Sulfur, nucleophiles ylids

A number of reactions have been developed involving sulfur ylids formed by attack of sulfur nucleophiles on arynes. For example, alkyl o- and / -(phenylthio)benzoates are obtained in modest yield by reaction of benzyne (from anthranilic acid) with the corre-... 

Contents Introduction and Principles. - The Reaction of Dichlorocarbene With Olefins. - Reactions of Dichlorocarbene With Non-Olefinic Substrates. -Dibromocarbene and Other Carbenes. - Synthesis of Ethers. - Synthesis of Esters. - Reactions of Cyanide Ion. - Reactions of Superoxide Ions. - Reactions of Other Nucleophiles. - Alkylation Reactions. - Oxidation Reactions. - Reduction Techniques. - Preparation and Reactions of Sulfur Containing Substrates. -Ylids. - Altered Reactivity. - Addendum Recent Developments in Phase Transfer Catalysis. 

A great deal of work has been carried out on the thianthrene radical ion(l+), which can be produced from thianthrene by a variety of one-electron oxidations. The radical cation reacts at sulfur with nucleophilic species, giving rise to 5-substituted products, oxides, ylids, and 5-R-thianthrenium salts. 

In the first step of the conversion catalyzed by pyruvate decarboxylase, a carbon atom from thiamine pyrophosphate adds to the carbonyl carbon of pyruvate. Decarboxylation produces the key reactive intermediate, hydroxyethyl thiamine pyrophosphate (HETPP). As shown in figure 13.5, the ionized ylid form of HETPP is resonance-stabilized by the existence of a form without charge separation. The next enzyme, dihydrolipoyltransacetylase, catalyzes the transfer of the two-carbon moiety to lipoic acid. A nucleophilic attack by HETPP on the sulfur atom attached to carbon 8 of oxidized lipoic acid displaces the electrons of the disulfide bond to the sulfur atom attached to carbon 6. The sulfur then picks up a proton from the environment as shown in figure 13.5. This simple displacement reaction is also an oxidation-reduction reaction, in which the attacking carbon atom is oxidized from the aldehyde level in HETPP to the carboxyl level in the lipoic acid derivative. The oxidized (disulfide) form of lipoic acid is converted to the reduced (mer-capto) form. The fact that the two-carbon moiety has become an acyl group is shown more clearly after dissocia-... 

The simplest sulfur ylids are formed from sulfonium salts 69 by deprotonation in base. These ylids react with carbonyl compounds to give epoxides.18 Nucleophilic attack on the carbonyl group 70 is followed by elimination 71 of dimethylsulfide 72 and formation of the epoxide 73. You should compare diagram 71 with diagram 23 in chapter 15. The phosphonium ylid reacted by formation of a P-0 bond and an alkene in the Wittig reaction. The sulfonium compound reacts by formation of a C-O bond 71 as the S-O bond is much weaker than the P-0 bond. The sulfonium salt 69 can be reformed by reaction of 72 with Mel. 

There are many variations on the Pummerer rearrangement but they all involve the same steps a leaving group is lost from the sulfur atom of a sulfonium ylid to create a cationic intermediate that captures a nucleophile at the a carbon atom. Often the starting material is a sulfoxide. 

Treatment of a sulfoxide, particularly one with an anion-stabilizing substituent to help ylid formation, produces cations reactive enough to combine with nucleophiles of all sorts, even aromatic rings. The product is the result of electrophilic aromatic substitution (Chapter 22) and, after the sulfur has been removed with Raney nickel, is revealed as a ketone that could not be made without sul-... 

A Lewis acid (SnCl4) is used to remove the oxygen from the sulfoxide and the ketone assists ylid formation. The sulfur atom stabilizes the cation enough to counteract the destabilization by the ketone. The Lewis acid is necessary to make sure that no nucleophile competes with benzene. 

When sodium hydroxide was used as nucleophile, salt 3c was rapidly converted to alkyne 63. This alkyne now features only a single stereocenter, and this is evident from its spectra. Its structure was initially assigned incorrectly, but the alkyne structure (63) has been rigorously established by X-ray crystallography. It is curious that azide and hydroxide should attack on the periphery of the TTF ring system, while the bulkier malonate anion attacks internal carbons. It is also intriguing that none of the observed modes of attack give rise to the sulfur ylid 64, which should be more stable than 61. 

These two reports clearly demonstrate that thiophene can form ylids, despite the considerably reduced nucleophilicity of the sulfur atom and that stable thiophenium ylids might be found. This was subsequently confirmed with the observation that the photolysis of dimethyl diazomalonate in thiophene result in the formation of 15, which was isolated in low yield as a stable crystalline solid (77JOC3365). It was subsequently demonstrated by my own group that thiophenium bis(alkoxycarbonyl)methylides could be formed in high yield using rhodium(II) acetate-catalyzed addition of diazomalonate... 

Reaction with an aldehyde starts by the removal of a proton with quite a weak base (usually a tertiary amine) to give the ylid 189 in which the negative charge is stabilised partly by electrostatic interaction (the ylid) and partly by the sulfur atom. Nucleophilic attack on the aldehyde gives 190 which can transfer a proton from C to O to give uncharged 191. 

If the diene is unsymmetrical, particularly if the monoepoxide of the less substituted and therefore less nucleophilic alkene is wanted, alternative methods are required. The enone 269 provides both epoxides 270 and 267. The sulfur ylid route converts the enone directly to one epoxide while base-catalysed epoxidation followed by a Wittig reaction provides the other. 

Reactions of chiral allylic boranes with carbonyl compounds Reactions of chiral allyl boranes with imines Asymmetric Addition of Carbon Nucleophiles to Ketones Addition of alkyl lithiums to ketones Asymmetric epoxidation with chiral sulfur ylids Asymmetric Nucleophilic Attack by Chiral Alcohols Deracemisation of arylpropionic acids Deracemisation of a-halo acids Asymmetric Conjugate Addition of Nitrogen Nucleophiles An asymmetric synthesis of thienamycin Asymmetric Protonation... 

However, unlike the triaryIsulfonium salts, these compounds undergo reversible photoinduced ylid formation rather than homolytic carbon-sulfur bond cleavage. Because the rate of the thermal back reaction is appreciable at room temperature, only those monomers that are more nucleophilic than the ylid will polymerize. Epoxides, vinyl ethers, and cyclic acetals undergo facile cationic polymerization when irradiated in the presence of dialkylphenacylsulfonium salts as photoinitiators. 

However, iV-ammonium salts as well as the IV-imines possess further acidic hydrogen atoms. In 0.2 N NaOD, (V-aminopyridinium salts (14) exchanged their hydrogen atoms at the 2-, and 4-, and 6-positions for a D atom within the time the NMR spectra could be measured.17 For the 4-amino-s-triazolium salts (93) base catalysis is not needed for the hydrogen exchange.134 The ylid or nucleophilic carbene structures 94 and 95 are intermediates (see also Wanzlick135 and Quast and Hunig136) and can be intercepted by sulfur or ethyl acetoacetate.134... 

Sulfur ylides represent another family of nucleophiles structurally coupled with a leaving group. It is therefore to be expected that they will react with imines to give aziridines via an addition-substitution sequence. In fact, the sulfur ylid obtained by metallation c trimethylsulfonium iodide with n-butyl lithium reacts at -30 C in THF with both silylimines and p-methoxyphenyl imines to give the corresponding aziridines. Again a single isomer is obtained in the case of (S)-lactaldehyde imines (Scheme 22). 

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