Encyclopedia of Reagents for Organic Synthesis || 3-Methyl-1-phenyl-Phospholane 1-Oxide
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3-METHYL-1-PHENYL-PHOSPHOLANE 1-OXIDE 1 3-Methyl-1-phenyl-phospholane 1-Oxide P O [34868-22-9] C 11 H 15 OP (MW 194.21) InChI = 1S/C11H15OP/c1-10-7-8-13(12,9-10)11-5-3-2-4-6-11/ h2-6,10H,7-9H2,1H3 InChIKey = NMWVKRPDPIADRN-UHFFFAOYSA-N (catalyst for Wittig reaction) Physical Data: clear viscous oil containing a mixture of isomers (2:1). 31 P NMR (CDCl 3 ) δ (ppm) 62.2 for the major and 62.5 for the minor isomer. 1 13 C NMR (CDC1 3 ) δ (ppm) major: 20.9 (J = 13.7 Hz, Me), 30.6 (J = 65.9 Hz, C 5 ), 33.5 (J = 8.3 Hz, C 3 ), 33.9 (J = 5.7 Hz, C 4 ), 37.3 (J = 67.6 Hz, C 2 ), 133.8 (J = 89.1 Hz, C 1 ); minor: 21.0 (J ∼ 9 Hz, Me), 29.5 (J = 65.9 Hz, C 5 ), 32.7 (J = 5.6 Hz, C 3 ), 34.6 (J = 9.1 Hz, C 4 ), 37.8 (J ∼ 60 Hz, C 2 ); common signals: 128.5 (J = 11.1 Hz, C 2 − ), 129.7 (J = 9.6 Hz, C 3 − ), 131.6 (C 4 ). 1 MS, m/z (rel. int.) 194 (M + , 100), 193 (86), 179 (26), 125 (48), 77 (24); HRMS, M + found = 194.0851, C 11 H 15 OP requires 194.0861. 1 Solubility: soluble in halogenated solvents such as CH 2 Cl 2 and CHCl 3 . Preparative Method: the reagent can be easily prepared us- ing McCormack’s synthesis. 2 The synthesis proceeds via a cheletropic reaction between the dichlorophenylphosphine and commercially available isoprene, followed by hydrolysis and reduction of the carbon–carbon double bond. Purification: it can be purified by fractional distillation. Handling, Storage, and Precautions: product is somewhat hygroscopic. Preparation. The reagent can be prepared through a chele- tropic reaction between dichlorophenylphosphine and isoprene (eq 1). 2 A commercially available antioxidant is added to suppress the formation of unwanted polymeric by-products. 2 The reaction proceeds over the course of a week. The white crystalline solid formed (2) is very sensitive to hydrolysis and can be hydrolyzed in a controlled fashion (using ice) to give a crude mixture with phos- phine oxide 3 following basic workup (eq 2). The pure phosphine oxide 3 is obtained by fractional distillation as a pale yellow oil that solidifies below 60–65 ◦ C to give a white solid. 2 Precursor 3 can be reduced at room temperature with borane dimethyl sulfide over 24 h, or at 63 ◦ C over 7 h (eq 3). The reaction at room tem- perature affords quantitative yield after hydrolysis and workup. 1,3 Precursor 3 can also be reduced at rt using the H-Cube Midi R :a solution of 3 in methanol is reduced on 10% Pd/C using hydro- gen gas to give 1 as a 2:1 mixture of diastereomers. Alternatively, LiAlH 4 can also be employed to reduce 3 to 1. 4 Cl 2 PPh P Cl Cl (2) (1) P Cl Cl P O (3) H 2 O (2) P O P O (1) 10% Pd/C/H 2 CH 3 OH, rt P O (1) 1. Me 2 S–BH 3 (2.2 equiv) rt, 24 h, CHCl 3 2. H 2 O (3) Wittig Catalysis. The Wittig reaction is among a handful of organic protocols allowing formation of carbon–carbon dou- ble bonds, along with the Peterson, 5 Julia–Lythgoe, 6,7 Julia– Kocienski, 8,9 and metathesis 10 reactions. This stoichiometric re- action uses phosphorus ylides prepared in situ that react with aldehydes or ketones to give olefins and phosphine oxide. The Wittig reaction generally offers good Z/E selectivity in the resulting olefin, and the phosphine structure along with the elec- tronic properties of the generated ylide can be manipulated to con- trol the selectivity. 11 As the high oxophilicity of the phosphorus atom drives the reaction forward, reducing the phosphine oxide to recycle can be particularly challenging. 11 Arsenines 12 and tellurides 12 have been successfully employed in the Wittig-type chemistry to bestow a catalytic process, but these toxic heavy metal reagents make the corresponding proto- cols less appealing for industrial applications. The reagent 1, when paired with a silane reducing agent, was successfully employed in the catalytic-in-phosphine Wittig protocol. 11 Silanes, such as H 3 SiPh or H 2 SiPh 2 , are known to reduce phosphine oxides (with retention of configuration 11,13 ) even in the presence of carbonyl compounds. Relief of aliphatic ring strain around phosphorus is believed to be crucial in facilitating the reduction of the catalyst, when compared to that of acyclic phosphine oxides. For instance, reactions carried out using triphenylphosphine oxide in place of 1 do not yield appreciable product. 11 O H Br CO 2 Me CO 2 Me 1 (10 mol %) H 2 SiPh 2 (1.1–1.5 equiv) Na 2 CO 3 (1.5 equiv) toluene, 100 ºC, 24 h (4) 74%, E:Z >95:5 Reagent 1 catalyzes the olefination of several substrates in the presence of various alkyl/aryl halides. Representative examples are shown in eqs 4–9. 11 Reasonable to excellent yields (61–81%) and E/Z selectivity (60:40 to >95:5) are observed with a variety of aldehydes and halo derivatives. The optimal conditions for this
Transcript of Encyclopedia of Reagents for Organic Synthesis || 3-Methyl-1-phenyl-Phospholane 1-Oxide
3-METHYL-1-PHENYL-PHOSPHOLANE 1-OXIDE 1
3-Methyl-1-phenyl-phospholane 1-Oxide
PO
[34868-22-9] C11H15OP (MW 194.21)InChI = 1S/C11H15OP/c1-10-7-8-13(12,9-10)11-5-3-2-4-6-11/
h2-6,10H,7-9H2,1H3InChIKey = NMWVKRPDPIADRN-UHFFFAOYSA-N
(catalyst for Wittig reaction)
Physical Data: clear viscous oil containing a mixture of isomers(2:1). 31P NMR (CDCl3) δ (ppm) 62.2 for the major and 62.5 forthe minor isomer.1 13C NMR (CDC13) δ (ppm) major: 20.9 (J =13.7 Hz, Me), 30.6 (J = 65.9 Hz, C5), 33.5 (J = 8.3 Hz, C3), 33.9(J = 5.7 Hz, C4), 37.3 (J = 67.6 Hz, C2), 133.8 (J = 89.1 Hz, C1);minor: 21.0 (J ∼ 9 Hz, Me), 29.5 (J = 65.9 Hz, C5), 32.7 (J = 5.6Hz, C3), 34.6 (J = 9.1 Hz, C4), 37.8 (J ∼ 60 Hz, C2); commonsignals: 128.5 (J = 11.1 Hz, C2− ), 129.7 (J = 9.6 Hz, C3− ),131.6 (C4′ ).1 MS, m/z (rel. int.) 194 (M+, 100), 193 (86), 179(26), 125 (48), 77 (24); HRMS, M+
found = 194.0851, C11H15OPrequires 194.0861.1
Solubility: soluble in halogenated solvents such as CH2Cl2 andCHCl3.
Preparative Method: the reagent can be easily prepared us-ing McCormack’s synthesis.2 The synthesis proceeds via acheletropic reaction between the dichlorophenylphosphine andcommercially available isoprene, followed by hydrolysis andreduction of the carbon–carbon double bond.
Purification: it can be purified by fractional distillation.Handling, Storage, and Precautions: product is somewhat
hygroscopic.
Preparation. The reagent can be prepared through a chele-tropic reaction between dichlorophenylphosphine and isoprene(eq 1).2 A commercially available antioxidant is added to suppressthe formation of unwanted polymeric by-products.2 The reactionproceeds over the course of a week. The white crystalline solidformed (2) is very sensitive to hydrolysis and can be hydrolyzed ina controlled fashion (using ice) to give a crude mixture with phos-phine oxide 3 following basic workup (eq 2). The pure phosphineoxide 3 is obtained by fractional distillation as a pale yellow oilthat solidifies below 60–65 ◦C to give a white solid.2 Precursor 3can be reduced at room temperature with borane dimethyl sulfideover 24 h, or at 63 ◦C over 7 h (eq 3). The reaction at room tem-perature affords quantitative yield after hydrolysis and workup.1,3
Precursor 3 can also be reduced at rt using the H-Cube Midi©R : asolution of 3 in methanol is reduced on 10% Pd/C using hydro-gen gas to give 1 as a 2:1 mixture of diastereomers. Alternatively,LiAlH4 can also be employed to reduce 3 to 1.4
Cl2PPh P
Cl
Cl
(2)
(1)
P
Cl
Cl
P
O
(3)
H2O
(2)
P
O
P
O
(1)10% Pd/C/H2
CH3OH, rt
P
O
(1)
1. Me2S–BH3 (2.2 equiv) rt, 24 h, CHCl32. H2O
(3)
Wittig Catalysis. The Wittig reaction is among a handfulof organic protocols allowing formation of carbon–carbon dou-ble bonds, along with the Peterson,5 Julia–Lythgoe,6,7 Julia–Kocienski,8,9 and metathesis10 reactions. This stoichiometric re-action uses phosphorus ylides prepared in situ that react withaldehydes or ketones to give olefins and phosphine oxide. TheWittig reaction generally offers good Z/E selectivity in theresulting olefin, and the phosphine structure along with the elec-tronic properties of the generated ylide can be manipulated to con-trol the selectivity.11 As the high oxophilicity of the phosphorusatom drives the reaction forward, reducing the phosphine oxide torecycle can be particularly challenging.11
Arsenines12 and tellurides12 have been successfully employedin the Wittig-type chemistry to bestow a catalytic process, butthese toxic heavy metal reagents make the corresponding proto-cols less appealing for industrial applications. The reagent 1, whenpaired with a silane reducing agent, was successfully employedin the catalytic-in-phosphine Wittig protocol.11 Silanes, such asH3SiPh or H2SiPh2, are known to reduce phosphine oxides (withretention of configuration11,13) even in the presence of carbonylcompounds. Relief of aliphatic ring strain around phosphorus isbelieved to be crucial in facilitating the reduction of the catalyst,when compared to that of acyclic phosphine oxides. For instance,reactions carried out using triphenylphosphine oxide in place of1 do not yield appreciable product.11
O
H Br CO2Me
CO2Me
1 (10 mol %)
H2SiPh2 (1.1–1.5 equiv)
Na2CO3 (1.5 equiv)
toluene, 100 ºC, 24 h
(4)
74%, E:Z >95:5
Reagent 1 catalyzes the olefination of several substrates in thepresence of various alkyl/aryl halides. Representative examplesare shown in eqs 4–9.11 Reasonable to excellent yields (61–81%)and E/Z selectivity (60:40 to >95:5) are observed with a varietyof aldehydes and halo derivatives. The optimal conditions for this
2 3-METHYL-1-PHENYL-PHOSPHOLANE 1-OXIDE
catalytic Wittig protocol are obtained in toluene at 100 ◦C witha slight excess of H2SiPh2 as reducing agent. Sparingly solublesodium carbonate is used for the in situ generation of the phos-phonium ylide.
O
H Br CO2Me
CO2Me
S
S
1 (10 mol %)
H2SiPh2 (1.1–1.5 equiv) Na2CO3 (1.5 equiv) toluene, 100 ºC, 24 h
73%, E:Z >95:5
(5)
H
O
Br CO2Me
CO2Me
1 (10 mol %)
H2SiPh2 (1.1–1.5 equiv)
Na2CO3 (1.5 equiv)
toluene, 100 ºC, 24 h
68%, E:Z >95:5(6)
+
O
H Br CO2Me
CO2Me
1 (10 mol %)
H2SiPh2 (1.1–1.5 equiv) Na2CO3 (1.5 equiv)toluene, 100 ºC, 24 h
77%, E:Z 83:17
(7)
+
H
OBr CN
CN
1 (10 mol %)
H2SiPh2 (1.1–1.5 equiv)
Na2CO3 (1.5 equiv)
toluene, 100 ºC, 24 h
(8)
66%, E:Z 67:33
+
O
HCF3
Br
CF3
1 (10 mol %)
H2SiPh2 (1.1–1.5 equiv) Na2CO3 (1.5 equiv)toluene, 100 ºC, 24 h
(9)
70%, E:Z 60:40
+
1. Keglevich, G.; Fekete, M.; Chuluunbaatar, T.; Dobo, A.; Bocskei, Z.;Toke, L., Synth. Commun. 2000, 30, 4221.
2. McCormack, W. B., Org. Synth., Coll. Vol. V 1973, 787.
3. Keglevich, G.; Gaumont, A.-C.; Denis, J.-M., Heteroatom. Chem. 2001,12, 161.
4. Macpherson, A. J.; Smith, D. J. H., J. Chem. Res., Synop. 1984, 32.
5. Peterson, D. J., J. Org. Chem. 1968, 33, 780.
6. Julia, M.; Paris, J. M., Tetrahedron Lett. 1973, 14, 4833.
7. Kocienski, P. J.; Lythgoe, B.; Ruston, S., J. Chem. Soc., Perkin Trans. 11978, 829.
8. Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O., Tetrahedron Lett. 1991,32, 1175.
9. Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A., Synlett 1998,26.
10. Nicolaou, K. C.; Bulger, P. G.; Sarlah, D., Angew. Chem., Int. Ed. 2005,44, 4490.
11. O’Brien, C. J.; Tellez, J. L.; Nixon, Z. S.; Kang, L. J.; Carter, A. L.;Kunkel, S. R.; Przeworski, K. C.; Chass, G. A., Angew. Chem., Int. Ed.2009, 48, 6836 and references therein.
12. Kuehn, F. E.; Santos, A. M., Mini-Rev. Org. Chem. 2004, 1, 55.
13. Marsi, K. L., J. Org. Chem. 1974, 39, 265.
Mauro Fianchini & Christopher J. O’BrienUniversity of Texas at Arlington, Arlington, TX, USA
