Ever-evolving catalyst advances in synthetic protocols using water as a reaction medium have enriched the understanding of sustainable organic chemistry. Because conventional classification and definitions were ambivalent, it is proposed here that catalytic reactions using water be collectively called to be "in water", with further classification into seven types. When accelerated in water as heterogeneous mixtures, the reactions can be regarded as following an "on-water" mechanism. The original term "on water" coined by Sharpless is incongruous with catalytic reactions, whereas on-water used in this review covers all the interfaces involving water where chemical reactions are accelerated. As a result of the unconcluded dispute on the antiquated catalyst-free "on water" model, the modified model defines three water layers: water molecules that are oriented to extrude protons toward the oil phase in the inner layer, those enwrapped by a secondary layer, and finally the bulk water layer. In light of the latitudinous outlook on the role of water at the interface, selected examples of reactions, in particular those reported over the past decade, that follow an "on-water" mechanism are reviewed herein.

Reactions in Water Involving the "On-Water" Mechanism.

Unprecedented double S2- templated Ag27 clusters have been stabilized by 5,10,15,20-tetra(4-pyridyl)porphyrin (TPyP-H2 ) ligands to afford a robust 2D metal-organic framework (Ag27-MOF). This silver cluster-assembled material serves as a highly efficient heterogeneous catalyst for the cyclization of both terminal and internal propargylamines with CO2 under atmospheric pressure. Density functional theory (DFT) calculations illustrate that the high catalytic activity and broad substrate scope are attributable to the saddle-shaped metallic node in Ag27-MOF, which features an accessible platform with high-density silver atoms as π-Lewis acid sites for activating C≡C triple bonds. As a result, different sterically hindered alkyne substrates can be effectively activated through π-interactions with these cationic silver centers.

Ambient Chemical Fixation of CO2 Using a Robust Ag27 Cluster-Based Two-Dimensional Metal-Organic Framework.

C-H functionalization has been emerging as a powerful method to establish carbon-carbon and carbon-heteroatom bonds. Many efforts have been devoted to transition-metal-catalyzed direct transformations of C-H bonds. Metal carbenes generated in situ from transition-metal compounds and diazo or its equivalents are usually applied as the transient reactive intermediates to furnish a catalytic cycle for new C-C and C-X bond formation. Using this strategy compounds from unactivated simple alkanes to complex molecules can be further functionalized or transformed to multi-functionalized compounds. In this area, transition-metal-catalyzed carbene insertion to C-H bonds has been paid continuous attention. Diverse catalyst design strategies, synthetic methods, and potential applications have been developed. This critical review will summarize the advance in transition-metal-catalyzed carbene insertion to C-H bonds dated up to July 2021, by the categories of C-H bonds from aliphatic C(sp3)-H, aryl (aromatic) C(sp2)-H, heteroaryl (heteroaromatic) C(sp2)-H bonds, alkenyl C(sp2)-H, and alkynyl C(sp)-H, as well as asymmetric carbene insertion to C-H bonds, and more coverage will be given to the recent work. Due to the rapid development of the C-H functionalization area, future directions in this topic are also discussed. This review will give the authors an overview of carbene insertion chemistry in C-H functionalization with focus on the catalytic systems and synthetic applications in C-C bond formation. 

Recent advances in transition-metal-catalyzed carbene insertion to C–H bonds

Aliphatic azides are a versatile class of compounds found in a variety of biologically active pharmaceuticals. These compounds are also recognized as useful precursors for the synthesis of a range of nitrogen-based scaffolds of therapeutic drugs, biologically active compounds, and functional materials. In light of the growing importance of aliphatic azides in both chemical and biological sciences, a vast array of synthetic strategies for the preparation of structurally diverse aliphatic azides have been developed over the past decades. However, to date, this topic has not been the subject of a dedicated review. This review aims to provide a concise overview of modern synthetic strategies to access aliphatic azides that have emerged since 2010. The discussed azidation reactions include (a) azidation of C-C multiple bonds, (b) azidation of C-H bonds, (c) the direct transformation of vinyl azides into other aliphatic azides, and (d) miscellaneous reactions to access aliphatic azides. We critically discuss the synthetic outcomes and the generality and uniqueness of the different mechanistic rationale of each of the selected reactions. The challenges and potential opportunities of the topic are outlined.

New Strategies for the Synthesis of Aliphatic Azides.

The azido group is found in large numbers of natural products, drugs, biochemicals and materials and to date, many elegant and useful methods for the synthesis of organic azides and their transformations have been documented. In this review, we provide a summary of the state of the art of radical azidation for the construction of C(sp3)-N3 bonds. There is a specific emphasis on the synthetic reactions involving C(sp3)-H azidation, decarboxylative azidation and difunctionalized azidation of olefins. This review will be useful to those working in this field and hopefully could inspire further development of radical azidation reactions.

Radical azidation as a means of constructing C(sp3)-N3 bonds

Alkynes are one of the most abundant chemicals in organic chemistry, and therefore the development of catalytic reactions to transform alkynes into other useful functionalities is of great value. In recent decades, extraordinary advances have been made in this area with transition-metal catalysis, and silver-based reagents are ideal for the activation of alkynes. This high reactivity is probably due to the superior π-Lewis acidic, carbophilic behavior of silver(I), allowing it to selectively activate carbon-carbon triple bonds (C≡C) through the formation of a silver-π complex. Within this field, we have been interested in the activation and subsequent reactions of readily accessible terminal alkynes for the synthesis of nitrogen-containing compounds, which has generally received less attention than methods involving internal alkynes. This is possibly due to the lack of suitable reactive reaction partners that are compatible under transition metals. Therefore, a thorough understanding of the factors that influence homogeneous silver catalysis and the identification of the appropriate reaction partners can provide a powerful platform for designing more efficient silver-catalyzed reactions of terminal alkynes. In this context, we envisioned that using readily available, environmentally benign, and inexpensive trimethylsilyl azide (TMSN3) or an isocyanide as the nitrogen-donor would be the key to develop novel reactions of terminal alkynes.This Account describes our efforts since 2013 toward the development of novel silver-catalyzed tandem reactions of terminal alkynes with either TMSN3 or isocyanides for the assembly of various nitrogen-containing compounds. The first section of this Account discusses the initial developments in the silver-catalyzed hydroazidation of terminal alkynes with TMSN3 and the subsequent advances made in our laboratory. We first describe the discovery and experimental and computational mechanistic investigations of silver-catalyzed hydroazidation reactions, which is the most efficient strategy reported to date for accessing vinyl azides. Mechanistic study of this hydroazidation reaction provides an alternative activation mode for terminal alkyne conversion in transition metal catalysis. We then present the chemistry of in situ generated vinyl azides, including one-pot tandem radical addition/cyclization or migration reactions of terminal alkynes to access a variety of nitrogen-containing molecules. Finally, we discuss the one-pot, multistep tandem hydroazidation and 1,2-azide migratory gem-difluorination of terminal alkynes for the synthesis of β-difluorinated alkyl azides. The second section describes the silver-catalyzed coupling reactions between terminal alkynes and isocyanides, which offer a straightforward method for accessing synthetically useful building blocks, such as pyrroles, allenamides, benzofuran, vinyl sulfones, indazolines, propiolonitriles, and pyrazoles. The high efficiency, mild conditions, low cost, broad substrate scope, high chemo- and regioselectivity, step economy, and ecofriendliness of the developed approaches make them attractive and practical. The progress in this area provides guiding principles for designing new reactions of terminal alkynes that can be extended to various nitrogen-containing molecules of interest to medicinal and materials chemists.

Silver-Catalyzed Activation of Terminal Alkynes for Synthesizing Nitrogen-Containing Molecules.

Site-Selective C–H Benzylation of Alkanes with N-Triftosylhydrazones Leading to Alkyl Aromatics

Diazo compounds and isocyanides are reactive functionalities and valuable building blocks commonly utilized in organic synthesis. Their cross-coupling for the synthesis of useful isolable ketenimin...

Palladium(II)-Catalyzed Cross-Coupling of Diazo Compounds and Isocyanides to Access Ketenimines

The hydroazidation of alkynes is the most straightforward way to access vinyl azides—versatile building blocks in organic synthesis. We previously realized such a fundamental reaction of terminal a...

AgN3-Catalyzed Hydroazidation of Terminal Alkynes and Mechanistic Studies.

The [2+1] cycloaddition reaction of a metal carbene with an alkene can produce important cyclopropane products for synthetic intermediates, materials, and pharmaceutical applications. However, this reaction is often accompanied by side reactions, such as coupling and self-coupling, so that the yield of the cyclopropanation product of non-silver transition-metal carbenes and hindered alkenes is generally lower than 50 %. To solve this problem, the addition of a low concentration of diazo compound (decomposition of sulfonyl hydrazones) to alkenes catalyzed by either CuOAc or PdCl2 was studied, but side reactions could still not be avoided. Interestingly, however, the yield of cyclopropanation products for such hindered alkenes were as high as 99 % with AgOTf as a catalyst. To explain this unexpected phenomenon, reaction pathways have been computed for four different catalysts by using DFT. By combining the results of these calculations with those obtained experimentally, it can be concluded that the efficiency of the silver catalyst is due to the barrierless concerted cycloaddition step and the kinetic inhibition of side reactions by a high concentration of alkene.

Shanshan Cao

Papers

Silver-Catalyzed Activation of Terminal Alkynes for Synthesizing Nitrogen-Containing Molecules.

Site-Selective C–H Benzylation of Alkanes with N-Triftosylhydrazones Leading to Alkyl Aromatics

Palladium(II)-Catalyzed Cross-Coupling of Diazo Compounds and Isocyanides to Access Ketenimines

AgN3-Catalyzed Hydroazidation of Terminal Alkynes and Mechanistic Studies.

Computational Insights into Different Mechanisms for Ag-, Cu-, and Pd-Catalyzed Cyclopropanation of Alkenes and Sulfonyl Hydrazones.