Cyclized radicals, steric factors

Entry 11 involves generation and cyclization of an alkoxymethyl radical from a selenide. The cyclization mode is the anticipated 5-exo with a cis ring juncture. This is a case in which the electronic characteristics of the radical are not particularly favorable (ERG oxygen in the radical), but cyclization nevertheless proceeds readily. The reaction in Entry 12 was used to prepare a precursor of epibatidine. Entry 13 shows a 6-endo cyclization that is favored by steric factors. The 6-endo cyclization is also favored with a tetrahydropyranyloxy substituent in place of the ester, indicating that the electronic effect is not important. Entries 14 to 16 involve acyl radicals generated from selenides. The preferred 6-endo cyclization in Entry 15 is thought to be due to the preference for the less-substituted end of the double bond. Entry 17 is an example of a 5-exo-dig cyclization. 

A final feature of radical cyclizations is that they are mainly influenced by steric factors and are practically insensitive to inductive effects. Since free radicals are charge neutral, dieir reactivity is not greatly influenced by either electron-donating or electron-withdrawing groups. For instance, the following cyclizations occur widi similar efficiencies even diough the electronic character of the cycliz-ing radicals are vastly different ... 

The pent-l-en-5-yl radical does not cyclize in any of the matrices. Non-terminal addition would involve very severe steric factors and necessitate the formation of a cyclobutyl structure which would be highly strained. Addition to the terminal end to form the cyclopentyl radical might be expected to occur but steric models again show that approach in the plane of the 77-orbital is impossible and that only approach in the nodal plane can occur. 

From a synthetic point of view, the regioselectivity and stereoselectivity of the cyclization are of paramount importance. As discussed in Section 12.2.2 of Part A, there is usually a preference for ring formation in the order 5 > 6 > 7 because of stereoelectronic factors.234 The other major influence on the direction of cyclization is the presence of substituents. Attack at a less hindered position is favored, both by steric effects and by the stabilizing effect that most substituents have on a radical center. For relatively rigid cyclic... 

Reaction outcomes have been reported for 1,6-hexadiene (W=CH2, X=Br, I), diallyl sulfide (W=S, X=Br, I), diallyl ether (W=0, X=Br, diallyl sulfone (W=S02, X=Br, I), diallylmalonates [W=C(C02R)2, X=C1, Br, ], diallyl sulfonamide (W=N-Ts, X=C1, Br), and diallyl carboxyamide (W=N-C02R, X=C1, Br, ). Changing the steric and electronic character of the olefins can infiuence the regiochemical outcome in these systems. Less-substituted olefins (eq 3), electron-rich acetylenes (eq 4), and allenes (eq 5) react preferentially. Bis-allenic and 1,6-diyne systems also undergo radical cyclization. These factors are exemplified below. 

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