Nucleophilic sulfonyl substitution

The nucleophilic aromatic substitution reaction for the synthesis of poly(arylene ether ketone)s is similar to that of polysulfone, involving aromatic dihalides and aromatic diphenolates. Since carbonyl is a weaker electron-withdrawing group titan sulfonyl, in most cases, difluorides need to be used to afford high-molecular-weight polymers. Typically potassium carbonate is used as a base to avoid the... 

A long series of studies of aromatic nucleophilic substitution included the kinetics of reactions of l-chloro-2,4-bis(trifluoromethylsulfonyl)benzene, 3-nitro-4-chlorophenyl trifluoromethyl sulfone and 2-chlorophenyl trifluoromethyl sulfone with sodium methox-ide or ammonia in methanol . The SO2CF3 group was found to have an enormous accelerating effect, in accord with the value of 1.65, based on the dissociation of anilinium ion. Further examples of the promotion of nucleophilic aromatic substitution by fluoro-substituted sulfonyl groups are given by Yagupol skii and coworkers . 

Pyridine A-oxides were converted to tetrazolo[l,5-a]pyridines 172 by heating in the presence sulfonyl or phosphoryl azides and pyridine in the absence of solvent <06JOC9540>. 3-R-5-Trinitromethyltetrazolo[l,5-a]-l,3,5-triazin-7-ones 173 have been prepared from the alkylation of 5-trinitromethyltetrazolo[l,5-a]-l,3,5-triazin-7-one silver salt with different alkylation agents <06CHE417>. The use of 2-fluorophenylisocyanide in the combinatorial Ugi-tetrazole reaction followed by a nucleophilic aromatic substitution afforded tricylic tetrazolo[l,5-a]quinoxaline 174 in good yields and with high diversity <06TL2041>. 

Let us conclude this discussion of the elimination-addition pathway for sulfonyl substitutions by noting some points about the behavior of sulfenes in their reactions with nucleophiles. Attack of a nucleophile Nu- on a sulfene normally occurs at sulfur to give the a-sulfonyl carbanion C—S02Nu. 

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. 

Polymers such as polyetherketones and polyethersulfones can be prepared by electrophilic aromatic substitution using aromatic acid chlorides and aromatic sulfonyl chlorides, respectively [Eq. (25)]. However, due to ortho-substitution in addition to the desired para-substitution, it is difficult for these Friedel-Crafts acylations to compete with nucleophilic aromatic substitution of activated aromatic halides which are usually used for their synthesis. 

So far the reactivity of epoxides has involved their use as an electrophile. However, oxtranyl anions can serve as functionalized nucleophiles in their own right. Thus, the sulfonyl substituted epoxide 107 can be deprotonated with -butyllithium to provide a stabilized anion which engages in facile Sn2 reaction with triflate 108 <03JOC9050>. Other examples of such stabilized epoxide anions include those derived from oxazolinyloxiranes (e.g., 110), which react with nitrones to provide the spirotricyclic heterocycles of type 112, Hydrolysis provides the epoxy amino acids 113, in which the carboxylic acid moiety was provided by the oxazoline nucleus and the amine functionality was derived from the nitrone <03OL2723>. A recent report has demonstrated that oxiranyl anions can also be stabilized by the amide functionality <03H(59)137>. 

We have begun examining Route A using a niline (19) as a model for 7 (Scheme 6). Reaction of 19 with commercially available 4-fluorobenzene-sulfonylchloride (6) gave 20 in 90% yield. Compound 20 results from selective reaction at the sulfonyl chloride in the presence of the aromatic fluoride. The temperature of the reaction was cmcial for success at 40°C, a mixture of 20 and 21 was obtained, but at 0°C, only 20 was formed. Compound 21 arises from a double addition of an iline. This latter reaction gives us reason to believe that the nucleophilic aromatic substitution needed to prepare our key model compound 22, representing 17 in Route A (Scheme 5), will be possible. 

A tandem Suzuki-Miyaura coupling/nucleophilic aromatic substitution to carba-zoles was developed by St. Jean et al. (Scheme 51) [210]. Reaction of A -sulfonyl-protected 2-aminophenylboronates 216 with l-bromo-2-fluorobenzenes 217 under palladium(0)-catalysis provides the Af-sulfonyl-protected carbazoles 218. This annulation is compatible with a variety of electron-withdrawing groups (e.g., aldehydes, esters, and sulfones) and has been applied to an efficient synthesis of glycosinine (147) (four steps, 50% overall yield). 

The functional group transformations are derived from either electrophilic aromatic substitution or nucleophilic aromatic substitution reactions. The electrophilic aromatic substitution functional group transform is shown with a simple X group, where X is chlorine, bromine, nitro, or sulfonyl. The reagents are different, but the basic principle for the formation of such compounds is the same. 

Miller and coworkers prepared and investigated 2,5-bis-(sulfonyl)pyr-azines 153 as building blocks and studied their nucleophilic aromatic substitution reactions (Scheme 76) (13TL1938). In most cases, such as with phenols, alkoxides, anilines, aliphatic amines, heterocychc amines, and a carbanion formed from diethyl malonate with sodium hydride, only the monosubstituted sulfonylpyrazine was obtained. Reactions with two equivalents of either thiols or thiophenols, however, yielded only bis-thiopyrazines, such as compound 154, shown in Scheme 76. While the yields for the reactions with the other nucleophiles were good to high, those for reactions with aliphatic amines or anilines as the nucleophile were low to moderate. 

Thiophene sulfonation can be achieved by electrophilic substitution (see Sect. 2.6). Nucleophilic sulfonylation of thiophene, with displacement of a leaving group, is... 

An advantage that sulfonate esters have over alkyl halides is that their prepara tion from alcohols does not involve any of the bonds to carbon The alcohol oxygen becomes the oxygen that connects the alkyl group to the sulfonyl group Thus the configuration of a sulfonate ester is exactly the same as that of the alcohol from which It was prepared If we wish to study the stereochemistry of nucleophilic substitution m an optically active substrate for example we know that a tosylate ester will have the same configuration and the same optical purity as the alcohol from which it was prepared... 

Sulfonate esters are especially useful substrates in nucleophilic substitution reactions used in synthesis. They have a high level of reactivity, and, unlike alkyl halides, they can be prepared from alcohols by reactions that do not directly involve bonds to the carbon atom imdeigoing substitution. The latter aspect is particularly important in cases in which the stereochemical and structural integrity of the reactant must be maintained. Sulfonate esters are usually prepared by reaction of an alcohol with a sulfonyl halide in the presence of pyridine ... 

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