5-exo-trig mode

Iodoetherification (vide supra) of ( )-aIlyl alcohols 99 followed by transannular radical cyclization in a 5-exo-trig mode was reported to provide ci s-fused bicyclic acetals with high diastereoselectivities. To illustrate, an example is given below <00SL1193>. 

Most of the results recently reported in this field relate to free-radical cyclisa-tions (Eq. 9) which are useful processes to make mainly five-membered rings via the 5-exo-trig mode, with eventually a given stereochemistry [65] ... 

A convenient preparation of dihydrobenzofurans has been achieved from the appropriately functionalized ort/ o-halophenol derivatives. Treatment of the aryl iodide (5)-33 with (TMS)3SiH and EtsB in the presence of air at room temperature, gave the aryl radical which cyclized in a 5-exo-trig mode and provided the bicyclic derivatives 34/35 as a 29 1 mixture of diastereoisomers in favour of 34 (Reaction 7.40) [51]. 

The ethoxycarbocation intermediate (363) produced by the action of acid on the cyclobutenedione monoacetal (362) has been found to react with bis(trimethylsilyl)-acetylene to afford a 2-methylenecyclopent-4-ene-l,3-dione derivative (365). The authors426 proposed that the rearrangement results from an unprecedented cationic 1,2-silyl migration on the alkynylsilane, subsequent ring expansion via a vinyl cation intermediate (364), and re-closure by intramolecular addition of an acyl cation to a silylallene in a 5-exo-trig mode (see Scheme 90). 

An intramolecular reductive addition of a,a-difluoro acetal radicals to olefins in a 5-exo-trig mode has been reported [95TL3531]. The reaction with the corresponding a-bromo-a,a-difluoroacetates gave no cyclized products. This method provides ready access to a,a-difluoro-y-lactones 34 in good yields. 

The synthesis of a variety of dihydrobenzofuranes can be accomplished via the Aryl SN1 mechanism. The acetone-sensitized irradiation of various o-chlorophenyl allyl ethers in polar solvents affords the aryl cation, which adds onto the tethered double bond following the 5-exo-trig mode leading to (dihydro)benzofurans. The reaction is solvent-dependent, and byproducts are also generally obtained. The best results are found when ethyl acetate is used. Depending on the substrate employed, the cation intermediate can yield products as a result of proton elimination or trapping by chloride ions (Scheme 10.54) [70],... 

Thus indirect electroreduction of haloethers 69 and 71 led to the corresponding cyclized tetrahydrofuran derivatives 70 and 72, respectively, in good yields via 5-exo-trig mode [23], On the other hand, A -allyl-a-bromoamide 73 gave the corresponding pyrrolidone 74 in DMF in the presence of 2 equiv of a hydrogen donor, diphenylphosphine, whereas A -allyl-cx-iodoamide 75 gave the iodinated pyrrolidone 76 in acetonitrile [24],... 

Since the Baldwin mles are not exclusive, disfavored cyclization can take place when the reaction conditions are properly changed. In basic medium the enone form of 2 reacts, and the alkoxy anion approaches the P-C atom of the C=C bond in the disfavored 5-endo-trig mode. In the acidic medium, protonation of the carbonyl group promotes the formation of enol in equilibrium with enone. This reactive species enters cyclization in 5-exo-trig mode (Scheme 7.17). TM 7.10 is isolated in 84% yield on prolonged heating in dichloroethane in the presence of a catalytic amount of p-TsOH. 

Roth expected the phosphorane (112) to react with hetero-allenes to give betaines, after which two modes of cyclization would be possible. However, because of the ability of the sulphur atoms to stabilize the negative charge at the p-carbon, further reaction occurs. The 5-exo-trig mode of cyclization is more favourable than the alternative 6-endo-trig, and facile loss of triphenylphosphine from (113) generates the imidazolidine (114). 

Carbon radicals obtained from thiohydroxamates can also be trapped intramolecularly by unactivated alkene functions especially in the 5-exo-trig mode, as can aminyl radicals generated in the same way better yields of cyclic products are obtained in the presence of a weak acid which presumably protonates the A(-centered radical prior to cyclization (eq 18). ... 

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