Azide, diphenylphosphoryl, reaction with acids

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. 

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. 

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. 

To a solution of 7.04 g l-benzyl-3-cyanopyrrole-2-carboxylic acid (31.12 mmol) in 75 mL A, A -dimethylformamide at 0°C was added 7.65 mL diphenylphosphoryl azide (DPPA, 9.72 g, 35.30 mmol, 1.1 eq.) and 4.75 mL triethylamine (3.42 g, 33.80 mmol, 1.1 eq.). The solution was allowed to stir at room temperature for 6 h. Methanol (7 mL) was added, and the reaction mixture was heated at 65°C for 8 h. The solvents were evaporated in vacuo, and the resulting residue was dissolved in 140 mL EtOAc. The solution was then extracted with 1 N aqueous HCl solution (3 x 80 mL), washed with saturated aqueous NaHCOs solution (3 x 80 mL), dried over anhydrous MgS04, and concentrated to dryness. The residue was recrystallized from ethanol to give 4.695 g l-benzyl-2-methoxycarbonylamino-3-cyanopyrrole, in a yield of 59%, m.p. 140-142°C. 

The second series has been prepared from isocyanates 247, which were readily produced by Cuitius rearrangement of cinnamic acid with diphenylphosphoryl azide in the presence of triethylamine (Scheme 49). Isocyanates 247 were engaged with lithium derivatives 244 or 246. After deprotective reaction of phosphinate ester, phosphinic acids 242a-f were obtained [172]. One example of saturated structure 242d was synthesized by reduction of the alkene [172]. 

N-Protected a, 8-dehydroamino-acids and a,j8-dehydroamino-esters can be coupled simply by formation of the acid chloride of the former using PClg. " Dehydropeptides can also be prepared by reaction of a-amino-acid chlorides with adducts of a-azido-a,j8-unsaturated esters and triethyl phosphite. " Peptides can be cyclized using diphenylphosphoryl azide, on a large scale if necessary, in 40—50% yields in favourable cases. ... 

The reaction of carboxylic acids with diphenylphosphoryl azide (DPPA) and subsequent Curtins rearrangement can be used for the conversion of malonic esters 304 into protected (/ )-2-methylcysteine 308. Monomethylation of dimethyl malonate followed by alkylation with t-butylchloromethyl sulfide gives the achiral diester 305. Enantioselec-... 

Cul-catalyzed coupling of o-bromobenzylamines 208 with L-proline at llO C afforded pyrrole-fused l,4-benzodiazepin-3-ones 209 directly (Scheme 73) [118], Other amino acids were found suitable for iV-arylation reaction, but did not give cyclization products directly. However, through treatment of the coupling mixture with diphenylphosphoryl azide (DPPA), the desired l,4-benzodiazepin-3-ones 210 could be prepared in 35-60% yields. 

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