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Synlett 2002(1): 0061-0064
DOI: 10.1055/s-2002-19322
LETTER
© Georg Thieme Verlag Stuttgart · New York

Highly Selective Preparation of 2-(Hydroxymethyl)vinylphosphonates by Insertion of Ketones into Zirconacycle Phosphonates

Abed Al Aziz Quntara, Artem Melmanb, Morris Srebnik*a
a Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Hebrew University, Jerusalem, 91120, Israel
b Department of Organic Chemistry, Institute of Chemistry, Hebrew University, Jerusalem, Israel
Fax: +97(22)6758201; e-Mail: msrebni@md2.huji.ac.il;
Further Information

Publication History

Received 22 October 2001
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

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8

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.