Chloromethyldiphenylphosphine Oxide

[89302-51-2]  · C13H12ClOP  · Chloromethyldiphenylphosphine Oxide  · (MW 250.66)

(useful reagent in the synthesis of phosphinylacetaldehydes which are stereoselectively transformed into 3,3-disubstituted allylic alcohols5)

Solubility: sol THF.

Preparative Methods: chlorination of Ph2P(O)CH2OH1 with Phosphorus(V) Chloride/Calcium Carbonate2 or reaction of Diphenylphosphinic Chloride/Aluminum Chloride with 1-1.1 mol % Paraformaldehyde and Hydrogen Chloride at 120-150 °C.3 Reaction of Ph2P(O)SiMe3 with R1CH2Cl gives yields of 50-95%4

3,3-Disubstituted Allylic Alcohols via Phosphinoylacetaldehydes.

Condensation of chloromethyldiphenylphosphine oxide with ketones and subsequent treatment of the resultant epoxides (1) with Boron Trifluoride Etherate provides a,a-disubstituted (diphenylphosphinyl)acetaldehydes (2) (eq 1).

3,3-Disubstituted allylic alcohols are obtained from (2) via a vanadium(II)-mediated intermolecular pinacol cross-coupling5 followed by Horner-Wittig elimination,6 as shown in eq 2. The diols (3) are obtained stereoselectively through the chelation controlled pinacol coupling with threo/erythro ratios of 7.5-99:1.

This methodology provides a general stereoselective route to allylic alcohols which are important synthetic intermediates7 as well as constituents in many natural products.8 Alternative phosphorus-based methods involving alkenation of ketones generally lack stereospecificity, especially when the two substituents are similar in size.9

Alternatives to phosphorus methods are the stereospecific carbometalation of terminal alkynes,10 and the reaction of alkynic esters with cuprates and subsequent reduction or addition to the ester.11 Both methods are limited by the organometallic reagents.

1. Marmor, R. S.; Seyferth D. JOC 1969, 34, 748.
2. Carman, R. M.; Shaw, I. M. AJC 1976, 29, 133.
3. Chauzov, V. A.; Studnev, Yu. N.; Iznoskova, M. G.; Fokin, A. V. Otkryt. Izobret. 1989, 44, 78 (CA 1990, 113, 24 238m).
4. Chauzov, V. A.; Studnev, Yu. N.; Iznoskova, M. G.; Fokin, A. V. ZOB 1987, 57(1), 54 (CA 1988, 108, 37 933f).
5. Park, J.; Pedersen, S. F. JOC 1990, 55, 5924.
6. Buss, A. D.; Warren, S. J. JCS(P1) 1985, 2307.
7. (a) Johnson R. A.; Sharpless, K. B. COS 1991, 7, 389. (b) Hoffmann, R. W. CRV 1989, 89, 1841.
8. Tius, M. A. CRV 1988, 88, 719.
9. Maryanoff, B. E.; Reitz, A. B. CRV 1989, 89, 863.
10. Negishi, E. PAC 1981, 53, 2333. (b) Normant, J. F.; Alexakis, A. S 1981, 841.
11. Corey, E. J.; Katzenellenbogen, J. A. JACS 1969, 91, 1851.

Brian E. Marron

Glaxo Research Institute, Research Triangle Park, NC, USA

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