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Regioselective difunctionalization of pyridines via 3,4-pyridynes.

ABSTRACT: A new regioselective 3,4-difunctionalization of 3-chloropyridines via 3,4-pyridyne intermediates is reported. Regioselective lithiation of 3-chloro-2-ethoxypyridine and a related 2-thio-derivative followed by treatment with aryl- and alkylmagnesium halides as well as magnesium thiolates at -78 °C produced 3,4-pyridynes during heating to 75 °C. Regioselective addition of the Grignard moiety in position 4 followed by an electrophilic quench in position 3 led to various 2,3,4-trisubstituted pyridines. This method was adapted into a continuous flow set-up. As an application, we have prepared a key intermediate for (±)-paroxetine.

SUBMITTER: Heinz B

PROVIDER: S-EPMC8098683 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Regioselective difunctionalization of pyridines via 3,4-pyridynes.

Heinz Benjamin B Djukanovic Dimitrije D Filipponi Paolo P Martin Benjamin B Karaghiosoff Konstantin K Knochel Paul P

Chemical science 20210325 17

A new regioselective 3,4-difunctionalization of 3-chloropyridines via 3,4-pyridyne intermediates is reported. Regioselective lithiation of 3-chloro-2-ethoxypyridine and a related 2-thio-derivative followed by treatment with aryl- and alkylmagnesium halides as well as magnesium thiolates at -78 °C produced 3,4-pyridynes during heating to 75 °C. Regioselective addition of the Grignard moiety in position 4 followed by an electrophilic quench in position 3 led to various 2,3,4-trisubstituted ...[more]

PMID: 33996011

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