Bromoamines, from amines

The Hofmann-Loeffler-Freytag reaction has been described with A-chloro-as well as A-bromoamines—the former however usually give better yields. A-chlorinated primary amines react well in the presence of Fe-(II) ions. Just like the Barton reaction, the Hofmann-Loeffler-Freytag reaction has been applied mainly in steroid chemistry. An interesting example from alkaloid chemistry is the synthesis of nicotine 12 by Loeffler ... 

We considered A-bromoamines which generated in situ from the reaction of NBS and various amines, should promote the o/t/io-dibromination of phenol. The results of the bromination with NBS in the presence of amines are summarized in Table 2. 

The mechanism of the orf/to-dibromination of phenol with NBS in the presence of amines is considered as follows. The hydrogen bonding between phenol and N-bromoamine which are generated from the reaction of NBS and amines (ref. 14), is the driving force, and causes the bromination at one o/t/io-position of phenol and regeneration of the amines. A catalytic amount of the amines is enough because of the regeneration of the amines. The repetition of the above process causes one more substitution at the other orf/io-position of 2-bromophenol. In the cases of 2-substituted phenols the orf/io-bromination can occur only once (Scheme 5). 

Diastereoselective 1,2- and 1,4-Additions of Chiral Aminals. The organolithium reagent derived from a chiral bromoaminal and BuLi adds to pentanal to afford an optically active lactol. Subsequent oxidation affords the optically active lactone with 88% ee (eq 3). ... 

The reduction of carboxylic acids by lithium in methylamine can be stopped at the imine stage the imines can be further reduced to secondary amines. Diamines are available from 2- or 3-bromoamines via the corresponding phosphoramides (Scheme 108) the flexibility of this route has been enhanced by the demonstrated potential of the intermediate / -aminophos-phoramides to undergo alkylation. 

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