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...
Gespeichert in:
Veröffentlicht in: | Chemistry : a European journal 2020-04, Vol.26 (19), p.4236-4241 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
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 |