Total Synthesis of α-Tocopherol through Enantioselective Iridium-Catalyzed Fragmentation of a Spiro-Cyclobutanol Intermediate.
作者： Friederike Ratsch , Waldemar Schlundt , Dominik Albat , Anne Zimmer , Jörg‐Martin Neudörfl
关键词: Stereochemistry 、 Enyne 、 Desymmetrization 、 Chemistry 、 Enantioselective synthesis 、 Enyne metathesis 、 Alkene 、 Chiral ligand 、 Catalysis 、 Total synthesis
摘要: A conceptionally new strategy for the asymmetric (2R-selective) synthesis of α-tocopherol (vitamin E) was developed. In stereocontrolled key step, a prochiral spiro[chromane-2,3'-cyclobutanol] unit is effectively desymmetrized under C-C bond activation in an unprecedented iridium-catalyzed transformation using (S)-DTBM-SegPhos as chiral ligand (e.r. 97:3). To complete synthesis, side chain attached through Ru-catalyzed cross-metathesis employing alkene derived from (R,R)-hexahydrofarnesol. suppress epimerization during final hydrogenation, PtO2 had to be used catalyst instead Pd/C. alternative approach (employing propargyl-substituted spiro-cyclobutanol), constructed prior Ir-catalyzed ring fragmentation (>99:1 d.r.) enyne (using (R)-dihydrocitronellal) followed by Cr-catalyzed 1,4-hydrogenation and (diastereoselective) Pfaltz hydrogenation resulting triple-substituted olefin. The work demonstrates potential iridium catalysis enantioselective activation.
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