Hydrogen Transfer and Cyclization

While often considered undesirable pathways in the past, radical hydrogen transfers have also been shown to constitute intriguing possibilities for organic synthesis. Curran has for instance defined the concept of protection and radical translocation (PRT) groups, fii this context, 2-0-(2-bromo-aryl)dimethylsilyl ethers, aryl amides and 2-bromo-4-methoxyphenyl ethers 

We observed that vinyl radicals show exquisite reactivity for efficient and chemoselective H-abstraction [64]. The resulting translocated radical can then undergo various types of inter- or intramolecular transformations. Interestingly, we have also shown that the hydrogen transfer step can serve as a driving force for the unfavorable 4-exo-dig mode of cychzation [65]. 

A bromobenzyl moiety is a versatile moiety for triggering radical translocations. When it is attached to a nitrogen atom, the resulting cz-amino radical can be an interesting intermediate for alkaloid synthesis as demonstrated by Jones in an elegant approach to the ABCE-rings of the Aspidosperma and Strychnos families [75]. 

Our continuing interest in the radical cyclization processes involving carbonyl derivatives has brought new insights to the light [76]. While non- 

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When methanol is reacted on HZSM-5 zeolites, and hydrogen transfer and cyclization is avoided, then instead of producing aromatic gasoline, the process is directed to the production of light olefins (213,214). Different 8 MR zeolites (215,216) have been used to convert methanol to olefins and the results obtained (217) are compared in Table 13 with those obtained with ZSM-5 zeolite. 

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... 

In the course of the reaction, Michael adduct 43 cyclizes initially under base catalysis to the dihydropyridone 45, which forms dianion 46. Electron transfer (an SET process leads to radical anion 47, which is finally transformed into pyridone 44 through an aromati/ation that includes hydrogen transfer and another SET process. 

A highly diastereoselective radical cascade involving addition of a phenylthiyl radical to a terminal alkyne followed by a [1,5]-hydrogen transfer and a 5-exo-cyclization (g) has been reported (Scheme 112).165... 

Photocyclization of the toluquinone (446) to (447) has been reported. The mechanism favoured by the authors involves intramolecular hydrogen abstraction, proton transfer, and cyclization. 

As shown in Scheme 6.54, the mechanism of this process starts with the formation of imine 371, from compounds 368 and 369. Then, imine 371 is attacked by enamine 367. After proton transfer and cyclization, product 370 is obtained. The pure jyn-stereoselectivity is assumed over the hydrogen bond of intermediate 373. 

This approach has been further developed to encompass polycyclic compounds. The reaction proceeds by a sequential 5-exo-digonal cyclization, followed by 1,5-hydrogen transfer, and then... 

Wawzonek et al. first investigated the mechanism of the cyclization of A-haloamines and correctly proposed the free radical chain reaction pathway that was substantiated by experimental data. "" Subsequently, Corey and Hertler examined the stereochemistry, hydrogen isotope effect, initiation, catalysis, intermediates, and selectivity of hydrogen transfer. Their results pointed conclusively to a free radical chain mechanism involving intramolecular hydrogen transfer as one of the propagation steps. Accordingly, the... 

The rare [1,4] hydrogen transfer has been observed in radical cyclizations. With respect to [1,7] hydrogen shifts, the rules predict the thermal reaction to be antarafacial. Unlike the case of [1,3] shifts, the transition state is not too greatly strained, and such rearrangements have been reported, for example,... 

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