Radical relay chlorination

The templates can be simply coordinated rather than attached. For example, complex 100 directed the radical relay chlorination to C-9, although the process was not as clean as with the attached templates [173]. We also used template-directed chlorina-tions to determine the conformations of flexible chains, just as we had previously with the benzophenone probes [174]. Also, by use of a set of tandem free radical chain reactions we could direct the formation of carbon-bromine and carbon-sulfur bonds, again with geometric control by the attached template [175]. 

The selectivity of the radical relay chlorination is striking. In the case of the enone (13 Sdieme 18), and in related compounds with A-ring dienones, the m-iodobenzoate template at C-17 directs chlorination to C-9 and not to die preexisting functional groups of (13). The selective chlorination of C-9 seems to be quantitative, although in the first report the A "Lalkene (14) was isolated in only 77% yield. Later work has shown that the overall introduction of this double bond can have yields in the 90-93% range, and good yields for this reaction have also been reported from another laboratory. Template-directed radical relay chlorination on the a-face of steroids has also been successful in the a/b cu-coprostanol steroid series,and in the cholestanol series with iodophenyl templates linked by amide, ether, or sulfonate functions rather than carboxylic esters. ... 

Binding of Cl- to an aryl iodide may well involve sp d hybridization at iodine to accommodate the ninth electron, but the involvement of a d-oibital in bonding at sulfur is more controversial. Recently it was discovered that even first row elements can form Cl- complexes the evidence indicates that th complexes utilize three-electron bonds, not d-orbitals. Best explored are templates for radical relay chlorination using nitrogen atoms. 

Template-catalyzed remote chlorination reactions have also been examined in molecular complexes. In one early study (Scheme 24), ion pairing was used to hold a charged template near a chaig substrate. Selective catalyzed radical relay chlorination was observed, but the selectivity was not as good as has been seen when the template is covalently attached to the substrate. In more recent work better selectivity and some catalytic turnover has been observed. 

Catalytic turnover has also been seen in radical relay chlorinations in which the template is temporarily linked to the substrate in a mixed metal complex. The steroid phosphate (22) and catalytic ligand... 

Catalytic turnover has also been seen in radical relay chlorinations in which the template is temporarily linked to the substrate in a mixed metal complex. The steroid phosphate (22) and catalytic ligand (23) both bind to zinc in a mixed complex, and the iodine atom of (23) directs chlorination of (22) at C-9 with reasonable selectivity (Scheme 25). Five or more turnovers are seen, when only 10% of the catalyst (23) is used. ... 

We also attached three steroid substrates to an iodophenyl template in 16 (Scheme 6-7) using a tris-silyl ether link, and saw that the template could direct selective radical-relay chlorination to all three tethered substrate species in the same work we reported a similar finding when a thiophene ring was the triply tethered template [49]. Thus the sulfur atom of thiophene can perform radical relay. In these triple catalytic functionalizations, the more reactive sulfuryl chloride was the preferred reagent. 

We have largely been describing reactions on steroid substrates, which are conforma-tionally rigid and permit selective functionalizations by appropriate tethered templates. However, when the templates are linked to flexible chains, the results can be used to learn about the conformational preferences of such flexible chains. In one study [56], we examined the positional selectivities of insertion reactions into flexible chains by attached benzophenone units, a process we had also examined earlier [31], and compared the results with those from the intramolecular chlorination of such flexible chains by attached aryliodine dichlorides. The results were complementary. In another study [57] we used long-chain alkyl esters of nicotinic acid in radical relay chlorination, and saw some interesting selectivities reflecting conformational preferences in these nominally flexible cases. 

The sulfur atom of thiophene can function as a template for radical-relay chlorinations. An excellent application of this concept is in the regiospecific chlorination of a steroid molecule <82JA2045>. Reaction of (2-thienyl)trichlorosilane with 3a-cholestanol gave the tris(cholestanyl)-silylether (623). When this was irradiated in CH2CI2 solution with 2 equiv. of sulfuryl chloride and a catalytic amount of AIBN, the 9(1 l)-olefin was produced in 45% yield after alkaline hydrolysis and elimination of HCl. Apparently, a chlorine atom becomes attached to the sulfur of the thiophene ... 

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