In radical cyclization

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,... 

Several functional groups containing carbon-nitrogen double bonds can participate in radical cyclizations. Among these are oxime ethers, imines, and hydrazones.337 Hydrazones and oximes are somewhat more reactive than imines, evidently because the adjacent substituents can stabilize the radical center at nitrogen.338 Cyclization at these functional groups leads to amino- substituted products. 

The major product of the keto olefin cyclizations often corresponds to what one would predict, assuming the intermediate ketyl behaves like the corresponding monoradical (Eq. 34). For example, given an option between a 5-exo and a 6-endo-trig cyclization, the former predominates in radical cyclizations [51], and constitutes the exclusive cyclization path in the electrochemical counterpart, 110 - 112 [47]. In addition, the stereochemical outcome parallels that of the radical... 

For a study of facial selectivity and regio- and stereo-control in radical cyclizations of related chiral enamides, see A. G. Schultz, P. R. Guzzo and D. M. Nowak, J. Org. Chem., 1995, 60, 8044. 

The a-silyloxy alkyl radical generated by the addition of (TMS)3Si radical to the aldehyde moiety of 45 has been employed in radical cyclization of (3-aminoacrylates (Reaction 7.53) the trans-hydroxy ester and the lactone in a 2.4 1 ratio were the two products [62]. 

The chemistry of 5-methylene-2,2-dimethyl-l,3-dioxane derivatives in radical cyclizations (Equation 36, Section... 

C. Lesueur, R. Nouguier, M. P. Bertrand, P. Hoffmann, and A. De Mesmaeker, Stereocontrol in radical cyclization on sugar templates. Tetrahedron 50 5369 (1994). 

Cyclization of unsaturated enol silyl ethers.1 Oxidation of certain 8,8- and 8,p-unsaturated enol silyl ethers with either CAN or Cu(OTf)2 can result in radical cyclization. 

The group of activated olefins, which has so far probably received most attention in radical cyclizations, are enamides. Syntheses of various natural products, especially alkaloids, have been successfully completed using this strategy. Cyclizations onto enamides of the 6-endo type led to erysotrine [76] and lycorine alkaloids [77-79]. The skeleton of hydroapoerysopines [80] was successfully constructed by a 1-endo cyclization. Two new examples of radical tandem reactions, which commence with a 1-endo type cyclization, have appeared in recent literature. Construction of the cephalotaxine core structure 29 was achieved from enamide 30 in only one step (Scheme 11) [81]. 

Moreover, it was demonstrated that not only alkenes may serve as radical acceptors in radical cyclizations. Substrates with polar carbonyl and cyano groups afforded cyclic alcohols and ketones in 30-87% yield [146, 159]. 

Example 5.6. exo and endo ring closure in radical cyclization. 

Aryl radicals participate in radical cyclization reactions when the aromatic ring has an alkene or alkyne substituent. o-Iodo aryl allyl ethers cyclize to benzofuran derivatives, for example, when treated with AIBN, aqueous H3PO2 and NaHCOs in ethanol. Cyclization of an o-bromo-A-acyl aniline (a methacrylic acid derivative) with AIBN/BusSnH gave an indolone under the typical conditions used for cyclization of alkenes. 

The first directed application of the phenomenon toward high-yielding organic synthesis is due to Studer.4-81 He employed the reversible dissociation of alkoxyamines for the generation of cyclized derivatives to avoid the usual use of tin—organic compounds in radical cyclizations. One example is shown in Scheme 23. 

In radical cyclizations of 134 the ratio of the finally formed cis- and trans-cyclopentanes cis- and trans-141 is normally 3.8 91). If l-methyl-5-hexenyl halides 136 PC = Cl, Br) are reacted with Na+ N" in dimethoxyethane (DME) or THF at room temperature the ratio varies between 0.62 and 2.8 for sodium mirror reactions the cis/trans ratio of 141 can be as low as 0.32 96). This suggests that under the reaction conditions, 1-methyl-5-hexenylsodium also cyclizes, with a trans preference, giving [(2-methylcyclopentyl)methyl]sodium trans-139, M+ = Na+. Most of the other anion cyclizations show a similar strong trans preference 94). 

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