Cyclization ketone trapping

By using various trapping reagents, it has been deduced that the transannular fragmentation is rapidly reversible. The cyclization of the fragmented radical C is less favorable, and it is trapped at rates which exceed that for recyclization under most circumstances. " Radicals derived from ethers and acetals by hydrogen abstraction are subject to fragmentation, with formation of a ketone or ester, respectively. 

In this context Fernandez-Mateos and his group reported efficient cyclizations with aldehydes and ketones as radical traps [115]. The authors propose a reduction of the intermediate alkoxyl radicals by a second equivalent of... 

Treatment of the acetylenic ketones 186 with lithium dialkylcuprates and trapping the resultant enolates with acetic anhydride produced the enyne-allene 187 (Scheme 20.39) [72], Regeneration of the oxyanion-substituted enyne-allene system using methyllithium at -20 °C led to the formation of either the indanones 188 or the ben-zofluorenones 189 through a Schmittel cyclization reaction. 

Welch s stereoselective synthesis centered about the tandem conjugate addition of a methyl group and allylation to produce 583 (Scheme XLVI). A second methylation, combined with oxidation of the allyl sidechain, gave 584 which was successfully cyclized under Claisen conditions. Trapping of the enolate as in 585 permitted differentitation between the two potential ketone carbonyl groups. 

A synthesis of this compound was devised by Ohmizu, Iwasaki and co-workers and featured a three-component tandem conjugate addition/enolate trapping as key step (Scheme 12.24) [82]. In this synthesis, the acyl anion equivalent cyanohydrin 165 was first treated with LDA and allowed to react with methyl crotonate 166. The resulting enolate was trapped with 2,3,5-trimethoxy benzylbromide 168 to afford crude intermediate 169, which was immediately deprotected in situ to afford ketone product 170. Both the ester and the ketone functionalities were then reduced at low temperature to afford the corresponding diol 171. Upon treatment with trifluoroacetic acid, the desired Friedel-Craft cyclization adduct 172 was obtained. The latter tricyclic compound was then further elaborated to the final target 164 through a short sequence of standard transformations. 

Cyclization reactions by 1,3-dehalogenation or dehydrohalogenation d> have provided additional routes to cyclopropanones. The application of the former reaction to the formation of 3-ring ketones was suggested by the isolation of the cycloadduct 37 from the reaction of a, -dibromo-benzyl ketone with sodium iodide in the presence of the trapping agent furan.39> More recently, Giusti n> has synthesized several cyclopropanone... 

Aryl radical cyclization.10 Sml2 in HMPA/THF at 25° can effect cyclization of l-allyloxy-2-iodobenzene to a Sm(III) intermediate (a) that can be trapped by electrophiles, including aldehydes or ketones. The report suggests that a similar mechanism operates in the Barbier-type coupling generation of an alkyl radical followed by formation of RSml2, which adds to a carbonyl compound to form an adduct that is hydrolyzed to an alcohol. 

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