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DOI: 10.1055/s-2002-19322
Highly Selective Preparation of 2-(Hydroxymethyl)vinylphosphonates by Insertion of Ketones into Zirconacycle Phosphonates
Publication History
Publication Date:
01 February 2007 (online)
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Abstract
Three-member zirconacycles insert ketones exclusively at C-2 to give five-member zirconacycle phosphonates that can be hydrolyzed to give 2-(hydroxymethyl)vinylphosphonates, 2, in excellent yields. Other regioisomers were not detected. The reaction works well for both aromatic and aliphatic ketones. Competitive studies indicate that ketones and aldehydes insert at about the same rate and that both react much faster than alkynes. Compounds 2 undergo chlorination with thionyl chloride without rearrangement.
Key words
alkynylphosphonates - zirconacycles - regioselective insertion - 2-(hydroxymethyl)vinylphosphonates - chlorination
- Drugs and investigative compounds:
-
1a
Holstein SA.Cermak DM.Wiemer DF.Lewis K.Hohl RJ. Bioorg. Med. Chem. 1998, 6: 687 -
1b
Abbas S.Hayes C. Tetrahedron Lett. 2000, 41: 4513 -
1c
Jung K.-Y.Hohl RJ.Wiemer AJ.Wiemer DF. Bioorg. Med. Chem. 2000, 8: 2501 -
1d
Harnden MR.Parkin A.Parratt MJ.Perkins RM. J. Med. Chem. 1993, 36: 1343 -
1e
Smeyers YG.Romero-Sanchez FJ.Hernandez-Laguna A.Fernandez-Ibanez N.Galvez-Ruano E.Arias-Perez S. J. Pharm. Sci. 1987, 76: 753 -
1f
Megati S.Phadtare S.Zemlicka J. J. Org. Chem. 1992, 57: 2320 -
1g
Lazrek HB.Rochdi A.Khaider H.Barascut JL.Imbach JL.Balzarini J.Witvrouw M.Pannecouque C.De Clerq E. Tetrahedron 1998, 54: 3807 -
1h
Smith PW.Chamiec AJ.Chung G.Cobley KN.Duncan K.Howes PD.Whittington AR.Wood MR. J. Antibiot. Tokyo 1995, 48: 73 -
1i
Chance LH, andMoreau JP. inventors; US Patent 3910886. Agrochemicals: - Polymers:
-
2a
Römp Lexikon Chemie 10
Vol. 6:
Falbe J.Regitz M. Georg Thieme Verlag; Stuttgart: 1999. -
2b
Jin S.Gonsalves KE. Macromolecules 1998, 31: 1010 -
2c
Ebdon JR. Recent Adv. Flame Retard. Polym. Materials 1997, 8: 161 -
3a Review:
Minami T.Motoyoshiya J. Synthesis 1992, 333 -
3b Reactions:
De La Crux MA.Shabany H.Spilling CD. Phosphorous, Sufur, Silicon Related. Elem. 1999, 146: 181 - 4 Review of α-phosphonovinyl carbanions:
Minami T.Okauchi T.Kouno R. Synthesis 2001, 349 - 5 Review of the preparation and chemstry of 1-alkynylphosphonates:
Iorga B.Eymery F.Carmichael D.Savignac P. Eur. J. Org. Chem. 2000, 3103 -
6a
Negishi E.Takahashi T. Acc. Chem. Res. 1994, 27: 124 -
6b
Negishi E. In Comprehensive Organic Synthesis Vol. 5:Paquette LA. Pergamon Press; New York: 1991. p.1163 - 7
Quntar AA.Srebnik M. Org. Lett. 2001, 3: 1379 - For other synthesis of β-hydroxyallylic phosphonates:
-
9a
Orsini F. Tetrahedron Lett. 1998, 39: 1425 -
9b
Takaki K.Itono Y.Nagafuji A.Naito Y.Shishido T.Takehira K.Makioka Y.Taniguchi Y.Fujiwara Y. J. Org. Chem. 2000, 65: 475 - 10
Kouno R.Tsubota T.Okauchi T.Minami T. J. Org. Chem. 2000, 65: 4326 ; and references cited therein -
11a
Cristau H.-J.Mbianda XY.Bexiat Y.Gasc M.-B. J. Organomet. Chem. 1997, 529: 301 -
11b
Gil JM.Oh DY. J. Org. Chem. 1999, 64: 2950 - 12
Muthiah C.Kumar KP.Mani CA.Swamy KCK. J. Org. Chem. 2000, 65: 3733 - 13
Jang WB.Oh DY.Lee C.-W. Tetrahedron Lett. 2000, 41: 5103
References
Quntar, A. A.; Srebnik, M. J. Org. Chem. in press.
14
General Procedure: To 0.584 g(2mmol) zirconocene dichloride dissolved in 6 mL dry THF at -78 °C, 2.5 mL of 1.6 M n-BuLi (4 mmol) were added dropwise and the mixture was stirred for 3 h. Then 0.39 g (1.8 mmol) of 1-alkynylphosphonate was added and the mixture was warmed gradually to r.t. and stirred overnight. Then 1.1 mmol of freshly distilled ketone was added and the mixture was stirred for additional 24 h. The reaction mixture was worked up with dilute HCl and the product was extracted with ether and separated on a silica gel column (petroleum ether:EtOAc, 3:1). All new compounds were analyzed by NMR, LCMS and gave satisfactory elementary analysis.
Selected NMR data: 2a: 1H NMR (300 MHz): δ = 0.77 (t, 3 H, J
HH = 7.5 Hz), 1.25 (t, 6 H, J
HH = 6.9 Hz), 1.12-1.38 (overlap, 4 H), 1.71 (s, 3 H), 2.25 (m, 2 H), 2.81 (s, 1 H), 3.97-4.10 (m, 4 H), 5.94-6.00 (d, 1 H, 2
J
PH = 16.8 Hz), 7.20-7.40 (m, 5 H); 31P NMR (300 MHz): δ = 19.17; 13C NMR (75.5 MHz): δ = 170.43 (d, 2
J
pc = 7.20 Hz), 145.1, 128.4, 127.6, 126.1, 109.7 (d, 1
J
pc = 189.4 Hz), 77.1 (d, 3
J
pc" = 21.8 Hz, trans), 61.4 (d, 2
J
pc = 6.0 Hz), 33.3, 31.0, (d, 3
J
PC = 8.1 Hz), 28.0, 23.7, 16.5 (d, 3
J
pc = 6.5 Hz),13.9; 2b: 1H NMR (300 MHz): δ = 0.85 (t, 3 H, J
HH = 7.5 Hz), 1.27 (t, 6 H, J
HH = 6.9 Hz), 1.30 (s, 6 H), 1.22-1.60 (overlap, 4 H), 2.40 (m, 2 H), 3.00 (broad s, 1 H), 3.94-4.01 (m, 4 H), 6.22-6.30 (d, 1 H, 2
J
PH = 17.1 Hz); 31P NMR (300 MHz): δ = 19.83; 13C NMR (75.5 MHz): δ = 172.8 (d, 2
J
pc = 4.08 Hz), 108.90 d, 1
J
pc = 186.5 Hz), 74.6 (d, 3
J
pc" = 21.2 Hz, trans), 61.3 (d, 2
J
pc = 6.1 Hz), 33.3, 29.4, 23.7, 16.9 (d, 3
J
pc = 6.6 Hz), 16.2; 2c: 1H NMR (300 MHz): δ = 0.80 (overlap, 6 H), 1.27 (t, 6 H, J
HH = 6.9 Hz), 1.23 (s, 3 H), 1.22-1.60 (overlap, 8 H), 2.20 (m, 2 H), 2.40 (m, 2 H), 2.85 (broad s, 1 H), 3.80-4.00 (m, 4 H), 5.6-5.70 (d, 1 H, 2
J
PH = 17.1 Hz); 31P NMR (300 MHz): δ = 19.72; 13C NMR (75.5 MHz): δ = 172.0 (d, 2
J
pc = 6.95 Hz), 109.6 (d, 1
J
pc = 189.7 Hz), 76.5 (d, 3
J
pc" = 20.9 Hz, trans), 61.3 (d, 2
J
pc = 6.0 Hz), 41.0, 33.0, 30.6 (d, 3
J
PC = 7.1 Hz), 28.0, 25.9, 23.7, 23.0, 16.4 (d, 3
J
pc = 6.6 Hz), 14.3, 13.9; 2d: 1H NMR (300 MHz): δ = 0.84 (t, 3 H, J
HH = 67.5 Hz), 1.27 (t, 6 H, J
HH = 6.6 Hz), 1.29-1.80 (overlap, 12 H), 2.32 (m, 2 H), 2.70 (broad s, 1 H), 3.90-4.01 (m, 4 H), 5.75-5.81 (d, 1 H, 2
J
PH = 17.7 Hz); 31P NMR (300 MHz): δ = 19.75; 13C NMR (75.5 MHz): δ = 170.7 (d, 2
J
pc = 7.5 Hz), 109.4 (d, 1
J
pc = 194.0 Hz), 85.1 (d, 3
J
pc" = 21.2 Hz, trans), 61.1 (d, 2
J
pc = 5.7 Hz), 39.3, 33.0, 30.5 (d, 3
J
PC = 6.8 Hz, cis), 23.8, 23.3, 16.2 (d, 3
J
pc = 6.6 Hz), 13.6; 2e: 1H NMR (300 MHz): δ = 0.84 (t, 3 H, J
HH = 7.5 Hz), 1.27 (t, 6 H, J
HH = 6.6 Hz), 1.29-1.80 (overlap, 14 H), 2.28 (broad s, 1 H), 2.42 (m, 2 H), 3.90-4.01 (m, 4 H), 5.72-5.78 (d, 1 H, 2
J
PH = 17.1 Hz); 31P NMR (300 MHz): δ = 20.06; 13C NMR (75.5 MHz): δ = 173.2 (d, 2
J
pc = 6.6 Hz), 109.2 (d, 1
J
pc = 190.0 Hz), 75.4 (d, 3
J
pc" = 20.9 Hz, trans), 61.1 (d, 2
J
pc = 5.7 Hz), 35.7, 33.2, 30.2 (d, 3
J
PC = 7.1 Hz, cis), 25.2, 23.5, 21.5, 16.2 (d, 3
J
pc = 6.5 Hz), 13.7; 2f: 1H NMR (300 MHz): δ = 0.77 (t, 3 H, J
HH = 7.5 Hz), 1.27 (t, 6 H, J
HH = 6.6 Hz), 1.29-1.50 (overlap, 4 H), 1.81 (m, 2 H), 1.95 (m, 2 H), 2.42 (m, 2 H), 2.73 (broad s, 1 H), 2.65-2.80 (m, 2 H), 3.90-4.01 (m, 4 H), 5.85-5.91 (d, 1 H, 2
J
PH = 17.7 Hz), 7.01-7.10 (m, 4 H); 31P NMR (300 MHz): δ = 19.28; 13C NMR (75.5 MHz): δ = 170.6 (d, 2
J
pc = 7.8 Hz), 137.2, 128.7, 127.7, 127.3, 126.1, 111.7 (d, 1
J
pc = 188.8 Hz), 76.6 (d, 3
J
pc" = 24.9 Hz, trans), 61.8 (d, 2
J
pc = 5.7 Hz), 35.8, 33.7, 30.9 (d, 3
J
PC = 6.3 Hz, cis), 23.1, 18.7, 16.2 (d, 3
J
pc = 6.5 Hz), 13.4; 2g: 1H NMR (300 MHz): δ = 0.84 (t, 3 H, J
HH = 7.5 Hz), 1.27 (t, 6 H, J
HH = 6.6 Hz), 1.29-1.99 (overlap, 10 H), 2.42 (m, 2 H), 2.50 (broad s, 1 H), 3.90-4.01 (m, 4 H), 5.47-5.51 (d, 1 H, J
HH = 9.9 Hz), 5.69-5.74 (d, 1 H, 2
J
PH = 17.1 Hz), 5.88 (m, 1 H); 31P NMR (300 MHz): δ = 19.31; 13C NMR (75.5 MHz): δ = 170.96 (d, 2
J
pc = 6.6 Hz), 131.3, 130.5, 111.0 (d, 1
J
pc = 189.4 Hz), 74.3 (d, 3
J
pc" = 22.7 Hz, trans), 61.1 (d, 2
J
pc = 5.7 Hz), 35.5, 33.2, 30.1 (d, 3
J
PC = 7.1 Hz, cis), 24.7, 23.4, 18.5, 16.2 (d, 3
J
pc = 6.5 Hz), 13.7; 2h: 1H NMR (300 MHz): δ = 0.88 (t, 3 H, J
HH = 6.8 Hz), 1.00-1.07 (t, 6 H, J
HH = 6.9 Hz), 1.24 (s, 3 H), 1.25-1.50 (overlap, 6 H), 3.40(s, 1 H), 3.53-3.74 (m, 4 H), 6.19-6.25 (d, 1 H, 2
J
PH = 18.3 Hz), 7.10-7.26 (m, 5 H); 31P NMR (300 MHz): δ = 17.99; 13C NMR (75.5 MHz): δ = 168.2 (d, 2
J
pc = 3.8 Hz), 138.0 (d, 3
J
pc = 8.3 Hz, cis), 128.7, 127.6, 127.5, 114.6 (d, 1
J
pc = 192.3 Hz), 76.0 (d, 3
J
pc" = 18.9 Hz, trans), 61.3 (d, 2
J
pc = 6.0 Hz), 39.7, 27.6, 25.9, 23.1, 16.3 (d, 3
J
pc = 6.6 Hz); 2i: 1H NMR (300 MHz): δ = 1.02 (t, 6 H, J
HH = 6.7 Hz), 1.64 (s, 3 H), 3.53-3.74 (m, 4 H), 4.12 (broad s, 1 H), 6.40-6.46 (d, 1 H, 2
J
PH = 18.3 Hz), 7.10-7.36 (m, 10 H); 31P NMR (300 MHz): δ = 17.60; 13C NMR (75.5 MHz): δ = 166.8 (d, 2
J
pc = 4.30 Hz), 137.2 (d, 3
J
pc = 8.0 Hz, cis), 129.3, 128.2, 127.1, 114.4 (d, 1
J
pc = 192.0 Hz), 77.5 (d, 3
J
pc" = 19.2 Hz, trans), 61.4 (d, 2
J
pc = 6.0 Hz), 27.6, 16.3 (d, 3
J
pc = 6.7 Hz); 2j: 1H NMR (300 MHz): δ = 0.98 (t, 6 H, J
HH = 6.8 Hz), 1.22 (s, 6 H), 3.53-3.74 (m, 4 H), 4.12 (s, 1 H), 6.22-6.30 (d, 1 H, 2
J
PH = 18.3 Hz), 7.10-7.26 (m, 5 H); 31P NMR (300 MHz): δ = 18.19; 13C NMR (75.5 MHz): δ = 169.0 (d, 2
J
pc = 4.08 Hz), 137.7 (d, 3
J
pc = 8.3 Hz, cis), 128.4, 127.2, 127.1, 113.1 (d, 1
J
pc = 192.9 Hz), 73.4 (d, 3
J
pc" = 19.2 Hz, trans), 61.3 (d, 2
J
pc = 6.0 Hz), 28.4, 16.3 (d, 3
J
pc = 6.6 Hz); 2k: 1H NMR (300 MHz): δ = 1.22 (t, 6 H, J
HH = 6.7 Hz), 1.81 (m, 4 H), 2.59 (m, 2 H), 3.38 (s, 1 H), 3.46 (t, 2 H), 3.69 (s, 3 H), 3.84-3.95 (m, 4 H), 5.67-5.75 (d, 1 H, 2
J
PH = 16.2 Hz), 6.75-7.28 (m, 9 H); 31P NMR (300 MHz): δ = 18.35; 13C NMR (75.5 MHz): δ = 167.2 (d, 2
J
pc = 6.9 Hz), 135.7, 130.5, 127.6, 127.3, 126.3, 111.3 (d, 1
J
pc = 186.6 Hz), 78.8 (d, 3
J
pc" = 21.2 Hz, trans), 61.2 (d, 2
J
pc = 6.0 Hz), 54.9, 45.2, 33.1, 28.4 (d, 3
J
PC = 6.6 Hz), 16.0 (d, 3
J
pc = 6.5 Hz); 2l: 1H NMR (300 MHz): δ = 1.20 (t, 6 H, J
HH = 6.8 Hz), 1.29 (s, 6 H), 2.00 (m, 2 H), 2.53 (m, 2 H), 3.50 (broad s, 1 H), 3.51 (t, 2 H, J
HH = 5.4 Hz), 3.90-4.11 (m, 4 H), 5.74-5.80 (d, 1 H, 2
J
PH = 17.1 Hz); 31P NMR (300 MHz): δ = 19.14; 13C NMR (75.5 MHz): δ = 170.9 (d, 2
J
pc = 6.3 Hz), 109.8 (d, 1
J
pc = 189.4 Hz), 74.1 (d, 3
J
pc" = 21.2 Hz, trans), 61.3 (d, 2
J
pc = 6.1 Hz), 45.2, 33.4, 29.1, 27.9 (d, 3
J
PC = 7.2 Hz), 16.2 (d, 3
J
pc = 6.6 Hz); 2m: 1H NMR (300 MHz): δ = 0.75 (m, 1 H), 1.20 (t, 6 H), 1.37 (m, 4 H), 1.76 (m, 2 H), 2.28 (t, 2 H), 3.30 (t, 2 H), 3.38 (broad s, 1 H), 3.84-3.95 (m, 4 H), 6.00-6.06 (d, 1 H, 2
J
PH = 17.1 Hz), 7.14-7.42 (m, 5 H); 31P NMR (300 MHz): δ = 18.78; 13C NMR (75.5 MHz): δ = 167.1 (d, 2
J
pc = 6.9 Hz), 142.6, 126.8, 126.3, 125.6, 110.1 (d, 1
J
pc = 187.4 Hz), 75.9 (d, 3
J
pc" = 32.3 Hz, trans), 61.2 (d, 2
J
pc = 6.1 Hz), 44.2, 32.2, 27.5 (d, 3
J
PC = 6.8 Hz), 17.0, 16.2 (d, 3
J
pc = 6.5 Hz); 2n: 1H NMR (300 MHz): δ = 1.20 (t, 6 H, J
HH = 6.8 Hz), 1.61 (m, 2 H), 2.55 (m, 2 H), 3.31 (t, 2 H), 3.84-3.95 (m, 4 H), 4.17 (s, 1 H), 5.57-5.63 (d, 1 H, 2
J
PH = 18.3 Hz), 7.3 (broad, 10 H); 31P NMR (300 MHz): δ = 17.80; 13C NMR (75.5 MHz): δ = 167.8 (d, 2
J
pc = 7.5 Hz), 143.9, 127.8, 127.3, 126.6, 115.1 (d, 1
J
pc = 186.7 Hz), 84.1 (d, 3
J
pc" = 23.3 Hz, trans), 61.2 (d, 2
J
pc = 6.0 Hz), 45.2, 33.2, 29.3 (d, 3
J
PC = 6.9 Hz, cis), 16.2 (d, 3
J
pc = 6.4 Hz); 4: 1H NMR (300 MHz): δ = 0.91 (overlap, 6 H), 1.27 (t, 6 H, J
HH = 6.7 Hz), 1.23 (s, 3 H), 1.22-1.80 (overlap, 8 H), 2.20 (m, 2 H), 2.70 (m, 2 H), 4.00-4.12 (m, 4 H), 5.68-5.72 (d, 1 H, 2
J
PH = 13.8 Hz); 31P NMR (300 MHz): δ = 18.3; 13C NMR (75.5 MHz): δ = 172.6 (d, 2
J
pc = 8.1 Hz), 112.3 (d, 1
J
pc = 189.2 Hz), 76.5 (d, 3
J
pc" = 20.9 Hz, trans), 61.3 (d, 2
J
pc = 6.0 Hz), 41.0, 33.0, 30.6 (d, 3
J
PC = 7.1 Hz), 28.0, 25.9, 23.7, 23.0, 16.4 (d, 3
J
pc = 6.6 Hz), 14.3, 13.9.