Total Synthesis of (±)‐Paroxetine by Diastereoconvergent Cobalt‐Catalysed Arylation. Issue 20 (27th May 2014)

• Record Type: Journal Article
• Authors: Despiau, Carole F.; Dominey, Andrew P.; Harrowven, David C.; Linclau, Bruno
• Is Part Of: European journal of organic chemistry. Issue 20(2014)
• Page Start: 4335
• Page End: 4341
• Publication Date: 2014-05-27
• Subjects: Total synthesis -- Homogeneous catalysis -- Nitrogen heterocycles -- Cross‐coupling -- Cobalt -- Radicals; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201402108
• Languages: English
• ISSNs: 1434-193X

Abstract

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. Abstract : A diastereoconvergent cobalt‐catalysed cross‐coupling between p ‐fluorophenylmagnesium bromide and a tert ‐butoxycarbonyl‐protected 3‐substituted 4‐bromopiperidine gave the desired trans ‐coupling product irrespective of the relative configuration of the substrate, with good de . This transformation has been used as the key step in a synthesis of (±)‐paroxetine.