Synthesis of Homochiral 2-(2-Arylethyl)piperazines

Abstract

The synthesis of a series of (S)-2-(2-arylethyl)piper­azines was achieved from (S)-1,4-dibenzyl-2-vinylpiperazine via a tandem hydroboration/Suzuki coupling sequence followed by cleavage of the N-benzyl protecting groups.

Key words

Suzuki reaction - hydroboration - cross-coupling - aryl­ation - palladium

References

• 1 Aicher TD, Chen Z, Chen Y, Faul MM, Krushinski JH, LeHeurou Y, Pineiro-Nunez MM, Rocco VP, Ruley KM, Schaus JM, Thompson DC, and Tupper DE. inventors; PCT Int. Appl. WO  2003082877.  ; Chem. Abstr. 2003, 139, 307804
• 2a Behun JD. Levine R. J. Org. Chem.  1961,  26:  8879 
• 2b Hendrix JA, Strupczewski JT, Bordeau KJ, Brooks S, Hemmerle H, Urmann M, Zhao X, and Mueller PJ. inventors; PCT Int. Appl. WO  2002066468.  ; Chem. Abstr. 2002, 137, 201306
• 3 Tsuda T. Kiyoi T. Saegusa T. J. Org. Chem.  1990,  55:  3388 
• 4a Uozumi Y. Tanahashi A. Hayashi T. J. Org. Chem.  1993,  58:  6832 
• 4b Yamazaki A. Achiwa K. Tetrahedron: Asymmetry  1995,  6:  1021 
• 4c Nakano H. Yokoyama J. Fujita R. Hongo H. Tetrahedron Lett.  2002,  43:  7761 
• 4d Ito K. Imahayashi Y. Kuroda T. Eno S. Saito B. Katsuki T. Tetrahedron Lett.  2004,  45:  7277 
• 5 Miyaura N. Ishiyama T. Sasaki H. Ishikawa M. Satoh M. Suzuki A. J. Am. Chem. Soc.  1989,  111:  314 
• 6a Palani A. Shapiro S. Josien H. Bara T. Clader JW. Greenlee WJ. Cox K. Strizki JM. Baroudy BM. J. Med. Chem.  2002,  45:  3143 
• 6b Guillena G. Kruithof CA. Coasado MA. Egmond MR. van Koten G. J. Organomet. Chem.  2003,  668:  3 
• 7 Ram S. Spicer LD. Tetrahedron Lett.  1987,  28:  515 
• 8a Olofson RA. Martz JT. Senet J. Piteau M. Malfroot T. J. Org. Chem.  1984,  49:  2081 
• 8b

  For those cases in which debenzylation was not complete, the crude reaction product was resubjected to the reaction conditions.