As companies grow ever more mindful of the sustainability aspects of their products and supply chains, an increasing focus on the environmental impact of pharmaceutical manufacture spurs innovation from chemists who support this industry. Metal catalysis has the potential to greatly enhance the sustainability of pharmaceutical products, leading to shorter and more efficient synthetic routes and more direct access to single stereoisomeric products. This perspective article seeks to highlight a number of important considerations for the design of new and improved sustainable metal-catalyzed transformations in order to facilitate rapid adoption by the pharmaceutical industry.
Green and sustainable drug manufacturing goes hand in hand with forward-looking visions seeking to balance the long-term sustainability of business, society, and the environment.
Under the shielding
effect of nanomicelles, a sustainable micellar
technology for the design and convenient synthesis of ligand-free
oxidizable ultrasmall Pd(0) nanoparticles (NPs) and their subsequent
catalytic exploration for couplings of water-sensitive acid chlorides
in water is reported. A proline-derived amphiphile, PS-750-M, plays
a crucial role in stabilizing these NPs, preventing their aggregation
and oxidation state changes. These NPs were characterized using
13
C nuclear magnetic resonance (NMR), infrared (IR), and surface-enhanced
Raman scattering (SERS) spectroscopy to evaluate the carbonyl interactions
of PS-750-M with Pd. High-resolution transmission electron microscopy
(HRTEM) and energy-dispersive X-ray spectroscopy (EDX) studies were
performed to reveal the morphology, particle size distribution, and
chemical composition, whereas X-ray photoelectron spectroscopy (XPS)
measurements unveiled the oxidation state of the metal. In the cross-couplings
of water-sensitive acid chlorides with boronic acids, the micelle’s
shielding effect and boronic acids plays a vital role in preventing
unwanted side reactions, including the hydrolysis of acid chlorides
under basic pH. This approach is scalable and the applications are
showcased in multigram scale reactions.
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