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Enantioselective Palladium‐Catalyzed Total Synthesis of Vitamin E by Employing a Domino Wacker–Heck Reaction
Author(s) -
Tietze Lutz F.,
Stecker Florian,
Zinngrebe Julia,
Sommer Konrad M.
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200600849
Subject(s) - enantioselective synthesis , heck reaction , chemistry , palladium , enantiopure drug , catalysis , total synthesis , organic chemistry , medicinal chemistry
An enantioselective total synthesis of vitamin E in which a novel palladium‐catalyzed domino reaction was employed as the key step is described. This reaction allows the formation of the chiral chroman framework and the concurrent introduction of part of the side chain of vitamin E. The sequence comprises an enantioselective Wacker cyclization and a subsequent Heck reaction. Accordingly, reaction of alkenylphenol 12 with methyl vinyl ketone ( 13 ) in the presence of catalytic amounts of Pd(OTFA) 2 (TFA = trifluoroacetate), the enantiopure ligand ( S , S )‐Bn‐BOXAX ( 8 b ; Bn = benzyl, BOXAX = 2,2′‐bis(oxazolyl)‐1,1′‐binaphthyl, and p ‐benzoquinone ( 9 ) as an oxidant gives access to chiral chroman 10 with an enantioselectivity of 97 % ee in 84 % yield. Chroman 10 is then converted into 24 by an aldol condensation reaction with (3 R )‐3,7‐dimethyloctanal ( 11 ). Subsequent 1,2‐addition of methyllithium, elimination of water, and hydrogenation yields vitamin E.