calcd. 352.1202). Dibenzyl (2-azido-2-phenylethyl)phosphonate (4x)

1H NMR (400 MHz, CDCl3, ppm) δ 7.37 – 7.24 (m, 15 H), 5.04 – 4.94 (m, 2 H), 4.90 – 4.79 (m, 3 H), 2.43 – 2.32 (m, 1 H), 2.29 – 2.19 (m, 1 H); 13C NMR (100 MHz, CDCl3, ppm) δ 138.7 (d, J = 11.1 Hz), 136.1 (d, J = 6.1 Hz), 136.0 (d, J = 6.1 Hz), 129.0, 128.8, 128.6 (d, J = 2.3 Hz), 128.5, 128.0 (d, J = 2.4 Hz), 126.8, 67.6 (d, J = 6.2 Hz), 67.4 (d, J = 6.3 Hz), 60.8 (d, J = 1.9 Hz), 33.6 (d, J = 141.6 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 27.17; HRMS-ESI: m/z 408.1476 ([M+H]+, C22H23N3O3P +

calcd. 408.1477). Ethyl (2-azido-2-phenylethyl)(phenyl)phosphinate (4y)

1H NMR (400 MHz, CDCl3, ppm) δ 7.82 – 7.77 (m, 1 H), 7.67 – 7.62 (m, 1 H), 7.56 – 7.46 (m, 2 H), 7.41 – 7.19 (m, 6 H), 4.97 – 4.86 (m, 1 H), 4.12 – 3.77 (m, 2 H), 2.63 – 2.48 (m, 1 H), 2.43 – 2.28 (m, 1 H), 1.31 – 1.18 (m, 3 H); 13C NMR (100 MHz, CDCl3, ppm) δ 139.2 (d, J = 10.5 Hz), 138.8 (d, J = 9.1 Hz), 132.4 (d, J = 2.5 Hz), 132.3 (d, J = 2.5 Hz), 131.6 (d, J = 10.1 Hz), 131.4 (d, J = 10.1 Hz), 130.1 (d, J = 34.6 Hz), 128.8 (d, J = 11.6 Hz), 128.7 (d, J = 12.2 Hz), 128.6 , 128.5 (d, J = 6.5 Hz), 126.7 (d, J = 3.6 Hz), 60.9 (d, J = 6.3 Hz), 60.7 (d, J = 6.1 Hz), 60.4 (d, J = 22.3 Hz), 37.5 (d, J = 22.8 Hz), 36.5 (d, J = 23.5 Hz), 16.4 (d, J = 6.5 Hz), 16.2 (d, J = 6.5 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 39.67 , 39.19; HRMS-ESI: m/z 316.1209 ([M+H]+, C16H19N3O2P +

calcd. 316.1215).

13

(2-Azido-2-phenylethyl)diphenylphosphine oxide (4z)

1H NMR (400 MHz, CDCl3, ppm) δ 7.84 – 7.79 (m, 2 H), 7.64 – 7.60 (m, 2 H), 7.55 – 7.42 (m, 4 H), 7.39 – 7.34 (m, 2 H), 7.29 – 7.24 (m, 5 H), 5.15 – 5.10 (m, 1 H), 2.94 – 2.84 (m, 1 H), 2.72 – 2.64 (m, 1 H); 13C NMR (100 MHz, CDCl3, ppm) δ 139.3 (d, J = 8.8 Hz), 133.3 (d, J = 16.3 Hz), 132.3 (d, J = 15.8 Hz), 131.9 (d, J = 2.7 Hz), 131.8 (d, J = 2.6 Hz), 130.8 (d, J = 9.5 Hz), 130.6 (d, J = 9.5 Hz), 128.9 , 128.7 (d, J = 6.4 Hz), 128.6 (d, J = 6.9 Hz), 126.8, 60.2 (d, J = 2.3 Hz), 37.4(d, J = 69.1 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 27.95; HRMS-ESI: m/z 348.1271 ([M+H]+, C20H19N3OP +

calcd. 348.1266). Diethyl (2-amino-2-phenylethyl)phosphonate (5a)

1H NMR (400 MHz, CDCl3, ppm) δ 7.38 (d, J = 7.4 Hz, 2 H), 7.33 (t, J = 7.7 Hz, 2 H), 7.25 (t, J = 7.1 Hz, 1 H), 4.44 – 4.38 (m, 1 H), 4.11 – 4.03 (m, 4 H), 2.21 (s, 2 H), 2.18 – 2.11 (m, 2 H), 1.30 (t, J = 7.0 Hz, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 145.4 (d, J = 15.3 Hz), 128.7 , 127.5 , 126.2 , 61.7 (m), 51.2 (d, J = 3.7 Hz), 36.0 (d, J = 136.6 Hz), 16.5 (d, J = 2.3 Hz), 16.4 (d, J = 2.3 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 29.13; HRMS-ESI: m/z 280.1077 ([M+Na]+, C12H20NNaO3P +

calcd. 280.1078). Diethyl (2-((4-(tert-butyl)benzyl)amino)-2-phenylethyl)phosphonate (5b)

1H NMR (400 MHz, CDCl3, ppm) δ 7.42 (d, J = 7.4 Hz, 2 H), 7.39 – 7.34 (m, 4 H), 7.29 (t, J = 4.4 Hz, 1 H), 7.22 (d, J = 8.3 Hz, 2 H), 4.23 – 3.86 (m, 5 H), 3.63 (d, J = 13.4 Hz, 1 H), 3.50 (d, J = 13.0 Hz, 1 H), 2.29 – 2.19 (m, 1 H), 2.13 – 2.03 (m, 1 H), 1.33 (s, 9 H), 1.28 – 1.22 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 149.8 (s), 137.2 (s), 132.2 (d, J = 9.8 Hz), 128.7 (s), 128.0 (s), 127.6 (s), 127.2 (s), 125.3 (s), 61.8 (d, J = 6.7 Hz), 61.7 (d, J = 6.3 Hz), 57.0 (s), 51.0 (s), 35.7 (s), 34.5 (s), 31.5 (s), 16.5 (d, J = 4.0 Hz); 31P NMR (162 MHz, CDCl3, ppm) δ 28.83; HRMS-ESI: m/z 426.2171 ([M+Na]+, C23H34NNaO3P+

calcd. 426.2174). Dimethyl (2-(diethoxyphosphoryl)-1-phenylethyl)(methyl)phosphoramidate (5c)

14

1H NMR (400 MHz, CDCl3, ppm) δ 7.41 (d, J = 7.6 Hz, 2 H), 7.34 (t, J = 7.7 Hz, 2 H), 7.29 (d, J = 7.1 Hz, 1 H), 5.21 – 5.13 (m, 1 H), 4.06 – 3.95 (m, 4 H), 3.68 (d, J = 11.2 Hz, 3 H), 3.58 (d, J = 11.2 Hz, 3 H), 2.63 – 2.53 (m, 1 H), 2.46 (d, J = 9.6 Hz, 4 H), 1.27 – 1.19 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 139.1 (d, J = 8.0 Hz), 128.3, 128.1, 127.9, 61.9 (d, J = 6.6 Hz), 61.6 (d, J = 6.6 Hz), 55.0 (d, J = 5.7 Hz), 53.1 (d, J = 5.7 Hz), 52.9 (d, J = 5.8 Hz), 29.0 (d, J = 141.2 Hz), 28.0 (d, J = 3.6 Hz), 16.3 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 27,33 , 11.63; HRMS-ESI: m/z 402.1209 ([M+Na]+, C15H27NNaO6P2

+ calcd. 402.1211).

Diethyl (2-phenyl-2-(4-phenyl-1H-1,2,3-triazol-1-yl)ethyl)phosphonate (5d)

1H NMR (400 MHz, CDCl3, ppm) δ 7.80 (d, J = 6.4 Hz, 3 H), 7.4 (d, J = 6.6 Hz, 2 H), 7.40 – 7.28 (m, 6 H), 6.02 – 6.00 (m, 1 H), 4.01 – 3.79 (m, 4 H), 3.34 – 3.24 (m, 1 H), 2.84 – 2.74 (m, 1 H), 1.19 – 1.11 (m, 6 H); 13C NMR (100 MHz, CDCl3, ppm) δ 147.7 (s), 138.6 (d, J = 9.6 Hz), 130.5 (s), 129.0 (d, J = 28.3 Hz), 128.5 (d, J = 81.3 Hz), 127.1 (s), 125.7 (s), 119.8 (s), 62.0 (d, J = 6.5 Hz), 60.6 (s), 33.1 (s), 31.7 (s), 16.2 (m); 31P NMR (162 MHz, CDCl3, ppm) δ 24.6; HRMS-ESI: m/z 408.1451 ([M+Na]+, C20H24N3NaO3P +

calcd. 408.1453).

15

1H and 13C NMR spectra

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44