New Greener Synthetic and Catalytic Technologies Relevant to Industrial Processes in the Fine Chemicals Industry

Chemical synthesis is entering a pivotal era shaped by demands for scalable, resource-efficient, and environmentally responsible technologies. This presentation highlights our group’s multidisciplinary advances across micellar catalysis, green and sustainable chemistry, and emerging AI-enabled approaches for reaction design and process optimization. We will showcase how aqueous micellar media enable a broad range of organic transformations—including C–C and C–N cross-couplings and other catalytic processes traditionally limited to organic solvents—under mild, waste-minimizing, and electrochemically driven conditions. Ongoing efforts in cross-metathesis at the palladium center for highly safe cross-coupling chemistry, along with strategies to understand and overcome catalyst death through next-generation catalyst design, will also be discussed. These innovations collectively show how key green chemistry principles can be transformed through innovation into practical, industrially relevant solutions. These solutions reduce costs, minimize waste, and expedite the development of cleaner, more sustainable manufacturing platforms.

Metrics from the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable have led to an estimate that solvents utilized contribute 80–90% of the waste streams of pharmaceutical manufacturing processes.^[1] Additionally, organic solvents play a dominant role in the overall toxicity profile of most processes and are the chemicals of greatest concern. As such, implementing strategies to reduce the economic and environmental impact of solvents is critically important.

This presentation will highlight innovative chemical synthesis platforms aimed at addressing the sustainability challenge in the pharmaceutical industry. Key approaches include the use of water as the reaction solvent and mechanochemistry – two technologies showing considerable promise. We will present progress from industry-academic collaborations e.g. on the rational design of ligands for metal-catalyzed reactions in aqueous media,^[2] as well as advancements in transitioning batch processes to continuous flow setups for water-based chemistry. ^[3]

Furthermore, the development of simple, robust catalyst delivery systems – such as capsules and tablets – designed to improve robustness and reproducibility will be showcased. ^[4] As a practical example, we will share results from an undergraduate laboratory course led by our collaborator, Prof. Handa, featuring catalyst capsules used for a copper-catalyzed tandem click reaction in water.^[5] Additional results and ongoing projects from industry-academic collaborations and consortia will be presented, emphasizing both innovation and real-world application.

References
P. Richardson, M.C. Bryan, L. Diorazio, F. Gallou, S. Keily, I. Martinez, S. Plummer, A.B. Reed, R. Sheppard, J. Shields, G. Wrigley, C. Yeung, A. Enriquez-Garcia, J. Med. Chem. 2025, 68, 25625−25664
A.R. Ickes, J.P. Liles, N. Borlinghaus, J. Henle, R. Swiatowiec, N.P. Kaushik, W.M. Braje, K.C. Harper, S. Shekhar, M.S. Sigman, J. Am. Chem. Soc. 2025, 147, 28981−28992
S.H.A. Rajendran, S. Kogler, P. Kögl, W.M. Braje, S.B. Ötvös, C.O. Kappe, ACS Sustainable Chem. Eng. 2025, 13, 6423-6432.
a.) N. Borlinghaus, J. Kaschel, J. Klee, V. Haller, J. Schetterl, S. Heitz, T. Lindner, J.D. Dietrich, W.M. Braje, A. Jolit, J. Org. Chem. 2021, 86, 1357-1370; b.) N. Borlinghaus, B. Schönfeld, S. Heitz, J. Klee, S. Vukelic, W.M. Braje, A. Jolit, J. Org. Chem. 2021, 86, 16535-16547.
K. Kaur, A. Chhetri, A. Akram, R. Zainab, W.M. Braje, N.V. Handa, S. Handa, J. Chem. Educ. 2026, 103, 530-537.

We report the development of a novel cobalt(II) organometallic complex synthesized from readily available precursors, thereby providing a sustainable alternative to rare and costly noble-metal catalysts.¹ Distinguished by its exceptional air- and moisture-stability, the catalyst remains intact during chromatographic purification, facilitating efficient recovery and minimizing metal leaching, a critical requirement for pharmaceutical applications. By eliminating the need for rigorous solvent desiccation and reducing the number of synthetic steps, this catalytic system offers a waste-minimized pathway for C-H activation (Figure 1). The practical utility of this method is underscored by a successful bench-scale synthesis of up to 68 g of alkylated product, demonstrating its potential for industrial-scale applications. This presentation will highlight the catalyst’s versatility in the synthesis of fine chemicals and its efficacy in the late-stage functionalization of complex bioactive molecules.

Reference:
Nigade,A.; Parmar, S. V.; Avasare, V. Chem. Sci., 2026, 10.1039/D5SC09264G

Organometallic catalysis using platinum group metals (PGMs) has proven to be a powerful tool in organic chemistry. Since the introduction of the Green Chemistry principles in 1998, environmental concerns related to the use of precious and rare metals have been addressed through two complementary strategies. The first strategy exploits the high reactivity of PGMs—such as Ir, Pd, Rh, Ru, and Pt—by increasing turnover numbers and enabling reactions to be performed under milder and more sustainable conditions. The second approach focuses on the development of catalytic systems based on earth-abundant metals, including Ni, Cu, Co, and Fe.
Within this context, a rigorous approach to sustainability cannot be based solely on metal abundance. Instead, it requires a comprehensive evaluation of the entire catalytic process, encompassing reaction protocols, catalyst preparation and lifetime, ligands, auxiliaries, solvent selection, process efficiency, metal recovery and recycling, as well as the environmental impact associated with waste generation and wastewater treatment. Only by considering these factors together can the true sustainability of a catalytic system, whether based on PGMs or earth-abundant metals, be meaningfully assessed.

Reduction of Nitro groups to corresponding amines is a very commonly used chemisty in pharmaceutical, speciality and fine chemicals industry. Conventional technologies like Catalytic Hydrogenation (using Pd/C, Raney Ni, etc), Hydrazine Hydrate, Stannous Chloride / HCl, Zn / HCl, Metal / Acid Reductions, Caustic / Sulphur, etc have some or the other safety and environmental concerns – Concerns like high pressure reaction, use of hydrogen gas, use of precious metal and pyrophoric catalysts, use of acids or alkali, etc.

Newreka has been working with CDMO companies globally to replace the above-mentioned conventional technologies with a more safer and environmentally benign alternative for nitro reductions. Newreka Reduction Technology (NRT) effectively reduces nitro compounds to amine, using water as a source of Hydrogen and a high surface area, Iron-based reducing agent, at atmosphric pressure, nominal conditions of temperature and pressure. This technology doesn’t require any high pressure vessel, hydrogen gas, acid or alkali, nor precious metal catalysts.

NRT has been specifically very effective in cases where along with the nitro compound, there is a halogen substitution or another competing functional group (e.g. ketone, aldehyde, double bond, etc) which can get knock-off or reduced, respectively. With this process, nitro group is selectively reduced to amine with minimum dehalogenation or reduction of other competing groups.

Several new technologies will be discussed, with each under the blanket of environmentally responsible chemistry.

These will include, time-permitting:

(1) A new surfactant as a “drop in” replacement for previous designer amphiphiles

(2) Relatively rapid Suzuki-Miyaura cross-couplings catalyzed by low loadings of a Pd-based oxidative addition complex, in water

(3) Very rapid Pd-catalyzed aminations of highly functionalized coupling partners under very green conditions

(4) Oxidations of highly functionalized alcohols using a new, virtually free metal-based technology, in water

.

Cross-coupling chemistry exemplifies significant incremental innovation in classical carbon-carbon (C–C) bond formation, evolving from pioneering palladium-catalyzed techniques developed in the 1970s to the recognition of this work with the Nobel Prize in Chemistry in 2010. Since 1995, advancements in both C–C and C-heteroatom coupling have been driven by highly efficient palladium catalysts, which have greatly enhanced the sustainability of active pharmaceutical ingredient (API) and fine chemical synthesis. These catalysts reduce the number of synthetic steps, accelerate development timelines, and minimize waste, thereby contributing to more efficient processes. The progression of catalyst design parallels advancements in modern technologies, yielding enhanced performance and broader applicability. Key developments include the formulation of an ideal catalyst for the commercial manufacture of ledipasvir, a crucial component of the hepatitis C drug Harvoni®, alongside the tri(tertiarybutyl)phosphine based Pd-G6 catalyst that effectively addresses particularly challenging Suzuki–Miyaura and Buchwald–Hartwig coupling reactions. In addition to fundamental advancements, this talk will also cover the synthesis of high-purity palladium precursors to enable cost-effective generic drug production