The Catalyst Review January 2020 - 7

INDUSTRY PERSPECTIVES

The views expressed are those of the individual author and may not reflect those of The Catalyst Review or TCGR
Industry Perspectives (continued from page 1)

With the secret now out, what methodologies do we have available today, documenting this "new rule" that the greater the binding
constant of the catalyst (or pre-catalyst) for the micellar interior, the lower the level of loading needed for the intended chemistry?
Actually, we have many such examples. Here are just three, highlighting different "name" reactions, each catalyzed by Pd at the ppm
level.
Example 1: Suzuki-Miyaura (SM) cross couplings. Using a newly designed ligand, HandaPhos, that forms a 1:1 complex with Pd,
couplings can be run in water
at rt at the 1000 ppm level of
Pd catalyst within nanomicelles
composed of the designer
surfactant Nok. Below are just
two examples of the potential
of this technology.
Sources: Handa et al., 2016; Klumphu and Lipshutz 2016.
Example 2: Sonogashira couplings. By combining two commercially available precursors (i.e., a Pd(II) salt and Takasago's cBRIDP
phosphine, below), a catalyst results that can
be used at the 1000 ppm level of Pd to effect
these valued couplings in aqueous TPGS-750-M
at 45 °C. Using two such couplings allowed for
synthesis of the key intermediate en route to
ponatinib (Iclusig; an FDA-approved tyrosine
kinase inhibitor).
Source: Jin et al., 2019.
Example 3. Buchwald-Hartwig aminations. These important Pd-catalyzed C-N couplings are notoriously dependent on nonsustainable levels of catalyst loading
(typically 2-10 mol %, or 20,000100,000 ppm Pd). But today, using
only 1000 ppm of a readily available
pre-catalyst, in nanomicelles
composed of 2 wt % TPGS-750-M
in water, the desired bonds can be
Source: Zhang et al., 2019.
made under mild conditions. Some
examples are shown below, as is a recently reported drug intermediate that, by way of comparison, makes the same C-N bond but
with 100 times more Pd.
In conclusion, the message that the future of "chemo-catalysis", as with "bio-catalysis", in general, is here and is in water is, hopefully,
becoming clearer based on the many technological advances already in hand. And given the match between micellar and precious
metal catalysis that leverage newly gained insights that follow Nature's lead, why would anyone opt to not do Pd catalysis at the ppm
level in water at room temperature?
References

Andersson MP, Gallou F, Klumphu P, et al. (2018). "Structure of Nanoparticles Derived from Designer Surfactant TPGS-750-M in Water, as
Used in Organic Synthesis." Chem. Eur. J. (24): 6778.
BullionbyPost. (2019). "Palladium Price in USD per Troy Ounce for Last 10 Years."
https://www.bullionbypost.co.uk/palladium-price/10year/ounces/usd/
Handa S, Anderson MP, Gallou F, et al. (2016). "A general Ligand Enabling Sustainable ppm Levels of Palladium-Catalyzed Cross-Couplings in
Water at Room Temperature." Angew. Chem., Int. Ed. (55): 4914.
Jin B, Gallou F, Reilly J, (2019). "ppm Pd-catalyzed, Cu-free Sonogashira Couplings in Water Using Commercially Available Catalyst
Precursors." Chem. Sci. (10): 3481.
Klumphu P and Lipshutz BH. (2014). "Nok: A Phytosterol-Based Amphiphile Enabling Transition Metal-Catalyzed Couplings in Water at Room
Temperature." J. Org. Chem. (79): 888.
Lipshutz BH, Ghorai S, Abela AR, et al. (2011). "TPGS-7450-M: ASecond-Generation Amphiphile for Metal-Catalyzed Cross-Couplings in
Water at Room Temperature." A. J. Org. Chem. (76): 4379.
Zhang Y, Takale BS, Gallou F, et al. (2019). "Sustainable ppm Level Palladium-catalyzed Aminations in Nanoreactors Under Mild, Aqueous
Conditions." Chem. Sci. (10): 10556.
continue on page 8
The Catalyst Review 										

January 2020

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The Catalyst Review January 2020

Table of Contents for the Digital Edition of The Catalyst Review January 2020

The Catalyst Review January 2020 - cover
The Catalyst Review January 2020 - contents
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