Water As the Reaction Medium in Organic Chemistry: from Our Worst Enemy to Our Best Friend

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2021 Jun 24

PMID 34163692

Citations 54

Authors

Margery Cortes-Clerget

Julie Yu

Joseph R A Kincaid

Peter Walde

Fabrice Gallou

Bruce H Lipshutz

Affiliations

Soon will be listed here.

Abstract

A review presenting water as the logical reaction medium for the future of organic chemistry. A discussion is offered that covers both the "on water" and "in water" phenomena, and how water is playing unique roles in each, specifically with regard to its use in organic synthesis.

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References

Lee B . The physical origin of the low solubility of nonpolar solutes in water. Biopolymers. 1985; 24(5):813-23. DOI: 10.1002/bip.360240507. View

Beare K, McErlean C . Revitalizing the aromatic aza-Claisen rearrangement: implications for the mechanism of 'on-water' catalysis. Org Biomol Chem. 2013; 11(15):2452-9. DOI: 10.1039/c3ob40118a. View

Bora P, Bihani M, Plummer S, Gallou F, Handa S . Shielding Effect of Micelle for Highly Effective and Selective Monofluorination of Indoles in Water. ChemSusChem. 2019; 12(13):3037-3042. DOI: 10.1002/cssc.201900316. View

Zhang Y, Luo L, Ge J, Yan S, Peng Y, Liu Y . "On Water" Direct Organocatalytic Cyanoarylmethylation of Isatins for the Diastereoselective Synthesis of 3-Hydroxy-3-cyanomethyl Oxindoles. J Org Chem. 2019; 84(7):4000-4008. DOI: 10.1021/acs.joc.8b03194. View

Jung Y, Marcus R . On the nature of organic catalysis "on water". J Am Chem Soc. 2007; 129(17):5492-502. DOI: 10.1021/ja068120f. View

Andersson M, Gallou F, Klumphu P, Takale B, Lipshutz B . Structure of Nanoparticles Derived from Designer Surfactant TPGS-750-M in Water, As Used in Organic Synthesis. Chemistry. 2018; 24(26):6778-6786. DOI: 10.1002/chem.201705524. View

Han J, Zhang J, Zhang W, Gao Z, Xu L, Jian Y . "On Water" Catalytic Aldol Reaction between Isatins and Acetophenones: Interfacial Hydrogen Bonding and Enamine Mechanism. J Org Chem. 2019; 84(12):7642-7651. DOI: 10.1021/acs.joc.9b00441. View

Cicco L, Sblendorio S, Mansueto R, Perna F, Salomone A, Florio S . Water opens the door to organolithiums and Grignard reagents: exploring and comparing the reactivity of highly polar organometallic compounds in unconventional reaction media towards the synthesis of tetrahydrofurans. Chem Sci. 2018; 7(2):1192-1199. PMC: 5975938. DOI: 10.1039/c5sc03436a. View

Butler R, Cunningham W, Coyne A, Burke L . The influence of water on the rates of 1,3-dipolar cycloaddition reactions: trigger points for exponential rate increases in water-organic solvent mixtures. Water-super versus water-normal dipolarophiles. J Am Chem Soc. 2004; 126(38):11923-9. DOI: 10.1021/ja040119y. View

10.

Slack E, Gabriel C, Lipshutz B . A palladium nanoparticle-nanomicelle combination for the stereoselective semihydrogenation of alkynes in water at room temperature. Angew Chem Int Ed Engl. 2014; 53(51):14051-4. PMC: 4448917. DOI: 10.1002/anie.201407723. View

11.

Narayan S, Muldoon J, Finn M, Fokin V, Kolb H, Sharpless K . "On water": unique reactivity of organic compounds in aqueous suspension. Angew Chem Int Ed Engl. 2005; 44(21):3275-9. DOI: 10.1002/anie.200462883. View

12.

Cortes-Clerget M, Akporji N, Zhou J, Gao F, Guo P, Parmentier M . Bridging the gap between transition metal- and bio-catalysis via aqueous micellar catalysis. Nat Commun. 2019; 10(1):2169. PMC: 6520378. DOI: 10.1038/s41467-019-09751-4. View

13.

Du Q, Freysz E, Shen Y . Surface vibrational spectroscopic studies of hydrogen bonding and hydrophobicity. Science. 1994; 264(5160):826-8. DOI: 10.1126/science.264.5160.826. View

14.

Beattie J, McErlean C, Phippen C . The mechanism of on-water catalysis. Chemistry. 2010; 16(30):8972-4. DOI: 10.1002/chem.201001705. View

15.

Zhou F, Li C . En route to metal-mediated and metal-catalysed reactions in water. Chem Sci. 2019; 10(1):34-46. PMC: 6334721. DOI: 10.1039/c8sc04271c. View

16.

Klibanov A . Improving enzymes by using them in organic solvents. Nature. 2001; 409(6817):241-6. DOI: 10.1038/35051719. View

17.

Dilauro G, DellAera M, Vitale P, Capriati V, Perna F . Unprecedented Nucleophilic Additions of Highly Polar Organometallic Compounds to Imines and Nitriles Using Water as a Non-Innocent Reaction Medium. Angew Chem Int Ed Engl. 2017; 56(34):10200-10203. DOI: 10.1002/anie.201705412. View

18.

Lee N, Cortes-Clerget M, Wood A, Lippincott D, Pang H, Moghadam F . Coolade. A Low-Foaming Surfactant for Organic Synthesis in Water. ChemSusChem. 2019; 12(13):3159-3165. DOI: 10.1002/cssc.201900369. View

19.

Butler R, Coyne A . Water: nature's reaction enforcer--comparative effects for organic synthesis "in-water" and "on-water". Chem Rev. 2010; 110(10):6302-37. DOI: 10.1021/cr100162c. View

20.

Zaks A, Klibanov A . Enzyme-catalyzed processes in organic solvents. Proc Natl Acad Sci U S A. 1985; 82(10):3192-6. PMC: 397741. DOI: 10.1073/pnas.82.10.3192. View