Azide, diphenylphosphoryl, reaction with

The synthesis of 6-azidomethyl-S,6,7,8-tetrahydropterin 108 has been carried out from 106 via the intermediate 107 using the Mitsunobu reaction with diphenylphosphoryl azide followed by deprotection <95MI09 %CA(124)232123>. 

Cyclobutanecarboxylic acid azides react in a similar manner. The azides were either made from the acid chloride and sodium azide44,45 or directly from the acid by reaction with diphenylphos-phoryl azide.37,46,47 The carboxylic acid azides rearrange via the isocyanates. An example is the reaction of (+ )-ra-2-acetoxycyclobutanecarboxylic acid with diphenylphosphoryl azide to give 4 in quantitative yield.37... 

Macrocyclic lactams.1 These lactams have generally been prepared by reaction of dicarboxylic acid chlorides and diamines under high dilution. Yields are generally mediocre because linear polyamides are also formed. Actually, free dicarboxylic acids, when activated by diphenylphosphoryl azide, can condense with diamines to... 

The MTX y-peptide (VIII.239), in which the y-carboxyl is joined to 4-ami-nobutyric acid, has been synthesized [352] as a de(carboxy) analogue of MTX -I- G,. Condensation of a-benzyl L-glutamate with MeAPA by the diethyl phosphorocyanidate procedure gave a 94% yield of a-benzyl MTX, which on reaction with methyl 4-aminobutyrate in the presence of diphenylphosphoryl azide and subsequent ester hydrolysis with Ba(OH)2 was converted to (VIII.239) in 50% overall yield. 

Three new synthetic methods for the conversion of alcohols into azides (and hence potentially into amines) have been published. One route involves a further application of the chemistry of 2-alkoxypyridinium salts (formed in situ from an alcohol and the 2-fluoropyridinium salt) in their reaction with azide ion " (Scheme 17). Another extends the utility of the triphenylphosphine-ethyl diazodicarboxylate system, using diphenylphosphoryl azide as azide donor (Scheme 18), but is sensitive to steric hindrance at the alcohol carbon. The third route (Scheme 19) achieves oxygen activation through the alkoxyphosphonium salts (39), which are prepared from the alcohol, a phosphine, and a positive halogen donor such as carbon tetrachloride (with primary alcohols) or Af-chlorodi-isopropylamine (in... 

Diphenylphosphoryl azide reacts with alcohols in the presence of triphenylphosphine and DEAD.76 Hydrazoic acid, HN3, can also serve as the azide ion source under these conditions.77 These reactions are examples of the Mitsunobu reaction. 

Two other results will now be pointed out which presumably also require reinterpretation in the light of the reaction behavior of iminooxophosphoranes. Thus the gas phase pyrolysis of diphenylphosphoryl azide is reported to give monomeric 92 50) and the dehydrohalogenation of phenylphosphoric adamantylamidic chloride with methylhydrazine the heterocumulene 93 51), which is even considered resistant to water. Since partly correct analytical values are available, 92 and 93 may well be oligomers. 

Diphenylphosphoryl azide (DPPA) 58 was first introduced as a reagent for peptide synthesis by Yamada in 197233 and has been widely used since it gives good yields and very little racemization. It may also be used to bring about a modified Curtius reaction in which a carboxylic acid, R CC H and an alcohol, R2OH, react in the presence of triethylamine to afford the carbamate R1 NHCO2R2.33 In Protocol 15, the use of DPPA to form a macrocyclic lactam 61 is illustrated. The 82% yield of the product using this method should be compared with the value of 24% for reaction of the bis(acid chloride) of 59 with the diamine 60. 

Several different methods have been employed for the preparation of diazo(trimethylsilyl)meth-ane (1). At present, the best synthetic method seems to be the diazo transfer reaction between diphenylphosphoryl azide and (trimethylsilyl)methylmagnesium chloride.However, the product often contains (chloromethyl)trimethylsilane and hexamethyldisiloxane as impurities. This method can also be employed for the synthesis of diazo(triethylsilyl)methane and diazo(di-ethylmethylsilyl)methane. The diazo transfer reaction can also be carried out with (trimethyl-silyl)methyllithium and tosyl azide. Other methods are the silylation of diazomethane with (trimethylsilyl)trifluoromethanesulfonate or chloro(trimethyl)silane and the base-induced cleavage of A-nitroso-A-[(trimethylsilyl)methyl]urea or the related carbamate or acet-amide.2° =... 

---