Unsaturated system reactions

Addition of hydrazines to 1,3-difunctional compounds is one of the most common methods employed for the preparation of pyrazoles. For example, several synthesis of pyrazoles have been reported where azide reagents are added to a,P-unsaturated systems. Reactions of trifluoroacetyl enol ether (thiophene) 1 with hydrazines afforded 3-(2-furyl) or 3-(2-thienyl)pyrazoles 2 <05S2744>. A regiospecific one-pot synthesis of trifluoromethyl-substituted heteroaryl pyrazolyl ketones has also been disclosed <05JHC631, 05JHC1055>. 1,3,5-... 

There is a known regioselectivity in cytochrome P450-catalyzed hydroxylations for carbon atoms adjacent (a) to an unsaturated system (reaction 3) or an heteroatom such as N, 0, or S (reaction 4-A). In the former cases, hydroxylation can easily be followed by dehy-... 

Table 18. Isomerizations, H/D exchanges, additions to unsaturated systems, reactions of carbonyl compounds...

Tautomerism of the A-2-thiazoline-5-thiones has not been investigated intensively. A recent report shows that 2-phenylthiazo e-5-thiols exist in the thiol form in both polar and nonpolar solvents (563). This behavior is in contrast with that of corresponding thiazolones. Addition reactions involve only the exocyclic sulfur atom, and thiazole-5-thiols behave as typical heteroaromatic thiols towards unsaturated systems, giving sulfides (1533) (Scheme 80) (563),... 

Many of these reactions occur in the course of synthesis of fully or partly unsaturated products after initial ring closure, giving rise to more unsaturated systems, e.g. in the pyrido[2,3-pipemidic acids (Section 2.15.4.1) and their derivatives, e.g. (16a) -> (17) (74JAP(K)7444000). Examples are also found in the pyrido[3,2-[Pg.205]

Nucleophilic attack on ring atoms of large heterocycles is largely confined to saturated systems, saturated parts of partially unsaturated systems, and to carbonyl functions and the like. These reactions are not fundamentally different from those of corresponding acyclic systems, except for transannular reactions. 

The meaning of the word aromaticity has evolved as understanding of the special properties of benzene and other aromatic molecules has deepened. Originally, aromaticity was associated with a special chemical reactivity. The aromatic hydrocarbons were considered to be those unsaturated systems that underwent substitution reactions in preference to addition. Later, the idea of special stability became more important. Benzene can be shown to be much lower in enthalpy than predicted by summation of the normal bond energies for the C=C, C—C, and C—H bonds in the Kekule representation of benzene. Aromaticity is now generally associated with this property of special stability of certain completely conjugated cyclic molecules. A major contribution to the stability of aromatic systems results from the delocalization of electrons in these molecules. 

The photochemical addition of trifiuoroiodomethane to unsaturated systems has been thoroughly investigated by Haszeldine. Little use has been made of this reaction in the steroid field. Irradiation of the enol ether (64) in trifiuoroiodomethane containing pyridine in a quartz vessel furnishes in 60 %... 

The first example of a cycloaddition reaction of a multiple bond to a diene was reported in 1917 Surprisingly, it was found that benzal azine adds to 2 equivalents of several unsaturated systems, when offered in excess, to yield bicyclie compounds. This reaction was named criss-cross" cycloaddition [190], Exploitation of the preparative potential of criss-cross cycloaddition began only in the early 1970s, when hexafluoroacetone azine became available on a larger scale [191,192] The study of this reaction proved to be an impetus tor the development of azine chemistry [183, 193]... 

The reactivity of the unsaturated system of oxepin gives rise to a variety of cycloaddition reactions. A number of 3,6-bridged oxepins have been reacted with peracids to give 2,3-ep-oxyoxepins i,129 154.213.218 At higher temperature, the 2,3,6,7-diepoxy derivatives 2 are formed.164... 

All other methods for obtaining bacteriochlorins are by partial synthesis from porphyrins, chlorins or chlorin derivatives. The bacteriochlorin is thereby produced by reactions which occur at the peripheral /J-C — C double bonds of the higher unsaturated systems. The main problem of these syntheses is the lack of regio- and stereoselectivity because three or four C —C double bonds, which are present in the starting products may be attacked, so that rcgio-and stcreoisomcric products can be formed. 

A number of studies have found that increasing nucleophilieity of the attacking radical favors abstraction over addition to an unsaturated system (benzene ring or double bond).41 ns 119 Bertrand and Siirzur149 surveyed the literature on the reactions of oxygcn-ccntcrcd radicals and observed that the ratio of abstraction to addition increased as shown in Figure 1.10. 

Table 6 gives a selection of reactions of sulfonyl halides with different unsaturated systems. 

In the same manner as described before, arenesulfonyl thiocyanates are able to show self-addition to conjugated systems yielding sulfones243,244. More important, however, is that reactions of selenosulfonates with unsaturated systems as well as with nucleophilic carbon have been proved. 

Michael addition is a 1,4-addition reaction of a nucleophile to an a, /1-unsaturated system in which the double bond is conjugated with a carbonyl group, enabling the formation of the corresponding enolate as an intermediate (equation 27). 

The unconventional structure of fulvenes with a unique C=C bond conjugation leads to unusual cycloaddition reactions with other unsaturated systems. For example, alkenylcarbene complexes react with fulvenes leading to indanone or indene derivatives which can be considered as derived from a [6S+3C] cycloaddition process [118] (Scheme 72). The reaction pathway is well explained by an initial 1,2-addition of the fulvene to the carbene carbon followed by [1,2]-Cr(CO)5-promoted cyclisation. 

Foremost among the classes of the nonaromatic unsaturated systems is that of compounds in which the substituent is bonded to a carbon-carbon double bond. It is convenient to divide the data sets for carbon-carbon double bonds into five categories vinyl, vinylidene, frans-vinylene, cis-vinylene, and reactions of carbon-carbon double-bond sets. 

The general term metallation describes that process in which reaction of an unsaturated system with a metal or an electrophilic metal salt results in formation of an unsaturated organometallic compound by formal replacement of a C—H bond by a C—metal bond, as for example in the mercuration of benzene (Scheme 3). The term oxymetallation is used to describe the... 

Monoalkylthallium(III) compounds can be prepared easily and rapidly by treatment of olefins with thallium(III) salts, i.e., oxythallation (66). In marked contrast to the analogous oxymercuration reaction (66), however, where treatment of olefins with mercury(II) salts results in formation of stable organomercurials, the monoalkylthallium(III) derivatives obtained from oxythallation are in the vast majority of cases spontaneously unstable, and cannot be isolated under the reaction conditions employed. Oxythallation adducts have been isolated on a number of occasions (61, 71,104,128), but the predominant reaction pathway which has been observed in oxythallation reactions is initial formation of an alkylthallium(III) derivative and subsequent rapid decomposition of this intermediate to give products derived by oxidation of the organic substrate and simultaneous reduction of the thallium from thallium(III) to thallium(I). The ease and rapidity with which these reactions occur have stimulated interest not only in the preparation and properties of monoalkylthallium(III) derivatives, but in the mechanism and stereochemistry of oxythallation, and in the development of specific synthetic organic transformations based on oxidation of unsaturated systems by thallium(III) salts. 

Tl(III) < Pb(IV), and this conclusion has been confirmed recently with reference to the oxythallation of olefins 124) and the cleavage of cyclopropanes 127). It is also predictable that oxidations of unsaturated systems by Tl(III) will exhibit characteristics commonly associated with analogous oxidations by Hg(II) and Pb(IV). There is, however, one important difference between Pb(IV) and Tl(III) redox reactions, namely that in the latter case reduction of the metal ion is believed to proceed only by a direct two-electron transfer mechanism (70). Thallium(II) has been detected by y-irradiation 10), pulse radiolysis 17, 107), and flash photolysis 144a) studies, butis completely unstable with respect to Tl(III) and T1(I) the rate constant for the process 2T1(II) Tl(III) + T1(I), 2.3 x 10 liter mole sec , is in fact close to diffusion control of the reaction 17). 

The utility of thallium(III) salts as oxidants for nonaromatic unsaturated systems is a consequence of the thermal and solvolytic instability of mono-alkylthallium(III) compounds, which in turn is apparently dependent on two major factors, namely, the nature of the associated anion and the structure of the alkyl group. Compounds in which the anion is a good bidentate ligand are moderately stable, for example, alkylthallium dicar-boxylates 74, 75) or bis dithiocarbamates (76). Alkylthallium dihalides, on the other hand, are extremely unstable and generally decompose instantly. Methylthallium diacetate, for example, can readily be prepared by the exchange reaction shown in Eq. (11) it is reasonably stable in the solid state, but decomposes slowly in solution and rapidly on being heated [Eq. (23)]. Treatment with chloride ion results in the immediate formation of methyl chloride and thallium(I) chloride [Eq. (24)] (55). These facts can be accommodated on the basis that the dicarboxylates are dimeric while the... 

The reactions of TTN with a variety of unsaturated systems have been studied systematically during the last two years, and the results obtained clearly establish the synthetic utility of the reagent as a specific oxidant. Attempts were made in 1966 by Uemura et al. 162) to oxidize a,)8-unsatur-ated carbonyl compounds with thallium(III) acetate, but were unsuccessful. In 1970, however, Ollis and his co-workers 121-123) reported that prolonged treatment of highly activated chalcones (Scheme 20) with thal-... 

Table 2-1 lists some examples of carboxylic acid imidazolides of various structures prepared by the use of A -carbonyldiimidazole (CDI), A -thiocarbonyldiimidazole (Im-CS-Im), and A -sulfinyldiimidazole (Im-SO-Im). Independent of the specific method applied, the data in Table 2-1 show that reasonable yields of imidazolides and diimidazolides are quite general, irrespective of various substituents and of steric factors. The rather mild reaction conditions also permit the formation of imidazolides of highly unsaturated systems. As a further advantage, it should be mentioned that almost all imidazolides are crystalline compounds, which can be conveniently handled. Melting points are therefore included for the imidazolides listed in Table 2—1. 

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