o-Xylylene N,N-Diethylphosphoramidite

(1; R = Et)

[82372-35-8]  · C12H18NO2P  · o-Xylylene N,N-Diethylphosphoramidite  · (MW 239.28) (2; R = Me)

[69813-53-2]  · C10H14NO2P  · o-Xylylene N,N-Dimethylphosphoramidite  · (MW 211.22)

(phosphitylating reagents for alcohols to provide phosphoric monoesters and mixed diesters)

Physical Data: (1) bp 95-96 °C/0.1 mmHg; nD 1.543. (2) bp 78-80 °C/0.03 mmHg; nD 1.555.

Solubility: insol cold H2O; sol CH2Cl2, THF, MeCN.

Form Supplied in: (1): crystalline solid; commercially available.

Analysis of Reagent Purity: dP (C6H6) +143 (1), +142 (2).

Preparative Methods: a mixture of hexaethyl- or Hexamethylphosphorous Triamide and 1,2-Bis(hydroxymethyl)benzene is heated until evolution of amine ceases.

Purification: distillation under reduced pressure.

Handling, Storage, and Precautions: these reagents can be stored for extended periods (>6 months) in the absence of moisture and air. The stability of (1) is greater than that of (2).

Phosphoric Monoester Synthesis.1

The phosphoramidites react smoothly with a variety of sterically hindered alcohols and polyols in the presence of 1H-tetrazole to afford the phosphorous triesters, which are oxidized in situ with m-Chloroperbenzoic Acid to give cyclic phosphoric triesters in high yields (eqs 1-3).2-4 The triesters are deprotected by hydrogenolysis on Palladium on Carbon to furnish phosphoric monoesters.

The reagents are potent alternatives to dibenzyl phosphoramidites. The former reagents can be prepared in one step and are easily purified by distillation, while the acyclic amidites require two steps. See Dibenzyl N,N-Diethylphosphoramidite and Dibenzyl Phosphorochloridate; dibenzyl phosphorofluoridate and tetrabenzyl pyrophosphate are used for the same purpose.

Phosphoric Diester Synthesis.5

o-Xylylene N,N-diethylphosphoramidite can be used for sequential phosphorylation of two different alcohols to afford the corresponding triester (eq 4), which is converted to the phosphoric mixed diester by deprotection employing hydrogenolysis or disodium disulfide.

1. Watanabe, Y.; Komoda, Y.; Ebisuya, K.; Ozaki, S. TL 1990, 31, 255.
2. Watanabe, Y.; Mitani, M.; Morita, T.; Ozaki, S. CC 1989, 482.
3. Ozaki, S.; Kondo, Y.; Shiotani, N.; Ogasawara, T.; Watanabe, Y. JCS(P1) 1992, 729.
4. Pietrusiewicz, K. M.; Salamonczyk, G. M.; Bruzik, K. S.; Wieczorek, W. T 1992, 48, 5523.
5. Watanabe, Y.; Komoda, Y.; Ozaki, S. TL 1992, 33, 1313.

Shoichiro Ozaki & Yutaka Watanabe

Ehime University, Matsuyama, Japan

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