Synthesis of 2,6-Disubstituted Piperazines by a Diastereoselective Palladium-Catalyzed Hydroamination Reaction

A highly diastereoselective intramolecular hydroamination is the key step in a modular synthesis of 2,6-disubstituted piperazines. The requisite
hydroamination substrates were prepared in excellent yields by nucleophilic displacement of cyclic sulfamidates derived from amino acids.
A variety of alkyl and aryl substituents at the 2-position were tolerated. The stereochemistry of the piperazines was determined to be trans
by X-ray crystallography, which also showed the preferred conformation of the 2,6-disubstituted piperazine to be a twist-boat due to A1,3
strain.