Asymmetric synthesis of (2R,6R) and (2S,6S)-2,6-dimethylpiperazine

✍ Scribed by John W. Mickelson; E.Jon Jacobsen

• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 179 KB
• Volume: 6
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/0957-4166(94)00341-8

✦ Synopsis

The title compounds were prepared via two efficient routes. The first sequence utilized a diastereospecific triflate alkylation in the key bond forming step while the second method relied on a novel intramolecular Mitsunobu reaction to set the required stereochemistry.

Many pharmaceutical agents contain piperazine derivatives as part of their core smactures. Examples can be found in the quinolone antibiotics, 1 5HT-anxiolytics, 2 HIV protease inhibitors, 3 antihypertensives, 4 and Kreceptor agonists. 5 Thus, the asymmetric synthesis of substituted piperazines continues to be of interest. 6 As part of our ongoing research towards the development of anxiolytic agents containing substituted piperazines, we had the need to prepare both enantiomers of trans-2,6-dimethylpiperazine. Although a synthesis of racemic trans-2,6-dimethylpiperazine was reported by Cignarella and Gallo, it suffered from poor regioselectivity and stereoselectivity. 7 These problems, in combination with a low overall yield, precluded an