Radical coupling ketones

Termination is principally via radical coupling forming hexabutylditin, or to a lesser degree via the coupling of ketyl radicals. In the case of the mr ketones a different mechanism is proposed. The rate of abstraction of H from the tributyltinhydride by benzylic radicals is slower than the corresponding abstraction by alkyl radicals. Since the rate at which the tributyltin radical will add to aromatic carbonyls is similar to the addition rate to aliphatic carbonyls, the dominant radical species for the tttt systems is the ketyl radical. The primary termination process involves the coupling of the predominant radical species resulting in pinacol formation. 

The propargylic alcohol 102, prepared by condensation between 100 and the lithium acetylide 101, was efficiently reduced to the hydrocarbon 103, which on treatment with potassium tert-butoxide was isomerized to the benzannulated enyne-allene 104 (Scheme 20.22) [62], At room temperature, the formation of 104 was detected. In refluxing toluene, the Schmittel cyclization occurs readily to generate the biradical 105, which then undergoes intramolecular radical-radical coupling to give 106 and, after a prototropic rearrangement, the llJ-f-benzo[fo]fluorene 107. Several other HJ-f-benzo[fo]fluorenes were likewise synthesized from cyclic aromatic ketones. 

The addition of RLi and other nucleophiles to carbonyl functions in general proceeds via one of the two possible reaction pathways, polar addition (PL) and electron transfer (ET)-radical coupling (RC) sequence (equation 5). Current reaction design for the synthetic purpose of additions of common nucleophiles to aldehydes and ketones is mostly based on the polar mechanism, but apparently the ET process is involved in some reactions of, for example, Grignard reagents Mechanistically there are three possible variations the PL pathway, the ET rate-determining ET-RC route and the RC rate-determining ET-RC route. 

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. 

An instance of photoreduction of ketones by complexation with alkylbenzenes177,178 (as electron donors) is shown in Scheme 41. Products shown in Scheme 41 have been formed by radical coupling reactions. The investigations (using a combination of flash kinetics, steady-state quenching and quantum yield measurements) of the substituents and isotope (H/D) effect indicate that ketones react predominantly through CT complexes. 

In an example of solid-state photochemistry, an unexpected exo-selective formation of bicydic oxetane was reported by Kang and Scheffer (Scheme 7.29) [47]. When a solid-state ketone was irradiated using a medium-pressure Hg lamp, via a Pyrex filter (>290 nm), the exo-selective oxetane formation of oxetane was predominant (yield 91%). In acetonitrile-solution photochemistry, the radical coupling product (43%) was the only isolable product. 

As mentioned in Sec. 15.2.2, hydrogen abstraction of benzylic hydrogens by the /77i triplet state of ketones is generally efficient and offers an access to benzylic radicals. However, the method is rarely of preparative interest since benzylic and ketyl radicals couple statistically giving a mixture of bibenzyls, alcohols, and pinacols, although the initial hydrogen abstraction may show some interesting intramolecular selectivity with polymethylbenzenes and substituted alkylbenzenes [220,221]. However, in... 

In such an insertion the benzophenone is excited to its triplet state, resembling a C-0 diradical. The oxygen atom of the ketone then removes a hydrogen atom from the methylene group, leading to a carbinyl radical and the hydroxy diphenylmethyl radical formed by hydrogen atom addition to the benzophenone. This pair of radicals couples... 

Phenolate radical coupling in synthesis and biosynthesis Pummererys ketone... 

The pioneer in phenolate radical coupling was Pummerer. In 1925 he showed1 that one electron oxidation of />-cresol using potassium ferricyanide afforded a nicely crystalline ketonic dimer of the radical in up to 25 % yield. Pummerer s ketone, as it became known, was considered to result from the coupling of two p-cresol radicals to give the dienone 1. This then underwent spontaneous cyclization to furnish 2. As proof of the structure... 

Finally, there is one aspect of the photoreduction of phenyl ketones which has been resolved only recently. It is now well established that benzyl radicals couple to form l-alkylidene-2,5-cyclohexadienes as well as bibenzyls, the ratio depending primarily on steric factors 121>. Schenck first showed that the semi-pinacol radicals involved in the photoreduction of benzophenone also form such products 122>. These compounds absorb very strongly in the near UV and often... 

When salt crystals of the aryl 1-phenylcyclopenty 1 ketone carboxylic acid 40 with chiral amines such as (+ )-bomylamine or (—)-1-phenylethylamine were irradiated, the optically active exo- and endo-oxetanes 41 or 42 were formed in low to moderate enantiomeric excesses (Scheme 10) [57]. The formation of the oxetanes is believed to occur through Norrish type 1 cleavage and hydrogen abstraction, producing an alkene and an aldehyde, followed by a Paterno-Buchi reaction within the crystal lattice cage. In contrast, solution photolysis of 40 in acetonitrile afforded product 43 as the only isolable product via a typical Norrish type I a-cleavage followed by radical coupling. 

Thus, the cyclization of 2-(3-hydroxyphenyl)ethyl ketone 0-2,4-dinitrophenyloximes 80 does not proceed by an S 2-type reaction but by radical coupling via an alkylideneaminyl radical intermediate or its equivalent as shown in Scheme 41. In oxime 80, intramolecular electron transfer occurs from the phenolate moiety to the dini-trophenyl group to generate a phenoxy radical-dinitrophenyl anion... 

One of the key steps used in a new synthesis of the bis(tetrahydrofuran) moiety of Asteltoxin (94) is the photoaddition of the propanal (95) to 3,4-dimethylfuran, yielding the adduct (96). This cycloaddition is a common outcome of the irradiation of aldehydes or ketones with furans. An analogous adduct (97) results from the photoreaction of butyl glyoxalate with 2-methylfuran. Two other products [(98) and (99)] are also formed, the first of which is presumably the result of ring opening of the isomeric oxetane (100), while (99) is produced by a hydrogen abstraction radical coupling pathway. 

Electrolytic formation of carbon bonds during formation of heterocyclic compounds occurs in the reduction of ketones to pinacols, in the hydrodimerization reaction, in some radical coupling reactions, and in the oxidative coupling of activated aromatic systems. 

Lunarine (26), one of the typical neolignans, is biosynthesized by the ortho-para radical coupling between two molecules of p-hydroxycinnamic acid. In this connection, oxidative coupling reactions of 4-substituted phenols have been extensively stndied using thallium trifluoroacetate (TTFA), potassium ferricyanide (K3[Fe(CN)g]) and other reagents. p-Cresol (27) was also electrolyzed at a controlled potential (+0.25 V vi. SCE) in a basic medium to afford Pummerer s ketone 28 in 74% yield. The snggested mechanism is given in Scheme 4. 

Alcohols are usually oxidized to aldehydes or ketones in these reactions cholestanone has been isolated 128> from reaction of cholestanol and phenanthrenequinone in benzene solution. Two cases have been reported, both involving reactions in methanol, where the intermediate hydroxymethyl radical coupled (in part) with semidione radical. Thus, the 1,2-adducts (34%) 84 and 55 were obtained "> with camphorquinone at 2537 A in addition to 82 and83 (66%). 1,2-Adduct (35%) predominated 6°) over reduction product (18%) in reaction of 73 in methanol. This reaction led to a very complex mixture of products, some or all of which may reflect reactions of the monohemiketal since light filtered through Pyrex was used and decolorization of the dione was observed in methanol solution. 

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