The Development of Catalytic Nucleophilic Additions of Terminal Alkynes in Water

Abstract

One of the major research endeavors in synthetic chemistry over the past two decades is the exploration of synthetic methods that work under ambient atmosphere with benign solvents, that maximize atom utilization, and that directly transform natural resources, such as renewable biomass, from their native states into useful chemical products, thus avoiding the need for protecting groups. The nucleophilic addition of terminal alkynes to various unsaturated electrophiles is a classical (textbook) reaction in organic chemistry, allowing the formation of a C-C bond while simultaneously introducing the alkyne functionality. A prerequisite of this classical reaction is the stoichiometric generation of highly reactive metal acetylides. Over the past decade, our laboratory and others have been exploring an alternative, the catalytic and direct nucleophilic addition of terminal alkynes to unsaturated electrophiles in water. We found that various terminal alkynes can react efficiently with a wide range of such electrophiles in water (or organic solvent) in the presence of simple and readily available catalysts, such as copper, silver, gold, iron, palladium, and others. In this Account, we describe the development of these synthetic methods, focusing primarily on results from our laboratory. Our studies include the following: (i) catalytic reaction of terminal alkynes with acid chloride, (ii) catalytic addition of terminal alkynes to aldehydes and ketones, (iii) catalytic addition of alkynes to C=N bonds, and (iv) catalytic conjugate additions. Most importantly, these reactions can tolerate various functional groups and, in many cases, perform better in water than in organic solvents, clearly defying classical reactivities predicated on the relative acidities of water, alcohols, and terminal alkynes. We further discuss multicomponent and enantioselective reactions that were developed. These methods provide an alternative to the traditional requirement of separate steps in classical alkyne reactions, including the pregeneration of metal acetylides with stoichiometric, highly basic reagents and the preprotection of sensitive functional groups. Accordingly, these techniques have greatly enhanced overall synthetic efficiencies and furthered our long-term objective of developing Grignard-type reactions in water.

Glycerol: A promising Green Solvent and Reducing Agent for Metal-Catalyzed Transfer Hydrogenation Reactions and Nanoparticles Formation

“…Nowadays, most solvents employed are substances derived from fossil fuels and have a negative impact on the health and the environment. In addition to water [24][25][26][27], biomass-derived chemicals are probably the most promising alternatives to replace these harmful solvents [19][20][21][22]. Its renewable origin and unique combination of physicochemical properties, such as high polarity, low toxicity and flammability, high boiling point, ability to form strong hydrogen bonds and to dissolve both organic and inorganic compounds (salts, acids, bases and transition metal complexes), make glycerol a good candidate to be employed as green reaction medium for synthetic chemistry [28].…”

Synthesis, structural characterization, and reactivity of (thiolato)bismuth complexes as potential water-tolerant Lewis acid catalysts

“…1 Central to this is the identification of catalysts that are stable under these conditions. 2,3,4,5 Compounds of low toxicity main group metals, such as bismuth salts (e.g.…”

Synthesis and Spectral Investigation of Co(II), Ni(II), Cu(II) and Zn(II) Complexes with Novel N4 Ligands

“…The coordination compounds of transition metals are found to have added a great deal of chemistry and made it more interesting and applied oriented and applications span the areas such as biological, industrial, pharmaceutical, catalysis and material chemistry, etc., [1][2][3][4][5][6][7]. Among different types of ligands that influence the chemistry of transition metals and modify their spectral, catalytic and biological properties, the Schiff bases occupy a special place [7][8][9][10][11][12][13].…”