Amino protecting groups with tosyl function

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

The tosyl group has been used for protection of side-chain amino as well as of a-amino groups (see Section 2.1.1.5). The resulting tosylamides are very stable functionalities, resistant to acid, base, and nucleophiles. They are usually prepared by reacting an amine with tosyl chloride in the presence of base. Traditional removal requires use of sodium in liquid ammonia, which can lead to unwanted side reactions. The photochemical electron transfer reaction discussed above allows for the mild removal of the tosyl protection. No cleavage of peptide bonds or Boc groups has been observed under these conditions. 

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