Total Synthesis of (2RS)‐α‐Tocopherol through Ni‐Catalyzed 1, 4‐Addition to a Chromenone Intermediate. Issue 16 (17th April 2014)

• Record Type: Journal Article
• Authors: Termath, Andreas Ole; Velder, Janna; Stemmler, René T.; Netscher, Thomas; Bonrath, Werner; Schmalz, Hans‐Günther
• Is Part Of: European journal of organic chemistry. Issue 16(2014)
• Page Start: 3337
• Page End: 3340
• Publication Date: 2014-04-17
• Subjects: Natural products -- Oxygen heterocycles -- Conjugate addition -- Nickel -- Radicals; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201402240
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: A novel strategy for the total synthesis of α‐tocopherol ("vitamin E") was elaborated on the basis of the conjugate addition of AlMe3 (as a methyl anion equivalent) to a 2‐substituted chromenone. Starting from trimethylhydroquinone and ( R, R )‐hexahydrofarnesol, the required chromenone substrate was efficiently prepared in a short sequence exploiting a TiCl4 ‐mediated Fries rearrangement and a KO t Bu‐induced Baker–Venkatamaran rearrangement. The envisioned key step, which sets up the quaternary center at C2, was performed in virtually quantitative yield through Ni‐catalyzed conjugate addition of AlMe3 . However, this transformation, which likely proceeds through a radical mechanism, could not be rendered stereoselective by means of chiral ligands. Nevertheless, the elaborated synthesis of (2 RS, 4′ R, 8′ R )‐α‐tocopherol ( 2 ‐ ambo ‐α‐tocopherol) is efficient and challenges the future development of suitable protocols for the asymmetric 1, 4‐addition. Abstract : The total synthesis of 2 ‐ ambo ‐α‐tocopherol is elaborated starting from trimethylhydroquinone and ( R, R )‐hexahydrofarnesol. In the key step, the quaternary center is established through Ni‐catalyzed 1, 4‐addition of AlMe3 to a chromenone intermediate This transformation, which likely proceeds through a radical mechanism, cannot be rendered stereoselective by means of chiral ligands.