Ethyl Diphenylphosphinite

[1733-57-9]  · C14H15OP  · Ethyl Diphenylphosphinite  · (MW 230.26)

(amide and peptide formation from azides and carboxylic acids; Staudinger reaction)

Alternate Name: ethoxydiphenylphosphine.

Physical Data: d 1.066 g cm-3.

Solubility: sol chloroform (50 mg mL-1).

Form Supplied in: colorless liquid.

Handling, Storage, and Precautions: irritant; moisture sensitive; stored under N2; needs refrigeration.

Peptide Synthesis.

The preparation of carboxylic amides via activation of the amino fragment through the Staudinger reaction1 has been reported independently by Garcia2 and Roberts.3 The strategy involves the electrophilic addition of an azide to a phosphorus(III) center (1) followed by elimination of N2 giving the iminophosphorane (2) (also known as phosphazene). Phosphorane (2) reacts with carboxylic acids to form amides (eq 1). While Triphenylphosphine (1a) and ethyl diphenylphosphinite (1b) have been used as phosphorus reagents, the latter has proven more advantageous. First, coupling with the carboxylic acid takes place at lower temperatures. Second, during the workup the phosphine oxide byproduct is hydrolyzed to diphenylphosphinic acid which is subsequently extracted out of the reaction mixture.

More recently, an approach to amide/peptide synthesis that bypasses the use of nonpolar solvents has been developed. This is based on the reduction of an azide to the corresponding amine in situ and in the presence of a preformed activated carboxyl component.4

Phosphoramide Synthesis.

A homolog of phosphinite (1b), namely methyl diphenylphosphinite (3), has been used in the synthesis of phosphoramides (eq 2).5

1. Gololobov, Y. G.; Kasukhin, L. F. T 1992, 48, 1353.
2. Garcia, J.; Urpí, F.; Vilarrasa, J. TL 1984, 25, 4841.
3. Zaloom, J.; Calandra, M.; Roberts, D. C. JOC 1985, 50, 2601.
4. Ghosh, S. K.; Singh, U.; Mamdapur, V. R. TL 1992, 33, 805.
5. Hassner, A.; Keogh, J. JOC 1986, 51, 2767.

Gerald B. Hammond

University of Massachusetts Dartmouth, North Dartmouth, MA, USA

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