Dibenzyl N,N-Diisopropylphosphoramidite1

[108549-23-1]  · C20H28NO2P  · Dibenzyl N,N-Diisopropylphosphoramidite  · (MW 345.42)

(phosphitylating reagent for alcohols; the resulting alkyl dibenzyl phosphite is transformed to the phosphoric monoesters by oxidation and subsequent debenzylation)2

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

Analysis of Reagent Purity: NMR: dP (CDCl3) +148.2.

Preparative Methods: there are several synthetic methods,2-4 among which the reaction of benzyl alcohol with N,N-diisopropylphosphoramidous dichloride in the presence of t-amine in diethyl ether, THF, or dioxane is convenient.5

Purification: chromatography on silica gel.

Handling, Storage, and Precautions: can be stored in the absence of moisture and air for more than several months. A stock solution can be also prepared.

Phosphoric Monoester Synthesis.

Dibenzyl phosphoramidites such as dibenzyl N,N-diisopropylphosphoramidite (1) (see also Dibenzyl N,N-Diethylphosphoramidite) react quickly with various alcohols in the presence of 1H-tetrazole at room temperature to afford the phosphorus triesters which are oxidized in situ with an oxidant such as m-Chloroperbenzoic Acid, t-Butyl Hydroperoxide, or 30% Hydrogen Peroxide to give the corresponding alkyl dibenzyl phosphoric triesters in excellent yields. The triesters are deprotected by simple and clean catalytic hydrogenolysis on a Pd catalyst such as Palladium on Carbon or Palladium(II) Hydroxide. The usefulness of the sequence has been demonstrated by many examples which involve synthesis of phosphate derivatives of amino acids,2,6 peptides,7 sugars,8 and cyclitols (eq 1).4

Dibenzyl phosphoric triesters are prepared alternatively by using Dibenzyl Phosphorochloridate, tetrabenzyl pyrophosphate, or dibenzyl phosphorofluoridate. See also cyclic homologue of (1), o-Xylylene N,N-Diethylphosphoramidite. These amidite reagents are more effective than PV reagents, especially for phosphorylation of sterically hindered or base-sensitive alcohols, due to their high reactivity under milder conditions.

1. For a related review, see Beaucage, S. L.; Iyer, R. P. T 1992, 48, 2223.
2. Bannwarth, W.; Trzeciak, A. HCA 1987, 70, 175.
3. Smirnova, L. I.; Malenkovskaya, M. A.; Predvoditelev, D. A.; Nifant'ev, É. E. ZOR 1980, 16, 1011.
4. Yu, K.-L.; Fraser-Reid, B. TL 1988, 29, 979.
5. Fukase, K.; Kamikawa, T.; Iwai, Y.; Shiba, T.; Rietschel, E. T.; Kusumoto, S. BCJ 1991, 64, 3267.
6. de Bont, H. B. A.; Veeneman, G. H.; van Boom, J. H.; Liskamp, R. M. J. RTC 1987, 106, 641.
7. Perich, J. W.; Johns, R. B. TL 1988, 29, 2369.
8. Ichikawa, Y.; Sim, M. M.; Wong, C.-H. JOC 1992, 57, 2943.

Shoichiro Ozaki & Yutaka Watanabe

Ehime University, Matsuyama, Japan

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