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Total Synthesis of (±)-Paroxetine by Diastereoconvergent Cobalt-Catalysed Arylation.

Despiau CF, Dominey AP, Harrowven DC, Linclau B - European J Org Chem (2014)

Bottom Line: A total synthesis of paroxetine is reported, with a diastereoselective and diastereoconvergent cobalt-catalysed sp(3)-sp(2) coupling reaction involving a 3-substituted 4-bromo-N-Boc-piperidine (Boc = tert-butoxycarbonyl) substrate as a key step.A 9:1 diastereoselectivity was obtained, while a control experiment involving a conformationally locked 3-substituted 4-bromo-tert-butyl cyclohexane ring proceeded with essentially complete stereoselectivity.

View Article: PubMed Central - PubMed

Affiliation: Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK http://www.southampton.ac.uk/chemistry/about/staff/linclau.page.

ABSTRACT

A total synthesis of paroxetine is reported, with a diastereoselective and diastereoconvergent cobalt-catalysed sp(3)-sp(2) coupling reaction involving a 3-substituted 4-bromo-N-Boc-piperidine (Boc = tert-butoxycarbonyl) substrate as a key step. A 9:1 diastereoselectivity was obtained, while a control experiment involving a conformationally locked 3-substituted 4-bromo-tert-butyl cyclohexane ring proceeded with essentially complete stereoselectivity.

No MeSH data available.


Diastereoconvergent coupling reactions;3a,3b a) FeCl3 (5 mol-%), ArMgBr (1.3 equiv.), TMEDA (1.2 equiv.), THF, room temp., 30 min; b) CoCl2 (5 mol-%), PhMgBr (1.2 equiv.), (R,R)-N,N,N′,N′-tetramethyl-1,2-cyclohexanediamine (6 mol-%), THF, 25 °C, 15 min.
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sch01: Diastereoconvergent coupling reactions;3a,3b a) FeCl3 (5 mol-%), ArMgBr (1.3 equiv.), TMEDA (1.2 equiv.), THF, room temp., 30 min; b) CoCl2 (5 mol-%), PhMgBr (1.2 equiv.), (R,R)-N,N,N′,N′-tetramethyl-1,2-cyclohexanediamine (6 mol-%), THF, 25 °C, 15 min.


Total Synthesis of (±)-Paroxetine by Diastereoconvergent Cobalt-Catalysed Arylation.

Despiau CF, Dominey AP, Harrowven DC, Linclau B - European J Org Chem (2014)

Diastereoconvergent coupling reactions;3a,3b a) FeCl3 (5 mol-%), ArMgBr (1.3 equiv.), TMEDA (1.2 equiv.), THF, room temp., 30 min; b) CoCl2 (5 mol-%), PhMgBr (1.2 equiv.), (R,R)-N,N,N′,N′-tetramethyl-1,2-cyclohexanediamine (6 mol-%), THF, 25 °C, 15 min.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4255755&req=5

sch01: Diastereoconvergent coupling reactions;3a,3b a) FeCl3 (5 mol-%), ArMgBr (1.3 equiv.), TMEDA (1.2 equiv.), THF, room temp., 30 min; b) CoCl2 (5 mol-%), PhMgBr (1.2 equiv.), (R,R)-N,N,N′,N′-tetramethyl-1,2-cyclohexanediamine (6 mol-%), THF, 25 °C, 15 min.
Bottom Line: A total synthesis of paroxetine is reported, with a diastereoselective and diastereoconvergent cobalt-catalysed sp(3)-sp(2) coupling reaction involving a 3-substituted 4-bromo-N-Boc-piperidine (Boc = tert-butoxycarbonyl) substrate as a key step.A 9:1 diastereoselectivity was obtained, while a control experiment involving a conformationally locked 3-substituted 4-bromo-tert-butyl cyclohexane ring proceeded with essentially complete stereoselectivity.

View Article: PubMed Central - PubMed

Affiliation: Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK http://www.southampton.ac.uk/chemistry/about/staff/linclau.page.

ABSTRACT

A total synthesis of paroxetine is reported, with a diastereoselective and diastereoconvergent cobalt-catalysed sp(3)-sp(2) coupling reaction involving a 3-substituted 4-bromo-N-Boc-piperidine (Boc = tert-butoxycarbonyl) substrate as a key step. A 9:1 diastereoselectivity was obtained, while a control experiment involving a conformationally locked 3-substituted 4-bromo-tert-butyl cyclohexane ring proceeded with essentially complete stereoselectivity.

No MeSH data available.