Cyclization, radicals with ketenes

The intramolecular cyclization dominates other possible reactions even in solvents highly susceptible to free radical attack (110). Thus, irradiation of 4,5-octanedione in butanal gives 2-hydroxy-3-methyl-2-propylcyclobutanone in 92% yield (110). Irradiation of 1,2-cyclo-decanedione (Formula 264) gives 1-hydroxybicyclo [6.2.0 ]decan-10-one (Formula 265) in 74% yield and cyclooctanone (Formula 266) in 9% yield (111). The cyclooctanone is produced together with ketene by a secondary photolysis of Formula 265 (111). 

The N,0- and N,S-heterocyclic fused ring products 47 were also synthesized under radical chain conditions (Reaction 53). Ketene acetals 46 readily underwent stereocontrolled aryl radical cyclizations on treatment with (TMSlsSiH under standard conditions to afford the central six-membered rings.The tertiary N,0- and N,S-radicals formed on aryl radical reaction at the ketene-N,X(X = O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from (TMSlsSiH was investigated and found to provide higher selectivities than BusSnH. 

Partially saturated derivatives can also be prepared through aryl radical cyclization of A-2-halobenzoyl cyclic ketene-iVA-acetals <2005TL3801>. In this event, treatment of ketene-acetal 418 with Bu3SnH afforded good yield of cyclized products 419 and 420, as a mixture of two diastereoisomers, but with a total regioselectivity (Scheme 108). 

Scheme 29 describes a plausible mechanism for the formation of the products which fit the observed coulometric (n 0.45 F/mol) and preparative results. The intramolecular cyclization process involves a dimerization between a radical cation 52a and the ketene imine 52 to form the intermediate radical cation 52b which then cyclizes to the radical 52c which can abstract a hydrogen atom leading to 54 or can be further oxidized and transformed through a cyclization and deprotonation reaction to 53 which involves 1 F/mol. However, it seems that the [2 -1- 3]-cycloaddition between the parent compound 52 and the cation 52d giving rise to 55 is the fastest reaction as compared with the intramolecular cyclization of 52d to 53. This can also explain the low consumption of electricity. 

The PET-oxidative cyclization of unsaturated O-alkyl-O-trimethylsilyl ketene acetals 23 and 27 yields cyclic esters 24, 25, and 28, accompanied by the formation of considerable amounts of non-cyclic esters 26 and 29, respectively [89], The cyclization mode is found to be in accordance with free radical cyclizations of the appropriate esters 26 and 29, performed by heating with organic peroxides [90]. Since organic electrochemistry can be used to oxidize... 

Radical-anion and radical-cation intermediates, for example, reaet with each other after PET in donor-acceptor systems. After proton reorganization they undergo cyclization to provide a direct synthetic route to macrocycles and A-heterocycles with a variety of ring sizes [230]. Cycloadditions via radical ion pairs [231] and the C -C bond formation between Ceo and A,0-ketene acetals [232] also fit this eategory. 

There are many synthetic examples that use radical cyclization as a key step, and the radical precursor is not limited to iodides or bromides. In Pattenden s synthesis of pentalenene, conjugated selenyl ester 156 was treated with Bu3SnH and AIBN to give a 45% yield of tricyclic ketone 159. Loss of PhSe generated the acyl radical 157, which exists in equilibrium with the ketene radical 156. Radical cyclization via the latter intermediate leads to 159. Cyclization via aryl radicals is also possible. In Schultz s synthesis of hexahydro-phenanthren-2-one derivatives, " aryl bromide 160 was cyclized to 161 in 78% yield under standard conditions. Radical cascade reactions have become quite popular for the synthesis of polycyclic ring systems. In these reaction, polyenes are subjected to radical cyclization, generating tricyclic or even tetracyclic ring systems. 5 Chiral auxiliaries have been used effectively in radical cyclization reactions. ... 

The reaction of lithium diisopropylamide with propargyl acetate 3.559 followed by treatment of the enolate formed with trimethylchlorosilane at —78°C affords ketene acetal 3.561. After heating the reaction mixture to 40°C, the intermediate vinylpropargyl ether 3.560 undergoes the Claisen rearrangement to produce silyl ester 3.561, which after hydrolysis forms allenyl-acetic acid 3.562 with a 50% overall yield (Scheme 3.42) [281]. This reaction is of interest as a synthetic strategy for obtaining the benzoannelated enyne-allene that by radical cyclization forms polycyclic aromatic compounds with an embedded fluorene section [281]. (Scheme 3.43)... 

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