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Synlett 2002(7): 1089-1092
DOI: 10.1055/s-2002-32587
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Substituted Cyclopropylphosphonates by Michael Induced Ring Closure (MIRC) Reactions

Christian V. Stevens*, Gino Van Heecke, Carmen Barbero, Krystyna Patora, Norbert De Kimpe, Roland Verhé
Department of Organic Chemistry, Faculty of Agricultural and Applied Biological, Sciences, Ghent University, Coupure links 653,9000 Gent, Belgium
Fax: +32(9)2646243; e-Mail: Chris.Stevens@rug.ac.be;
Further Information

Publication History

Received 4 April 2002
Publication Date:
07 February 2007 (online)

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Abstract

A variety of cyclopropylphosphonates were prepared in moderate to good yields by Michael Induced Ring Closure of trialkyl phosphites with the corresponding β-bromoalkylidene cyanoacetates and malonates.

Key words

Michael additions - ring closure - phosphorylations - cyclizations - carbocycles

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General Procedure for the Bromination of Alkylidenemalonates or Cyanides. A solution of 10 mmol of Knoevenagel adduct 2, 13 mmol of NBS and 10 mg of BPO in 5 mL of CCl4 was refluxed under UV irradiation for approximately 2 hours. The end of the reaction was monitored carefully by 1H NMR. Evaporation of the solvent gave almost pure bromoalkylidene malonates or cyanides 4 in good yields.

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Spectral data of 4k: 1H NMR [CDCl3, δ (ppm)]: 1.06 (6 H, t, J = 7.3 Hz, Me2), 2.30 (4 H, m, CH2), 3.91 (3 H, s, OMe), 7.74 (1 H, s, CH=). 13C NMR [CDCl3, δ(ppm)]: 10.31 (Me), 34.06 (CΗ2); 42.64 (CBr), 53.71 (OMe); 106.37 (=C); 113.31 (CN); 161.83 (CH=); 162.74 (COOMe). IR (cm-1): 2231 (CN), 1740 (C=O), 1621 (C=C). MS (m/z) (%): 234 (0.5); 182(12); 181(100); 148(60); 122(12); 121(29); 107(14); 94(14); 84(13); 49(12). Anal. Calcd. for C10H14BrNO2: C 46.17; H 5.42; N 5.38. Found: C 46.35; H 5.53; N 5.02.

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General Procedure for the Preparation of the Cyclopropylphosphonates. A mixture of 2.5 mmol bromoalkylidenemalonate or -cyanide 4 and 3 mmol of trialkyl phosphite was stirred under nitrogen atmosphere for the appropriate time (Table [1] ). The volatile compounds formed and the excess of phosphite were then removed by evaporation under vacuum and the mixture was purified by flash chromatography or by distillation.

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Spectral data of 7a: 1H NMR [CDCl3, δ (ppm)]: 1.24 (3 H, d, J= 1.3 Hz, Me); 1.58 (3 H, s, Me); 1.86 (1 H, d, J = 1.9 Hz, CH-P); 3.76 (3 H, s, OMe); 3.77 (3 H, d, J =1.9 Hz, OMe); 3.78 (3 H, d, J = 1.6 Hz, OMe); 3.81 (3 H, s, OMe). 13C NMR [CDCl3, δ(ppm), J P-C(Hz)]: 19.53 (Me, 5); 22.21 (Me, 5.1); 27.65 (CHP, 188); 30.38 (CMe2, 3.6); 43.56 [C(COOMe]2, 3.6); 52.15 (OMe, 6.1); 52.65 (OMe); 52.99 (OMe, 4.9); 53.03 (OMe); 166.64 (COOMe, 123.3); 167.92 (COOMe). 31P NMR referenced to H3PO4 [CDCl3, δ(ppm)]: 25.00. IR (cm-1): 1256 (P=O), 1733 (C=O). MS (m/z) (%): 294 (M+, 0.5); 235(12); 231(20); 229(30); 220(8); 203(21); 186(9); 185(86); 153(100); 125(12); 110(14); 109(18); 93(11); 79(12). Anal. Calcd. for C11H19O7P: C 44.90; H 6.51.
Found: C 44.65; H 6.63.

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For details of Reaction rates see Table 2.


Table 2 Kinetic Data of the Reactions of the electrophilic Allyl Halides 4 with Trivalent Nucleophiles to 7 at 35 °C.
Entry X K 1/mol.s Rel. K
a Br 95.8 × 10-6 1.00
a′ Cla 57.6 × 10-6 0.60
b Br 6.6 × 10-3 68.89
c Br 33.2 × 10-3 346.56
d Br 28.9 × 10-6 0.30
e Br 8.2 × 10-6 0.19
f Br 14.6 × 10-6 0.15
g Br 176.1 × 10-6 2.88
h Br 139.0 × 10-6 1.45
I Br 16.1 × 10-6 0.17
a The chloro derivative was prepared according to the literature procedure by condensation of the chloroaldehyde and the malonate using titanium (IV)chloride and pyridine. [24]