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Functionalization of Piperidine Derivatives for the Site-Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate.

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-?-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.

SUBMITTER: Liu W

PROVIDER: S-EPMC7187323 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Functionalization of Piperidine Derivatives for the Site-Selective and Stereoselective Synthesis of Positional Analogues of Methylphenidate.

Liu Wenbin W Babl Tobias T Röther Alexander A Reiser Oliver O Davies Huw M L HML

Chemistry (Weinheim an der Bergstrasse, Germany) 20200309 19

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 combina ...[more]

PMID: 31873946

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