Sulfur Stabilized Ylids

Trimethylsulfonium iodide undergoes ylid formation by reaction with 50% aqueous sodium hydroxide in the presence of catalytic tetrabutylammonium iodide [16]. The ylid thus formed reacts with aldehydes and ketones to form the corresponding epoxides (Eq. 14.7). The yields with aldehydes are considerably better than those with ketones. The fact that the reaction is slow (48 hours) may be due to the iodide of the catalyst. On the other hand, lauryldimethylsulfonium chloride undergoes reaction with ketones and aldehydes to yield epoxides under alkaline phase transfer conditions considerably more rapidly (6—10 hours). The enhanced rate of this methylene transfer reaction is probably due to the greater organic solubility of the lauryldimethylsulfonium cation [17]. Catalyst poisoning is observed with lauryldimethylsulfonium iodide. Similar reactions have been conducted under ion pair extraction conditions [18]. 

The reaction of trimethylsulfonium iodide with benzaldehyde under basic phase transfer conditions catalyzed by chiral quaternary ammonium salts such as (-)-N,N-dimethyl-ephedrinium bromide has been reported to yield styrene oxide in high optical purity [19], which may be somewhat overestimated [20]. 

Likewise, trimethylsulfoxonium iodide undergoes ylid formation by reaction with 50% aqueous sodium hydroxide under phase transfer conditions. This ylid reacts with benzaldehyde to give styrene oxide, the expected product of methylene transfer in 20—30% yield (Eq. 14.8). The ylid, however, adds to o ,i3-unsaturated ketones to con- 

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The photolysis of dialkylphenacylsulfonium salts and dialkyl-4-hydroxyphenyl-sulfonium salts is different from that of triphenylsulfonium salts. The latter compounds undergo irreversible photoinduced carbon-sulfur bond cleavage the former compounds, however, react by reversible photodissociation and form resonance-stabilized ylids as shown in Fig. 5. Because of the slow thermally induced reverse reaction, only small equilibrium concentrations of the ylid and acid arc present during irradiation and the concentration will rapidly decrease when photolysis has been terminated. Therefore, in contrast to triarylsulfonium salt initiation, no dark reaction will continue after the irradiation step. 

Trost and co-workers used this type of rearrangement to generate oxaspiropentane derivatives that were converted to cyclo-butane derivatives. In section 8.8.B.ii, oxaspiropentanes such as 61 were prepared by the reaction of ketones and sulfur stabilized cyclopropyl ylids. Treatment of 61 with aqueous tetrafluoroboric acid (HBF4) gave cation 62, which rearranged to 63. Loss of a proton gave the final product, ketone 64. ... 

The mobility of the proton in position 2 of a quaternized molecule and the kinetics of exchange with deuterium has been studied extensively (18-20) it is increased in a basic medium (21-23). The rate of exchange is close to that obtained with the base itself, and the protonated form is supposed to be the active intermediate (236, 664). The remarkable lability of 2-H has been ascribed to a number of factors, including a possible stabilizing resonance effect with contributions of both carbene and ylid structure. This latter may result from the interaction of a d orbital at the sulfur atom with the cr orbital out of the ring at C-2 (21). 

The proton in the thiazolium ring is relatively acidic (p Ta about 18) and can be removed by even weak bases to generate the carbanion or ylid an ylid is a species with positive and negative charges on adjacent atoms. This ylid is an ammonium ylid with extra stabilization provided by the sulfur atom. 

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-... 

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. 

The key part of the molecule for reactivity is the thiazolium salt in the middle. The proton between the N and S atoms can be removed by quite weak bases to form an ylid. You saw sulfonium ylids in Chapter 46, and there is some resemblance here, but this ylid is an ammonium ylid with extra stabilization from the sulfur atom. The anion is in an sp2 orbital, and it adds to the reactive carhonyl group ofpyruvate. 

There can now be little doubt that the reaction of singlet carbenes and car-benoids with thiophene proceeds by attack of the carbene at the ring sulfur atom to generate the S,C-ylid. However, only in the special cases indicated above do these ylids enjoy any real stability. In the majority of cases, other products usually result from rearrangement of the intermediate ylids and the nature of the products formed is remarkably sensitive to both steric and electronic effects. Broadly speaking, six major reaction pathways have been observed (1) 2-substituted thiophene formation, (2) 2H-thiopyran formation, (3) formation of derivatives of 2-thiabicyclo[3.1.0]hex-3-ene, (4) 3-substituted thiophene formation, (5) oxathiocin formation, and (6) carbenic fragmentation. 

Phosphorus is like sulfur in this regard you can compare the phosphonium ylid with the sulfonyl-stabilized anions you met earlier. 

Condensation of die stabilized sulfur ylid A(,A( dimethyl-2-dimethylsulfuranylidene-acetamide (Me2S=CHCONMe2) with aldehydo-sagaK gave mixtures of the two diastereomenc rrflftf-cpoxyamides, such as 30. When hemiacetals were used, the reaction proceeded with considerable stereoselectivity, and the inirial epoxyamide underwent intramolecular cyclizadon when 2,3- -isopropylidene-D-ribose was employed, the product 31 could be isolated in 85% yield, and the reaction with di-isopropylidene-D-mannose was also investigated. ... 

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