Curtius rearrangement, of acyl azide

Warren, J. D., Press, J. B. Trimethylsilylazide/KN3/18-crown-6. Formation and Curtius rearrangement of acyl azides from unreactive acid chlorides. Synth. Commun. 1980, 10, 107-110. 

We anticipated that a similar strategy would be applicable to the synthesis of l,3-oxazine-2,4-diones, involving the in situ formation of isocyanates by thermal Curtius rearrangement of acyl azides under the same conditions of the Wolff rearrangement. Indeed, tenperature-regulated microwave irradiation of a 1 1 mixture of a 2-diazo-1,3-diketone and an acyl azide afforded the desired l,3-oxazine-2,4-dione products 33 (Scheme 3.281. This sequence nicely illustrates the utilization of microwave activation for the selective one-pot thermal rearrangements of azido and diazo compounds. 

Lactone 286 was transformed into aminomonocarba-disaccharide 288 using a five-step procedure involving the Curtius rearrangement of acyl azide 287 formed from the appropriate acid chloride (Scheme 3,43), ... 

The Curtius rearrangement of acyl azide in the original synthetic procedure at high temperature may cause explosion. 

Rearrangement of acyl azides in the presence of water (Curtius)... 

Reaction between amides, bromine, and alkoxides (Hofmann), and similar rearrangement reactions 8-15 Rearrangement of acyl azides in the presence of alcohols (Curtius)... 

A closely related reaction of general applicability is the Curtius rearrangement222 of acyl azides. The rearranging species in the Schmidt reaction (see p. 898) is in fact also a protonated acyl azide these azides are readily prepared by the action of nitrous acid on acyl hydrazides which are themselves formed from esters and hydrazine (Section 9.6.17, p. 1269). On heating in aprotic solvents the acyl azides decompose to yield the corresponding isocyanates in good yield. 

The Curtius degradation of acyl azides (Figure 14.43) expels molecular nitrogen and at the same time leads to the [1,2]-rearrangement of the substituent that is attached to the carboxyl carbon. It is the simultaneous occurrence of these two events that prevents the formation of an energetically unacceptably disfavored acylnitrene intermediate. The rearranged product is an isocyanate. 

Trimethylsilyl azide (TMS-A) in the presence of catalytic amounts of pyridine turned out to be very useful in the preparation of acyl azides, as this reagent will not only transform acyl chlorides and mixed anhydrides into azides, but also works with reactive esters and lactones (Scheme 40). 2 - 4S Many of these reactions have, however, been run under conditions which will lead to the Curtius rearrangement of the azide intermediates. Pyridine as a catalyst can be replaced by the combination KNa/18-crown-6. Diazidodiphenylsilane, which was investigated as well, will probably not become a standard reagent. 

Curtius rearrangement Thermal or photochemical rearrangement of acyl azides to give isocyanates. 116... 

With no fear, we pushed on to the Curtius rearrangement sequence needed to transform ferf-butyl ester 44 into the amide needed for sorbicillactone A. In the same fashion as the model substrate, the ester was first converted into acyl azide 45. Heating the acyl azide in a solution of f-BuOH under microwave conditions gave the rearranged product as ferf-butyl carbamate 46. Alternatively, and more directly, the rearrangement of acyl azide 45 to the isocyanate could be performed in THF. Subsequent hydrolysis with aqueous K2CO3 afforded the amine, which was acylated with fumarate 30 to give amide 47. 

Curtius rearrangement with various acid chlorides,including phenoxy acetyl chloride. Heating in dioxane provided 32 the trimer of isocyanate 31, formed by rearrangement of acyl azide 30. 

Curtius rearrangement of these azides leads to ketones via loss of an isocyanic acid (HN=C=0) equivalent, which can be trapped in situ as shown for 49 where benzophenone resulted and addition of aniline to the isocyanic acid gave urea 50. or-Alkoxy- and or-amino acyl azides, meanwhile, are precursors to hemiaminals and hisaminals, respectively. Examples in complex natural product synthesis are shown for 81 and 66 in the Variations and Improvements Section. 

A third approach to 3-amino-/3-lactams is by Curtius rearrangement of the corresponding acyl azides. These are readily prepared from r-butyl carbazides, available via photochemical ring contraction of 3-diazopyrrolidine-2,4-diones in the presence of f-butyl carbazate (c/. Section 5.09.3.3.2). Thus treatment of (201) with trifluoroacetic acid followed by diazotiz-ation gives the acyl azide (202) which, in thermolysis in benzene and subsequent interception of the resulting isocyanate with r-butanol, yields the protected 3-amino-/3-lactam (203) (73JCS(P1)2907). 

The Curtius rearrangement involves the pyrolysis of acyl azides to yield isocy-anates. " The reaction gives good yields of isocyanates, since no water is present to... 

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