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Functionalization of Piperidine Derivatives for the Site-Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate |
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| Authors: | Wenbin Liu Tobias Babl Alexander Röther Prof. Dr. Oliver Reiser Prof. Dr. Huw M. L. Davies |
| Affiliation: | 1. Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA, 30322 USA;2. Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA, 30322 USA Institute of Organic Chemistry, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany;3. Institute of Organic Chemistry, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany |
| Abstract: | 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. |
| Keywords: | C−H functionalization diastereoselectivity piperidines regioselectivity rhodium |