Radicals, intramolecular additions olefins

It is also worthwhile comparing the intramolecular photochemical cycloaddition reactions of ethylenic aldehydes and ketones with free radical intramolecular additions. For instance, irradiation of 5-hexen-2-one (470) (Scheme 161) in the gas phase gives the oxetane 471 as only cyclized product, as expected from the known photochemical intermolecular reaction between olefins and ketones. If the irradiation is conducted in solution 470 gives 471 (26%) and 472 (18%). With other y,< -unsaturated ketones, the bicyclic compound analogous to 472 may become the major product. With 2-allylcyclanones such as 473 (Scheme 161) bicyclic compounds are obtained (80% yield) as a mixture of 474 and 475, with 475 being the major product, but such compounds are difficult to isolate. " In the same manner, selective irradiation of the carbonyl group of 2-acyl-2,3-dihydro-4/f-pyrans (476) leads exclusively (23% yield) to exo-brevicomin (477) (a sex attractant), neither oxetane formation nor Norrish type II reaction being observed. The formation of the compounds 472, 475, and 477 which was considered as unexpected... 

This reaction is extended to the intramolecular ring closure of the intermediate radical 224 with olefinic or trimethylsilylacetylenic side chains [121]. Cu(BF4)2 is also effective as an oxidant (Scheme 89) [122]. Conjugate addition of Grignard reagents to 2-eyclopenten-l-one followed by cyclopropanation of the resulting silyl enol ethers gives the substituted cyclopropyl silyl ethers, which are oxidized to 4-substituted-2-cyclohexen-l-ones according to the above-mentioned method [123]. (Scheme 88 and 89)... 

After initial one-electron oxidation of 9 to the radical cation 10, intramolecular addition to the olefinic double bond takes place to yield the cyclic radical... 

Intramolecular addition of heteroatom radicals to olefins constitutes a convenient method for the synthesis of heterocycles. The photochemical ring closure reaction of oxyl radical derived from 44 provides access to tetrahydrofuran 45 [95JOC6706]. The regioselectivity in this cyclization is excellent, however, the stereoselectivity is only modest. The stereoselectivity was dependent on the temperature of the reaction. 

Intramolecular addition of vinyl radicals to olefins as a method for heterocycle synthesis has been examined. The vinyl radicals can be conveniently generated from vinyl bromides and samarium(II) diiodide [95JOC7424], The intermediate radical after cyclization undergoes a further electron transfer from samarium to furnish a carbanion which is quenched at the end of the reaction. A samarium(II) diiodide mediated aryl radical cyclization onto a dihydrofuran has been reported [95T8555],... 

Molander and co-workers have studied the stereoselective intramolecular addition of ketyl radicals to olefins [95JOC872]. The ketyl radicals are generated from ketone by treatment with samarium(II) diiodide. A similar reaction sequence using 61 gave only elimination products. 

The generation of ketyl radicals and their intramolecular addition to tethered olefin to obtain cyclopentanol derivatives have also been achieved by Pandey et al. [102] by using such as those shown in Figures 8.2. An interesting application of this strategy is demonstrated by the synthesis of C-furanosides 231 (Scheme 8.64). 

C-C bond formation in inter- or intramolecular additions starting with olefin [ 199, 200], ketyl [201] (generated by PET [202], chemical or cathodic [24, 203] reduction) [204, 205] or imine radical anions [206] has become a versatile method. In general, the intramolecular addition is highly suitable for the construction of five membered rings, less so for six-, and not effective for seven-membered ring formation. 

It has also been shown that Ni complexes can successfully carry out intramolecular or intermolecular electroreductive addition of alkyl radicals to activated olefins. Thus bicyelic ketones 78 and 80 are conveniently prepared in good yields from 2-bromoalkyl-2-cyclohexenone 77 and 3-bromoalkyl-2-cyclohexenone 79, respectively [25]. Alkyl bromides also react with a,) -unsaturated esters and nitriles to give 1,4-addition products in moderate yields [26]. 

In contrast, aminyl radicals complexed to metal ions, such as neutral aminyl radicals, do not undergo Hofmann-Loffler reaction. The Hofmann-Loffler reaction is unable to compete with intramolecular aromatic amination, with intramolecular addition to olefins, and with intermolecular addition to dienes [7],... 

Oxy radicals add to olefins by both intermolecular and intramolecular mechanisms. Experimental evidence has indicated that intramolecular addition (Reaction H) may be much more important than its intermolecular counterpart (10, 11). 

A new approach to construction of 3-aminosugar moieties by stereospecific intramolecular addition of a carbon-free radical to hydrazone 125 derived from crotonaldehyde was recently demonstrated by Friestad. This synthesis, comprising asymmetric dihydroxylation, PhS radical-induced C = N bond alkylation (C-vinylation) and subsequent Wacker oxidation [88] of terminal olefin 128, which afforded L-daunosaminide derivative 129, in overall 32% yield, is outlined in Scheme 23 [89]. 

Except for this last example which involves a Cy3/Cy4 case it is of interest to emphasize that the examples of intramolecular addition to carbethoxy groups so far reported deal exclusively with the formation of (Cy 5) radicals in Cy5/Cy4 cases. This cyclization was already observed with the carbonyl group (Section X.1), but other cyclization modes such as Cy6/Cy5 were also observed. What is particularly striking with the carbethoxy group is that a search for Cy5/Cy6 cyclizations, for example, with the next higher homolog of 205, failed. This is the opposite of the behavior of olefinic bonds and is in disagreement with Baldwin s rules. ... 

Treatment of 3-acylacrylates and 2-acylfiimarates 208 with irifluoroacetic anhydride and PPhs yielded 3,4,5-substituted 2-(trifluoromethyl)furans 209. The plausible mechanism of the reaction includes slow Michael addition of triphenylphosphine to enone fragment with fast trifluoroacetylation of resulted adduct and subsequent intramolecular Wittig olefination. An alternative mechanism via trifluoroacetyl radical arising from interaction of irifluoroacetic anhydride and triphenylphosphine is also possible [133]. 

If the radical addition reaction is performed in an intramolecular fashion, olefin activation with an electron-withdrawing group will not be a prerequisite for C-glycosylation, because the cyclization event competes well with hydrogen abstraction. In such examples, ring size and the stereochemistry of the ring substituents greatly influence the stereoselectivity and efficiency of the cyclization reaction. 

Under these conditions, amine radical cation la is deprotonated to form a-amino radical Ilia, which reacts with the olefin to form radical adduct Ka. Since no external oxidant is present, the adduct radical presumably turns over Ru to Ru and is reduced to the anion. Protonation of the enolate forms the product. For intramolecular additions, dehydrogenation occurs rather than reduction to provide 5,6-dihydroindolo[2,l-a]-THIQs such as 18. 

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