The Catalyst Review January 2020 - 1

INDUSTRY PERSPECTIVES

The views expressed are those of the individual author and may not reflect those of The Catalyst Review or TCGR

Development of ppm Level Active Pd Catalysts
for Use Under Aqueous Micellar Conditions
Ask any industrial process chemist what they want for Christmas and chances are they'll say, "I want my chemistry to go faster, better
and cheaper." That's not an unreasonable request! How to achieve all three is a tougher question, but fortunately, as the world of
organic chemistry must begin to make the "switch" from a petroleum- to a water-based discipline to achieve sustainability, there are
technologies now available to assist with this transition. And in doing so, new rules under which chemistry in water are operating
are being revealed, along with which are coming new opportunities for increasing reaction rates, selectivities, yields, and overall
productivity, while lowering costs significantly.
One very important aspect associated with this "switch"
includes a critical change in the amounts of endangered
transition metals currently used as catalysts, and none is
more important to the synthetic community today and in
the future than palladium. The world's access to Pd is based
on its limited technological know-how to mine this metal,
not to mention geopolitical issues that may exist, both
combining to highlight the shortage coming. Just one look at
the recent rate at which this precious metal is priced today
(Figure 1) should be enough to encourage development by
the chemical enterprise of new ways of effecting the same
essential catalysis with Pd, but for which far less metal is
required; "far less" meaning at least one order of magnitude
lower in loading of Pd catalyst per reaction. Such an
accomplishment would effectively increase our access to this
crucial metal for catalysis indefinitely.

Figure 1. Cost of palladium over time. Source: Bullionbypost; 2019.

A focus on Pd is only part of the ticket to a sustainable discipline. There are, not one, but three issues that must be addressed: (1)
replace organic solvents as reaction media with recyclable water; (2) minimize the energy invested (i.e., little-to-no heating of cooling
of reaction mixtures), and (3) reduce the typical 1-5 mol % level of Pd used in catalysis to ≤0.1 mol % (or 1000 ppm). These are
challenging reaction parameters, but each has been achieved; in fact, the technology is already available, and it is even getting better
with time.
The key to the enabling technology that makes chemistry in water at room temperature possible, and that allows for ppm loadings
of Pd that lead to the same crucial C-C and C-N bond formations, is rooted in the concepts behind aqueous micellar catalysis. Hence,
while surfactants come in many forms, and they usually self-aggregate into micelles upon dissolution in water, their use in synthesis
had been essentially "hit or miss;" try one or two and hope it helps to dissolve educts in water and then, that the desired chemistry
occurs, efficiently. How to choose the surfactant, what type of micelles are formed, why it might be the one for a given reaction, or
when to use which and how much of it are questions for which the synthesis community had no answers. Indeed, such questions had
never been asked.
Over the past decade or so, they have not
only been asked, but answered! Rather
than unrealistically screening every known
surfactant, new surfactants have been
engineered to match the intended synthetic
goals with environmental restrictions;
that is, each "designer" surfactant must
Figure 2. (A) Structure of TPGS-750-M; (B) Picture of nanomicelles within a larger nanomiocelle.
not only be enabling, but environmentally
Sources: Lipshutz et al., 2011; Andersson et al., 2018.
benign (i.e., "benign by design"). Today,
the leading amphiphile for carrying out a
multitude of valuable synthetic chemistry is TPGS-750-M (Figure 2A), which spontaneously forms a unique structure (Figure 2B)
in water comprising "micelles within a micelle." The inner lipophilic cores, unlike the "lock and key" requirements of enzymes, are
non-discriminating; they house substrates and catalysts leading to high internal concentrations (oftentimes >2 M; since nothing is
soluble in water). Hence, reactions ensue therein under very mild conditions. And what is the impact on catalyst loadings? Answer:
by choosing, or designing, wisely the ligand on the metal that together form the catalyst; that is, by maximizing catalyst attraction for
the micellar core, more will find its way inside and be localized at these high concentrations, together with the reaction partners. The
result? Less catalyst is needed, leading to ppm levels of Pd catalysis, in water, under these very mild conditions. BOOM!
continue on page 7

The Catalyst Review

January 2020

The Catalyst Review January 2020

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