Wolff rearrangement ring-contracting

To synthesize the very strained tricyclic system of 4 (Fig. 3.12), a photochemical Wolff rearrangement was chosen when MM predicted that the skeleton of 4 should be about 109 kJ mol less stable than that of the available 5. Photolysis of the diazoketone 6 gave a high-energy carbene which lay above the carbon skeleton of 4 and so was able to undergo Wolff rearrangement ring contraction to the ketene precursor of 4. 

Several ring contraction routes to /3-lactams have been developed. One of the most important is the photochemical Wolff rearrangement of 3-diazopyrrolidine-2,4-diones (178), which provides a general route to 3-carboxyazetidin-2-ones (179). Lack of stereoselectivity is a problem, but facile epimerization is possible because of the electron withdrawing 3-substituent (78T1731). 

D. Cyclic a-Diazoketones Ring-Contraction in Photolytic Wolff Rearrangements... 

Scheme 10.14 gives some other examples of Wolff rearrangement reactions. Entries 1 and 2 are reactions carried out under the classical silver ion catalysis conditions. Entry 3 is an example of a thermolysis. Entries 4 to 7 are ring contractions done under photolytic conditions. Entry 8, done using a silver catalyst, was a step in the synthesis of macbecin, an antitumor antibiotic. Entry 9, a step in the synthesis of a drug candidate, illustrates direct formation of an amide by trapping the ketene intermediate with an amine. 

The photochemical Wolff rearrangement represents a generally useful ring contraction technique. 

The Wolff rearrangement can be used for the ring contraction of simple oc-diazocyclopen-tanones, as well as for the construction of certain steroids and highly strained polycycles (sec Houben-Wcyl, Vol. 4/4, pp 94-119 and Vol. 10/4, pp 482, 632 and 858 see also refs 2 6), and is also of interest for industrial purposes.7... 

It has been demonstrated that x-diazo ketones, e.g. 8, may photochemically equilibrate with their isomeric a-oxodiazirines, e.g. 9, but the Latter upon irradiation also undergo Wolff rearrangement with ring contraction.46... 

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.

Fig. 11.27. Ring contraction via Wolff rearrangement. The 10-membered cyclic diazoketone C rearranges in aqueous media to give the nine-membered ring carboxylic acid E via the ketene D.

Earlier studies [11,12] have shown that photo excitation of aqueous 2-chloro-phenol or 2-bromophenol leads to contraction of the aromatic cycle to give cyclopentadienic acids (an example of a Wolff rearrangement [13]), and to substitution of the halogen by OH (photohydrolysis), with moderate quantum yields (< = 0.01-0.04). A carbene (2-oxocyclohexa-3,5-dienylidene) was suggested as a possible intermediate in the ring contraction pathway [11]. 

Oxirenes arising out of cycloalkyne oxidations have been implemented in several transformations (Scheme 61), ultimately resulting in bicyclic ketones, a-dicarbonyls, 0 ,/3-unsaturated ketones, and ring-contracted products via Wolff rearrangement. 

The photo-Wolff rearrangement has proved of particular value in the synthesis of compounds containing four-membered rings. The first [4.4.4.5]fenestrane derivative (64) to be characterized was obtained in this way by irradiation of the diazocyclopentanone (65) in methanol, and the 4-diazopyrrolidine-2,3-diones (66) have similarly served as useful precursors in a novel approach to /3-lactams (67) and penams. " The related ring contraction... 

In the first step of the reaction sequence a methyl ester is formed via a Wolff rearrangement. The Wolff rearrangem ent provides acids, esters or amides from a-diazo ketones and is often used in a ring contractive way to form strained ring systems, which are not accessible by other sequences.It also occurs as the key step in the Arndt-Eistert homologation of carboxylic acids. ... 

Irradiation of diazo quinoline 153 in alcohol provided the corresponding indole-3-carboxylic esters in 8-61% yield. Mechanistically, the transformation is a Wolff rearrangement and involves the formation of an intermediate carbene, ring contraction to ketene, and its solvolysis (76S754). 

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