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DOI: 10.1055/s-2006-948208
Synthesis of 3,5-Disubstituted Piperazinones via Palladium(II)-Catalyzed Amination
Publikationsverlauf
Publikationsdatum:
09. August 2006 (online)
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Abstract
The synthesis of 3,5-disubstituted piperazinones has been achieved in quantitative yields via an intramolecular palladium(II)-catalyzed allylic amination in the presence of LiCl and without a reoxidizing system. These conditions, that allow higher diastereoselectivities than those reported earlier using Pd(0), are associated to a different and irreversible process. Conveniently, the stereoselectivity is reversed if the reaction is performed in the absence of LiCl.
Key words
palladium - amination - ring-closure - stereoselectivity - piperazinones
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References and Notes
In this case, catalytic amounts of Pd(OAc)2 can be used since the cyclized organopalladium intermediate evolves via deacetoxypalladation rather than dehydropalladation.
11Pd(OAc)2 (45 mg, 0.2 mmol.) and LiCl (212 mg, 5 mmol) were added to a solution of precursor 1 (445 mg, 1 mmol) in dry DMF (20 mL) under argon atmosphere. After 4 h of stirring at 80 °C, the reaction mixture was cooled to r.t. and Et2O (100 mL) was added. The organic phase was washed three times with H2O (50 mL). The organic phase was dried over MgSO4 and concentrated under reduced pressure. Flash chromatography gave the pure piperazinone as a pale yellow oil (376 mg, 98%). Spectral data were in agreement with those previously reported by us. See ref. 8.
12In the absence of palladium sources, quantitative recovery of starting material is observed.
14An equimolar mixture of the isolated piperazinone trans-12 and its precursor 6 was deliberately chosen for this test in order to reproduce the original reaction conditions. Indeed, interaction between the precursor and the catalytic system, such as reduction to a Pd(0) species, cannot be ruled out.