Homo-Roche Ester Derivatives
by Asymmetric Hydrogenation
and Organocatalysis
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Abstract
Asymmetric
hydrogenation routes to homologues of The Roche ester
tend to be restricted to hydrogenations of itaconic acid derivatives,
that is, substrates that contain a relatively unhindered, 1,1-disubstituted
alkene. This is because in hydrogenations mediated by RhP<sub>2</sub> complexes, the typical catalysts, it is difficult to obtain high
conversions using the alternative substrate for the same product,
the isomeric trisubstituted alkenes (<b>D</b> in the text).
However, chemoselective modification of the identical functional groups
in itaconic acid derivatives are difficult; hence, it would be favorable
to use the trisubstituted alkene. Trisubstituted alkene substrates
can be hydrogenated with high conversions using chiral analogs of
Crabtree’s catalyst of the type IrN(carbene). This paper demonstrates
that such reactions are scalable (tens of grams) and can be manipulated
to give optically pure homo-Roche ester chirons. Organocatalytic fluorination,
chlorination, and amination of the homo-Roche building blocks was
performed to demonstrate that they could easily be transformed into
functionalized materials with two chiral centers and α,ω-groups
that provide extensive scope for modifications. A synthesis of (<i>S,S</i>)- and (<i>R,S</i>)-γ-hydroxyvaline was
performed to illustrate one application of the amination product