Conspectus
In heterogeneous catalysis,
the long-standing challenge is to achieve
extremely high activity and chemoselectivity in liquid-phase organic
transformations comparable to that of homogeneous or enzymatic processes.
Single-atom catalysts (SACs) with atomically precise coordination
are developed with the objectives to mimic the homogeneous pathways
but face stability issues due to metal leaching or clustering. Additionally,
the practical application of SACs in chemical production is hampered
by the lack of standard preparation protocols and low conversion using
laboratory batch reactors.
This Account focuses on our recent
studies in both catalyst design
and reactor-level engineering for the flow synthesis of fine chemicals
via SACs. At the catalyst and reaction level, we will discuss the
intrinsic mechanism that controls reactivity and chemoselectivity
in the SAC-catalyzed process and highlight examples where SACs outperform
other catalytic approaches. Specifically, we reported the SAC-mediated
preparation and late-stage functionalization of pharmaceutical drugs,
including lonidamine, Tamiflu, cavosonstat, indomethacin, and many
others by chemoselective transformations in a sequential or multicomponent
manner. The ability of ultrahigh loading SACs in providing a multisite
pathway for organic transformations involving two or more reactants
is highlighted and contrasted with the single-site pathway in conventional
SACs. Molecular-level understanding on the dynamic catalytic cycle
obtained using operando X-ray absorption spectroscopies provides guidance
for the design of more effective and leach resistant SACs. This also
calls for the transformation of laboratory powder-based catalysts
into industrially viable monolithic catalysts via formulation to further
enhance the leach resistance. At the reactor level, we will highlight
the importance of continuous-flow techniques in maximizing productivity
and simplifying process transfer from laboratory to commercial production.
Particularly, we discuss the use of fuel cell-type flow stacks for
quantitative production of fine chemicals, including the synthesis
of multifunctional anilines at a 5.8 g h–1 productivity
using a Pt SAC module (3.2 mg Pt). Insight into multiscale reactor
processes, for instance, the fluid diffusion kinetics, heat transfer,
and influence of porosity and the gas–liquid–solid interface
are provided by computational fluidic dynamics calculations as well
as experimental techniques. In many cases, catalytic processes are
more limited by mass diffusion than the intrinsic activity of the
catalyst, calling for process optimization and engineering at the
reactor level to enhance the productivity. Finally, we also identify
technical barriers that need to be overcome in SAC research and offer
our perspective on standardized and scalable protocols for mass production,
the production cost analysis of typical SACs, high-throughput screening
platforms, and novel flow reactor designs involving photochemical
and electrochemical reactions for up-scaling chemic...