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 A(1,3) strain.
D000586:Amination; D002384:Catalysis; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D010879:Piperazines; D010165:Palladium