Photolytic Ring Contraction

In his investigations of strained bicycHc systems, Meinwald 4) has explored the photolytic rearrangement of a-diazoketones to carboxylic acids according to the reactions. The procedure given below is an example of this process, employing as the 

Starting material camphor quinone (Chapter 1, Section XI) and resulting in the formation of Horner s acid (5). 

Camphor Quinone Monotosylhydrazone To 22 g (0.133 mole of camphor quinone in 150 ml of chloroform is added 26.1 g (0.14 mole) of p-toluenesulfonylhydrazide in one batch. The reaction vessel is protected with a drying tube and fitted with a magnetic stirrer, and the mixture is stirred at room temperature for 24 hours. The monotosyl-hydrazone is not isolated. 

Diazocamphor A large wide-diameter chromatography column (8.5 cm diameter) is packed with 1000 g of basic chromatography grade alumina. The previously prepared solution of the monotosylhydrazone is filtered, if necessary, to remove solids, then poured directly onto the alumina, and the column is eluted with chloroform. The solution of diazocamphor thus obtained is evaporated yielding the desired product. It may be recrystallized from hexane, mp IS.  

6-TrimethylbicycIo[2.1.1 ]hexane-5-carboxylic Acid A solution of 17.8 g (0.10 mole) of diazocamphor in 500 ml of dioxane and 4(X) ml of water is deoxygenated with a slow stream of nitrogen for 20 minutes. The solution is then irradiated for 3 hours in a quartz vessel using a 500 watt Hanovia mercury lamp. (The completion of the reaction is verified by the disappearance of the diazo IR absorption at 4.85 ix.) The solution is placed on a rotary evaporator to remove about of the solvent, and the remaining aqueous solution is made definitely alkaline by the addition of aqueous sodium carbonate. The alkaline solution is washed several times with ether to remove neutral materials, and the ether is discarded. The aqueous solution is then carefully acidified with cold dilute sulfuric acid to pH 4. The mixture is extracted twice with ether, and the combined ether extracts are washed with water and dried. Evaporation of the ether gives the crude product, which may be recrystallized from aqueous methanol, mp 100-101°. 

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The preparative application of photolytic ring contraction reactions of cyclotetrasi-lanes, which also lead to the formation of cyclotrisilanes, is largely impeded by the limited stability of the cyclotrisilane moiety. The photolysis of octaisopropylcyclote-trasilane, for instance, affords the corresponding cyclotrisilane only as an intermediate, which can be detected by UV spectroscopy. Further silylene extrusion gives rise to the... 

Another synthetic route to )8-lactams involves the photolytic ring contraction of 4-diazopyrrolidine-2,3-diones. Diazo compounds 49 undergo Wolff... 

Scheme 7-35 Synthesis of the parent carbocycle 150 of the NCS chromophore by photolytic ring contraction of the bis-propargylic sulfone 148 (Wender et al.).

In other cases the tetrachlorobicyclo[4.2.0]octadiene cleaves off tetrachlorobenzene when irradiated through quartz glass with a low pressure mercury lamp. In this reaction the cyclobutene ring of the educt becomes degraded which is of synthetic value if the cyclobutene ring results from a photolytic ring contraction (eq 19) or from a Diels-Alder reaction with 7,8-dichlorobicyclo-[4.2.0]octadiene. 

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

Retropinacol rearrangement, 416 Ring contraction in photolytic cyclic a-diazoketones rearrangements, 316 12- p/-rockogenin mesylate, 400... 

The photolytic cleavage of cyclic ketones 14 leads to formation of a diradical species, that can undergo analogously the various reactions outlined above. The decarbonylation followed by intramolecular recombination yields a ring-contracted cycloalkane 15 ... 

In general, 1//-azepines are fragile ring systems which undergo facile ring contraction to arene derivatives under acidic, thermal, and photolytic conditions. 

Azepines, although more stable than 1/f-azepines. readily undergo ring contraction to pyridine derivatives under acidic, basic, thermal, and photolytic conditions. 

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. 

Carbenes are known intermediates in the thermolytic or photolytic decomposition of the lithium or sodium salts of tosylhydrazones, which, for endocyclic carbenes, results in ring contraction when the elimination of / - or y-hydrogens is impeded. Simple cyclobutanes generally cannot be prepared by this route from monocyclic cyclopentanone tosylhydrazones. However, the lithium salt of bicyclo[2.2.1]heptan-7-one tosylhydrazone gave bicyclo[3.2.0]hept-l-ene (4) as the major product (74%) by vacuum pyrolysis at 185 JC/20 Torr, together with bicyclo[2.2.1]heptane (14%) and tricyclo[2.2.1.02,7]heptane (12%) in 80% overall yield.67... 

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

Photolytically induced valence bond isomerism of heterocycles is a useful method 2-amino-5-chloropyridine gives (1) (61JA2967), and (2) — (3) illustrates the conversion of a seven-membered ring into a 4,5-fused derivative (71JOC1934). Benzazetidines are available by ring contraction (4 — 5) (80CC471). 

Diphenyl-l,2-diaza-l-cycloheptene (98) undergoes a similar type of ring contraction, accompanied by the formation of nitrogen, on exposure to UV light.79 In the solid state, this photolysis is stereospecific and the product is cis-1,2-diphenylcyclopentane (99). Both thermal and photolytic decompositions in solution yield a mixture of cis- and trans-1,2-diphenylcyclopentane in addition to cis- and... 

A variety of mono- and bi-cyclic heterocycles undergo ring interconversions leading to (5,5)-fused heterocycles. Both thermal and photolytic, and acid- and base-catalyzed, rearrangements, ring enlargements and ring contractions are known. 

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). 

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