Enones radical reactions

Finally, a rather early (but from a mechanistic viewpoint a very interesting) sequence of radical reactions has been described by Pattenden and coworkers, in which an acetylenic oxime ether 3-312 was converted into the bicyclic oxime 3-319 in 70% yield (Scheme 3.78) [126]. Hydrolysis of 3-319 led to the bicyclic enone 3-320, which in fact can also more easily be synthesized by a Robinson annulation. 

Interesting variations of these reactions are observed when the a-silylamine donor funtion is tethered to an enone. For example, the intramolecular ET reaction of 143 results in two divergent cyclizations. Methanol assists the cleavage of the C—Si bond the resulting biradical anion 146 couples protonation and tautomer-ization then leads to 147. In acetonitrile, on the other hand, transfer of an a proton to the enone radical anion function forms biradical 144 coupling and tautomer-ization then generates 145. " ... 

As with epoxides, carbanions can add in a 1,4 fashion to enones or nitrosugars. Nitromethane anion has been used [64], Dithiane anion has been successfully used in the addition to nitroolefins [65] and to enones [66], Accordingly, C-5 branched-chain glucose derivatives 47 and 48 have been prepared from nitroolefin 46 (Scheme 20) [67,68], Sugar-derived enones have been also used as acceptors in free radical reactions to trap alkyl radicals as well as anomeric radicals (see Schemes 29 and 30). 

Intramolecular free radical reactions have been also exploited using silicon temporary attachment [97]. Reduction of enone 134, gave the corresponding allylic alcohol, which is transformed into the bromomethyl-(dimethylsilyl) ether 137 (Scheme 47). Radical cy-... 

Reductive alkylation of a, -enones. This reaction can be effected by a photo-stimulated free-radical reaction with RHgCl and a base (K1/K2S208, Nal, DABCO).1... 

Another approach involves the use of an electron-poor olefin acting both as an absorbing electron acceptor and as a radical trap. In this case, a PET reaction between a cyclohexenone derivative and a silylated amine led to a radical ion pair. Desilylation of the silyl amine radical cation intermediate in polar protic solvent (e.g., MeOH) and subsequent aminoalkyl radical attack onto the enone radical anion yielded the alkylated cyclohexanones [23]. 

A different approach must be used for the photochemical hydrophosphination of electron-poor olefins, and this involves a PET reaction. Silyl phosphites (e.g., 30) were used as electron donors, whereas conjugated ketones have the double role of electron acceptors and absorbing species. Thus, the irradiation of a mixture containing 2-cydohexenone and 30 generated an ion pair. The phosphoniumyl radical cations decomposed to give trimethylsilyl cations (which in turn were trapped by the enone radical anion) and phosphonyl radicals. A radical-radical combination afforded the 4-phosphonylated ketones in yields ranging from 78% to 92% (Scheme 3.20) [49]. This reaction was exploited for the preparation of substituted phosphonates, which serve as key intermediates in the synthesis of a class of biologically active compounds. 

By pairing an addition to an enone in the final step with an initial intramolecular radical cyclization, it is possible to accomplish tandem radical reactions of cobalamine(III) alkyls356. Tandem cyclizations are also most often done, with the final termination step being elimination to the alkene or trapping with styrene (equation 182)357. It is also possible to enter into ring-expansion reactions by retrograde radical cyclization-recyclization processes in modest yields358. 

Chuard et al. introduced a two-step radical alternative to the oxy-Cope reaction [95]. It relied on the opening of a strained cz-oxetanyl radical to the allyloxy radical. Because of the favorable geometry, further fragmentation delivered enone radicals that could undergo a 6-endo-trig cyclization, which led to bicyclic ketones in 69% yield. 

Lee and Larock found that the characteristic tricyclic core of prostacychnes could be easily obtained by tandem radical reaction involving the trapping of a radical issued from a 5-exo-trig cyclization by an excess of stannyl enones [134]. 

Success of the above-mentioned convergent pathways depended critically upon the employment of 1,2-enones as the key starting compounds capable of undergoing controlled Michael addition/enolate alkylation. Additional opportunities for elaboration of convergent strategies can also be generated from consideration of entirely different chemical reactions of polyfunctional substrates. As an illustration of the diversity of available options, we have chosen additional examples from the fast-growing area of the synthetic utilization of radical reactions. ... 

Raney niekel can be used for the ehemoselective reduction of a,y9-unsaturated ketones, esters, acids, nitriles, and nitroalkenes to give the corresponding saturated carbonyl compounds and carbonyl analogs in excellent yields. From trapping experiments it became evident that electron transfer from nickel to give the enone radical anion initiates the reaction which then proceeds via proton transfer and second electron-proton transfer cycle (Scheme 8) [37]. 

Sugar-derived enones have been also used as acceptors in free radical reactions to trap alkyl radicals as well as anomeric radicals (see Schemes 29 and 30). 

A single electron transfer mechanism is involved in the phototransformation of the enones (38) into (39) in the presence of phosphites. The reactions are carried out in acetonitrile and proceeded by the triplet enone to which an electron is transferred from the phosphite to give the radical cation/radical anion pair (A). Collapse of radical cation component of (A) gives (B) which then reacts by addition to the enone radical anion. The products (39) are isolated after hydrolysis of the corresponding silyl ethers. The influence of ring size and substituents was also examined and these results are given in Scheme... 

Cyclopentanols (134) are formed by the photo-reductive cyclization of the enones (135). Reactions are carried out in HMPA and irradiation of the enones (135) in this medium effects electron transfer to yield the radical anion of the carbonyl group. Cyclization follows the "Rule of Five" and yields the cyclopentanols. ... 

The mechanism of action of the nickel addend proceeds probably through a reduced form of nickel (e.g. nickel(I)) which is involved in a electron transfer process with the enone. Further reaction with the organozirconium reagent affords the addition product through transfer of the organic radical from zirconium to the nickel center, followed by a reductive elimination step (see [45] for a similar mechanistic proposal). 

For certain types of radical reaction, AIBN may not always give optimal results. Keck and Burnett found in their synthesis of PGp2a that the introduction of the lower side chain, involving radical addition onto a B-stannyl enone, was inefficient when AIBN was used as initiator at 65 °C. By conducting the reaction in refluxing toluene (110°C), and replacing AIBN with the related IJ -Azobis-l-cyclohexanenitrile (ACN), a markedly better yield of the desired adduct was obtained (eq 10). ... 

Most enones are reduced to anion radicals by organo cuprates. It is likely, that this reaction is connected with the alkylation. Both the formation of anion radicals and of conjugate adducts are not observed, when the redox potential of the enone becomes too negative (H.O. House, 1976). 

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