Diphenylphosphoryl azide Curtius rearrangement

Cyclohexylpropionic acid was deprotonated with 2.2 equivalent of lithium diisopropylamide and the resulting dianion was condensed with trifluoroacetaldehyde which was generated in situ from its ethyl hemiacetal. The P-hydroxy acid 1 was isolated as a racemic mixture of two diastereomers. Silylation with tert-butyldimethylsilyl triflate was followed by ester hydrolysis to give the acid 2. A Curtius rearrangement with diphenylphosphoryl azide in the presence of benzyl alcohol afforded the protected P-amino alcohol 3 which was used in the preparation of the trifluoromethyl alcohol I. Oxidation using the Dess-Martin periodinane reagent (9) yielded the trifluoromethyl ketone II as a mixture of diastereomers. The signal for the carbonyl carbon in the 13C-NMR spectrum of this ketone appeared at 94.5 ppm and this is consistent with the hydrated form of the trifluoromethyl ketone. 

The TAN1251A synthesis starts from acid 124, which was prepared from p-hydroxybenzoic acid according to the reported procedure [65]. a-Alkylation of 124 (Scheme 38) with allyl bromide followed by a Curtius rearrangement [66], using diphenylphosphoryl azide (DPPA) [67] and trapping the isocyanate formed with benzylalcohol, resulted in carbamate... 

Ester 23c has been used in a short synthesis of (5)-isoserine (17) (Scheme 2) [28]. Treatment of 23c with diphenylphosphoryl azide gives an intermediate isocyanate 24 via a Curtius rearrangement. Spontaneous cyclization results in the formation of cyclic carbamate 25 in 74% yield. Alkaline hydrolysis affords 17 in high yield without any racemization. 

The Curtius rearrangement can be initiated directly from the carboxylic acid using diphenylphosphoryl azide (DPPA), (PhOjPONj. 

Carboxylic acids are converted to Curtius-rearranged urethanes in one pot using diphenylphosphoryl azide (DPPA, 68), triethylamine, and an alcohol. ... 

Diphenylphosphoryl azide (DPPA) and triethylamine were formerly employed by Yamada and co-workers in a simple one-pot synthesis of urethanes from carboxylic adds [250]. This procedure involved treatment of a carboxylic acid with triethylamine to produce the triethylammonium carboxylate salt, followed by heating in the presence of DPPA to yield the isocyanate via a Curtius-type rearrangement of the acyl azide. An alcohol was then introduced, functionalizing the isocyanate in situ to yield the urethane. 

Diphenylphosphoryl azide (15), a stable, non-explosive liquid, functions as a convenient reagent for a modified Curtius reaction and as a coupling agent (Scheme 52) the yields in either reaction are high. Similarly, tri-methylsilyl azide is recommended for the Curtius rearrangement of acid anhydrides to isocyanates. 

Another three syntheses discussed in the section on lupin alkaloids diverged at relatively late stages to give epiquinamide analogs (Scheme 280). (—)-Methyl lupinoate (1035 cf Scheme 129 Section 4.6.3), prepared by Fustero et al., was hydrolyzed to the carboxyhc acid prior to Curtius rearrangement with diphenylphosphoryl azide to form the amine 2213. Acetylation then gave (4-)-l-ept-epiquinamide (ent-2105) in 37% yield over the three steps. The quinohzidin-l-ol (—)-1048... 

---