Templated radical macrocyclization

Two distinct but related strategies that rely on templates to control the number of monomers incorporated into an oligomeric product can be envisioned. One of these approaches, shown in Scheme 8-2, relies on templated radical macrocyclization reactions to control telomer size [14, 15]. This strategy requires attachment of all of the monomer units to the template backbone and uses macrocyclization, which faces competition from intermolecular chain transfer, to control the telomer length. The chain transfer agent T-I (i.e., telomerization terminator) is not attached to the template. 

One approach to oligomer control in a free-radical polymerization utilizes bound monomers and relies on templated radical macrocyclization reactions. Successful execution of this strategy requires that cyclotelomerization effectively compete with intermo-lecular chain transfer. Scheme 8-2 in Section 8.1 depicts this chemistry schematically wherein radical addition (A), cyclization (C), and chain transfer (T) provide an =3 telomer. The key macrocyclizations (cyclotelomerizations) must precede chain transfer. These transformations are well precedented by systematic investigations of free-radical macrocyclizations that appeared in the 1980s [19-23] and by the seminal contributions of Kammerer, Scheme 8-4 [24-34]. 

Exposure of 14 (m = 3, R = rcrf-Bu) to cyclohexyl iodide, allyltributylstannane, and AIBN leads to a macrocycle 15 with two new stereogenic centers. The allyl group provides additional functionality for further transformations and also creates a new stereocenter in the process. In order to effect the desired macrocyclization, addition of the first-formed radical to the proximal acrylamide moiety must be faster than addition to the chain transfer agent allyltributylstannane, a requirement that can be fulfilled under appropriate reaction conditions. Premature chain transfer in this particular system, under conditions that discourage bimolecular reaction between two templates, leads to two simple n = 1 products (vide infra). 

Exploration of the template controlled free-radical oligomerization of other activated olefins began with standard monomers utilized in bulk polymer synthesis and the template 63. Vinyl acetate and acrylonitrile led only to uncontrolled polymerization, while vinylene carbonate did not react under the standard experimental conditions. More exotic monomers, such as vinyl trifluoroacetate and rert-butyl acrylate, were also unsuccessful. Only methyl acrylate polymerization was arrested by template 64 to provide the macrocyclized product 96 in modest yield as a mixture of five diastereomers (Scheme 8-25). Subsequent studies with the more effective thiophenyl-bearing template 63 at lower temperatures improved this yield to 35%. The diastereomer distribution was reminiscent of the methyl methacrylate-derived product, although no stereochemical assignments were made in this case either. 

This curious observation refocuses concerns about yield loss to a critical choice that a template-bound pMMA radical 99 faces macrocyclization to afford the controlled-... 

These four experiments were designed to test two related hypotheses (1) in an actual template system, bimolecular termination is suppressed as a consequence of the demanding steric environment about the terminator moiety. Observation of greater macrocycle yield with the bulkier terminator 107 present compared with the smaller analogue 106 in either solvent, given that these species have equivalent intrinsic reactivity with a small radical, would support this premise. (2) More pronounced solvent-solute interactions in benzene as compared to non-aromatic solvents contribute to favoring intramolecular termination (—> 94) over bimolecular monomer addition 100) for radical 99. Observation of rela-... 

These data can be recast to expose the differing effects of solvent on yield suppression with each terminator (Scheme 8-30). With either 106 or 107, the yield of macrocycle 94 was greater in benzene than in methyl isobutyrate. Thus, intermolecular trapping of an intermediate template-bound radical is less significant in benzene than in methyl isobutyrate. In these experiments, the differences are large (-20%) and suggest that a template-bound radical (e.g., 99) is not as accessible to either added terminator, 106 or 107, in benzene as it is in methyl isobutyrate. 

Cleavage of the C-C bond becomes possible imder these reaction conditions because the protonated aromatic radical is quite a stable group. The subsequent fast recombination of the saturated biradicals into a 14-membered macrocycle must be entropically more favourable than seven-membered ring formation by each of them individually. The high yield of the macrocycle LI30 indicates the template role of the metal ion. 

By modification of the Leigh protocol,electron donor Fc derivatives were added to a macrocycle in a fullerene-stoppered rotaxane (Figure 2.34). " The distance from the Fc units to the fullerene was important to increase the lifetimes of the radical pair species, which arise from 9 to 26 ns when a triethyleneglycol spacer was added between the 1,4-diamide template and Moreover, the addition of a component (hexafluoroisopropanol) able to distnrb the hydrogen bonds in the solution decreased the relative distance between the electron donors and the fullerene, together with the lifetimes of the radical pairs, reduced at 13 ns. This, together with other photophysical... 

A related radical-initiated iron-template reaction between l,2-bis(phos-phino)ethane and diallylphosphines gave complex 12 with nonsymmetric 3-methyl-1,4,7-triphosphacyclodecane ligand (Scheme 12.5). This macrocycle is the result of two intramolecular hydrophosphination reactions the first one generates a five-membered (chelate) ring with an exo-methyl group and the second gives a six-membered chelate. 

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