Ketones photochemical reduction

The reaction pathways by which the net transfer of a hydrogen atom from an amine to a photoexcited ketone has been extensively examined in the nanosecond [23, 25-30], picosecond [20, 22, 31-33], and femtosecond [24] time domains. The following mechanism, as it pertains to the photochemical reduction of benzophenone (Bp) by N, A-dimethylaniline (DMA), is derived from these numerous studies. Only an overview of the mechanism will be presented. The details of the studies leading to the mechanism will not be given for specifics, the reader is referred to the original literature. 

The photochemical reduction of benzophenone to benzopinacol in the presence of ferrocene31 apparently relates to a high concentration of ketone so that sufficient unquenched benzophenone triplets are present and proceed to the dimer in the usual fashion. 

In the pinacol coupling, two ketones are reductively coupled to give a 1,2-diol. (Compare the photochemical pinacol coupling discussed in Section 5.3.1.) The two ketones are usually identical, but intramolecular dimerizations can give unsymmetrical 1,2-diols. The reaction proceeds by electron transfer to the ketone to give a ketyl radical anion. This compound dimerizes to give the 1,2-diol. 

Water has been used to accelerate reductions, as in photochemical reduction of the ketone 28 (Figure 4.16) [51], Surfactants have also been shown to aid reactions in water, when sodium dodecyl sulfate was added, the ee rose from 61% to 94% in the preparation of 29 (Figure 4.16) [52]. 

Under normal conditions, excited carbonyl compounds isomerize to cyclobutanols (see Section 7. A.1.1.5.) via intramolecular y-hydrogen abstraction and closure of the intermediate 1,4-biradical. Nevertheless, a similar, formally /i-hydrogen abstraction, step leading to cyclopropanols occurs with several A-functionalized ketones (see Houben-Weyl, Vol. 4/5 b, p 797, literature up to 1971, and Vol. 6/la, part 2, pp 788-799, literature up to 1975 for a general mechanistic description of the formation of alcohols by photochemical reduction of carbonyl compounds, see Vol. 6/1 b, p432). 

Having developed effective synthetic methodology for the construction of seven-membered cyclic ethers, we were confident that the problem of the frans-fused bis(oxepane) system could now be addressed on a solid foundation. It was our hope that the breve-toxin-type bis(oxepane) system could be assembled by a stepwise strategy utilizing both photochemical dithioester and reductive hydroxy ketone cyclization methods. 

Scheme 11. Bis(oxepane) synthesis using a photochemical dithioester cyclization and a reductive hydroxy ketone cyclization.

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

The synthesis of the non-natural ( )-7,14-epz-l(15),8-dolastadien-7,14-ol (rac-7yl4-epi-l09) was published by Paquette in 1986 and is highlighted by a photochemical rearrangement of the 6,6,6-tricyclic a,yS-epoxy ketone 148 into the 5,7,6-tricyclic dolastane skeleton (149) (Scheme 23) [84]. The succeeding hydroxylation of carbon atom by photo oxygenation with singlet oxygen as well as a DIBAH reduction of a keto function proceeded with an undesired substrate-induced diastereoselectivity to provide the racemic 7,14-epimer of the natural dolastane 109. 

The Dauben-Walker approach has yielded the smallest and most strained fenestrane known to date Following the intramolecular Wadsworth-Enunons cyclization of 443 which also epimerizes the butenyl sidechain to the more stable exo configuration, intramolecular photocycloaddition was smoothly accomplished to provide 444. Wolff-ELishner reduction of this ketone afforded the Cj-symmetric hydrocarbon 445. Application of the photochemical Wolff rearrangement to a-diazo ketone 446 p,ve 447. 

The above reactions proceed via free radical coupling. An alternative system for photochemically driven hydrocarbon functionalization evidently proceeds via the carbanion, which is obtained from reduction of the initially formed free radical3. The carbanion reacts with acetonitrile to give, after in situ hydrolysis, the methyl ketone, e.g., formation of (tricyclo[3.3.1.13-7]dec-1-yl)ethanone6. 

Padwa, Bergmark, and Pashayan were able to demonstrate that 22 and other ketimines are photochemically unreactive and that all of the reduction observed upon direct irradiation is due to hydrogen abstraction by the corresponding ketone formed either by hydrolysis or by oxidation of the imine.120 The results with 23 may have a similar explanation. 

Also, by the introduction of the enzyme ferredoxin reductase, a photochemical NADPH regeneration cycle has been established. The NADPH has been utilized in the reduction of ketones to alcohols in the presence of a secondary enzyme, alcohol dehydrogenase. 

No attention is given to the mechanistic importance of a reaction rather, an attempt has been made to concentrate on reactions that have an actual (potential) synthetic role. This is not always an obvious selection, because photochemistry has not been sufficiently used in such syntheses, and mechanistic studies are not necessarily a reliable guide towards this aim. As an example, hydrogen abstraction by ketones (Scheme 1.3), which probably is the most thoroughly studied photochemical reaction, is not mechanistically discussed. Neither is presented the resultant photoreduction of ketones (Scheme 1.3, path a), because this will hardly ever become a sensible synthetic alternative for the reduction. However, other reactions arising from the same primary photoprocess, namely bimolecular reduction (path b) and... 

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