Functionalization of Piperidine Derivatives for the Site‐Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate

Rhodium‐catalyzed C−H insertions and cyclopropanations of donor/acceptor carbenes have been used for the synthesis of positional analogues of methylphenidate. The site selectivity is controlled by the catalyst and the amine protecting group. C−H functionalization of N‐Boc‐piperidine using Rh2(R‐TCPT...

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Veröffentlicht in:Chemistry : a European journal 2020-04, Vol.26 (19), p.4236-4241
Hauptverfasser: Liu, Wenbin, Babl, Tobias, Röther, Alexander, Reiser, Oliver, Davies, Huw M. L.
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Sprache:eng
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Zusammenfassung:Rhodium‐catalyzed C−H insertions and cyclopropanations of donor/acceptor carbenes have been used for the synthesis of positional analogues of methylphenidate. The site selectivity is controlled by the catalyst and the amine protecting group. C−H functionalization of N‐Boc‐piperidine using Rh2(R‐TCPTAD)4, or N‐brosyl‐piperidine using Rh2(R‐TPPTTL)4 generated 2‐substitited analogues. In contrast, when N‐α‐oxoarylacetyl‐piperidines were used in combination with Rh2(S‐2‐Cl‐5‐BrTPCP)4, the C−H functionalization produced 4‐susbstiuted analogues. Finally, the 3‐substituted analogues were prepared indirectly by cyclopropanation of N‐Boc‐tetrahydropyridine followed by reductive regio‐ and stereoselective ring‐opening of the cyclopropanes. Attention, please: Regio, diastereo‐ and enantioselective C‐2, C‐3 and C‐4 functionalization on piperidine ring controlled by catalysts and protecting groups has been employed for the synthesis of positional analogues of methylphenidate (Ritalin).
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201905773