Wolff rearrangement of diazoketone

The Arndt-Eistert reaction (Scheme 2.1) which involves the Wolff rearrangement of diazoketones 13 (prepared from the corresponding commercially available N-protected-a-amino acids 12 by reaction of their mixed anhydrides with diazomethane a cautionary note is warranted here the generation and handling of diazomethane require special precautions) has been used extensively by Seebach and coworkers for the preparation of N-protected /9 -amino acids 14 and /9 -amino acid esters 15 and 16. 

Silver clusters 2.5 nm in diameter displayed unusual electrocatalytic properties in Wolff rearrangements of diazoketones.67 The reaction proceeds with electron transfer to and from the silver cluster. The presence of an a-ketocarbene/ketene was confirmed using pyridine as a nucleophilic probe and by UV-visible spectroscopy. Electrochemistry was used to support the role of the silver particles in the rearrangement. 

The reaction most commonly formulated as involving the rearrangement of a carbene is the Wolff rearrangement of diazoketones to give nitrogen and a ketene as shown in equation (25). The reaction can be... 

The rearrangement has a mechanism similar to those of the Hofmann rearrangement of amides, the Lossen rearrangement of acylhydroxamic esters, the Schmidt rearrangement of carbonyl compounds and the Wolff rearrangement of diazoketones. Evidence concerning the mechanism of one can often be applied to the others, and the whole family has been reviewed briefly . Sometimes the distinction is made that the conversion of an acyl azide into an isocyanate or urethane is the Curtius rearrangement whereas the overall sequence is the Curtius reaction, but usually the former name is used for both processes. 

Wolff rearrangement. Finding that the Wolff rearrangement of diazoketones with silver oxide and methanol gave erratic, highly variable results, Newman and Beal developed a procedure for carrying out the reaction in homogeneous solution under mild conditions. A solution of diazoacetophenone in methanol was treated at room temperature with a few drops of a filtered solution of 0.004 mole of silver... 

Scheme 31 Wolff rearrangement of diazoketone 125 to give the A -Fmoc-pro-tected jS -amino acid 102b [62].

The photochemical Wolff rearrangement of diazoketones 9 derived from protected amino acids led to the ketene intermediates 12, which were trapped with iV-benzylbenzaldimines 10 and 11 to afford p-lactams 13 and 14. Of the four possible diastereomers, only two were formed exclusively. The selectivity of this reaction depends on the bulkiness of the amino acid. 

The Wolff rearrangement of diazoketones 113 in the presence of silver benzoate in 1,4-dioxane-water (7 3) under microwave exposure for 40-60 sec using an unmodified domestic microwave oven afforded the Fmoc-P-amino acids 114 in excellent yields (91-95%). ... 

The first example reported involved the Ag(l)-catalyzed formation of pyrazoles from alkynyl a-diazoketones 11 [14], where the typical Wolff rearrangement of diazoketones was circumvented (Scheme 16.9). It was postulated that the acetylenic bond is activated by coordination with Ag(l) by either side-on or end-on coordination. 

Thiazole acid chlorides react with diazomethane to give the diazoketone. The later reacts with alcoholic hydrogen chloride to give chloroacetylthiazole (Scheme 16). However, the Wolff rearrangement of the diazoketone is not consistently satisfactory (82). Heated with alcohol in the presence of copper oxide the 5-diazomethylketone (24) gives ethyl 5-thiazoleacetate (25) instead of the expected ethoxymethyl 5-thiazolyl ketone (Scheme 17) (83). 

Photoelimination of nitrogen from diazoketones is complicated by Wolff rearrangement of the intermediate carbene, as shown below for diazoaceto-phenone<35) ... 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established 13 390), so that only a few new features of this reaction need to be considered here. Concerning its catalytic version, one knows that copper, rhodium and palladium catalysts tend to suppress the rearrangement390). A recent case to the contrary is provided by the Rh2(OAc)4-catalyzed decomposition of ethyl -2-diazo-3-oxopent-4-enoates 404 from which the p,y-unsaturated esters 405 are ultimately obtained via a Wolff rearrangement 236). The Z-5-aryl-2-diazo-3-oxopent-4-enoates undergo intramolecular insertion into an aromatic C—H bond instead (see Sect. 4.1). 

WOLFF REARRANGEMENT. Rearrangement of diazoketone to ketenes by action of heat, light or some metallic catalyst. The rearrangement is the key step in the Arndt-F.istert synthesis. 

The Arndt-Eistert Synthesis allows the formation of homologated carboxylic acids or their derivatives by reaction of the activated carboxylic acids with diazomethane and subsequent Wolff-Rearrangement of the intermediate diazoketones in the presence of nucleophiles such as water, alcohols, or amines. 

The key step of the Amdt-Eistert Homologation is the Wolff-Rearrangement of the diazoketones to ketenes, which can be accomplished thermally (over the range between r.t. and 750°C, photochemically or by silver(I) catalysis. The reaction is conducted in the presence of nucleophiles such as water (to yield carboxylic acids), alcohols (to give alcohols) or amines (to give amides), to capture the ketene intermediate and avoid the competing formation of diketenes. 

With very few exceptions ketenes cannot be isolated pure at room temperature (cf. Section 15.4). Consequently, they are prepared in situ and in the presence of the heteroatom nucleophile. The Wolff rearrangement of a-diazoketones is often used for this purpose (Section 14.3.2). a-Diazoketones can be obtained, for example, by the reaction between a carboxylic acid chloride and diazomethane (Figure 8.13 see also Figure 14.27) or hy treating the sodium enolate of a-formylketones with tosyl azide (Figure 14.29). 

Fig. 14.29. Preparation of an a-diazoketone (compound E) from a ketone (A) and subsequent Wolff rearrangement of the a-diazoketone. Initially, A is transformed to give the enolate B of its a-formyl derivative. In a Regitz diazo group transfer reaction, this will then be converted into the a-diazoketone E. Ring contraction via Wolff rearrangement occurs and the 10-membered cyclic diazoketone C rearranges in aqueous media to give the nine-membered ring carboxylic acid E via the ketene D.

The ketene-alkene cycloaddition gives cyclobutanones in a thermal reaction. Most ketenes are not kinetically stable, so they are usually generated in situ, either by E2 elimination of HC1 from an acyl chloride or by a Wolff rearrangement of an a-diazoketone (see Chapter 2). 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established so that only a few new features of this reaction need to be consi-... 

Photolysis of the o-diazoacetylbenzenesulfonamide 13 (R = Me) over seven days gives a reasonable yield of 47 (R = Me),10 presumably via the Wolff rearrangement of the diazoketone to a ketene intermediate (53). Heating 13 (R = Ph) in refluxing chlorobenzene gave only 30% of 47 (R = Ph).10... 

---