Hydrogen abstraction, ketones 1.8- biradicals

Lewis and Hirsch studied four a-cycloalkoxyacetophenones, in which the ring is even farther away from the carbonyl and the y-hydrogen is tertiary.Table 58.3 lists the results, which consist of oxas-piro[3,n]alkanol and cycloalkanone formation, via normal cyclization and cleavage of the 1,4-biradicals. Simple isopropoxyacetophenone is included for the sake of comparison to acyclic compounds. As with other a-alkoxy ketones, overall quantum yields are quite high and cyclization yields are reasonable, except for the cyclopropyloxy ketone. Hydrogen abstraction rate constants are very high and decrease as expected as the rings get smaller. 

Figure 7.26. Photo-induced hydrogen abstraction from the y-carbon leads to biradical 72, which can (a) revert to the starting ketone, (b) cyclize, or (c) cleave the 2,3-CC bond. The structure for y-H abstraction for the starting ketone is also shown and the ideal parameters defined and listed.

Hydrogen abstraction can occur from a position within the ketone molecule, and this generates a biradical that may cyclize by combination of the radical centres. The overall photocydization process is observed for a wide variety of compound types, and it has been used extensively to make cyclic or polycyclic systems, in an unconstrained system a ketone (n,n ) excited state shows a preference tor abstraction from the y-position (4.42), which can be understood on... 

Rather phase-insensitive Norrish II photoproduct ratios are reported from irradiation of p-chloroacetophenones with a-cyclobutyl, a-cyclopentyl, a-cycloheptyl, a-cyclooctyl, and a-norbonyl groups [282], In each case, the E/C and cyclobutanol photoproduct ratios are nearly the same in neat crystals as measured in benzene or acetonitrile solutions. On this basis, we conclude that the reaction cavity plays a passive role in directing the shape changes of these hydroxy-1,4-biradicals. As long as the initial ketone conformation within the cavity permits -/-hydrogen abstraction (and these ketones may be able to explore many conformations even within their triplet excited state lifetime), the cavity free volume and flexibility allow intramolecular constraints to mandate product yields. 

When an excited aldehyde or ketone has a y hydrogen, intramolecular hydrogen abstraction via a six-membered ring transition state usually occurs. The resulting 1,4-biradical may either cleave or cyclize to give the Norrish Type II products of Scheme 4. 

The latter example (reaction 36) already indicates that the Yang cydization can also be used to synthesize four-membered heterocycles. After light absorption, the a,(3-unsaturated carbonyl compound 84 undergoes intramolecular hydrogen abstraction at the a-position of the carbonyl moiety (reaction 37), leading to the 1,4-biradical intermediate XXX [87]. A radical combination then efficiently yields the spirocyclic P-lactam derivative 85, and only one stereoisomer is formed in this case. In this transformation, the a,P-unsaturated carbonyl function can be considered as being vinylogous to a simple ketone. 

One of the first examples of 8-hydrogen abstraction in acyclic ketones was the photocyclization of P-alkoxy ketones, in particular of P-ethoxypropiophenone (34), to the corresponding furanol derivatives 37 (Scheme 8.10). It was revealed that formation of enol 36 as well as a reversion to the starting ketone occur by 1,4-hydrogen transfer from the 1,5-biradical 35 causing the lower quantum efficiency for cyclization [12]. 

The Norrish-Yang reaction [63] is a widely used photochemical reaction, which consists of an intramolecular hydrogen abstraction by a photoexcited ketone, followed by carbon-carbon bond formation in the (l,n)-biradical intermediates (Scheme 9.38). 

Stiver and Yates have studied the photochemical reactions of some hydroxy-keto steroids (28, 29). Irradiation of the isomeric compounds (28a, 29a) showed that the products obtained, (30) and (31) respectively, had retained the configuration of the carbon to which the hydroxy group is attached. The use of deuteriated derivatives (28b, 29b) has identified the hydrogen abstraction processes involved in the conversion of these ketones into the lactones (30b) and (31b) respectively. The authors " propose that there are two major factors which control the stereospecificity of the reactions. These are the shape of the hydroxy-bearing C-atom and the hydrogen transfer within the biradical formed on Norrish Type I fission. The stability of the biradical intermediate clearly plays an important part in determining the outcome of the reactions. 

A common reaction of aliphatic ketones is intramolecular hydrogen abstraction from the y position (in rare instances from the 6 or even the p position). In addition to regenerating the reactant, the resulting biradical can cleave to give an olefin and an enol, or form a cycloalkanol. Scheme 9 illustrates the most important case of y hydrogen abstraction. 

A study of the photochemical reactivity of salts of the amino ketone (44) with enantiomerically pure carboxylates has been reported. The irradiations involved the crystalline materials using A, > 290 nm and the reactions are fairly selective which is proposed to be the result of hindered motion within the crystalline environment. Some of the many results, using (S)-(—)-malic acid, R-(+)-malic acid and (2R,3R)-(+)-tartaric acid, are shown in Scheme 1. The principal reaction in all of the examples is a Norrish Type II hydrogen abstraction and the formation of a 1,4-biradical. This leads mainly to the cis-cyclobutanol (45) by bond formation or the keto alkene (46) by fission within the biradical. A very minor path for the malate example is cyclization to the trn 5-cyclobutanol (47). A detailed examination of the photochemical behaviour of a series of large ring diketones (48) has been carried out. Irradiation in both the solid phase and solution were compared. Norrish Type II reactivity dominates and affords two cyclobutanols (49), (50) and a ring-opened product (51) via the conventional 1,4-biradical. Only the diketone (48a) is unreactive... 

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