Regioselectivity allylic halogenation

The influence of substituents on the regioselectivity of fluorination of allylic alcohols with DAST has been studied and halogenation of the nitrogen of carbohydrate A-acetyl side-chains by HOCl has been monitored. ... 

A simple synthesis of 3-substituted and 23-disubstituted 4-chloiofuians was accomplished. It involves a CuCl/bipy-catalyzed regioselective cyclization of l-acetoxy-2.22-trichloroethyl allyl ether followed successively by dechloroacetoxylation with Zn dust and tandem dehydro-halogenation-aromatization with tBuOK/18-crown-6 <99CC2267>. 

Since enolates also add via a ligand attack process, the regioselectivity that they exhibit is quite comparable to soft caibon nucleophiles. Alkyl or aiyl substituents at the allyl termini direct attack to the less substituted terminus (equations 228-232) functional groups such as COaMe and halogen at one allyl terminus direct attack to the remote terminus (equations 233 and 234). Remote functionalities such as —OR also direct addition to the allyl terminus more removed from the substituent (equations 23S and 236). 

The features of Red-Al are the following It easily reduces halogenated derivatives even if acetylenic (Section 2.1) tertiary amides lead to aldehydes (Section 3.2.8) and propargylic alcohols and amines are reduced to corresponding allylic alcohols and amines (Section 4.1). Epoxides remain intact unless they carry an alcohol functional group at the a position The reduction is then regioselective (Section 2.3). Aromatic nitriles are reduced, but aliphatic nitriles are not affected (Section 4.3). 

We know that the more stable the radical, the faster it can be formed. This means that a hydrogen bonded to either a benzylic carbon or an allylic carbon will be preferentially substituted in a halogenation reaction. As we saw in Section 9.4, bromination is more highly regioselective than chlorination, so the percent of substitution at the benzylic or allylic carbon is greater for bromination. 

Although there is a question of regioselectivity in the initial protonation, the allylic cation is symmetrical and attack by chloride at either end produces the same product. However, if the electrophile is a halogen rather than HCl or HBr then the reaction becomes regioselective as the cationic intermediate is no longer symmetrical. What happens is this ... 

Note that, as always, this combination of chain propagation steps adds up to the observed stoichiometry. This reaction is exactly like halogenation of alkanes, but is strongly regioselective for the allylic hydrogen because of its weak bond. 

Halogenation of a larger alkyl side chain is highly regioselective, as illustrated by the halogenation of ethylbenzene. When treated with NBS, the only monobromo organic product formed is 1-bromo-l-phenylethane.This regioselectivity is dictated by the resonance stabilization of the benzylic radical intermediate. The mechanism of radical bro-mination at a benzylic position is identical to that for allylic bromination (Section 8.6A). 

---