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Synlett 2009(13): 2180-2182  
DOI: 10.1055/s-0029-1217564
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

The First Synthesis of Diethyl α,α-Chlorofluorobenzylphosphonates

Di Wu, Yanhong He, Rongchang Tang, Zhi Guan*
School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, P. R. of China
Fax: +86(23)68254091; e-Mail: guanzhi@swu.edu.cn;
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Publication History

Received 5 January 2009
Publication Date:
15 July 2009 (online)

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Abstract

Starting from α-hydroxyphosphonates, a wide variety of diethyl α,α-chlorofluorobenzylphosphonates have been obtained in pure form in a two-step procedure. The first step was chlorination of α-hydroxyphosphonates with Ph3P and CCl4, while the second step was fluorination with N-fluorobisbenzenesulfonimide.

Key words

fluorinated phosphonates - chlorination - fluorination - diethyl α,α-chlorofluorobenzylphosphonates

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General Procedure for the Preparation of α-Chloro-benzylphosphonates from α-Hydroxyphosphonates
A solution of 1k (1.00 g, 3.46 mmol, 1.0 equiv) and Ph3P (1.36 g, 5.19 mmol, 1.5 equiv) in dry CCl4 (10 mL) is refluxed for 8 h under argon. Then, the mixture is evaporated under reduced pressure, and the semisolid residue is extracted with PE. The combined extracts are filtered, and the solvent is removed under reduced pressure. The crude material was purified by flash column chromatography on silica gel to yield 3k as yellow oil (0.81 g, 76%). ¹H NMR (300 MHz, CDCl3): δ = 1.26 (t, J = 7.0 Hz, 3 H), 1.35 (t, J = 7.0 Hz, 3 H), 4.00-4.14 (m, 2 H), 4.15-4.28 (m, 2 H), 5.00 (d, ² J PH = 15.2 Hz, 1 H), 7.73 (d, J = 8.6 Hz, 2 H), 8.25 (d, J = 8.6 Hz, 2 H) ppm. ¹³C NMR (75 MHz, CDCl3): δ = 16.2 (d, ³ J PC = 5.6 Hz), 16.4 (d, ³ J PC = 5.7 Hz), 52.5 (d, ¹ J PC = 156.4 Hz), 64.1 (d, ² J PC = 7.0 Hz), 64.6 (d, ² J PC = 7.0 Hz), 123.6, 129.8, 141.4, 148.0 ppm.

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General Procedure for the Preparation of α,α-Chloro-fluorobenzylphosphonates from α-Chlorophosphonates
To a solution of the α-chlorophosphonates 3k (0.31 g, 0.94 mmol, 1.0 equiv) in dry THF (10 mL) at -78 ˚C was added dropwise a solution of NaHMDS (1.69 mmol, 2.0 M in THF, 1.5 equiv) in dry THF (5 mL) under argon. The resulting dark green solution was stirred for 1 h at -78 ˚C. A solution of NFSI (0.41 g, 1.31 mmol, 1.3 equiv) in dry THF (5 mL) was added over a period of 10 min. After addition, the solution was stirred for 1 h and then allowed to warm to -30 ˚C. The reaction was quenched with 0.01 N HC1, and the resulting solution was extracted with CH2Cl2. The combined organic layer was dried over MgSO4, and the solvent was removed under reduced pressure. The crude material was purified via flash column chromatography on silica gel to yield 4k as yellow oil (0.24 g, 77%). ¹H NMR (300 MHz, CDCl3): δ = 1.25 (t, J = 7.0 Hz, 3 H), 1.41 (t, J = 7.0 Hz, 3 H), 4.05-4.19 (m, 2 H), 4.32-4.41 (m, 2 H), 7.86 (d, J = 8.5 Hz, 2 H), 8.29 (d, J = 8.6 Hz, 2 H) ppm; ¹³C NMR (75 MHz, CDCl3): δ = 16.3 (d, ³ J PC = 15.0 Hz), 65.3 (d, ² J PC = 7.2 Hz), 66.2 (d, ² J PC = 7.1 Hz), 105.6 (dd, ¹ J PC = 193.4 Hz, ¹ J FC = 259.1 Hz), 123.4, 127.5 (d, ³ J PC = 8.4 Hz), 142.5 (d, ² J PC = 21.0 Hz), 148.7 ppm. ³¹P NMR (121.5 MHz, CDCl3): δ = 5.13 (d, ² J PF = 88.1 Hz) ppm.

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We thank one of the reviewers for pointing out these possibilities.