Bis(2,2,2-trichloro-1,1-dimethylethyl) Phosphorochloridate

[17677-92-8]  · C8H12Cl7O3P  · Bis(2,2,2-trichloro-1,1-dimethylethyl) Phosphorochloridate  · (MW 435.33)

(phosphorylating reagent)

Physical Data: mp 81-82 °C.

Solubility: crystallized from pentane.

Form Supplied in: colorless solid.

Preparative Methods: the reagent1 is conveniently prepared by the reaction of 2-trichloromethyl-2-propanol with PCl3 in pyridine solvent to afford bis(2,2,2-trichloro-1,1-dimethylethyl) chlorophosphite (71%). The chlorophosphite is oxidized with (Diacetoxyiodo)benzene to give 65% of the desired phosphorochloridate (eq 1). This overall procedure represents an improved synthesis of the phosphorochloridate when compared to the different methods reported in the literature, which give mixtures of bis(2,2,2-trichloro-1,1-dimethylethyl) chlorophosphite and 2,2,2-trichloro-1,1-dimethylethyl dichlorophosphite.2,3

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

Phosphorylating Reagent.

Nucleoside derivatives are selectively phosphorylated and protected at the 5-OH group using bis(2,2,2-trichloro-1,1-dimethylethyl) phosphorochloridate.4 The chemospecificity favors the 5-phosphorylated oligonucleotides which are formed exclusively, in presence of a free 3-OH group (eq 2).5 Compared to those of other alkylmono- and dichlorophosphate reagents,6 the 2,2,2-trichloro-1,1-dimethylethyl group exhibits unusual stability towards acids and bases, which is a distinct advantage, especially when considering the different transformations required for effective oligonucleotide synthesis.7,8 The bis(2,2,2-trichloro-1,1-dimethylethyl) group can be readily removed by the supernucleophilic cobalt(I) phthalocyanine anion [Co1Pc]-.9

1. Kellner, H. A.; Ugi, I. ZN(B) 1979, 34, 1159.
2. (a) Gerrard, W. JCS 1944, 85. (b) Gerrard, W.; Wyvill, P. L. Research (London) 1949, 2, 536. (c) Gerrard, W.; Isaacs, M. J. D.; Machell, G.; Smith, K. B.; Wyvill, P. L. JCS 1953, 1920. (d) Gerrard, W.; Green, W. J.; Phillips, R. J. JCS 1954, 1148.
3. (a) Abramov, V. S.; Khairullin, V. K. JGU 1957, 27, 501. (b) Sasse, K. MOC 1964, XII/2, 45.
4. Schneiderwind-Stoecklein, R. G. K.; Ugi, I. ZN(B) 1984, 39, 968 (CA 1984, 101 211 642c).
5. Kellner, H. A.; Schneiderwind, R. G. H.; Eckert, H.; Ugi, I. K. AG(E) 1981, 20, 577.
6. (a) Eckstein, F.; Rizk, I. CB 1969, 102, 2362. (b) Ogilvie, K. K.; Beaucage, S. L.; Theriault, N.; Entwistle, D. W. JACS 1977, 99, 1277. (c) Letsinger, R. L.; Lunsford, W. B. JACS 1976, 98, 3655. (d) Imai, J.; Terrence, P. F. JOC 1981, 46, 4015.
7. Letsinger, R. L.; Groody, E. P.; Lander, N.; Tanaka, T. T 1984, 40, 137.
8. (a) Eckert, H.; Ugi, I. AG(E) 1975, 14, 825. (b) Eckert, H.; Ugi, I. LA 1979, 278. (c) Eckert, H.; Ugi, I.; Breuer, W.; Geller, J.; Lagerlund, I.; Listl, M.; Marquarding, D.; Stüber, S.; Zahr, S.; v. Zychlinski, H. PAC 1979, 51, 1219.
9. Eckert, H.; Listl, M.; Ugi, I. AG(E) 1978, 17, 361.

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

University of North Carolina, Chapel Hill, NC, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.