Bis(dimethylamino) Phosphorochloridate

[1605-65-8]  · C4H12ClN2OP  · Bis(dimethylamino) Phosphorochloridate  · (MW 170.58)

(reagent for protection of alcohols,1 ketones,2 thiols3 and amines;4 reductive deoxygenation of alcohols and ketones2)

Physical Data: fp >230 °C; d 1.152 g cm-3.

Form Supplied in: colorless liquid.

Handling, Storage, and Precautions: moisture sensitive; store in a dry, cool environment. Handle in a well-ventilated fume hood.

Protection and/or Reductive Deoxygenation of Alcohols and Ketones.

Bis(dimethylamino) phosphorochloridate constitutes a useful protecting reagent for hydroxyls,1 thiols3 and for ketones (i.e. enols).2 The phosphorodiamidates, prepared by phosphorylation of the corresponding alcoholate or enolate, are stable to various conditions and deprotection is accomplished under mild conditions in nearly quantitative yield.5

The phosphorodiamidates of alcoholates are readily reduced in high yield by lithium-ethylamine solution (eq 1).2 The two-step reductive deoxygenation of ketones (RCOR´ -> RCHOHR´ -> RCH2R´) has unique advantages over the traditional Wolff-Kishner reduction if the substrate is particularly sensitive to acid/base conditions or if the substrate exhibits severe steric congestion in the vicinity of the carbonyl moiety (eq 2). Bis(dimethylamino) phosphorochloridate6 (and diethyl phosphate)7 have been used to trap the kinetic enolate of enediones (e.g. analogs of the Wieland-Miescher ketones) prior to reduction to corresponding alkene.8

Glycopyranosyl N,N,N´,N´-tetramethylphosphorodiamidates appear to promote highly stereoselective 1,2-trans-b-glycosidation reactions.9 When comparison is made with other phosphorus-containing reagents10 that promote glycosidations (specifically, the diphenyl phosphate method,10a which affords similar reactivity and stereoselectivity), the glycosyl phosphorodiamidates have the advantage of being shelf-stable glycosyl donors (eq 3).9

Bis(dimethylamino)phosphorodiamidate has been employed as a directing agent for the a-lithiation of tetrahydroisoquinolines,11 the 3-lithiation of 2-furanol,12 and for the ortho-lithiation of phenols13 and naphthols.13b In the case of phenols, the ortho-lithiated species prepared by reaction of the derived phosphorodiamidates with s-Butyllithium at -105 °C can be subsequently trapped (ca. -105 °C) with a variety of electrophiles to afford ortho-substituted phosphorodiamidates (eq 4).

Protection of Primary Amines.

Protection of primary aliphatic amines employing the bis(dimethylamino)phosphoryl group gives N-alkylphosphoramides4 which can be subsequently substituted to afford N,N´-dialkyl or propargylic phosphoramides (eq 5).14

Hydroboration of N-alkylpropargylic phosphoramides occurs without nitrogen-boron complexation and with a regioselectivity and stereospecificity similar to that observed with alkynes,4 while substituted propargylic amines and ethylenic amino ketones are easily prepared from the corresponding phosphoramides.15

1. (a) Dhawan, B.; Redmore, D. JOC 1986, 51, 179. (b) Dhawan, B.; Redmore, D. JOC 1984, 49, 4018.
2. Ireland, R. E.; Muchmore, D. C.; Hengartner, U. JACS 1972, 94, 5098.
3. Binns, M. R.; Haynes, R. K.; Lambert, D. E.; Schober, P. A.; Turner, S. G. AJC 1987, 40, 281.
4. Benmaarouf-Khallaayoun, Z.; Baboulene, M.; Speziale, V.; Lattes. A. JOM 1986, 306, 283.
5. Crunden, E. W.; Hudson, R. F. JACS 1962, 84, 3591 and references therein.
6. Grieco, P. A.; Ferrino, S.; Oguri, T. JOC 1979, 44, 2594.
7. (a) Dhawan, B.; Redmore, D. SC 1985, 15, 411. (b) Hammond, G. B.; Calogeropoulou, T.; Wiemer, D. F. TL 1986, 27, 4625.
8. Ireland, R. E.; Pfister, G. TL 1969, 2145.
9. Hashimoto, S.; Yanagiya, Y.; Honda, T; Harada, H.; Ikegami, S. TL 1992, 33, 3523.
10. (a) Hashimoto, S.; Honda, T; Ikegami, S. JCS(C) 1989, 685. (b) Hashimoto, S; Honda, T; Ikegami, S. TL 1991, 32, 1653 and references therein.
11. Seebach, D.; Lohmann, J-J.; Syfrig, M. A.; Yoshifuji, M. T 1983, 39, 1963.
12. Nasman, J. H.; Kopola, N.; Pensar, G. TL 1986, 27, 1391.
13. (a) Watanabe, M.; Date, M.; Kawanishi, K.; Tsukazaki, M.; Furukawa, S. CPB 1989, 37, 2564. (b) Watanabe, M.; Date, M.; Kawanishi, K.; Hori, T.; Tsukazaki, M.; Furukawa, S. CPB 1990, 38, 2637.
14. Masse, G.; Sturtz, G. S 1988, 907.
15. Corbel, B.; Paugam, J-P.; Dreux, M.; Savignac, P. TL 1976, 11, 835.

Isabel Mathieu-Pelta & Slayton A. Evans, Jr.

University of North Carolina, Chapel Hill, NC, USA

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