Enynes free-radical cyclization

The free-radical cyclization of enynes as a synthetic strategy was introduced by Stork and coworkers using BusSnH/AIBN-mediated ethynyl cyclization (equation 34) ". From a mechanistic point of view, the first step is the selective addition of the stannyl radical to the triple bond of the enyne generating a vinyl radical, which can cyclize onto the double bond. In the absence of the methyl substituents on the olefinic moiety, the groups of Beckwith and Stork have both postulated, and demonstrated with the aid of kinetic studies, that the 6-endo radical 30 arises from a ring expansion of the kinetically favored... 

The rings 77 are available via intramolecular free radical cyclizations catalyzed by Bu"3SnH <2005T2037>, while 78 is available in good yield via a ruthenium-catalyzed cyclisation of an enyne <2002JM09>. 

Tin hydride 2 prepared from hydroxyl acid behaves like the conventional Bu3SnH in standard free-radical reactions, but the tin-containing by-products are easily removed by mild hydrolysis which converts them into base-soluble materials. The performance of these tin hydrides is evaluated for a range of radical reactions involving halides, selenides, Barton-McCombie deoxygenation, and enyne cyclizations.72... 

Insertion reactions using CO and CH2N,2. Radical cyclization reactions of azaenynes in the presence of butyl stannanes in carbonylation conditions furnished /3-lactams <2003JA5632>. Azocanone 150 (Scheme 62) was prepared in good yield from enyne 149. The reaction occurred via a-stannylmethylene lactam of type 154 (Scheme 63). This free radical-mediated stannyl carbonylation is quite versatile and provides a general [ -pl]-type annulation leading to 4-exo and 8-exo systems. The yield of the isolated stannylene lactam intermediate 154 was reported as 61%, while the destannylation to lactam 150 was quantitative. 

The methodology of EtsB-mediated addition of RsSnH to an acetylenic bond has also been successfully applied in the cyclization of enynes . An example is given in equation 35. The use of triphenylgermanium hydride, thiophenol, diphenyl diselenide (equation 36), tris(phenylseleno)borane, Se-phenyl areneselenosulfonates (equation 37) and diphenylphoshine under free-radical conditions induces cyclization of enynes like tributyltin hydride. That is, if the chain-transfer step in Scheme 11 is much faster than the ring expansion, the methylenecyclopentane adduct should be the sole product. 

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