Water as the reaction medium in organic chemistry: from our worst enemy to our best friend

Cortes‐Clerget, Margery; Yu, Tzu‐Yu; Kincaid, Joseph R. A.; Walde, Peter; Gallou, Fabrice; Lipshutz, Bruce H.

doi:10.1039/d0sc06000c

Cited by 377 publications

(253 citation statements)

References 123 publications

(166 reference statements)

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“…We recently reported an Fmoc/ t‐ Bu SPPS method in which DMF was replaced with the greener dimethyl sulfoxide (DMSO)/EtOAc, starting materials were minimized, and solvents were recycled and reused, which reduced both the environmental impact as well as the cost of the synthesis [29] . As water as Nature's own solvent is an attractive medium for organic synthesis [30] we envisaged that our approach to peptide synthesis based on efficient use of starting materials and recycling of solvents [29] could be elevated by advancing an aqueous variant of Fmoc/ t‐ Bu SPPS. In recent years, the challenge of amide bond formation under aqueous conditions has been overcome by various protocols for amide [31] and peptide [32] synthesis.…”

Section: Methodsmentioning

confidence: 99%

Circular Aqueous Fmoc/t‐Bu Solid‐Phase Peptide Synthesis

Pawlas

Rasmussen

2021

ChemSusChem

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Circular economy and aqueous synthesis are attractive concepts for sustainable chemistry. Here it is reported that the two can be combined in the universal method for peptide chemistry, fluorenylmethoxycarbonyl(Fmoc)/t‐Bu solid‐phase peptide synthesis (SPPS). It was demonstrated that Fmoc/t‐Bu SPPS could be performed under aqueous conditions using standard Fmoc amino acids (AAs) employing TentaGel S as resin and 4 : 1 mixture of water with inexpensive green solvent PolarClean. This resin/solvent combination played a crucial dual role by virtue of improving resin swelling and solubility of starting materials. In a model coupling, TCFH and 2,4,6‐collidine afforded a full conversion at only 1.3 equiv. AA, and these conditions were used in SPPS of Leu enkephaline amide affording the model peptide in 85 % yield and 86 % purity. A method to recycle the waste by filtration through a mixed ion exchange resin was developed, allowing reusing the waste without affecting quality of the peptide. The method herein obviates the use of unconventional or processed AAs in aqueous SPPS while using lower amounts of starting materials. By recycling/reusing SPPS waste the hazardous dipolar aprotic solvents used in SPPS were not only replaced with an aqueous medium, solvent use was also significantly reduced. This opens up a new direction in aqueous peptide chemistry in which efficient use of inexpensive starting materials and waste minimization is coupled with the universal Fmoc/t‐Bu SPPS.

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Section: Methodsmentioning

confidence: 99%

Circular Aqueous Fmoc/t‐Bu Solid‐Phase Peptide Synthesis

Pawlas

Rasmussen

2021

ChemSusChem

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“…This was chemistry truly 'in water', rather than 'on water', and certainly not 'with water.' 1,15 These are important distinctions to be made early and made unequivocally, especially if we wanted to avoid a future 'debunking' by Donna Blackmond! 16 Ouch!…”

Section: Account Synlettmentioning

confidence: 99%

Illuminating a Path4914. Copyright 2016 Wiley for Organic Synthesis Towards Sustainability. No One Said It Would Be Easy…

Lipshutz¹

2021

Synlett

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A personalized account is presented describing some of the stories behind the scenes in efforts to convert organic chemistry into a more sustainable discipline. These are part of a group ‘crusade’ started almost 15 years ago aimed at providing technologies illustrative of how key reactions used today can be ‘faster, better, cheaper’ when run in recyclable water. Hence, the option now exists to do organic synthesis in a far more environmentally responsible fashion. By contrast, most of organic chemistry developed over the past 200 years that relies on organic solvents continues to generate enormous amounts of pollution, while depleting finite petroleum reserves and our supplies of many precious and base metals. Making the switch to water, Nature’s chosen reaction medium, akin to that in which bio-catalysis is typically performed, is inevitable.1 The Story Begins: A Different Type of Prejudice2 Are We up to the Challenge? Too Late Now…3 ‘Impossible’ Reactive Metal Chemistry in Water4 Didn’t I Once Say: ‘It’s All about the Ligand’?5 What Happens When Our Supply of Palladium Runs Out?6 What Are the Implications from These Tales for Today and Tomorrow?7 What Is the ‘Broader Impact’ of This Work?8 The Bottom Line…

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“…From environmental, safety, and economic perspectives, heterogeneous catalysis using water as the reaction medium has attracted more and more attention, [ 14 ] owing to that water is cheap, abundantly available, nontoxic and nonflammable. This is particularly true for biocatalytic systems because water is the preferred solvent for enzymes.…”

Section: Background and Originality Contentmentioning

confidence: 99%

Polydopamine‐Encapsulated Dendritic Organosilica Nanoparticles as Amphiphilic Platforms for Highly Efficient Heterogeneous Catalysis in Water

et al. 2021

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Main observation and conclusion Aqueous heterogeneous catalysis is a green, sustainable catalytic process that attracts increasing attention, but it often suffers from poor mass transfer, substrate adsorption and catalyst dispersion. Herein, we synthesized a type of amphiphilic core‐shell catalysts with a hydrophilic polydopamine (PDA) shell and a hydrophobic dendritic organosilica nanoparticle (DON) core for heterogeneous catalysis in water. The hydrophilic shell allowed the catalyst dispersing well in water, and the hydrophobic core facilitated the absorption of organic reactants. The hierarchical core‐shell structure facilitated rational arrangement of the location of catalytic species to match the reaction sequence. The obtained metal, enzyme and metal‐enzyme amphiphilic catalysts demonstrated improved stability, selectivity and activity in aqueous reactions, including Pd‐catalyzed cross‐couplings (Suzuki, Liebeskind‐Srogl, Heck and Sonogashira), enzymatic enantioselective reduction, chemoenzymatic cascade synthesis of chiral compounds and chemoenzymatic cascade degradation of organophosphates. The amphiphilic catalysts could be easily in situ recovered, and their high catalytic performance was sustained for five cycles.

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Water as the reaction medium in organic chemistry: from our worst enemy to our best friend

Abstract: A review that highlights water as the logical reaction medium in which organic chemistry can be practiced. The key roles that water can play in directing reaction outcomes, including impacting mechanistic features, are discussed using selected examples.

Cited by 377 publications

References 123 publications

Circular Aqueous Fmoc/t‐Bu Solid‐Phase Peptide Synthesis

Circular Aqueous Fmoc/t‐Bu Solid‐Phase Peptide Synthesis

Illuminating a Path4914. Copyright 2016 Wiley for Organic Synthesis Towards Sustainability. No One Said It Would Be Easy…

Polydopamine‐Encapsulated Dendritic Organosilica Nanoparticles as Amphiphilic Platforms for Highly Efficient Heterogeneous Catalysis in Water

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