Intramolecular reactions of N-acyliminium intermediates

The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C, as well as synthesis of simplified lobatamide analogues, is reported. Cu(I)-mediated enamide formation methodology has been developed to prepare the highly unsaturated enamide side chain of the natural product and analogues. A key fragment coupling employs base-mediated esterification of a β-hydroxy acid and a salicylate cyanomethyl ester. Three additional stereoisomers of lobatamide C have been prepared using related synthetic routes. The stereochemistry at C8, C11, and C15 of lobatamide C was assigned by comparison of stereoisomers and X-ray analysis of a crystalline derivative. Synthetic lobatamide C, stereoisomers, and simplified analogues have been evaluated for inhibition of bovine chromaffin granule membrane V-ATPase. The salicylate phenol, enamide NH, and ortho-substitution of the salicylate ester have been shown to be important for V-ATPase inhibitory activity.

Lobatamide C: Total Synthesis, Stereochemical Assignment, Preparation of Simplified Analogues, and V-ATPase Inhibition Studies

Episulfonium ions: myth and reality

Publisher Summary There are three simple organic oxyacids of sulfur: (1) sulfenic acids (RSOH), (2) sulfinic acids (RSO2H), and (3) sulfonic acids (RSO3H). Of these, the sulfonic acids are the most stable, and they and their derivatives (RSO2Y) are very commonly encountered in organic chemistry. Sulfinic acids, while often somewhat unstable thermally, have also been known for a long time. Sulfenic acids, on the other hand, are for the most part elusive reactive intermediates. Only a few, possessing special structural features, have long enough lifetimes at room temperature to allow their actual isolation. Certain derivatives of sulfenic acids, such as their acid chlorides, RSCI, are well-known, isolable, albeit reactive, compounds. In sulfur chemistry, compounds that are formally the anhydrides of the organic oxyacids of sulfur, or are mixed anhydrides derived from two oxyacids of differing oxidation state, generally have quite distinctive chemistry of their own. In this context, the chapter discusses the structure and the behavior of a particular oxyacid of sulfur highlighting the behavior of the corresponding anhydride.

Mechanisms and Reactivity in Reactions of Organic Oxyacids of Sulfur and their Anhydrides

Publisher Summary This chapter discusses the experimental conditions, under which it is possible to obtain data relevant to the study of the bromination mechanism, and presents the evidence for the occurrence of charge transfer complexes and cationic intermediates on the reaction pathway. The chapter presents the kinetic substituent and solvent effects on this cation-forming halogenation; these effects are discussed in terms of kinetic selectivity, transition-state shifts and solvation. From an energetic point of view, free bromine addition can be considered as an ionization process leading from a neutral reagent to a cation-anion pair in a single elementary step, most work on this electrophilic addition can be used to understand how charge separation and stabilization occur in the organic reactions. Bromination thus appears as a suitable model, and is complementary to the conventional heterolytic substitutions. The association of kinetics and stereochemistry is particularly useful for obtaining data on the structure, open or bridged depending on the substituents of bromination intermediates.

Electrophilic Bromination of Carbon—Carbon Double Bonds: Structure, Solvent and Mechanism

Acid-catalyzed hydrolysis of N-vinylacetamides (enamides). Substituent effects of the acetamido and amino groups and linear free energy correlations of cyclohexene reactivities

THE INFLUENCE OF TEMPERATURE ON THE STEREOCHEMISTRY OF THE ADDITION OF p-CHLOROBENZENESULFENYL CHLORIDE TO cis- AND trans-2-BUTENE

Non-empirical SCF-MO calculations, using two different basis sets, were carried out on a cyclic sulphurane and a thiiranium–chloride ion-pair. The calculated energies indicated that in the gas phase the covalent cyclic sulphurane is favoured over the ionic species. The activation energy for the internal collapse of the cyclic sulphurane to product was calculated to be 42 kcal mol–1, well below the energy of the thiiranium–chloride ion-pair. These results support the suggestion that thiiranium ions prevail in polar solvents but tetracovalent sulphur intermediates are favoured in solvents of low polarity.

Ab initio SCF-MO study of the reaction intermediates formed by addition of thiohypochlorous acid to ethylene

The thero-anti-Markownikoff and threo-Markownikoff adducts are the products of addition of 4-chloro-and 2,4-dinitrobenzenesulfenyl chloride to cis-1-phenylpropene while only the erythro Markownikoff adduct is the product of addition to trans-1-phenylpropene. The addition reaction follows second order kinetics, first order in both olefin and arylsulfenyl chloride, with the rate of addition to the trans-olefin faster than to the cis. These results are consistent with a mechanism involving bridged transition states in both the rate and product determining steps.

The Addition of 4-Chloro- and 2,4-Dinitrobenzenesulfenyl Chloride to cis- and trans-1-Phenylpropene

The reactivity of a series of cyclopropylalkenes, as well as norbornene and cyclohexene, with p-chlorobenzenesulfenyl chloride in CH2Cl2 at 25 °C have been measured. Rates of reaction of several of...

Valeria M. Csizmadia

Papers

Acid-catalyzed hydrolysis of N-vinylacetamides (enamides). Substituent effects of the acetamido and amino groups and linear free energy correlations of cyclohexene reactivities

THE INFLUENCE OF TEMPERATURE ON THE STEREOCHEMISTRY OF THE ADDITION OF p-CHLOROBENZENESULFENYL CHLORIDE TO cis- AND trans-2-BUTENE

Ab initio SCF-MO study of the reaction intermediates formed by addition of thiohypochlorous acid to ethylene

The Addition of 4-Chloro- and 2,4-Dinitrobenzenesulfenyl Chloride to cis- and trans-1-Phenylpropene

Reactivity of cyclopropylalkenes with p-chlorobenzenesulfenyl chloride