Preparation,Structure, and Reactions of Halomalondialehdes

The present progress report provides a survey of the synthesis, structure, and reactions of halomalondialdehydes, including “cyanomalondialdehyde” (diformylacetonitrile), the only pseudohalogen compound so far known in this series. Halomalondialdehydes are reactive compounds, applicable in a variety of ways, and are characterized particularly by their cyclizations with bifunctional compounds. Many of the reactions discussed below can be applied to substituted malondialdehydes other than those specified.     

Reactions of Isocyanide Dihalides and their Derivatives

The readily obtainable isocyanide dichlorides can be used as starting materials for the preparation of many types of substances. Exchange reactions yield numerous derivatives of formic and carbonic acids, while heterocyclic products have been obtained by reaction with bifunctional partners. The present article deals not only with reactions that are known from the literature but also with the author's own work, some of which has not been published before.     

Synthetic Aspects of Metal-Catalyzed Oxidations of Amines and Related Reactions

The metabolism of amines is governed by a variety of enzymes such as amine oxidase, flavoenzyme, and cytochrome P-450. A wide variety of compounds are produced such as ammonia and alkaloids in selective and clean oxidation reactions that proceed under mild reaction conditions. Simulation of the functions of these enzymes with simple transition metal complex catalysts may lead to the discovery of biomimetic, catalytic oxidations of amines and related compounds. Indeed, metal complex catalyzed oxidations have been found to proceed with high efficiency. The first section of this review discusses the dehydrogenative oxidations of amines with transition metal catalysts by transition metal catalysts that simulate amine oxidase. The second section highlights the catalytic oxidation of secondary amines to nitrones by simulation of flavoenzymes. The third section describes the simulation of the function of cytochrome P-450 with lowvalent ruthenium complexes and peroxides. Biomimetic ruthenium-catalyzed oxidations of tertiary amines, secondary amines, and other substrates such as amides, β-lactams, nitriles, alcohols, alkenes, ketones, and even nonactivated hydrocarbons can be performed selectively under mild conditions. These three general approaches provide highly useful strategies for synthesis of fine chemicals and biologically active compounds such as alkaloids, amino acids, and β-lactams.     

Syntheses with ketones,sulfur, and ammonia or amines at room temperature

A large number of preparatively interesting compounds have become readily available by the simultaneous action of sulfur and ammonia or amines on ketones. Direct syntheses of Δ³-thiazolines, Δ³-imidazoline-5-thiones, 5,6-dihydro-4H-1,4-thiazines, and the 1,2,3,4,5,6-hexathiocane system from ketones, sulfur, and ammonia or amines, and further possibilities for the synthesis of these heterocyclic systems have been proposed. Other heterocycles containing N or N and S (thiazoles, thiophenes, thiazolidines, tetrahydrothiazolo[2,3-c]-1,4-thiazines, thiomorpholines, 4-amino-2H-imidazoles, etc.) are readily obtainable by further reactions of these compounds. Hydrolysis of the Δ³-thiazolines yields α-mercapto ketones, which are the starting materials for other syntheses. Most of the syntheses described proceed at room temperature and at normal pressure.     

Synthesis and Reactions of Cyanic Esters

In 1963, it was found that sterically unhindered esters of cyanic acid, which had previously been considered unobtainable, could be easily prepared from phenols and cyanogen halides. Another synthesis, involving the thermolysis of thiatriazole derivatives, was discovered in 1964. The aryl cyanates in particular have since been found to have many uses as starting materials for the preparation of numerous new classes of compounds [e.g. derivatives of esters of imidocarbonic acid (esters, amides, imides, hydrazides, hydroxylamides, sulfamides, sulfhydrazides, semicarbazides); esters of imidocarboxylic acids; s-triazines, pyrimidines, tetrazoles, triazoles, triazolones, oxadiazoles, thiadiazoles, benzoxazinones, etc.], mainly by addition of nucleophilic or 1,3-dipolar reactants, or as aids e.g. in the elimination of H₂O or H₂S or in the transfer of CN groups.     

Synthesis and Reactions of Some 1-Thiapyran-4-One Derivatives

The preparation of some 3,5-diarylidene-1-thipyran-4-one derivatives (Ia-e) was described. Oxidation of Ia, b and Ie with hydrogen peroxide gave the corresponding dioxides (IIa-c). Reaction of the 1-thiapyran-4-one derivatives with bromine, Grignard reagents, and amines were studied. Structural assignments are supported by spectral (UV, IR, and ¹HNMR) data.     

Homolytic Cyclizations of N-Chloroalkenylamines

Many N-chloroalkylamines with double bond(s) dissociate homolytically to give chlorine atoms and aminyl radicals which undergo intramolecular cyclization reactions. Here, the nature of the aminyl radicals (neutral, protonated, or complexed to metal salts) appears to be important. The reactivity varies strongly from one species to another, and their selectivities can be different towards addition, substitution, abstraction, or dimerization reactions. A good synthetic tool appears to be the “complexed radical”, which is generated under mild conditions. A variety of β-functionalized, substituted, fused, or bridged azaheterocycles with alkaloid part structures thus become easily accessible in high yields, in a regio- and, possibly, stereoselective manner. Many examples are discussed illustrating the synthetic possibilities, limitations, and mechanistic features of this cyclization process.     

Pyrylium Mediated Transformations of Primary Amino Groups into Other Functional Groups. New Synthetic Methods (41)

The first pyrylium salt was isolated some 80 years ago, yet up to the 1950s only moderate interest was taken in the preparation, properties and uses of such salts. However, the past thirty years has seen a phenomenal growth in the literature pertinent to this area of chemistry: the importance of pyrylium salts as intermediates has been realized. They are readily prepared by a variety of generally applicable routes, and they are highly reactive towards nucleophiles. Together, this enables the convenient synthesis of a great variety of acyclic and heterocyclic compounds. We have used highly substituted pyrylium salts for the two-step conversion of the amino group in alkylamines RNH₂ into numerous other functionalities. In the first step, the pyrylium salts are converted with the amines into N-substituted pyridinium salts, which, in the second step, react with Nu^? to give the desired products RNu. In some cases the R moiety is also changed, e.g. by elimination. Studies of the reactions of these pyridinium salts have allowed interesting insights into the mechanisms of nucleophilic substitution, in addition to rendering aliphatic amines important synthetic intermediates. Thus, the method complements the diazotization procedure for the transformation of arylamines.     

Selective Reactions with Organoaluminum Compounds

With the aid of selected examples an overview is given of the development trends in highly discriminative reactions using organoaluminum compounds. (1) Isomerization of substituted oxiranes into allyl alcohols has been effected both stereo- and regioselectively by means of a new organoaluminum reagent, diethylaluminum 2,2,6,6-tetramethylpiperidide (DATMP); this reaction which provides a new route for the regiospecific transformation of allyl alcohols into 1,3-dienes. (2) A novel nonenzymic heterolysis of allylic phosphates of terpenoids has been effected by organoaluminum compounds and has enabled development of a new method for the selective synthesis of cyclic terpenes. (3) The reductive condensation of α-haloketones with carbonyl compounds in the presence of diethylaluminum chloride and zinc affords β-hydroxy-carbonyl derivatives in good yields with exclusion of undesired self-condensations products.     

Organic Reactions at Alumina Surfaces

Recent examples are given to emphasize that alumina can cause many different and often unexpected chemical reactions of adsorbed organic molecules. Recent developments are summarized to publicize that reagent-doped alumina can be used deliberately to achieve some very mild and highly selective organic transformations. The scope and limitations of organic reactions at alumina surfaces are discussed, and the advantages of these heterogeneous reactions over the corresponding homogeneous ones are pointed out. The role of the alumina and future problems are discussed briefly.     

Preparation and Properties,Reactions, and Applications of Radialenes

Radialenes are alicyclic compounds in which every ring atom is sp²-hybridized and carries an exocyclic C? C double bond. Because of their unusual topology and electronic structures these hydrocarbons have aroused the interest of both preparative chemists and theoreticians. Although considerable progress has been achieved recently, directed and efficient syntheses of these molecules remain a challenge. The study of their chemical behavior offers vast opportunities. Very recently materials scientists have become interested in these unusual compounds in their search for organic conductors and ferromagnets.     

Phase-Transfer Catalyzed Two-Phase Reactions in Preparative Organic Chemistry

Quaternary ammonium and phosphonium salts catalyze reactions between substances located partly in an aqueous and partly in an organic phase. Use of such phase-transfer catalysts simplifies and accelerates numerous reactions traditionally conducted in nonaqueous media. These reactions include carbene reactions, nucleophilic substitutions, alkylations of ketones and nitriles, Wittig and Darzens reactions, formation of ethers and esters. Other reactions such as hydrolysis and oxidation can be accelerated.     

Tertiary Phosphane/Tetrachloromethane,a Versatile Reagent for Chlorination,Dehydration, and P?N Linkage

In this review the processes occurring on the treatment of triphenylphosphane with tetrachloromethane are first reported; a key role is played here by (trichloromethyl)phosphonium chloride which reacts with a further amount of the phosphane to give the stable salt [chloro(triphenylphos-phoranediyl)methyl]triphenylphosphonium chloride by way of dichlorophosphorane and (dichloromethylene)phosphorane that is detectable only as an intermediate. The preparative application of the two-component system as a chlorinating, dehydrating, and P—N-linking reagent is ascribable to “phosphorylation”

1 Here and below, “phosphorylation” is used lo mean in general the formation of a phosphorus derivative. In the narrower sense this term denotes the introduction of phosphoryl groups P(O).

of the substrate in question through several reactive species. In these applications the reactions with the substrate compete with reactions of the two-component system with itself, so that the overall course of the reaction is in nearly all cases much more complex than was previously assumed. Nevertheless. very good results can be achieved by the use of this reagent, high yields and mild reaction conditions being characteristic.     

Direct ring functionalisation of 1,4,7-trimethyl-1,4,7-triazacyclononane and its application in the preparation of functional [L2Mn2O3]-type complexes

Treatment of 1,4,7-trimethyl-1,4,7-triazacyclononane (metacn) with N-bromosuccinimide (NBS) gave a bicyclic ammonium intermediate, which was ring-opened to 2-cyano-1,4,7-trimethyl-1,4,7-triazacyclononane by reaction with potassium cyanide. Reduction to the amine followed by reaction with anhydrides gave amides, which could subsequently be converted to dinuclear tris-μ-oxo manganese complexes.     

Preparation and Reactions of Permethylated Cyclooligosilane Alkali Metal Derivatives

Abstract

A simple way for the synthesis of potassium undecametylcyclohexasilane is described and discussed.     

Umpolung of Amine Reactivity. Nucleophilic α-(Secondary Amino)-alkylation via Metalated Nitrosamines

There are basically two kinds of hetero atoms in organic molecules: one kind confers electrophilic character upon the carbon atom to which it is bound, and the other kind turns it into a nucleophilic site. The development of methods permitting transitions between the two resulting categories of reagents has become an important task of modern organic synthesis. The scope of such umpolung of the reactivity of functional groups is discussed for the case of amines as an example. A method of preparing masked α-secondary amino carbanions consists in nitrosation of the secondary amine, followed by metalation of the resulting nitrosamine α-to the nitrogen, reaction with electrophiles, and subsequent denitrosation. Many examples are given for each of these steps which illustrate the wide scope of the overall synthetic operation (electrophilic substitution at the α-C atom of the secondary amine). Preliminary applications and a method for avoiding the handling of nitrosamines are presented, and the report concludes with a brief account of the significance of nitrosamines in the study of carcinogenesis and mutagenesis.     

Domino Hydroformylation-Wittig Reactions

Methallyl and homomethallyl alcohols can undergo stereoselective hydroformylation-Wittig and hydroformylation-Wittig-hydrogenation reactions in one-pot domino processes. This sequential transformation allows the formation of C−C bonds and the generation of a new stereogenic center, and gives preparatively interesting compounds [Eq. (a)]. The reaction products are obtained in satisfactory to good yields and in diastereoselectivities of 90:10 to >98:2. CDG=catalyst-directing group; R′=H; R″=OEt, Me.     

Intramolecular Ene Reactions in Organic Synthesis

Thermal cyclizations of appropriate dienes, enynes and related unsaturated systems, some of them carried out on an industrial scale, demonstrate increasingly the preparative power of the intramolecular ene reaction. A variety of substituted, fused and bridged ring systems, including natural products, are thus easily accessible in a regio- and stereo-selective manner. Numerous examples are discussed systematically illustrating the possibilities, limitations, and common features of this cyclization reaction and its reverse ring-opening process.     

Substitution Reactions Which Proceed via Radical Anion Intermediates

A new type of substition process at a saturated carbon atom is described. These reactions, which proceed via a chain sequence in which radical anions and free radicals are intermediates, are noteworthy for providing novel and powerful means of synthesis: they occur readily under mild conditions, they give excellent yields of pure products, and, in contrast to S_N2 displacements, they are rather insensitive to steric hindrance. As a consequence, radical anion processes are especially valuable for the preparation of highly branched structures. Many inorganic and organic anions readily enter into these displacements and, indeed, amines are also effective. Systems which undergo substitutions via this electron transfer mechanism include benzylic, cumylic, strictly aliphatic, and heterocyclic molecules. It is of interest that a number of groups which do not behave as leaving groups in S_N2 displacements are readily displaced at room temperature from a satureted carbon atom via the radical anion-free radical pathway, e.g., nitro, azide, sulfone, and ether groups.     

N-t-butanesulfinyl amide: An optimised and versatile access from readily available starting materials

We report the synthesis of t-butanesulfinylphthalimide and its complete regioselective ring opening by a range of nucleophiles. Further treatment of the obtained N-t-butanesulfinyl amides under basic conditions has been shown to give t-butanesulfinamide. Although the involvement of chiral nucleophiles in this process did not allow the isolation of enantiomerically pure t-butanesulfinamide, we have accessed in a rapid and efficient fashion the original compounds bearing two H-bond sites and two chiral centers that shall potentially exhibit some organocatalytic activity by comparison with known structurally related compounds.