Halides, sulfonyl, addition reactions

The original reaction procedures have steadily been extended and improved, and an overwhelming number of catalyst systems are now known. Besides aryl halides, many additional substrates, for example aryl triflates, diazonium salts, sulfonyl and aroyl halides, carboxylic and phosphonic acids, and even arenes have been used as... 

Displacement of halides by secondary amines and of sulfonyl groups by alkoxides can also take place. Furoxancarboxylic acids are attacked by base to give acyclic products, but their derivatives can undergo nucleophilic acyl substitutions. Likewise nucleophilic addition reactions can be accomplished for ketofuroxans, although ring cleavage is also commonplace. The generation of new heterocyclic systems by reaction with nucleophiles is dealt with in Section 4.22.3.2.5. 

Some of these transformations were accompanied by additional reactions, e.g. formylation of the aromatic or heteroaromatic - nucleus or CH-acidic methyl groups further dehydration of amides to nitriles was observed. Adducts from amides and PCI3, sulfonyl halides or SO2CI2/SCXZI2 from which amidines can be obtained by reaction with amine derivatives (compare Section 2.7.2.5 and refs. 5 and 14) have not found wide application for this purpose. An interesting reaction is the preparation of the amidine (294 equation 158) from 7V-pentafluorophenylformamide. By thermal decomposition of the adducts from secondary amides and 7V,iV-dialkylcarbamoyl chlorides amidinium salts were synthesized from which the amidines (295 equation 159) were set free by treatment with bases. " ... 

Several thiols occur naturally for example, skunk secretion contains 3-methyll-butanethiol and cut onions evolve 1-propanethiol, and the thiol group of the natural amino acid cysteine plays a vital role in the biochemistry of proteins and enzymes (see Introduction, p. 2). Primary and secondary thiols may be prepared from alkyl halides (RX) by reaction with excess sodium thiolate (SN2 nucleophilic substitution by HST) or via the Grignard reagent and reaction with sulfur. Tertiary thiols can be obtained in good yields by addition of hydrogen sulfide to a suitable alkene. Thiols can also be prepared by reduction of sulfonyl chlorides (Scheme l).la,2a... 

Rh(TTP) reacts with alkyl halides, acyl halides, aroyl halides, and sulfonyl halides, but it shows no evidence of reaction with molecular hydrogen. These observations further emphasize the fact that Rh(TTP) is essentially a nucleophile and it therefore reacts with those reagents RX that can oxidatively add by nucleophilic attack (34). Rh(TTP) does not react with H2, and H2 seems always to add to (P complexes via a concerted mechanism (35). It appears that Rh(TTP) has very little diradical character, i.e. it is not a good analog of a carbene (35). It is possible that this unreactivity may be associated with the stereochemistry of chelation by the macrocyclic ligand. Earlier studies on the oxidative addition reactions of Rh(I) complex with a tetraaza macrocycle revealed that the Rh(I) had strong nucleophilic properties but the activation of molecular H2 was not reported (36, 37). This possibility is supported by reports that dialkyl sulfide complexes of rhodium chloride catalyze the hydrogenation of olefins (38). 

Normally, reactive derivatives of sulfonic acids serve to transfer electrophilic sulfonyl groups259. The most frequently applied compounds of this type are sulfonyl halides, though they show an ambiguous reaction behavior (cf. Section III.B). This ambiguity is additionally enhanced by the structure of sulfonyl halides and by the reaction conditions in the course of electrophilic sulfonyl transfers. On the one hand, sulfonyl halides can displace halides by an addition-elimination mechanism on the other hand, as a consequence of the possibility of the formation of a carbanion a to the sulfonyl halide function, sulfenes can arise after halide elimination and show electrophilic as well as dipolarophilic properties. 

Besides radical additions to unsaturated C—C bonds (Section III.B.l) and sulfene reactions (see above), sulfonyl halides are able to furnish sulfones by nucleophilic substitution of halide by appropriate C-nucleophiles. Undesired radical reactions are suppressed by avoiding heat, irradiation, radical initiators, transition-element ion catalysis, and unsuitable halogens. However, a second type of undesired reaction can occur by transfer of halogen instead of sulfonyl groups283-286 (which becomes the main reaction, e.g. with sulfuryl chloride). Normally, both types of undesired side-reaction can be avoided by utilizing sulfonyl fluorides. 

The free radical additions of sulfonyl halides to alkenes, catalyzed by light or typical chemical radical initiators (In), were first investigated in the 1950s69. The products which are / -halo sulfones (22) were obtained via a chain reaction in which RSO j acts as the chain carrier, namely61-62,70,71... 

The three steps 32-34 have been suggested77 to be equilibria, and the overall equilibrium must lie far to the left because no adduct 23 is found in the reaction mixture when the reaction of sulfonyl chloride with olefin is carried out in the absence of a tertiary amine. A second possible mechanism involving oxidative addition of the arenesulfonyl halide to form a ruthenium(IV) complex and subsequent reductive elimination of the ruthenium complex hydrochloride, [HRulvCl], was considered to be much less likely. 

In the thermal reaction of aliphatic and aromatic sulfonyl chlorides with acetylenes no adduct has been observed82. However, the light-catalyzed additions of sulfonyl iodides to acetylenes83 as well as the thermal addition of sulfonyl bromides to phenylacetylene84 to form 1 1 adducts have been shown to be stereoselective and to occur in good to excellent yields. The fact that the addition occurs in a trans manner forced the authors83,84 to suggest that chain transfer by the sulfonyl halide (k ) is much faster than isomerization of the intermediate vinyl radical (k2) (see Scheme 5). 

As a consequence of facile homolytic cleavages, sulfonyl halides (I > Br > Cl F unsuitable) are able to add to unsaturated C—C systems. To prevent (or reduce) competing polymerizations, the additions of sulfonyl chlorides have been recommended to be carried out in the presence of copper(I/II) salts (Asscher-Vofsi reaction ). Comprehensive surveys have been published on the resulting j8-halogeno sulfones (or their vinyloguous compounds) as well as on their dehalogenation products (vinyl sulfones, 1-sulfonyl-l, 3-dienes, etc.). Table 5 reviews a series of sulfonyl halide additions and facile hydrogen halide eliminations. 

The Darzens reaction is the base-promoted generation of epoxides XIII from aldehydes (or ketones) XI and alkyl halides XII, the latter carrying an electron withdrawing group, for example the carbonyl, nitrile, or sulfonyl, in the a-position (Scheme 6.83) [188, 189]. It is, formally, addition of a carbene to the C=0 double bond (Scheme 6.83, path B) and thus complements oxygen atom transfer to olefins... 

Mesylates are used for Ni-catalysed reactions. Arenediazodium salts 2 are very reactive pseudohalides undergoing facile oxidative addition to Pd(0). They are more easily available than aryl iodides or triflates. Also, acyl (aroyl) halides 4 and aroyl anhydrides 5 behave as pseudohalides after decarbonylation under certain conditions. Sulfonyl chlorides 6 react with evolution of SO2. Allylic halides are reactive, but their reactions via 7t-allyl complexes are treated in Chapter 4. Based on the reactions of those pseudohalides, several benzene derivatives such as aniline, phenol, benzoic acid and benzenesulfonic acid can be used for the reaction, in addition to phenyl halides. In Scheme 3.1, reactions of benzene as a parent ring compound are summarized. Needless to say, the reactions can be extended to various aromatic compounds including heteroaromatic compounds whenever their halides and pseudohalides are available. 

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