Diethyl phosphorocyanidate

One can also use diethyl phosphorocyanidate (DEPC) to effect a similar transformation. This was the reagent of choice in the generation of l-substituted-4-oxygenated-P-carbolines (49— 50). 

S)-2 are obtained by N-acylation using diethyl phosphorocyanidate (DEPC) (ref. 5), followed by hydrolysis. The results are summarized as follows. 

Among other reactions which are described in detail later are the following (1) A novel method for the introduction of the CN group is given in Chapter vi. Thus diethyl phosphorocyanidate (X) was prepared2 according to the equation ... 

We obtained diethyl phosphorocyanidate (V) in only small yield by the action of potassium cyanide on the corresponding phosphorochloridate. We were able to prepare it,6 however, by the action of cyanogen iodide on the phosphite. This is apparently a modified Arbusov reaction ... 

In addition to the most common methods for cyclization of linear peptides (vide supra), alternative coupling reagents have been used with varying success such as BOP-Cl, 140-142 norborn-5-ene-2,3-dicarboximido diphenyl phosphate (NDPP),119-143-144 pentafluorophenyl diphenylphosphinate (FDPP),1145-148 diethyl phosphorocyanidate (DEPC), 138-149 or T3P.197-1501... 

DEPC, diethyl phosphorocyanidate, diethyl phosphoryl cyanide, diethyl cyanophosphonate [2942-58-7]... 

ThiocyanatesSodium arenesulfinates, ArS02Na, are converted into aryl thiocyanates, ArSCN in about 60-75% yield by reaction with diethyl phosphorocyanidate in THF, This reaction is also possible with benzyl and adamantyl sulfinates but yields are only about 40%. Alkyl thiocyanates cannot be obtained in this way. 

RlR2C=0 - R CHfCNjR2.1 The cyanophosphates 1, readily obtained by reaction of ketones with diethyl phosphorocyanidate and LiCN (14, 187-188), are reduced by Sml2 (excess) and (-BuOH (1 equiv.) in THF at 25° to nitriles in 80-... 

More than a decade ago, Yamada and coworkers [70] developed two efficient reagents, diphenylphosphoryl azide (DPPA) and diethyl phosphorocyanidate (DEPC), for peptide done construction. The exact mechanism still remains speculative. For example, in the case of DPPA, the intermediacy of the carboxylic acid azide is tentative, but it seems attractive to consider a concerted process as shown in Figure 2 [70 a]. 

C-Acylation. Active methylene compounds can be C-acylated directly by carboxylic acids with diethyl phosphorocyanidate (1) in combination with tri-ethylamine. DMF is the preferred solvent TMEDA or DBU can replace tri-ethylamine. ... 

Diethyl phosphorocyanidate adds to a,/J-unsaturated aldehydes or ketones in the presence of lithium cyanide in a 1,2-fashion28. Boron trifluoride-diethyl ether complex catalyzed rearrangement of these allylic phosphates shows high E selectivity (>85 15) for the adducts derived from aldehydes and Z selectivity (>90 10) for ketone adducts. The selectivity of the rearrangement can be explained by assuming a chairlike transition state, in which the sterically more demanding x-substituent occupies the quasi-equatorial position. The steric requirement decreases in the order of R1 > CN > H. Thus, the cyano substituent occupies the quasi-equatorial position in the aldehyde-derived adduct (R1 = H), but the quasi-axial position in the ketone-derived adduct (R1 = CH3, C6H5). 

Adducts of cyclic enones (n = 1, 2 R = H or CH3) and diethyl phosphorocyanidate rearrange in a suprafacial fashion to give (3-cyano-2-cycloalkenyl) diethyl phosphates 1 under boron trifluoride-diethyl ether complex catalysis26,27. 

Yamada S, Ikota N, Shioiri T. Diphenyl phosphorazidate (DPPA) and diethyl phosphorocyanidate (DEPC). Two new reagents for solid-phase peptide synthesis and their application to the synthesis of porcine motilin. J. Am. Chem. Soc. 1975 97 7174-7175. 

Aromatic and aliphatic aldehydes in the presence of dialkylamines and an equivalent of acid such as hydrochloric, perchloric or p-toluenesulfonic acid give iminium salts, which add cyanide ion to form a-(dialkylamino)nitriles. An alternative preparation involves the reaction of the aldehyde with dialkylamines in the presence of acetone-cyanohydrin, a-(A, -dialkylamino)isobutyronitiiles, diethyl phosphorocyanidate or TMS-CN. Another route to a-aminonitrile starts with an aldehyde, the salt of an amine and KCN in organic solvents under solid-liquid two-phase conditions by combined use of alumina and ultrasound. Chiral a-aminonitriles were prepared by Strecker-type reactions, cyano-silylation of Schiffs bases, amination of a-siloxynitriles or from an A -cyanomethyl-l,3-oxazolidine synthon. Reaction of tertiary amines with CIO2 in the presence of 5.1 mol equiv. of aqueous NaCN as an external nucleophile affords a-aminonitrile. °... 

Diethyl phosphorocyanidate continues to be exploited for the purposes of conventional organic synthesis. Reported applications of the compound include a new conversion of carboxylic acids into esters or amides and also a ring-expansion reaction of 1,3-thiazoles in the penicillin series. Diphenyl phosphorazidate has been employed in a modified Curtius reaction/ in peptide synthesis, and for... 

Shioiri, T., Yokoyama, Y, Kasai, Y, andYamada. S.. Phosphorus in organic synthesis. Part 11. Amino acids and peptides. Part 21. Reaction of diethyl phosphorocyanidate (DEPC) with carboxylic acids. A new synthesis of carboxylic esters and amides. Tetrahedron. 32. 2211. 1976. 

---