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Dynamic Kinetic Asymmetric Transformation of Diene Monoepoxides: A Practical Asymmetric Synthesis of Vinylglycinol, Vigabatrin, and Ethambutol
journal contribution
posted on 2000-06-08, 00:00 authored by Barry M. Trost, Richard C. Bunt, Rémy C. Lemoine, Trevor L. CalkinsThe ability to perform a dynamic kinetic asymmetric transformation (DYKAT) using the palladium-catalyzed asymmetric allylic alkylation (AAA) is explored in the context of butadiene monoepoxide. The
versatility of this commercially available, but racemic, four-carbon building block becomes significantly enhanced
via conversion of both enantiomers into a single enantiomeric product. The concept is explored in the context
of a synthesis of vinylglycinol with phthalimide as the nitrogen source. The success of the project required a
new design of the ligand for palladium wherein additional conformational restraints were introduced. Thus,
the phthalimide derivative of vinylglycinol was obtained in nearly quantitative yield and had an ee of 98%
which, upon crystallization, was enhanced to >99%. This one-step synthesis of a protected form of vinylglycinol
provided short practical syntheses of the title compounds. Vigabatrin requires only four steps, and ethambutol
six. The intermediate to the existing synthesis of ethambutol is available in 87% yield in three steps. (R)-Serine derives from oxidative cleavage of the double bond. The reaction of phthalimide and isoprene
monoepoxide demonstrates the remarkable ability of the chiral ligands to control both regioselectivity and
enantioselectivity and demonstrates the effectiveness of this protocol in creating a quaternary center
asymmetrically.
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AAAchiral ligandsvinylglycinolethambutolDYKATisoprene monoepoxideallylic alkylationDynamic Kinetic Asymmetric Transformationabilitynitrogen sourceenantiomeric producttitle compoundsquaternary centerPractical Asymmetric Synthesisbutadiene monoepoxidephthalimidecontextsynthesisoxidative cleavageVigabatrin
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