6’Endo radical cyclization

P. Mayon and Y. Chapleur, Exclusive 6-endo radical cyclizations of a-silyl radicals derived from carbohydrate allylic silylethers, Tetrahedron Lett. 35 3703 (1994). 

If the products contain an enolizable hydrogen, overoxidation is a concern. When cyclopentanones are involved, the cyclic products are often more rapidly oxidized than the starting materials. However, further oxidation of the cyclic products is not necessarily undesirable. For example, Snider has developed a simple synthesis of phenols in which a manganese(III)-mediated 6-endo radical cyclization is followed by oxidative aromatization.154 An example of this process is provided in Scheme 34. Snider has also shown that the overoxidation can be blocked with a chlorine atom, as shown by the second example in Scheme 34.153... 

There are a number of examples of 6-endo radical cyclization of vinylic ether substrates. For example, Thomas reported synthesis of the tetrahydropyran fragment 76 of bryostatin 1 via radical cyclization reaction of the a-alkoxyacrylate 75, capitalizing on the higher activity of Z-vinyl radicals [51] (Scheme 27). In the syn-... 

As products, the substituted benzoquinones 145 were obtained in moderate to good yields (23-76%). The overall process can be characterized as a vicinal olefin difunctionalization. In the reaction, 5-exo, 6-exo, and 6-endo radical cyclizations are combined with an intermolecular radical capture, and increasing degrees of olefin substitution attenuate the efficiency of the process. 

This strategy was later refined by Stork and co-workers142 who used silicon (e.g. 164) as the tethering atom [Scheme 55a)]. The latter strategy was adapted by Sinay and co-workers143 for the synthesis of C-disaccharides (e.g. 169) by employing 8- and 9-endo radical cyclizations with the readily prepared silaketal connectors [Scheme 55b)]. 

Scheme 34. Construction of the hydroapoerysopine ring system via a 1-endo radical cyclization process...

Endo radical cyclization and removal of the acetal generate a C-linked derivative 272 of the a-L-Fuc(l— 2)-D-G1c dimer. 

Curran, D. P. Synthesis of substituted cyclooctanols by a samarium(ll) iodide promoted 8-endo radical cyclization process. On the stereoselectivity of radical 4-exo-trig-cyclization of optically active ethyl (2E)-6-oxohex-2-enoates with samarium(ll) iodide. Chemtracts Org. Chem. 1994, 7, 351-354. 

Cyclizations of pent-4-enyl radicals are very interesting, because neither the 4-exo trig nor the 5-endo trig cyclizations are considered favorable (Eq. 4). The 4-exo cyclizations are unfavorable because of the strain and rapid opening of the cyclo-butylmethyl radical to pent-4-enyl radical, whereas the 5-endo trig cyclization is disfavored based on Baldwin s rules of ring closures [18]. As in the case of 3-exo cyclizations, neither the 4-exo nor 5-endo radical cyclization reactions were reported in the literature prior to 1988. 

An intramolecular Michael-type 1-endo radical cyclization was reported by Kobayashi and coworkers [35] employing a trifluoromethyl substituted olefin as the internal radicophile. Thus, reaction of the iodide 123 with BuaSnH and AIBN furnished the 1-endo trig cyclized product 124 in 80% yield along with a minor amount of 6-exo trig cyclized product 125. 

Araki and coworkers [20] during their approaches to higher sugars discovered an efficient 1-exo trig cyclization. Reaction of the allofuranose derivatives bromoacry-lates 175 with Bu3SnH and AIBN furnished the bicyclic product 176 via 1-endo radical cyclization in a stereoselective manner. 

Another successful strategy has involved an intramolecular 1,5-hydrogen atom abstraction followed by a 5-endo radical cyclization (Scheme 17) [26]. 

Finally, a 5-endo radical cyclization approach to 5-alkylidene-3-pyrrolin-2-ones has been reported by Tang and Li (Scheme 53 2004OL3229). Treatment of 4-iodo-3-octenoamide 227 (R = Ph) with t-butyl hypochlorite gives 5-(butyhdene)-3-pyrrolin-2-one 228 the same reaction with the corresponding primary amide 227 (R = H) gives the iminoketone 229. 

Justicia J, Oller-Lopez JL, Campana AG, Oltra JE, Cuerva JM, Bunuel E, Cardenas DJ. 1-endo Radical cyclizations catalyzed by titanocene(III). Straightforward synthesis of... 

Radical cyclization of perhydro-l,3-benzoxazines 64, promoted by Bu4SuH in the presence of AIBN gave a mixture of perhydropyrido[2,l-6][1,3]benzoxazin-9-ones 65 and 66 and seven membered tricyclic derivatives 67 and 68, formed in a 6-exo and 7-endo cyclization process, respectively (99TL2421). Cyclization of parent acrylamide 64 (R = R = H) occured with moderate regioselectivity (6-exo/7-endo ratio 65 35) and poor stereoselectivity (65/66 ratio 42 43). The presence of a /3-methyl group in... 

A radical cyclization of a 2-chloroacyl enamine 157 was used to synthesize 2-substituted pyroglutamates 160. Usually, the radical 158 undergoes an initial 5-endo cyclization (path a) and the resulting intermediate 159 attacked electrophiles like methyl acrylate to give the pyroglutamate 160. Unexpectedly, the reaction with methyl methacrylate took another course and a seven-membered... 

Another Lewis acid-catalyzed atom-transfer domino radical cyclization, to produce various bicyclic and tricyclic ring skeletons, has been developed by Yang and coworkers [54]. Reactions of the a-bromo-(3-keto ester 3-125 with Yb(OTf)3 and Et3B/02 led to the bicycle 3-126 in 85 % yield (Scheme 3.33). The reaction proceeds via a (>-endo-Irig and 5-exo-trig cyclization after initial abstraction of the bromine... 

Scheme 3.59. Sevenfold domino radical 6-endo-trig cyclization.

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