Exo-mode

In the alkylative cyclization of the 1,6-enyne 372 with vinyl bromide, formation of both the five-membered ring 373 by exn mode carbopalladation and isomerization of the double bonds and the six-membered ring 374 by endo mode carbopalladation are observed[269]. Their ratio depends on the catalytic species. Also, the cyclization of the 1,6-enyne 375 with /i-bromostyrene (376) affords the endo product 377. The exo mode cyclization is commonly observed in many cases, and there are two possible mechanistic explanations for that observed in these examples. One is direct endo mode carbopalladation. The other is the exo mode carbopalladation to give 378 followed by cyclopropana-tion to form 379, and the subsequent cyclopropylcarbinyl-homoallyl rearrangement affords the six-membered ring 380. Careful determination of the E or Z structure of the double bond in the cyclized product 380 is crucial for the mechanistic discussion. 

Cycloaddidon of the cychc nitrone derived ftom prolide benzyl ester v/ith alkenes proceeds readily to give isoxazohdines v/ith good regio-and stereoselecdvity fEq 8 47i The reaction favors exo-mode addidon However, certin cycloaddidons are reversible and therefore the product distribndon may reflect thermodynamic rather than kinedc control... 

The results show that the dediazoniations afforded dihydrofuran derivatives which were functionalized exclusively at the site of the cyclized radical (10.58, Z = 0, n = 1) in very good yields for bromination and iodination, and moderate yields for chlorination, phenylthionation, and cyanation. All cyclizations take place in the exo mode, i.e., at the -CH= (second-last) carbon and not at the CH2 group (endo mode for nomenclature see Beckwith et al., 1980). 

More research efforts have focused on the ring-closing enyne metathesis, which usually [176] provides conjugated vinyl cycloalkenes (cf Fig. 2a, exo mode) useful for further manipulation, but also allows tandem metathesis processes for the formation of polycyclic compounds. 

Formation of the intermediate organomercury peroxide 56 was rationalised in terms of an allylic mercuration providing an unsaturated hydroperoxide 55 that can cyclise by the favoured 54) 5-exo mode (equation 42 X = 02CCF3). However, this was not the main reaction pathway and the yields (2.7% and 0.6% of 2,m-10-dibromo-8,9-dioxabicyclo[5.2.1]decanes 54 were an order of magnitude lower than those of the 2,6-dibromides 53 obtained from 1,4-cyclooctadiene. 

Cycloaddition of the cyclic nitrone derived from proline benzyl ester with alkenes proceeds readily to give isoxazolidines with good regio-and stereoselectivity (Eq. 8.47).68 The reaction favors exo-mode addition. However, certain cycloadditions are reversible and therefore the product distribution may reflect thermodynamic rather than kinetic control. 

The product of the previous reaction provides a Baylis-Hillman type product via an intermolecular addition of an allenoate to an epoxide. The first example of a true Morita-Baylis-Hillman reaction of an epoxide has recently been reported <06CC2977>. Treatment of enone 34 with Me3P provides a good yield of the epoxide-opened product 35. The reaction must be carried out at low concentrations in order to avoid the generation of a variety of side products. When the terminal end of the epoxide is substituted (e.g. 34) the exo-mode of cyclization is the only product observed. When the terminal end of the epoxide is unsubstituted (e.g. 36), the endo-mode of cyclization predominates providing 37. 

Disubstituted oxepanes have also been synthesised by (Bu3Sn>20/Zn(OTf)2-promoted cyclization of hydroxy epoxides via an Sn2 process with exo mode selectivity <00TL7697> and <00TL7701>. 

Rate constants at 65°C for ring closure of co-alkenyl radicals in the exo-mode (71) ... 

In addition to nucleophilic reactions, Baldwin s rules also apply to homo-lytic and cationic processes. Table 21 lists rate constants for ring closure of lower -alkenyl radicals (71), in which intramolecular addition to the double bond occurs in the exo-mode (Beckwith, 1981). It is unfortunate that EM-... 

Takasu et al. found that at high temperature a free radical reaction of polyolefinic vinyl iodides leads to phenanthrene derivatives via a 6-endo-6-exo-polycyclization while at low temperature a mono-cyclized product is obtained through a 5-exo mode.1501... 

Free-radical cyclization on to unsaturated CN bonds and also the cyclization of a range of nitrogen-centred radicals have continued to attract interest and have been reviewed. Aryl radicals, generated from BusSnH- or TTMSS-mediated homolytic cleavage of aryl-bromide bonds, have been shown to cyclize on to the nitrogen atom of imidate esters in the 5-exo mode (Scheme 9). Loss of an ethyl radical leads to the observed A-acylindolines. No cyclization in the 6-endo mode was detected. 

On the other hand, the analogous iodo derivative 81 with (TMS)3SiH at room temperature afforded a linear fused five-membered carbo-cycle in two isomeric forms and with an overall yield of 74% (Reaction 7.89) [102]. In this case, the cascade proceeds through 5-cxo, 5-cxo, and 5-exo modes of cyclization. 

The allyloxy and propargyloxy compounds are easily prepared by the opening of mono-substituted epoxides with sodium aryl tellurolates, followed by allylation and propargyla-tion of the obtained -hydroxytellurides, submitted to irradiation with a sun lamp in the presence of hexabutylditin, and suffer group-transfer cyclization under 5-exo-mode to give the 2,4-disubstituted tetrahydrofuran derivatives. ... 

Furthermore, when o-ethynylphenyl methyl ketone 104 (R = Me) was treated with W(CO)5(thf) in the presence of 5 equiv of water, o-acetylacetophenone 123 (R = Me) was obtained in about 50% yield. Direct observation of the reaction mixture inTHF-dg clearly showed the formation of a methyleneisobenzofuran derivative 122 (R = H) at rt. This compound is produced by the exo-mode of attack of the carbonyl oxygen on the W(CO)5-7i-complexed alkyne to give 121 (R = Me), followed by protonation of the C—W bond and deprotonation from the methyl group (Scheme 5.36). 

In the context of the synthesis of naturally occurring product cardamom peroxide (7), radical spirocyclizations of the hydroperoxides 190, 193 and 196 were studied (Scheme 44) . It was found that the DBPO-induced oxidative cyclization of 190 follows the 5-exo-mode to give the spiroendoperoxide 191, which was subsequently converted... 

Many aspects of intramolecular nitrile oxide cycloadditions are similar to those of the intermolecular ones. Due to the proximity of the reacting groups, however, there are also several items that differ significantly. While HOMO-LUMO interactions and steric effects direct the intermolecular nitrile oxide cycloaddition to 1-alkenes to produce 5-substituted isoxazolines, the intramolecular cases often show a different behavior. With most of them, regioselectivity is determined by geometric constraints and cycloadditions occur in the exo mode to furnish the annulated bicycle (Scheme 6.42). 

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