Wolff ring contraction

By repeating the Wolff ring contraction twice, the highly strained (94 kcal mol MM144) diasterane skeleton 7 was synthesized.45... 

The photolytic Wolff ring contraction of diazopyridones (181) is a synthesis of pyrrole-2-carboxylic acids via carbene (182) and ketene (183) intermediates (76S754). 

The photolytic Wolff ring contraction of diazopyridones 247 leads to pyrrole-2-carboxylic acids 250 via carbene 248 and ketene 249 intermediates <1976S754>. The thermolysis of 2-azidopyridine A-oxides 251 affords A-hydroxy-2-cyano-pyrroles 252 (Scheme 137) <1973JOC173> (see also Section 3.4.3.11). 

A ring-contraction reaction is rarely used to produce an aziridine. A Wolff ring contraction of a carbene generated from 6-diazopenicillanate 21 forms the intermediate ketene, which is then trapped by imines to give spiroaziridines 22 (86CC584). 

As shown by J.-P. Pete the hydroxyalkyl radical formed initially can also be trapped in an intramolecular reaction, for example, by an alkyne moiety. The resulting vinyl radical abstracts another hydrogen from an external source. The starting material for this reaction sequence can be prepared by photochemical Wolff ring contraction reaction (see also Chapter 2). 

In summary, the method described here provides an efficient and convenient route to a variety of a-diazo ketones including unsaturated derivatives that were not previously available by diazo transfer. a-Diazo ketones serve as key intermediates in a number of important synthetic methods including the Arndt-Eistert homologation, the photo-Wolff ring contraction strategy, and the carbenoid-mediated cyclopropanation reaction. We anticipate that improved access to a-diazo ketones will serve to enhance the utility of these valuable synthetic strategies. 

The formation of the tricyclic 9a-arylhydrolilolidine ring system is exemplified in the conversion of (154) to (155). Wolff ring contraction of the ketonic ring of (155) and further functional group modifications provided the Melodinus alkaloid ( )-meIoscine. (Scheme 55). 

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... 

Ring contraction of cyclic diazo ketones (Wolff)... 

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.

---