Intramolecular free radical addition

An intramolecular free radical addition was used to prepare the 1,2-thiazepine derivatives 30 and 31 from 29 (Equation 6). A further elegant intramolecular radical cyclization was then used to convert 30 to a new aza-bicyclic system with a bridgehead nitrogen <2001JOC3564>. 

The system is also present in the bicyclic molecules, which are formed by intramolecular free radical addition of a phosphine to an alkene. The particular product formed depends on the solvent used (85MI1). Compound 30... 

Intramolecular Free Radical Additions to Acceptor Groups. 167... 

With this information in hand, it seemed reasonable to attempt to use force field methods to model the transition states of more complex, chiral systems. To that end, transition state.s for the delivery of hydrogen atom from stannanes 69 71 derived from cholic acid to the 2.2,.3-trimethy 1-3-pentyl radical 72 (which was chosen as the prototypical prochiral alkyl radical) were modeled in a similar manner to that published for intramolecular free-radical addition reactions (Beckwith-Schicsscr model) and that for intramolecular homolytic substitution at selenium [32]. The array of reacting centers in each transition state 73 75 was fixed at the geometry of the transition state determined by ah initio (MP2/DZP) molecular orbital calculations for the attack of methyl radical at trimethyltin hydride (viz. rsn-n = 1 Si A rc-H = i -69 A 6 sn-H-C = 180°) [33]. The remainder of each structure 73-75 was optimized using molecular mechanics (MM2) in the usual way. In all, three transition state conformations were considered for each mode of attack (re or ) in structures 73-75 (Scheme 14). In general, the force field method described overestimates experimentally determined enantioseleclivities (Scheme 15), and the development of a flexible model is now being considered [33]. 

Radical cycUzation. The intramolecular free radical addition to an aldehyde in order to form a cyclohexanol is induced by PhiSnH-EtjB in the presence of air. 

A simpler case is due to Berson, Olsen, and Walia, who, in 1960, reported an intramolecular free radical addition (Scheme 2). 

In 1960, Julia, Surzur, and Katz published the first of a series of papers dealing with intramolecular free radical additions to olefins.At that time, they reported the results obtained with the intramolecular analog of a reaction described two years earlier, the free radical addition of ethyl cyanoacetate to olefins. The results obtained are summarized in Scheme 5. The reaction was conducted in boiling cyclohexane with BP as initiator and under high-dilution conditions to avoid polymerization the yields of Cy6H products were 51% (R = H), 65% (R = Me), and 78% (R = Et). 

Within a few years, a large number of papers devoted to intramolecular free radical addition reactions appeared, particular attention often being given to the matter of ring size. Before discussing these results we shall first endeavor to analyze and rationalize the behavior of 5-hexenyl radicals. 

At the same time, however, Hobson obtained only (Cy5) and no (Cy6) products from JV-chloro-iV-methylhept-4-enamine with silver salts. His conclusion, developed by further work, was that these products may arise from intramolecular free radical addition of aminyl radicals rather than from nitrenium intermediates. 

Thermolysis of aryl allyl selenides in quinoline leads to a mixture of (Cy5) and (Cy6) compounds, paralleling the results obtained in the thio-Claisen rearrangement. These compounds may arise by intramolecular free radical addition but, as discussed in Section 4.C for the thio-Claisen rearrangement, other pathways must be considered. 

The possibility of intramolecular free radical addition followed by a P-scission process has been proposed to explain some rearrangements. For instance, Reusch proposed that 1,2-acyl shift from 172 to 173 proceeded by a cyclic transition state, corresponding to a Cy3/Cy4 case (Scheme 77). 

In conclusion, intramolecular free radical addition may be a useful method of synthesizing bridged cyclic compounds. From the examples of the Cy5/Cy6 case noted in this section, it may be concluded that a large preference for the (Cy 5) radical formation again exists and that, in some cases, a very high stereoselectivity in the last transfer step may be observed. The same stereoselectivity is often observed in cationic-induced cyclizations. 

An interesting application of the intramolecular free radical addition process to the synthesis of polycyclic terpenes has been described in a Cy6/Cy7 case by Bakuzis (Scheme 126). Irradiation of 324 in the presence of... 

In this section we shall describe some reactions which present many features similar to intramolecular free radical additions, according to the mechanistic probes discussed in the preceding sections. These examples will permit a critical discussion of the use of the free radical intramolecular cycliza-tion probe. 

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