The hydrogen bond is the most important of all directional intermolecular interactions. It is operative in determining molecular conformation, molecular aggregation, and the function of a vast number of chemical systems ranging from inorganic to biological. Research into hydrogen bonds experienced a stagnant period in the 1980s, but re-opened around 1990, and has been in rapid development since then. In terms of modern concepts, the hydrogen bond is understood as a very broad phenomenon, and it is accepted that there are open borders to other effects. There are dozens of different types of X-H.A hydrogen bonds that occur commonly in the condensed phases, and in addition there are innumerable less common ones. Dissociation energies span more than two orders of magnitude (about 0.2-40 kcal mol(-1)). Within this range, the nature of the interaction is not constant, but its electrostatic, covalent, and dispersion contributions vary in their relative weights. The hydrogen bond has broad transition regions that merge continuously with the covalent bond, the van der Waals interaction, the ionic interaction, and also the cation-pi interaction. All hydrogen bonds can be considered as incipient proton transfer reactions, and for strong hydrogen bonds, this reaction can be in a very advanced state. In this review, a coherent survey is given on all these matters.

The hydrogen bond in the solid state.

In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.

Palladium-catalyzed cross-coupling reactions in total synthesis.

Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

The Diels-Alder reaction has both enabled and shaped the art and science of total synthesis over the last few decades to an extent which, arguably, has yet to be eclipsed by any other transformation in the current synthetic repertoire. With myriad applications of this magnificent pericyclic reaction, often as a crucial element in elegant and programmed cascade sequences facilitating complex molecule construction, the Diels-Alder cycloaddition has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. In celebration of the 100th anniversary of Alder's birth, selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of total synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized.

https://www.ch.ic.ac.uk/local/organic/pericyclic/DA.pdf

The Diels--Alder reaction in total synthesis.

Methods for Selective Modifications of Cyclodextrins.

In the reaction of p-nitrophenyl methanesulfonate (1) with alkali-metal ethoxides, it is found that potassium ethoxide in the presence of excess 2.2.2 cryptand is more reactive than potassium ethoxide alone or in the presence of excess 18-crown-6. An upward curvature in the plot of k[sub obs] vs [KOEt][sub o] in the presence of 2.2.2 cryptand is interpreted as arising from parallel reactions of free ethoxide ion and the ion pair of ethoxide ion with cryptated potassium ion ([K [contained in] 2.2.2][sup +]EtO[sup [minus]]), the latter being more reactive than the former. It is shown that the ester reacts predominantly by an E1cb-type elimination mechanism, and the potassium cryptate appears to stabilize the transition state for leaving-group departure by electrostatic interactions through an 18-membered ring window' in the cryptand. 13 refs., 3 figs., 6 tabs.

Potassium cryptate catalysis in the elimination reaction of a sulfonate ester

The rates of the nucleophilic displacement reactions of aryl benzenesulfonates with alkali-metal ethoxides (LiOEt, KOEt, and KOEt in the presence of complexing agents) in anhydrous ethanol at 25 o C have been studied by spectrophotometric techniques. For all esters studied, the order of reactivity if LiOEt<EtO − <KOEt. Metal ion catalysis (K + ) and inhibition (Li + ) are proposed to ocur via reactive alkali-metal ethoxide ion pairs. Second-order rate constants for free ethoxide and metal-ethoxide ion pairs are calculated. Hammett treatment of leaving-group effects results in correlation of rate data with σ 0 substituent constants and large ρ values of 3.0 (KOEt), 3.1 (LiOEt), and 3.4 (EtO − ). A rate-determining transition state having well-advanced EtO-S bond formation but little S-OAr bond breakage is proposed

Metal ion catalysis in nucleophilic displacement reactions at carbon, phosphorus, and sulfur centers. 4. Mechanism of the reaction of aryl benzenesulfonates with alkali-metal ethoxides: catalysis and inhibition by alkali-metal ions

An improved route for the synthesis of cyclodextrin (CD)-based enzyme models having catalytic groups on the secondary face is presented. An epoxide derived from heptakis(6-O-tert-butyldimethylsilyl)-β-CD was prepared via intermediates that can be purified by conventional flash chromatography on a preparative scale. Reaction of β-cyclodextrin with; tert-butyldimethylsilyl chloride in pyridine gave heptakis(6-O-tert-butyldimethylsilyl)-β-CD (1). Treatment of 1 with N-tosylimidazole and NaOMe in chloroform gave mono(2-O-tosyl) heptakis(6-O-tert-butyldimethylsilyl)-β-CD (2) in 22% yield. The latter was converted smoothly to mono(2A, 3A-anhydro) heptakis(6-O-tert-butyldimethylsilyl)-β-CD (3), in which one glucose subunit has been converted to a manno-epoxide, by treatment with KOEt in refluxing ethanol (87% yield). Compounds 1, 2, and 3 were characterized by a variety of one- and two-dimensional NMR techniques. These results open the door to attachment of catalytic groups to the cyclodextrin in a well-defined ...

Cyclodextrin-based enzyme models. Part 1. Synthesis of a tosylate and an epoxide derived from heptakis(6-O-tert-butyldimethylsilyl)-β-cyclodextrin and their characterization using 2D NMR techniques. An improved route to cyclodextrins functionalized on the secondary face

The rate of the nucleophilic displacement reaction of p-nitrophenyl benzenesulfonate (1) with alkali metal ethoxides in ethanol at 25 °C has been studied by spectrophotometric techniques. For lithium ethoxide, sodium ethoxide, potassium ethoxide, and cesium ethoxide, the observed rate constants increase in the order LiOEt < NaOEt < CsOEt < KOEt. The effect of added crown ether and cryptand complexing agents was also investigated. Addition of complexing agent to the reaction of KOEt results in the rate decreasing to a minimum value corresponding to the reaction of free ethoxide. Conversely, addition of complexing agent to the reaction of LiOEt results in the rate increasing to a maximum value that is identical to the minimum value seen in the reaction of KOEt in the presence of excess complexing agent. In complementary experiments, alkali metal ions were added in the form of unreactive salts. Addition of a K+ salt to the reaction of KOEt increases the reaction rate, while addition of a Li+ salt to the reac...

Metal ion catalysis in nucleophilic displacement reactions at carbon, phosphorus, and sulfur centers. III. Catalysis vs. inhibition by metal ions in the reaction of p-nitrophenyl benzenesulfonate with ethoxide

Metal-ion catalysis in nucleophilic displacement reactions at carbon, phosphorus, and sulfur centers. 5. Alkali-metal ion catalysis and inhibition in the reaction of p-(trifluoromethyl)phenyl methanesulfonate with ethoxide ion

Marko J. Pregel

Papers

Potassium cryptate catalysis in the elimination reaction of a sulfonate ester

Metal ion catalysis in nucleophilic displacement reactions at carbon, phosphorus, and sulfur centers. 4. Mechanism of the reaction of aryl benzenesulfonates with alkali-metal ethoxides: catalysis and inhibition by alkali-metal ions

Cyclodextrin-based enzyme models. Part 1. Synthesis of a tosylate and an epoxide derived from heptakis(6-O-tert-butyldimethylsilyl)-β-cyclodextrin and their characterization using 2D NMR techniques. An improved route to cyclodextrins functionalized on the secondary face

Metal ion catalysis in nucleophilic displacement reactions at carbon, phosphorus, and sulfur centers. III. Catalysis vs. inhibition by metal ions in the reaction of p-nitrophenyl benzenesulfonate with ethoxide

Metal-ion catalysis in nucleophilic displacement reactions at carbon, phosphorus, and sulfur centers. 5. Alkali-metal ion catalysis and inhibition in the reaction of p-(trifluoromethyl)phenyl methanesulfonate with ethoxide ion