Hydrogen atom transfer reaction conditions

It is important to emphasize that the hydroxy dithioketal cyclization can be conducted under mild reaction conditions and can be successfully applied to a variety of substrates.15 However, the utility of this method for the synthesis of didehydrooxocane-contain-ing natural products requires the diastereoselective, reductive removal of the ethylthio group. Gratifyingly, treatment of 13 with triphenyltin hydride and a catalytic amount of the radical initiator, azobisisobutyronitrile (AIBN), accomplishes a homolytic cleavage of the C-S bond and furnishes didehydrooxocane 14 in diastereo-merically pure form (95 % yield), after hydrogen atom transfer. 

To avoid these stability problems, it is necessary to minimize the proportion of chains that terminate by radical-radical reaction. One way of achieving this is to conduct the polymerization in the presence of an appropriate chain transfer agent. For example, if polymerization is performed in the presence of a H-donor chain transfer agent, conditions can be chosen such that most chains terminate by hydrogen-atom transfer. Bagby et al.iA examined the thermal stability of PMMA formed with dodecanethiol. These polymer chains will then possess, more... 

Taskinen and Nummelin (op. cit.) reported many other isomer equilibria in their paper. Most of these used cyclohexane as the solvent and I2 as the catalyst and so are not confounded by solvent effects. However, these authors noted that hydrogen atom transfer induced disproportionation (to form the aromatic benzene) dominates this reaction for the case of 49/50 isomerization and so they needed alternative reaction conditions. 

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

The hydrogen atom transfer method is most useful for electrophilic radicals (for example, malonate, acetoacetate, etc.). Because radicals are generated from C—H bonds, the preparation of cyclization precursors by alkylation is routine. The hydrogen atom transfer method is very good for conducting slow cyclizations. In addition reactions, the hydrogen donor is typically used in large excess relative to the acceptor to facilitate H-transfer however, cyclizations must use different conditions because the H-donor and the alkene acceptor are in the same molecule. 

Iodine atom transfer reactions between alkyl radicals and iodocarbonyls are very rapid (107 M-1 s-1 to 109 M-1 s-1).130 This means that, even when these iodides are cyclized by the tin hydride method, iodine atom transfer may supersede hydrogen transfer, and the reductively cyclized product will ultimately be derived from the reduction of a cyclic iodide. Tin hydride cyclizations of halocarbonyls also often require very low concentration to avoid reduction of the initial radical prior to cyclization. For these reasons, reductively cyclized products are best formed by atom transfer cyclization at high concentration, followed by reduction of the product in situ. In a recent full paper, we have described in detail the preparative and mechanistic features of these cyclizations,19 and Jolly and Livinghouse have reported a modification of our reaction conditions that appears to be especially useful for substrates that cyclize very slowly.131 Cyclizations of a-iodocarbonyls can also be promoted by palladium.132... 

Unsymmetrical disubstituted hydrazines (1,1-diphenylhydrazine and 1,1-dimethylhydrazine) do not exhibit a detectable reaction with O2"- in the gas phase nor in Me2SO within approximately 10 min. This is consistent with the hypothesis that only those substituted hydrazines with a secondary amine function react with O2 - by hydrogen-atom transfer. Although there is a report that 1,1-diphenylhydrazine reacts with superoxide ion to produce N-nitrosodiphenylamine, such a product is more consistent with a peroxide reaction (a likely possibility for the reaction conditions). 

A delocalized 0-stannyl radical anion can also be generated from the reaction of an a,/ -unsaturated ketone or aldehyde with tributyltin hydride and radical initiator AIBN [3, 4, 5a, 5b]. Thus, a,/ -unsaturated carbonyl compound 4 (R or R = H or alkyl), can be reacted with wBu SnH under standard free-radical conditions to give allylic O-stannyl ketyl species (5 6), shown in Scheme 2. After hydrogen atom transfer to the -position of 6, a synthetically useful tin(IV) enolate is produced [5b, 5d, 5g. Allylic 0-stannyl ketyls have both one- (radical) and two-electron (anionic) sites for reactivity. These reactions can proceed in a sequential manner - a rapidly-evolving methodology in organic synthesis [2, 5, 8j. If the one-electron reactivity in 6 is used with a radicophile, then the tin enolate or two-electron reactivity can be used in reactions with suitable electrophiles (E ). Note that the carbonyl species. 

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