The radical-mediated addition of triphenylphosphonium tetrafluoroborate to olefins (hydrophosphonation) is reported. Both standard radical initiators and photochemical conditions are effective, up to the gram scale. The phosphonium salts are shown to serve as Z-selective Wittig olefination reagents, even without purification

Daeffler, Christopher S.

Grubbs, Robert H.

English

Caltech Authors - Main

1 
 
Radical-mediated Anti-Markovnikov Hydrophosphonation of Olefins 
 
Christopher S. Daeffler and Robert H. Grubbs 
 
Division of Chemistry and Chemical Engineering 
California Institute of Technology MC 164-30 
Pasadena, California 91125 
 
rhg@caltech.edu 
 
Table of Contents 
 
General Information and Materials 
Synthetic methods  
Characterization of 4a-e 
References 
 
2 
3 
10 
25 
 
 
2 
 
 
General Information 
 NMR spectra were recorded in CDCl3 on Varian Mercury 300 MHz or INOVA 500 MHz 
spectrometers in the High-Resolution Nuclear Magnetic Resonance Facility at the California 
Institute of Technology (Caltech), unless otherwise noted.  1H and 13C chemical shifts are 
referenced relative to CDCl3 (δ=7.27 for 1H and δ=77.23 for 13C).  19F and 31P chemical shift are 
referenced automatically by the VnmrJ software program.  Spectral analysis was performed on 
MestReNova software.  High-resolution mass spectra were provided by the Caltech’s Mass 
Spectrometry Facility. 
 Photoreactions were performed using a 450 W medium pressure mercury arc lamp (Ace 
Glass) equipped with a water-cooled quartz jacket.  The reaction vessels were Pyrex tubes sealed 
with PTFE closures.  Pyrex glass has 90% transmittance at 350 nm. 
 
Materials 
CH2Cl2 and THF were purified by passage through solvent purification columns by the method 
of Grubbs et al.1  PhCl was purified by distillation from P2O5 under nitrogen atmosphere.  
Triphenylphosphine (PPh3) was purified recrystallization from EtOH.  1-hexene was vacuum-
transferred from CaH2 before use.  1,1’-azobisisobutyronitrile (AIBN) was purified by 
recrystallization from Et2O.  1,1′-azobis(cyclohexanenitrile) (ACN) was purified by 
recrystallization from MeOH.  All other commercially available materials were obtained from 
Aldrich Chemical Company and used as received unless otherwise noted. 
 
 
3 
 
Triphenylphosphonium tetrafluoroborate, [HPPh3][BF4] 
 
To a 300 ml Erlenmeyer flask equipped with a stirbar was added PPh3 (29.5 g, 112 mmol, 1.1 
eq).  The PPh3 was dissolved in Et2O (150 ml).  Upon addition of HBF4 in Et2O (54 wt%, 14 ml, 
100 mmol, 1 eq), a white solid precipitated.  The white solid was collected by filtration and 
washed with Et2O.  Recrystallization of the solid from CHCl3 (60 ml) gives [HPPh3][BF4] as 
colorless prisms in 55% yield (21.4 g, 55 mmol).  A discussion of synthesis, characterization and 
acidity of [HPR3][BF4] salts is presented in references 2 and 3 
 
Triphenylphosphonium hexafluorophosphate, [HPPh3][BF4] 
 
A 50 ml roundbottom flask was equipped with a stirbar and dried under vacuum.  Under Ar flow, 
the flask was charged with PPh3 (2 g, 7.6 mmol, 1.1 eq.), which was dissolved in Et2O (10 ml).  
A 65% aqueous solution of HPF6 (0.9 ml, 6.6 mmol, 1 eq) was added to the ethereal solution and 
a white solid precipitated.  The white solid, [HPPh3][PF6], was collected by filtration in 78% 
yield (2 g, 5.1 mmol) and used without further purification. 
 
9,9-diallylfluorene (3b). 
 
4 
 
A flame-dried 250 ml Schlenk flask with a stirbar was charged with KOtBu (1.2 g, 20 mmol, 2 
eq.), then evacuated and backfilled with Ar.  The flask was cooled to 0 °C in an ice water bath.  
THF (100 ml) was transferred to the cooled flask via cannula.  Fluorene (1.7 g, 10 mmol, 1 eq.) 
was added in one portion.  The solution was stirred at 0 °C for 20 minutes, during which time the 
solution changed from colorless to orange.  Allyl bromide (850 µl, 20 mmol, 2 eq) was added 
dropwise and the solution turned from orange to bright green.  The solution was allowed to warm 
overnight to room temperature.  Additional KOtBu (2 eq.) and allyl bromide (2 eq.) was added to 
the reaction and it was refluxed for 4 hours.  When the reaction was complete, it was cooled to 
room temperature and quenched with MeOH, the water.  The remaining water was removed by 
MgSO4, and all solids were filtered off.  Excess solvent was removed by rotary evaporation to 
yield viscous oil.  The oil was further purified by silica gel chromatography (hexanes, Rf=0.22) 
to yield 9,9-diallylfluorene (1.7 g, 6.7 mmol, 67%).  1H NMR (500 MHz, CDCl3): δ 7.73 (2H, d, 
J = 8 Hz), 7.44 (2H, d, J = 7 Hz), 7.36-7.31 (4H, m), 5.33-5.24 (2H, m), 4.86 (2H, dd, J = 17 Hz, 
1 Hz), 4.77 (2H, d, J = 10 Hz), 2.74 (4H, d, J = 7 Hz).  13C NMR (126 MHz, CDCl3) δ 149.29, 
140.71, 133.73, 127.08, 126.91, 123.62, 119.76, 117.48, 54.16, 43.49.  HRMS (EI+): calculated 
= 246.1408, found = 246.1408. 
 
Allyl trans-2-hexenyl ether (3d). 
 
A 2-neck 250 ml roundbottom flask was fitted with a PTFE valve inlet and a septum.  The flask 
was flame-dried.  THF (100 ml) was transferred to the flask via cannula.  The flask was then 
5 
 
cooled to 0 °C in an ice bath and NaH (60% in mineral oil, 1.1 g, 27.5 mmol, 1.1 eq) was added.  
Dropwise, trans-2-hexen-1-ol (2.9 ml, 25 mmol, 1 eq) was added to the suspension.  The 
reaction was allowed to stir for 90 minutes at 0 °C.  Allyl bromide (2.3 ml, 27.5 mmol, 1.1 eq) 
was added dropwise to the cooled reaction.  The mixture was allowed to warm overnight to room 
temperature.  The reaction was quenched with water (50 ml).  The aqueous layer was extracted 
with hexanes (2x25 ml), then the combined organic layers were washed with brine (50 ml).  The 
organic layer was dried over MgSO4, filtered and the solvent was removed by rotary evaporation.  
The crude oil was purified by silica gel chromatography (9:1 hexanes:ethyl acetate) to yield allyl 
trans-2-hexenyl ether (2.3 g, 16 mmol, 67%).  1H NMR (500 MHz, CDCl3) δ 5.94 (1H, m)), 5.70 
(1H, m), 5.59 (1H, m), 5.29 (1H, d, J = 17.2), 5.19 (1H, d, J = 9.9), 3.98 (2H, dd, J = 5.7, 1.2), 
3.95 (2H, d, J = 6.2) 2.04 (2H, dd, J = 14.5, 6.9), 1.43 (dq, J = 14.8, 7.4, 2H), 0.92 (t, J = 7.4, 
2H).  13C NMR (126 MHz, CDCl3) δ 134.81, 126.23, 116.98, 70.92, 34.38, 29.69, 22.22, 21.14, 
13.69.  HRMS (EI+): calculated = 140.1201, found = 140.1215. 
 
Allyl carbazole (3b). 
 
Carbazole (3.3 g, 20 mmol, 1 equiv.), KOH (1.6g, 30 mmol, 1.5 equiv.) and NaI (160 mg, 1 
mmol, 0.1 eq) were dissolved in DMSO (20 ml) in a 100 ml roundbottom flask.  Once all solids 
were dissolved, allyl bromide (1.8 ml, 22 mmol, 1.1 equiv.) was added via syringe.  The flask 
was capped and stirred at room temperature over night.  Water (25 ml) was added to the reaction 
and large amount of yellow solid crashed out.  The solid was filtered and recrystallized from 
6 
 
hexanes to give yellowish-brown crystals (2.2 g, 10.4 mmol, 52% isolated yield).  
Characterization matches the previously published data.4 
 
General Setup for Conditions Screen with Standard Radical Initiators 
PhCl, temp., 12 hrs.
x eq. initiator
y eq. [HPPh3][BF4]
z eq. PPh3
OMe OMe
Ph3P
BF4
-
1[BF4]  
A Schlenk tube with a stirbar and PTFE closure was flame-dried under vacuum.  The tube was 
backfilled under Ar atmosphere.  The appropriate amounts of initiator, [HPPh3][X] and PPh3 
were added to the tube.  The tube was then charged with the correct solvent (5 ml) and 4-
allylanisole (24 µl, 0.15 mmol).  The tube was sealed and heated to the appropriate temperature 
in an oil bath (AIBN: 80 °C; ACN: 110 °C; DBP: 110 °C).  After 12 hours, the tube was 
removed from the oil bath and cooled.  The solvent was removed by rotary evaporation and the 
conversion was measured by 1H NMR.  If the reaction required a pulsed addition of initiator 
and/or [HPPh3][BF4], the tube was removed from the oil bath after 6 hours, the additional 
reagents were added under Ar flow, the tube was resealed and heated for the final 6 hours.  The 
products were analyzed by 1H NMR. 
 
1[BF4]. 
 
1H NMR (500 MHz, CDCl3) δ 7.81-7.76 (3H, m), 7.72 – 7.56 (12H, m)), 7.10 (2H, d, J = 8.7), 
6.82 (2H, d, J = 8.7), 3.79 (3H, s), 3.35 – 3.20 (2H, m), 2.86 (2H, t, J = 7.1), 1.89 (2H, d, J = 
7 
 
8.2).  13C{1H} NMR (126 MHz, CDCl3) δ 158.21, 135.10 (d, JP-C = 3.0), 133.38 (d, JP-C = 9.9), 
131.92, 129.90, 130.50 (d, JP-C = 12.5), 118.05 (d, JP-C = 86.1), 114.04, 55.28, 34.64 (d, JP-C = 
16.8), 24.71 (d, J = 4), 20.69 (d, JP-C = 51.7). 
 
NMR-scale Kinetic Analysis of Photochemical Hydrophosphonation. 
 
In a nitrogen-filled glovebox, 1-hexene (38 µl, 0.3 mmol, 1 eq), [HPPh3][BF4] (268 mg, 0.75 
mmol, 2.4 eq), PPh3 (20 mg, 0.075 mmol, 0.25 eq) and 1,3,5-trimethoxybenzene (6.7 mg, 0.04 
mmol, internal standard) were dissolved in CD2Cl2 (5 ml).  The solution was divided into 
aliquots (5x1 ml) and placed in five screw-cap NMR tubes.  The sealed tubes were removed 
from the glovebox.  The NMR tubes were irradiated simultaneously in a photobox, and removed 
at the indicated intervals (O, 25 minutes; □, 40 minutes; Δ, 75 minutes; X, 135 minutes).  
Conversion was calculated from comparison to the 1,3,5-trimethoxybenzene internal standard.  
The spectral properties of 2[BF4] were similar to that of is commercially available bromide 
analogue. 
8 
 
 
 
General Photochemical Hydrophosphonation Conditions. 
 
A Pyrex Schlenk tube equipped with a stirbar and PTFE closure was flame-dried under vacuum.  
The tube was backfilled with Ar and charged with [HPPh3][BF4] (525 mg, 1.5 mmol, 1.5 eq) and 
PPh3 (262 mg, 1 mmol, 1 eq).  The tube was evacuated and backfilled with Ar.  The solids were 
dissolved in CH2Cl2 (10 ml).  The substrate (1 mmol) was added in one portion.  The Schlenk 
tube was sealed and placed in the photobox for 24 hours.  The solvent was removed from the 
reaction mixture via rotary evaporation.  The hydrophosphonation products were purified as 
outlined below. 
 
 
 
 
9 
 
Compound Purification Appearance 
1[BF4] trituration with EtOac powder 
4a in vacuo amorphous 
4b trituration with EtOac powder 
4c silica gel chromatography with acetone amorphous 
4d silica gel chromatography with acetonitrile amorphous 
4e trituration with EtOac then hexanes powder 
 
Wittig Olefination with 1[BF4] for the synthesis of styrene 5. 
 
A 50-ml Schlenk flask equipped with a stirbar was flame-dried under vacuum.  The flask was 
backfilled with Ar.  Under Ar flow, the flask was charged with 1[BF4] (500 mg, 1 mmol, 1 eq.), 
then evacuated and backfilled.  The flask was cooled to -78 °C in a CO2(s)/acetone bath and 
charged with THF (12 ml).  Potassium t-butoxide (340 mg, 3 mmol, 3 eq.) was added to the 
cooled suspension in one portion.  The reaction mixture was allowed to stir for 30 minutes at -78 
°C, becoming dark red.  Via syringe, p-tolualdehyde (240 µl, 2 mmol, 2 eq.) was added to the 
solution.  The reaction mixture was allowed to very slowly warm overnight.  The reaction was 
quenched first with methanol (2 ml), then water (2 ml).  The layers were separated.  The aqueous 
layer was extracted with diethyl ether (2x20 ml).  The combined organic layers were washed 
with brine (20 ml), dried over MgSO4 and filtered.  Excess solvent was removed by rotary 
10 
 
evaporation.  Characterization for Z-5 1H NMR (500 MHz, CDCl3) δ 7.17 – 7.12 (m, 6H), 6.85 
(m, 2H), 6.42 (d, J = 11.7, 1H), 5.66 (dt, J = 11.6, 7.0, 1H), 3.81 (s, 3H), 2.73 (m, 2H), 2.64 (dd, 
J = 15.0, 7.9, 2H), 2.35 (2, 3H).  13C NMR (126 MHz, CDCl3) δ 157.82, 136.23, 134.71, 133.65, 
131.21, 129.16, 128.69, 128.51, 128.45, 113.75, 55.26, 35.20, 30.71, 21.16.  HRMS (EI+): 
calculated = 252.1514, found = 252.1515. 
 
Octyltriphenylphosphonium Tetrafluoroborate (4a). 
 
1H NMR (500 MHz, CDCl3) δ 7.80 (m, 3H), 7.72 (m, 12H), 3.24 (m, 2H), 1.58 (b, 4H), 1.20 (b, 
8H), 0.84 (t, J = 7.0, 3H).  13C{1H} NMR (126 MHz, CDCl3) δ 135.16 (d, JP-C = 3.0), 133.39 (d, 
JP-C = 9.9), 130.56 (d, JP-C = 12.5), 118.13 (d, JP-C = 86.0), 44.99, 31.63, 30.31 (d, JP-C = 15.8), 
28.96 (d, JP-C = 1), 28.83, 22.54, 21.95 (d, JP-C = 51.0), 14.04.  HRMS (FAB+): calculated = 
375.2242, found = 375.2250. 
Hydrophosphonation product 4b. 
 
 
1H NMR (500 MHz, CDCl3) δ 8.08 (d, J = 7.7, 2H), 7.74 (m, 2H), 7.67 (m, 2H), 7.59 (m, 2H), 
7.54 – 7.40 (m, 12H), 7.24 (t, J = 6.9, 3H), 4.66 (t, 2H, J = 6), 3.35 (m, 2H), 2.326 (m, 2H).  
13C{1H} NMR (126 MHz, CDCl3) δ 140.28, 134.97, 133.21 (d, JP-C = 9.9), 130.36 (d, JP-C = 
12.6), 129.24 (d, JP-C = 13.5), 126.25, 122.79, 120.19, 119.23, 117.65 (d, JP-C = 86.4), 109.14, 
42.03 (d, JP-C = 19.1).  HRMS (FAB+): calculated = 470.2038, found = 470.2054. 
11 
 
Compound 4c, 1 H NMR (500 MHz, CDCl3 
 
12 
 
Compound 4c, 13C{1H} NMR (126 MHz, CDCl3) 
 
13 
 
Compound 4c, 31P{1H} (202 MHz, CDCl3) 
 
14 
 
Compound 4c, 31P HMBC (202 MHz, CDCl3) 
 
15 
 
Compound 4c, 1H COSY (500 MHz, CDCl3) 
 
16 
 
Compound 4d, 1 H NMR (500 MHz, CDCl3 
 
17 
 
Compound 4d, 13C{1H} NMR (126 MHz, CDCl3) 
 
18 
 
Compound 4d, 31P HMBC (202 MHz, CDCl3) 
 
19 
 
Compound 4d, 1H COSY (500 MHz, CDCl3) 
 
20 
 
Compound 4e, 1 H NMR (500 MHz, CDCl3 
 
21 
 
Compound 4e, 13C{1H} NMR (126 MHz, CDCl3) 
 
22 
 
Compound 4e, 31P HMBC (202 MHz, CDCl3) 
 
23 
 
Compound 4e, 1H COSY (500 MHz, CDCl3) 
 
24 
 
 
 
 
 
25 
 
 
 
                                                          
1
 Pangborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers, F. J. Organometallics 1996, 15, 1518. 
2
 Li, T.; Lough, A. J.; Zuccaccia, C.; Macchioni, A.; Morris, R. H. Can. J. Chem. 2006, 84, 164-175. 
3
 Li, T.; Lough, A. J.; Morris, R. H. Chem. Eur. J. 2007, 13, 3796-3803. 
4
 Jordan-Hore, J. A.; Johansson, C. C. C.; Gulias, M.; Beck, E. M.; Gaunt, M. J. J. Am. Chem. Soc. 2008, 130, 16184. 


Radical-Mediated Anti-Markovnikov Hydrophosphonation of Olefins

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Radical-Mediated Anti-Markovnikov Hydrophosphonation of Olefins

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