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DOI: 10.1055/s-0039-1691701
Stereoselective and Regioselective Functionalization of Piperidines through C–H Activation
Functionalization of Piperidine Derivatives for the Site Selective and Stereoselective Synthesis of Positional Analogs of Methylphenidate.
Chem. Eur. J. 2020;
DOI: 10.1002/chem.201905773
Publication History
Publication Date:
18 February 2020 (online)
Significance
Davies and co-workers expand on their work in the C–H insertion field by developing a regioselective functionalization of N-protected piperidines for the synthesis of methylphenidate analogues 3, 7, and 11. By variation of the steric and electronic effects of the dirhodium catalysts, C2- and C4-functionalization of piperidines was achieved. C3-functionalization was achieved through an asymmetric cyclopropanation and reductive ring-opening sequence.
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Comment
With increased value in late-stage functionalization of piperidines for biologically relevant compounds, this report describes an effective method for C2-, C3-, and C4-functionalization by varying the dirhodium catalyst. A small library of analogues of methylphenidate has previously been synthesized in moderate to good yields and enantioselectivities (J. S. Markowitz, K. S. Patrick J. Clin. Psychopharmacol. 2008, 28, S54).
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