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Functionalization of Piperidine Derivatives for the Site‐Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate
Author(s) -
Liu Wenbin,
Babl Tobias,
Röther Alexander,
Reiser Oliver,
Davies Huw M. L.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905773
Subject(s) - piperidine , stereoselectivity , chemistry , cyclopropanation , stereochemistry , selectivity , amine gas treating , surface modification , regioselectivity , rhodium , catalysis , organic chemistry
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 Rh 2 ( R ‐TCPTAD) 4 , or N ‐brosyl‐piperidine using Rh 2 ( R ‐TPPTTL) 4 generated 2‐substitited analogues. In contrast, when N ‐α‐oxoarylacetyl‐piperidines were used in combination with Rh 2 ( 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.