posted on 2019-04-29, 00:00authored byLee J. Durndell, Mark A. Isaacs, Chao’en Li, Christopher M.
A. Parlett, Karen Wilson, Adam F. Lee
Cascade
reactions represent an atom-economical and energy-efficient technology
by which to reduce the number of manipulations required for chemical
manufacturing. Biocatalytic cascades are ubiquitous in nature; however,
controlling the sequence of interactions between reactant, intermediate(s),
and active sites remains a challenge for chemocatalysis. Here, we
demonstrate an approach to achieve efficient cascades using chemical
catalysts through flow chemistry. Close-coupling of Pd/SBA-15 and
Pt/SBA-15 heterogeneous catalysts in a dual bed configuration under
continuous flow operation affords a high single pass yield of 84%
(a 20-fold enhancement over batch operation) and high stability for >14000
turnovers in the cascade oxidation of cinnamyl alcohol to cinnamic
acid, despite both catalysts being individually inactive for this
reaction. Judicious ordering of Pd (first bed) and Pt (second bed)
catalysts is critical to promote cascade oxidation with respect to
undesired hydrogenation and hydrogenolysis, the latter favored over
the reverse-bed sequence or a single mixed PdPt reactor bed. The intrinsic
catalytic performance of each bed is preserved in the optimal dual-bed
configuration, enabling quantitative prediction of final product yields
for reactants/intermediates whose individual oxidation behavior is
established. Continuous processing using contiguous reactor beds enables
plug-and-play design of cascades employing “simple”
catalysts.