Functionalization of Piperidine Derivatives for the Site-Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate
Open Access
- 1 April 2020
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 26 (19), 4236-4241
- https://doi.org/10.1002/chem.201905773
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 Rh-2(R-TCPTAD)(4), or N-brosyl-piperidine using Rh-2(R-TPPTTL)(4) generated 2-substitited analogues. In contrast, when N-alpha-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.Funding Information
- National Science Foundation of Sri Lanka (CHE-1700982, CHE 1531620, CHE 1626172)
- National Institutes of Health (GM099142)
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