Hydrogen abstraction and cyclization

Coumestrol has been prepared via a photocyclization of the glyoxylate ester shown below through consecutive 5-hydrogen abstraction and cyclization processes, and is followed by... 

Among the initiation methods available, photochemistry has already been used successfully for Pschorr reactions [122]. A new study, from which one example is shown in Scheme 24, revealed a dramatic influence of the substituents on the 2-bromobenzophenone 66. Methoxy groups in the radical ring led to a highly electrophilic cr-aryl radical which proved unreactive for hydrogen abstraction and cyclization. Substituents in the non-radical ring that stabilize the cyclohexadienyl... 

Scheme 12 Enantioselective y- and 8-hydrogen abstraction and cyclization using thti...

A study of bischromones such as (131) has been carried out. Irradiation (254 nm) in CH3CN of the derivative (131, n = 2) results in the formation of the two products (132) and (133) in low yields of 10% and 12%, respectively. The cyclization reaction is the result of Norrish Type II hydrogen abstraction and cyclization. The analogous reaction occurs with the corresponding phenyl derivatives. The cyclization is chain-length dependent and the reaction fails with (131, n = 0). ... 

Intramolecular carbon carbon bond formation is more efficient as demonstrated by Kim and Rawal, who reported the radical-induced fragmentation of epoxides followed by hydrogen abstraction and cyclization (Scheme 11). Kim s approach... 

Further work on the phthalimide system has shown that iV-methylphthalimide undergoes intramolecular hydrogen abstraction when irradiated in ethers (THF, dioxan, and diethyl ether) to yield the adducts (257).151 Hydrogen abstraction also occurs in the presence of cyclopentene or cyclohexene. Intramolecular hydrogen abstraction in the phthalimides (258) gives the oxazoloisoindoles (259).152 Similar hydrogen abstraction and cyclization in the phthalimides (260) affords a route to the multi-cyclic benzazepines (261) (Scheme 25).153 The... 

Attaching a 2-alkoxyethyl carboxylate group ortho rather than para on benzophenone provides an example of 0-hydrogen abstraction and cyclization of the 1,9-biradical to a lactone. ... 

A-Chloro-Af-methoxy-Af -arylureas (84) have been reported to cyclize in good yield to 2-benzimidazolinones (85) upon treatment with NaH. Af -Alkylation prevented the reaction and the process involves anilide formation by hydrogen abstraction and an intramolecular Sat2 displacement of chlorine by the electron-rich ortho carbon (equation 11) . ... 

In contrast to aminyl radicals, alkoxyl (and acyloxy) radicals are highly reactive. As illustrated in equation (7), their cyclization reactions are extremely rapid and irreversible. However, the rapidity of such cyclizations does not guarantee success because alkoxyl radicals are also reactive in inter- and intramolecular hydrogen abstractions, and -fragmentations (see Section 4.2.S.2). This lack of selectivity may limit the use of alkoxyl radicals in cyclizations, but S-exo cyclizations are so rapid that they should succeed in many cases, and other types of cyclizations may also be possible. 

The corresponding photocyclization of S-arylvinyl sulfides to dihydro-thiophens has been shown to proceed via short-lived thiocarbonyl ylide intermediates, formed in turn by cyclization of triplet excited states. 1-Phenylthio-3,4-dihydronaphthalene (49), for example, affords the colored thiocarbonyl ylide (50)44 the isolated products are derived by processes involving hydrogen abstraction and migration. The greater efficiency of the photocyclization of 2-thioaryloxyenones (51) to dihydrothiophens (52) has been attributed to the additional stabilization afforded to the ylide (53) by the carbonyl group.45 Other similar photocyclizations have been reported.46... 

In contrast to intramolecular cyclizations, the intermolecular addition of O-centered radicals to ti systems as initiating step in complex radical cyclization cascades has only recently attracted considerable attention. The reason for the low number of papers published on O radical addition to alkenes and alkynes could originate from the perception that O-centered radicals, such as alkoxyl radicals, RO, or acyloxyl radicals, RC(0)0", may not react with 7t systems through addition at rates that are competitive to other pathways, for example, allylic hydrogen abstraction and p-fragmentation in the case of RO" or decarboxylation in the case of RC(0)0" (Scheme 2.9). 

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... 

The bridged azidosulfonylbiaryls 398 cyclize to seven-membered rings (399) on thermolysis in dodecane 468 Products of hydrogen abstraction and insertion into the solvent are also formed. Moreover, 398b underwent a rearrangement to 400 (Eq. 137)468,469 in contrast, the azide 401 attacks the... 

The applications of such electronic effects extend to radical chemistry. For example, reactions of electrophilic oxygen-centered radicals display excellent chemoselectivity for cyclization onto the electron-rich silyl enol ether when competing with terminal alkene cyclization, 1,5-hydrogen abstraction, and p-fragmentation pathways (Figure 6.115). ... 

Photolysis of 3-buten-l-ol nitrite affords no cyclized products (Cy5/Cy4) neither does 5-hexen-l-ol nitrite (Cy6/Cy7). The same result is obtained on peroxydisulphate oxidation of 5-hexen-l-ol. In the Cy6/Cy7 case an important competitive pathway is probably 1,5-intramolecular ally lie hydrogen abstraction and, indeed, esr spin trapping by nitrosodurene " provides evidence of this. Cyclization in the Cy6/Cy7 case was considered to explain the reaction products of tetrahalogeno-o-benzoquinones with 2,3-dimethylbut-2-ene but was discarded in favor of a direct cycloaddition process on the basis of spin trapping and deuteration experiments. As discussed before, cyclization in the Cy3/Cy4 case must be difficult to observe because of the high j5-scission rate of oxyranylalkyl radicals. Nevertheless, this pathway has been used recently to explain the formation of diepoxides in the thermal-, photochemical-, or ferrous-salt-induced decomposition of unsaturated cyclic peroxides. In view of the multistep scheme involved this conclusion must await further confirmation. 

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