Double cyclization regioselective generation

If a radical is joined to a double bond by a chain of three or more carbons, intramolecular addition generates a ring. The regioselectivity of such additions is governed more by stereoelectronic factors than by substituents on the double bond. Thus, five-membered ring formation byway of a l°-cyclized radical dominates the products, as shown in Scheme 2.47. 

The pentacyclic triterpene skeleton hopane is generated by 2,7-, 6,11-, 10,15-, 14,19-, and 18,22-cyclization of the carbenium ion in a fivefold chair conformation (as drawn) arising from regioselective protonation of the 2,3-double bond of squalene (but not of the 2,3-epoxide). This explains why hopanes are usually not hydroxylated in the 3-position. 

An intermediate of potential use in the synthesis of macrocyclic antibiotics has been obtained starting from allylic and homo-allylic alcohols. The anions generated with BuLi react with carbon dioxide to give the transient anion (60) which cyclizes in the presence of iodine. Functionalization of the double bond is highly regioselective and the equatorial stereochemistry of the 6-membered example (61, n = 1) has been established by n.m.r. spectroscopy. 

As far as regioselectivity goes, one notices that the general mode of cyclizations follows the so called exo route, which generates only exo double bonds as in 427 and 430. 

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