Iodine atom templates

Breslow s template-directed remote oxidation of steroids utilizes an aryl iodide as a template to direct the oxidation of steroid tertiary carbons by the radical relay mechanism, in which a chlorine radical is transferred from a [9-1-2] [PhICl] radical to the iodine atom of the template and then relayed to a geometrically accessible hydrogen atom. This method allows a highly regioselective functionalization of nonactivated carbon atoms of steroids [Eq. (78)] [137,138]. 

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. ... 

Photoinitiated free-radical chlorination of (10) using phenyliodine dichloride is directed exclusively to the C(9) position, probably as a result of the conformation of the steroid placing the C(l) complexed to the template iodine atom close to the C(9) hydrogen. Dehydrochlorination then places a double bond in the C(9)-C(l) position. 

We irradiated a solution of phenyliodine dichloride with the w-iodobenzoate ester 12 of 3a-cholestanol and found that C-9 chlorination occurred selectively, while no such selectivity was seen without the iodine atom on the benzoate ester [37]. Various controls established that we were not simply converting the attached iodoaryl template to its... 

The most extensive studies we have done in geometrically directed functionalizations have involved the template directed chlorination of unactivated C-H bonds. These have been reviewed in detail [6], so only a few examples will be mentioned. The first system examined [7] involved attachment of an iodoaryl group to a steroid substrate, conversion of the iodine atom to an ICI2 group, and free radical chain chlorination. After initiation of the chain a radical was produced carrying a single chlorine on the iodine atom this chlorine then removed a hydrogen atom from the attached substrate. 

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. 

Since this study led to a number of extensions, it is desirable to explain why the process works, and what its advantages are. The rate advantage of a radical relay process is that the hydrogen abstraction is intramolecular, rather than the intermolecular abstraction that would occur without the relay by the template. However, this explains it only in part, since the relaying of a chlorine atom from the radical in solution to the iodine of the template is of course an intermolecular process. Why is the two-step sequence - intermolecular chlorine atom transfer, then intramolecular hydrogen abstraction - faster than an intermolecular hydrogen abstraction by the free radical in solution The answer is relat-... 

Some variants on the simple template-directed chlorination were also developed. For example, a steroid carrying a tethered iodophenyl group was chlorinated by electrolysis of a solution carrying chloride ion [54]. In this case, the electrolysis furnished CI2 in solution to carry a radical relay process and electrolysis also initiated the radical process by one-electron oxidation of the iodophenyl group. As another variant, the radical relay mechanism requires that it be a chlorine atom that attaches to the iodine or pyridine or sulfur to abstract hydrogen, since a complexed bromine atom is not reactive enough, but the new bond to the substrate does not have to be a carbon-chlorine link. That bond is formed by untemplated attack of the substrate carbon radical on a reagent in solution and, with an appropriate sequence of tandem reactions, other atoms can be linked to the substrate. 

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