Radical ring expansion

Scheme 3.5. Rare example of a domino radical ring expansion/cationic cyclization procedure.

Scheme 3.27. General scheme of domino radical ring expansion/cyclization procedure.

Sml2 can be also used for the same ring-expansion reaction. Thus, radical ring-expansion reaction of bicyclo[4.2.0]octanone (274) promoted by Sml2 provides a mixture of cyclooctanol (275a) and lactone (275b) (eq. 3.111). In this case, C02Me, CN, and Ph... 

TPDS can be also used for the preparation of biaryl through the intramolecular free radical // -substitution of A-(2-bromoaryl)arenesulfonamide (9) and radical ring expansion of a-haloalkyl cyclic (3-keto ester (11) (eqs. 12.5a and 12.5b). 

In a free radical ring expansion reaction discovered quite recently [24] [25], a methyl or ethyl cycloalkanone-2-carboxylate was first alkylated with methylene-dibromide [24] or bromomethylphenylselenide [25], Scheme VII/11. 

The use of 1,1-diiodomethane as an electrophile in the Birch reduction (with lithium in liquid ammonia) of electron-deficient pyrroles 915 furnished pyrrolines 916 (in high to excellent yields), which provided access to the synthetically important functionalized 5,6-dihydro-2(l//)-pyridinones 917 (via radical ring expansion), substructures commonly found in biologically active natural products (Scheme 177) <2004CC1422>. 2-(Chloroalkyl)-substituted pyrrolines 919 were duly prepared by the reductive alkylation (with l-chloro-3-iodopropane or 1-chloro -iodobu-tane) of electron-deficient pyrrole 918. Allylic oxidation then furnished lactams 920 (Scheme 178). 

More recently, the related indium-mediated radical reactions have been widely studied (Scheme 7.13).19 Indium iodide-mediated radical cyclisation was first reported by Cook et al.20 The indium-mediated 1,4-addition of alkyl radicals to (F)-but-2-enenitrile was investigated by using 1-ethylpiperidinum hypophosphite (EPHP) as a hydrogen donor in aqueous media (Scheme 7.13).21 Atom transfer radical cyclisation and reductive radical cyclisation were studied using indium and iodine.22 Indium mediated alkyl radical addition to dehydroamino acid derivatives was also reported.23 The indium-mediated radical ring expansion of a-halomethyl cyclic (3-keto esters, shown in Scheme 7.13, was achieved in aqueous alcohols.24... 

Radical ring expansion of propenylcyclobulanesf The substrates (2) arc obtained by alkylation of a spirocyclobutanone 1 with 1,3-dibromopropcnc. Treatment of 2 with Bu-,SnH/AIBN in refluxing benzene provides the tricyclic spiro ketone 3 together with the reduction product 4. 

Spiroannelationf A spirocyclobutan-2-one such as 1, prepared as shown from methylenecyclopcntenc, when treated with Bu3SnH and AIBN (2 cquiv., slow addition) undergoes radical ring expansion to a spirocyclohcptanonc (2). 

Radical ring expansion of cyclohexanones. This reaction is a useful route to medium-size ring systems. Thus the precursor 1, prepared in two steps from cyclohexenone, on treatment with Bu3SnH and A1BN furnishes the cyclodeccnone 2 in 78% yield. 

Scheme 1. Side-chain-incorporated free-radical ring expansion 0...

Free radical ring expansion of a-halo-a-bromoalkylcycloalkanones is synthetically useful. For example, in three steps an a,a-dichlorocyclobutanone is transformed to a cycloheptanone. 

Radical ring expansion of fm of an ring annelated product hecau reaction can be used to append... 

Radical ring expansion of fused cyclobutanones This reaction involves reaction of an ru-bromoalkylchloroketene with an alkene to form a cyclobutanone with an exo side chain. Treatment of this adduct with BuaSnH (AIBN) generates a radical that cyclizes to a ring annelated product because of relief of strain in the four-membered ring. This reaction can be used to append 7-, 8-, or higher-membered rings to appropriate alkenes. 

Macrocyclic 5,E-ethyIeneketones from 3-stannylcyclohexanones Geospecific radical ring expansion... 

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