Zinc Promoted Cross‐Electrophile Sulfonylation to Access Alkyl–Alkyl Sulfones DOI Creative Commons

Zhuochen Wang,

Rui Ma,

Chang Zhi Gu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: July 4, 2024

Abstract The transition metal‐catalyzed multi‐component cross‐electrophile sulfonylation, which incorporates SO 2 as a linker within organic frameworks, has proven to be powerful, efficient, and cost‐effective means of synthesizing challenging alkyl–alkyl sulfones. Transition metal catalysts play crucial role in this method by transferring electrons from reductants electrophilic organohalides, thereby causing undesirable side reactions such homocoupling, protodehalogenation, β ‐hydride elimination, etc. It is worth noting that tertiary alkyl halides have rarely been demonstrated compatible with current methods owing various undesired reactions. In work, zinc‐promoted sulfonylation developed through radical‐polar crossover pathway. This approach enables the synthesis sulfones, including 1°‐1°, 2°‐1°, 3°‐1°, 2°‐2°, 3°‐2° types, inexpensive readily available halides. Various functional groups are well tolerated resulting yields up 93%. Additionally, protocol successfully applied intramolecular homo‐sulfonylation insights gained work shall useful for further development access

Language: Английский

Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 1─Process History and Development Strategy DOI
Daniel A. DiRocco, Yong‐Li Zhong, Diane N. Le

et al.

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: 28(2), P. 404 - 412

Published: Feb. 5, 2024

An improved synthesis has been developed for belzutifan, a novel HIF-2α inhibitor the treatment of Von Hippel–Lindau (VHL) disease-associated renal cell carcinoma (RCC). The efficiency previous supply and commercial routes was encumbered by lengthy 5-step sequence, needed to install chiral benzylic alcohol traditional methods. Identification directed evolution FoPip4H, an iron/α-ketoglutarate dependent hydroxylase, enabled direct enantioselective C–H hydroxylation simple indanone starting material. While this enabling transformation set stage greatly synthesis, several other key innovations were made including development base-metal-catalyzed sulfonylation, KRED-catalyzed dynamic kinetic resolution, facile SNAr reaction in water. Together, these improvements resulted significantly shorter (9 steps) versus route (16 75% reduction process mass intensity (PMI), while also removing reliance on third-row transition metals toxic solvents.

Language: Английский

Citations

10
Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 5─Chemoenzymatic Diastereoselective Fluorination/DKR DOI
Scott D. McCann, Sean Hyun Dubina, Birgit Kosjek

et al.

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: 28(2), P. 441 - 450

Published: Feb. 7, 2024

A ketone fluorination/reduction dynamic kinetic resolution (DKR) was developed for a third-generation synthesis of belzutifan. This new process replaced precious metal catalyst with ketoreductase (KRED) in the DKR. Achieving this one-pot reaction required several rounds enzyme evolution that improved stability presence acetonitrile and methanol. To maintain development progress satisfy program timelines, around reaction, workup, isolation operations performed parallel ongoing modification, as variants were made available. Additionally, opportunities improvements to product quality robustness identified by resolving issues observed piloting experiments.

Language: Английский

Citations

5
Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 6─Development of a Nucleophilic Aromatic Substitution in Water DOI
Diane N. Le,

Timothy J. Wright,

Embarek Alwedi

et al.

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: 28(2), P. 451 - 459

Published: Feb. 5, 2024

A convergent nucleophilic aromatic substitution (SNAr) was developed as the final step in an improved manufacturing process to belzutifan. The reaction performed water enable a reactive crystallization and direct isolation of drug substance toward green sustainable process. Due sensitivity vapor phase composition, engineering controls around headspace pressure sweep rate were tuned balance reactivity selectivity maximize product yield purity. Ultimately, our investigation resulted robust process, which successfully demonstrated at pilot plant scale.

Language: Английский

Citations

4
Diversification of Pharmaceutical Manufacturing Processes: Taking the Plunge into the Non-PGM Catalyst Pool DOI Creative Commons
Hui Zhao, Anne K. Ravn, Michael C. Haibach

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(13), P. 9708 - 9733

Published: June 13, 2024

Recent global events have led to the cost of platinum group metals (PGMs) reaching unprecedented heights. Many chemical companies are therefore starting seriously consider and evaluate if where they can substitute PGMs for non-PGMs in their catalytic processes. This review covers recent highly relevant applications non-PGM catalysts modern pharmaceutical industry. By highlighting these selected successful examples non-PGM-catalyzed processes from literature, we hope emphasize enormous potential catalysis inspire further development within this field enable technology progress toward manufacturing We also present some historical contexts perceived advantages challenges implementing environment.

Language: Английский

Citations

4
Palladium-Catalyzed Addition of Aryl Halides to N-Sulfinylamines for the Synthesis of Sulfinamides DOI Creative Commons

Ming-Kai Wei,

Daniel. F. Moseley,

Robin M. Bär

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 19690 - 19695

Published: July 12, 2024

Sulfinamides are versatile, synthetically useful intermediates, and final motifs. Traditional methods to synthesize sulfinamides generally require substrates with preinstalled sulfur centers. However, these precursors have limited commercial availability, the associated synthetic routes often harsh reaction conditions highly reactive reagents, thus severely limiting their application. Herein, we report synthesis of from aryl alkenyl (pseudo)halides N-sulfinylamines, enabled by palladium catalysis. The reactions use mild achieved without preformed organometallic resulting in transformations broad generality high functional group tolerance. In particular, featuring protic electrophilic groups can be used successfully. modification complex cores natural product derivatives demonstrates utility this method.

Language: Английский

Citations

3
Recent Advances in Technology for Produced Water in the Oil and Gas Industry DOI Open Access

J. Walls,

Gisele Rogel,

Gideon Quaye

et al.

Published: April 28, 2024

Recent technological advancements in produced water for the oil and gas industry have a long history that spreads over centuries has roots with many mathematicians, physicists, engineers, inventors. Working to understand ideas questions helped bring technologies where we are today. Fluid mechanics is an essential factor world of engineering because it comes significant benefits when designing necessary equipment overcome challenging endeavors daily operations. Many us believe certain or products were developed within specific year not fully understanding idea concept might be hundreds years old. For example, think fluid mechanics, do Archimedes' immersing King Hiero II crown water. Archimedes did this determine displacement as he knew gold was denser than silver. one pioneers who part beginning mechanics. Another interesting fact first valve invented 1 AD by Heron Alexandria. This can described very hydraulic valve. The evolution technology made considerable innovations benefiting engineers all world. These come form PLCs, RTUs, PIDs, mathematical formulas, processing methods, SCADA systems.

Language: Английский

Citations

2
Zinc Promoted Cross‐Electrophile Sulfonylation to Access Alkyl–Alkyl Sulfones DOI Creative Commons

Zhuochen Wang,

Rui Ma,

Chang Zhi Gu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: July 4, 2024

Abstract The transition metal‐catalyzed multi‐component cross‐electrophile sulfonylation, which incorporates SO 2 as a linker within organic frameworks, has proven to be powerful, efficient, and cost‐effective means of synthesizing challenging alkyl–alkyl sulfones. Transition metal catalysts play crucial role in this method by transferring electrons from reductants electrophilic organohalides, thereby causing undesirable side reactions such homocoupling, protodehalogenation, β ‐hydride elimination, etc. It is worth noting that tertiary alkyl halides have rarely been demonstrated compatible with current methods owing various undesired reactions. In work, zinc‐promoted sulfonylation developed through radical‐polar crossover pathway. This approach enables the synthesis sulfones, including 1°‐1°, 2°‐1°, 3°‐1°, 2°‐2°, 3°‐2° types, inexpensive readily available halides. Various functional groups are well tolerated resulting yields up 93%. Additionally, protocol successfully applied intramolecular homo‐sulfonylation insights gained work shall useful for further development access

Language: Английский

Citations

2