Remote functionalization chlorination

Difluoroiodo)-and (dichloroiodo)arenes Chlorination. Remote Functionalism, of Steroids. Fluorination. Further Transformations. 

Remote chlorination (6, 298-300). Breslow has extended his remote functionalization of steroids to a double functionalization at C, and Cn of cholestanol. Thus the ester (2) of cholestanol, prepared from a p-iodophenylnicotinic acid, when treated with 1 (1.2 equiv.) is chlorinated selectively at C9 chlorination of the same ester with 3 equiv. of C6H5IC12 results in chlorination at C9 and at C17 in quantitative yield. The para-iodo group of the ester plays an important role in this remote chlorination. 

The majw work to date on synthetic applications of remote functionalization has involved free radical chlorination. The earliest studies involved the direct attachment of aryliodine dichloride units to the steroid substrates, then intramolecular free radical chain chlorination in benzene or chlorobenzene solution (Scheme 14). Yields were only in the 50% region, but fairly good selecdvities were observed compound (6) afforded chiefly the 9-chloro derivative, while compound (7) produced the 14-chloro steroid. The yields and selectivities were considerably improved when it was realized that aromatic solvents promote intermolecular random processes by forming complexes with C1-, and when the radical relay method was developed. 

Scheme 16. Remote functionalization by a complexed chlorine atom...

Remote functionalization of steroids (4,264-265 5,352-353). Breslow et al have modified their earlier procedure for chlorination of steroids at C9 or Ci4 by use of an external source of chlorine radicals, lodobenzene dichloride or sulfuryl chloride. Thus irradiation of the m-iodobenzoate of 3a-cholestanol (1) and lodobenzene dichloride in methylene chloride for 28 min. at 25° followed by saponification and acetylation leads to a mixture of 3a-cholestanyl acetate (18.4%) and the acetate of A -cholestene-3a-ol (2, 66%). Application of the... 

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]. 

A well-known but relatively seldom used strategy for the selective functionalization of nonactivated centers is remote chlorination . In the first experiments the oxidizing reagent was covalently attached to a sterol as an ester. An improvement since has been the development of a true turnover catalyst by an ion-pair association procedure188. 

In an undivided cell the yields are reduced substantially. Methyl hexanoate gave (co — 1) and also some (co — 2) products. The selectivity of the reaction is reminiscent of the ester chlorination with N-chloro amines . In the anodic oxidation, however, carbocations seem to be involved, being formed most remote from the ester function. In suitable cases carbocation rearrangements are observed. 

The chlorination of [MePhSi]n leads to a reactive group that is remote with respect to the main silicon chain. It is possible to modify the resulting functional polysilane in many ways. For example, recently Sakata and his research group have utilized this approach to anchor tetraphenylporphyrin units as pendant groups on the polysilane backbone (Fig. 7.21). It was observed that in this polymer an intramolecular charge transfer occurs from the silicon main-chain to the porphyrin side-chain [66]. 

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