Mechanochemistry: New Tools to Navigate the Uncharted Territory of “Impossible” Reactions

ChemSusChem, Journal Year: 2022, Volume and Issue: 15(17)

Published: July 21, 2022

Mechanochemical transformations have made chemists enter unknown territories, forcing a different chemistry perspective. While questioning or revisiting familiar concepts belonging to solution chemistry, mechanochemistry has broken new ground, especially in the panorama of organic synthesis. Not only does it foster "thinking outside box", but also opened reaction paths, allowing overcome weaknesses traditional exactly where use well-established solution-based methodologies rules out progress. In this Review, reader is introduced an intriguing research subject not yet fully explored and waiting for improved understanding. Indeed, study mainly focused on that, although impossible solution, become possible under mechanochemical processing conditions, simultaneously entailing innovation expanding chemical space.

Language: Английский

---

Advancing mechanochemical synthesis by combining milling with different energy sources

Nature Reviews Chemistry, Journal Year: 2022, Volume and Issue: 7(1), P. 51 - 65

Published: Nov. 21, 2022

Language: Английский

---

Salient Achievements in Synthetic Organic Chemistry Enabled by Mechanochemical Activation

Synthesis, Journal Year: 2023, Volume and Issue: 55(16), P. 2439 - 2459

Published: May 3, 2023

Abstract Although known for millennia, it is only recently that mechanochemistry has received serious attention by chemists. Indeed, during the past 15 years an extraordinary number of reports concerning solid-state chemical transformations through grinding and milling techniques have been recorded. This short review discusses circumstances led this renaissance, highlighting present intense interest in so-called green chemistry, enabling capacity to handle insoluble substrates, identification profound influence additives can on mechanochemically activated reactions. The core account focuses salient developments synthetic organic especially amino acid peptide­ mechanosynthesis, successful employment mechanochemical activation combination with asymmetric organocatalysis, promising enzymatic whole cell biocatalysis, remarkable achievement multicomponent selective reactions via complex, multistep reaction pathways, mechanosynthesis representative heterocycles. final section comments some pending tasks area, such as scaling-up processes be practical use industry, requirement easier more efficient control parameters monitoring devices, consequently careful analysis additional procedures a proper understanding phenomena. 1 Introduction 2 Brief History Mechanochemistry 3 Milling Equipment Reaction Parameters 4 Attributes That Propelled Its Present Renaissance 4.1 Enormous Attention Being Presently Paid Sustainable Chemistry 4.2 Reduced Energy Consumption 4.3 Additive-Based 4.4 Handling Insoluble Reactants 4.5 ‘Impossible’ Reactions Are Successful 4.6 Air- Water-Sensitive Reagents Ball 5 Salient Developments Mechanochemical Activation Synthetic Organic 5.1 Amino Acid Peptide Mechanosynthesis 5.2 Asymmetric Synthesis Organocatalysis under Ball-Milling Conditions 5.3 Mechanoenzymology 5.4 Multicomponent Activated 5.5 Heterocycles Modification 6 Future Directions 6.1 Scaling-Up Protocols 6.2 Temperature-Controlled 6.3 Understanding Transformations 6.4 Emerging Techniques 7 Conclusions

Language: Английский

---

Tinkering with Mechanochemical Tools for Scale Up

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(44)

Published: April 28, 2023

Mechanochemistry provides an environmentally benign platform to develop more sustainable chemical processes by limiting raw materials, energy use, and waste generation while using physically smaller equipment. A continuously growing research community has steadily showcased examples of beneficial mechanochemistry applications at both the laboratory preparative scale. In contrast solution-based chemistry, mechanochemical have not yet been standardized, thus scaling up is still a nascent discipline. The purpose this Minireview highlight similarities, differences challenges various approaches that successfully applied for range scales. We hope provide discussion starting point those interested in further developing commercial use and/or industrialisation.

Language: Английский

---

Mechanochemical Approach for Air‐Tolerant and Extremely Fast Lithium‐Based Birch Reductions in Minutes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: March 22, 2023

Birch reduction has been widely used in organic synthesis for over half a century as powerful method to dearomatize arenes into 1,4-cyclohexadiene derivatives. However, the conventional reaction using liquid ammonia requires laborious procedures ensure inert conditions and low temperatures. Although several ammonia-free modifications have reported, development of an operationally simple, efficient, scalable protocol remains challenge. Herein, we report lithium-based air without special operating ball-milling technique. This is characterized by its operational simplicity extremely short time (within 1 min), probably owing situ mechanical activation lithium metal, broad substrate scope, no requirement dry bulk solvents. The potential our flash also demonstrated efficient bioactive target molecules gram-scale synthesis.

Language: Английский

---

Mechanochemical Grignard Reactions with Gaseous CO₂ and Sodium Methyl Carbonate**

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(9)

Published: Dec. 23, 2021

Abstract A one‐pot, three‐step protocol for the preparation of Grignard reagents from organobromides in a ball mill and their subsequent reactions with gaseous carbon dioxide (CO 2 ) or sodium methyl carbonate providing aryl alkyl carboxylic acids up to 82 % yield is reported. Noteworthy are short reaction times significantly reduced solvent amounts [2.0 equiv. liquid assisted grinding (LAG) conditions]. Unexpectedly, bromides methoxy substituents lead symmetric ketones as major products.

Language: Английский

---

Mechanochemical techniques for the activation and use of zero-valent metals in synthesis

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(10), P. 763 - 775

Published: July 21, 2022

Language: Английский

---

Access to a Labile Monomeric Magnesium Radical by Ball‐Milling

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(15)

Published: Feb. 2, 2022

In order to isolate a monometallic Mg radical, the precursor (Am)MgI⋅(CAAC) (1) was prepared (Am=tBuC(N-DIPP)

Language: Английский

---

Temperature‐Controlled Mechanochemistry for the Nickel‐Catalyzed Suzuki–Miyaura‐Type Coupling of Aryl Sulfamates via Ball Milling and Twin‐Screw Extrusion.**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(44)

Published: Sept. 9, 2022

Abstract The use of temperature‐controlled mechanochemistry to enable the mechanochemical nickel‐catalyzed Suzuki–Miyaura coupling is herein described. Transitioning from a capricious room‐temperature protocol, through heated, PID‐controlled programmable jar heater manifold was required deliver an efficient method for aryl sulfamates (derived ubiquitous phenols) and boronic acid species. Furthermore, this process conducted using base‐metal nickel catalyst, in absence bulk solvent, air/moisture sensitive reaction set‐ups. This methodology showcased translation large‐scale twin‐screw extrusion enabling 200‐fold scale increase, producing decagram quantities C−C coupled material.

Language: Английский

---

Mechanochemically Generated Calcium‐Based Heavy Grignard Reagents and Their Application to Carbon–Carbon Bond‐Forming Reactions

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(41)

Published: July 20, 2022

In sharp contrast to the use of conventional magnesium-based Grignard reagents (R-MgX), application calcium-based heavy (R-CaX) in organic synthesis remains poorly explored. This is mainly due lack experimentally simple ways access such organocalcium nucleophiles from readily available starting materials under mild conditions. Here, we show that a mechanochemical technique using ball milling allows generation aryl halides and commercially calcium metal without complicated pre-activation processes. Notably, all experimental operations can be carried out air. Our operationally protocol enables rapid development novel cross-electrophile-coupling reactions mediated by arylcalcium nucleophiles, which are rather difficult reagents. method will allow synthetic chemists unique reactivity nucleophiles.

Language: Английский

---