Ylides as intermediates

Thia-[2,3]-Wittig sigmatropic rearrangement of lithiated carbanions 47, obtained by deprotonation of the S-allylic sulfides 46, affords the thiols 48 or their alkylated derivatives 49. The corresponding sulfonium ylides 51, prepared by deprotonation of the sulfonium salts 50 also undergoes a [2,3]-sigmatropic shift leading to the same sulfides 49 [36,38] (Scheme 13). As far as stereochemistry is concerned, with crotyl (R R =H,R =Me) and cinnamyl (R, R =H,R =Ph) derivatives, it has been shown that the diastereoselectivity depends on the nature of the R substituent and on the use of a carbanion or an ylide as intermediate. 

Wittig reactions of phosphonium fluorides in dipolar non-HBD solvents can be carried out without an additional base e.g. 4-nitrobenzaldehyde reacts slowly with (4-nitrobenzyl)triphenylphosphonium fluoride in refluxing acetonitrile to give 4,4 -nitro-stilbene in good yield (84 cmol/mol) [642], In this reaction, the fluoride ion attacks its own cation to give the corresponding Wittig ylide as intermediate. 

Prototropic routes to 1,3- and 1,5-dipoles, and 1,2-ylides as intermediates in synthesis of heterocycles 87CSR89. 

It has also proved possible to make alkenes in a one-pot process from diazo compounds N2CR2, where R is an electron-withdrawing group, and aldehydes or ketones by heating them in the presence of tributylstibine no base was required Reaction was assumed to proceed through a stibonium ylide as intermediate, although it proved impossible to isolate this ylide, which probably reacted further too rapidly to allow this. 

Thiazoles can be quaternized at nitrogen by reaction with a range of alkylating agents. These salts can form an ylide by deprotonation at C-2. This thiazolium 2-ylide is markedly stable because of the ability of sulfur to stabilize an adjacent carbanion. The reaction is of considerable importance due to the occurrence of thiazolium-2-ylides as intermediates in classical biochemical (thiamine action) and chemical (Stetter reaction) processes (see Section 3.06.12). Desilylation at C-2 can lead to a thiazolium 2-ylide as well. Thus, the formation of this type of intermediate has been formulated as a key step along the reaction pathway involving a 2-trialkylsilylthiazole and C-electrophiles (Dondoni reaction, see Section 3.06.12.12). Thiazolium salts are also susceptible to be oxidized by a variety of oxidants (see Section 3.06.5.4.8). 

The most popular mechanisms at present invoke oxonium ylides as intermediates. van den Berg et al. [20] proposed that DME is protonated by a Bronsted site, and the resultant ion suffers nucleophilic attack by a second molecule of DME to form TMO with release of MeOH. The TMO ion is then deprotonated by a basic site to form the dimethyloxonium methylide, which undergoes a Stevens-type rearrangement to give methylethyl-oxonium ion. MeOEt is subsequently formed upon p— elimination. No experimental evidence was offered in support of the scheme. 

Photfrfysis of a-Diazo Carbonyl Compounds - Some recent advances in the matrix photochemistry of diazoketones, including some heterocyclic species, have been reviewed. Flash photolysis of 10-diazo-9(10//)-phenanthrenone (35) in aqueous solution led to the detection of two transient species on the pathway to the final product, fluorene-9-carboxylic acid. These were identified, from solvent isotope effects and the nature of the observed acid-base catalysis, as fluorenylideneketene (36, X = CO) and the enol of fluorene-9-carboxylic acid (36, X = C(0H)2), formed by hydration of the ketene. In related studies, fluorenylideneketene was found to react with amines to give ylides as intermediates on the route to the amide final products. The product distribution from the photochemical reactions of 2-diazo-3-oxo-5,10,15,20-tetraphenylchlorins with alcohols strongly depends on the central metal ion of the irradiated diazoketones. ... 

Related cyclopropanations have also been reported using sulfonium and telluronium ylides as intermediates. In particular, the cyclopropanation of enones has been carried out employing an allyl bromide as the cyclopropa-nating reagent and sulfonium and telluronium salts 134 and 135 as pre-catalysts (Scheme 7.84). These species, in the presence of a base, generated the corresponding ylide which underwent the cascade Michael/intramolecular nucleophilic substitution and it is in this second step that the real catalytically active species is released, able to interact with another molecule of the allyl bromide and thus regenerating the sulfonium or telluronium salts pre-catalysts, which can afterwards continue in the catalytic cycle. The substitution at the... 

The formation of azomethyne ylides as intermediates in the photoreactions of N-(silylmethyl)phthalimides and 7V-phthaloyl derivatives of a-amino acids has been confirmed by laser flash photolysis and fluorescence spectroscopy. 

Concerted cycloadditions are observed with heterocyclics of all ring sizes. The heterocycles can react directly, or via a valence tautomer, and they can utilize all or just a part of unsaturated moieties in their rings. With three-membered rings, ylides are common reactive valence tautomers. Open chain 47T-systems are observed as intermediates with four-membered rings, and bicyclic valence tautomers are commonly reactive species in additions by large rings. Very often these reactive valence tautomers are formed under orbital symmetry control, both by thermal and by photochemical routes. 

Diazomalonic esters serve as intermediates for the synthesis of a wide variety of compounds including cyclopropanes, cyclo-propenes, cycloheptatrienes, sulfur ylides, lactones, and substituted malonates. ... 

In addition to nitrones, azomethine ylides are also valuable 1,3-dipoles for five-membered heterocycles [415], which have found useful applications in the synthesis of for example, alkaloids [416]. Again, the groups of both Grigg [417] and Risch [418] have contributed to this field. As reported by the latter group, the treatment of secondary amines 2-824 with benzaldehyde and an appropriate dipolarophile leads to the formation of either substituted pyrrolidines 2-823, 2-825 and 2-826 or oxa-zolidines 2-828 with the 1,3-dipole 2-827 as intermediate (Scheme 2.184). However, the yields and the diastereoselectivities are not always satisfactory. 

The CJS insertion reaction was suppressed completely upon catalytic decomposition of diazoketones 361, where the sulfur substituent was alkyl, acyl or thioacyl. It is presumed that sulfonium ylides occur as intermediates which give cepham (or cephem) derivatives in all cases270,343) rather than products of a Stevens rearrangement. 

The double bond in silenes is strongly polarized. They react with phosphorus ylides, as shown by Brook and MacMillan,45 like alkenes with the strongly polar C=C bond. Therefore, it is reasonable to suggest that the reaction also occur through the betaine intermediate (12) (Scheme 6). 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

Non-heteroatom-substituted carbene complexes can also be generated by treatment of electrophilic transition metal complexes with ylides (e.g. diazoalkanes, phosphorus ylides, nucleophilic carbene complexes, etc. Section 3.1.3). Alkyl complexes with a leaving group in the a-position are formed as intermediates. These alkyl complexes can undergo spontaneous release of the leaving group to yield a carbene complex (Figure 3.2). 

Compounds of the general formula 69 are prepared by cycloaddition of N-methyl- or A(-arylmaleimides with arylidene imines of AAs and in the presence of an aromatic aldehyde. Stabilized azomethine ylides are formed as intermediates, which then afford the cycloadducts. Several isomers are formed, and the influence of various metal salts and solvents was investigated (87BCJ4067 88T557). Similar transformations have been performed with A-ailyl glycine esters (91TL1359). 

For the formation of 15 (Figure 6.9) a different mechanism has been proposed [62]. Reaction of singlet oxygen with the corresponding amine (iminodiacetic methylester) leads - after two H-abstractions - to an azomethine ylide as a key intermediate. This ylide can add to the double bond via a [3-i-2]-cycloaddition related to the Prato reaction (Section 4.3.4). 

Whereas the thermal ring-opening reaction of oxrranes and aziridines is frequently used for generation of carbonyl ylides and azomethine ylides, the analogous procedure starting with thiiranes does not produce the expected thiocarbonyl ylides (8). However, in the case of tetraaryl-substituted thiiranes, the photolytically mediated reaction with tetracyanoethylene (TCNE) is believed to occur via a single electron transfer (SET) mechanism, also involving a thiocarbonyl ylide as a likely intermediate (75,76) (Scheme 5.14). 

As mentioned on pages 317 and 324, the 1,3-dipolar electrocycUzation of thiocarbonyl ylides leads to thiirane derivatives, which represents an excellent method for the preparation of those three-membered rings. Typically, thiiranes are isolated as the final products, but in some instances they are produced as intermediate compounds which spontaneously desulfurize to give alkenes [twofold extrusion (47,48)]. 

Ueno and Okawara (184) were the first to explicitly formulate a conjugated thiocarbonyl ylide as an intermediate in the reaction of l,3-dithiolane-2-thione with 4-bromophenacyl bromide. The initially formed thiocarbonyl ylide undergoes deprotonation with sodium hydride to give 2-(4-bromophenyl)-l-oxa-4,6,9-trithias-piro[4.4]non-2-ene. 1,3-Diacylated thiocarbonyl ylides of type 149 (Scheme 5.45) have also been proposed as intermediates in the reaction of 1,3-diphenylpropane-1,3-dione with thionyl chloride. This reaction leads to 2,2,4-tribenzoyl-5-phenyl-... 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Until now, the detailed mechanism involved in the MTG/MTO process has been a matter of debate. Two key aspects considered in mechanistic investigations are the following the first is the mechanism of the dehydration of methanol to DME. It has been a matter of discussion whether surface methoxy species formed from methanol at acidic bridging OH groups act as reactive intermediates in this conversion. The second is the initial C—C bond formation from the Ci reactants. More than 20 possible mechanistic proposals have been reported for the first C-C bond formation in the MTO process. Some of these are based on roles of surface-bound alkoxy species, oxonium ylides, carbenes, carbocations, or free radicals as intermediates (210). 

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