Ylide functionalized

Heterocyclic phosphorus ylides are a rather diverse and little known class of compounds. A variety of such structures are now known and in some cases these are of considerable synthetic value. In this chapter we have attempted to review all heterocyclic compounds containing one or more exocyclic phosphorus ylide functions, i.e. of general structure 1. It should be noted that in many cases these exist predominantly in the phosphonium ylide (P+—C ) form but for simplicity they are represented in the ylene form 1. Cyclic ylides 2 and 3 in which the phosphorus atom is within the ring are not included. 

Examples treated in this book are summarized in Table 9. One frequently found type consists of ring expansions of cyclic conjugated systems with an exocyclic ylide function, such as pyridine /V-oxides or /V-imides incorporation of the exocyclic half of the ylide function expands the ring by one member. 

The comparison of thiophene with thioethers on the one hand and with enol thioethers on the other, in regard to its behaviour towards conventional electrophiles, has been made in Section 3.02.2.3. Attack on carbon is the predominant mode of reaction (Section 3.14.2.4) reaction at sulfur is relatively rare (Section 3.14.2.5). Carbenes are known to act as electrophiles attack at both carbon and sulfur of thiophene has been reported. The carbene generated from diazomalonic ester by rhodium(II) catalysis attacks the sulfur atom of thiophene, resulting in an ylide. It has also been shown that the carbenoid species derived by thermolysis of such an ylide functions as an electrophile, attacking the a-carbon of a second molecule of thiophene (Section 3.14.2.9). Singlet nitrene is electrophilic. However, in contrast to carbenes, it invariably attacks only the carbon atom (Section 3.14.2.9). 

Azomethine ylides - functionalization with amino acids... 

The linking of two building blocks to form a double bond under the conditions of the Wittig reaction required that one of the building blocks has phosphorus ylide functionality and that the other has carbonyl functionality. The appropriate C5 building block for vitamin A can thus be either l-triphenyl-2-methyl-4-hydroxy-2-butenylidenephosphorane (26) 9) or P-formylcrotyl alcohol (2-methyl-4-hydroxy-2-butenal) (8 a). 

A C5 synthetic unit which has ylide functionality and which is likewise accessible from 2-hydroxy-2-methyl-but-3-enal-dimethylacetal (27) has proved suitable particularly for the synthesis of apocarotenals. The copper-catalyzed reaction of (27) with triphenylphosphine (15) in the presence of aqueous acid leads to 4-triphenyl-phosphonium-2-methyl-buten-2-al (33). The bifunctional C5 ylenal (34), which is important for carotenoid syntheses, is formed therefrom with proton acceptors. 

Note that the stereospecificity of the reaction in Scheme 2 follows the orbital symmetry predicted by the Woodward-Hoffmann rules [2] the oxide and ylide interconvert via a disrotatory mode. As is the case with all three-membered heterocycles mentioned here, UV irradiation of the heterocycle generates a highly colored ylide intermediate. Unfortunately, the stability of the ylides derived from monocyclic oxiranes is poor and photochromic behavior is evident only upon irradiation at low temperatures (77 K) [3]. This drawback has been somewhat circumvented in a few cases by annulation of the ylide functionality, which increases its stability. For example, 5-oxabicyclo[2.1.0] pentane develops a purple color when irradiated at 253.7 nm at room temperature [4], This reaction is shown in Scheme 3. 

This has been nicely demonstrated and exploited by Woodward s syntheses of bicyclic systems of the penem type. They are typically formed in moderate to good yields upon refluxing the requisite substituted starting -lactams in toluene or xylene for extended periods. The key step is the introduction of the ylidic moiety into the 1-position of a 4-functionalized azetidin-2-one which itself can be obtained as a relay substance by degradation of natural penicillins or from easily available 4-acetoxyazetidin-2-one. The ester ylide function is built up by reaction first with alkyl hemiacetals of glyoxylates to give a hemiaminal and then successive replacement of the OH-group of the latter by Cl with thionyl chloride and finally of the chlorine atom by triphenylphosphane under basic conditions. 

Reaction of simple ylides with dialkyldihalosilanes leads in a twofold transylidation to the formation of Si-bridged bisphosphoranes (equation 42), which can undergo consecutive reactions with excess starting materials leading to cyclic products. Bis(chlorodimethylsilyl)methane also reacts with dilithio-methylenetrimethylphosphorane to give a methylenephosphorane with an exocyclic ylide function (equation 43). 

Generally alkylidenephosphoranes that carry in addition to the ylidic function another reactive site (e.g. a second ylide function, an additional phosphonate group, a halogen or a silyl substituent) may react at this additional functional group thus providing a derivative of the original ylide. 

The bridging oxygen in aromatic carboxylic anhydrides may be exchanged by the ylide function in the reaction with hexaphenylcarbodiphosphorane e.g. equation 100). ... 

Carboxylic acids react with phenyliminovinylidenetriphenylphosphorane (equation 106) via the intermediates (1) with formation of the alkylidenephosphoranes (2), which, on heating, rearrange in an intramolecular acyl migration to ylides (3). By heating (2) in the presence of an alcohol the acyl ylides (4) and N-phenylurethanes are formed. - The reaction sequence allows the replacement of the OH group in carboxylic acids by the ylide function. 

The addition of acidic compounds to phosphacumulene ylides yielding substituted alkylidenephosphoranes is of particular interest in the reaction of those acidic molecules which carry, besides the Y— bond, a group capable of cyclization with the ylide function formed by addition. " ... 

The [2 + 2] cycloaddition and the [4 + 2] addition of vinylidenephosphorane with heteroallenes have been applied to the synthesis of a great variety of four- and six-membered heterocyclic compounds carrying an exocyclic ylide function. - ... 

Cycloaddition of a,3-unsaturated ketones, acyl ketenes, acyl, thioacyl, imidoyl and vinyl isocyanates, as well as the corresponding isothiocyanates, to the C=C bond of vinylidenephosphoranes leads to the formation of six-membered heterocycles carrying an exocyclic ylide function e.g. equation 117). In some instances the mentioned thioisocyanates, however, may undergo [2 + 2] cycloaddition at the C=S bond. Interestingly N-aryliminovinylidenetriphenylphosphoranes dimerize in a [4 2] cycloaddition on heating alone. 

Scheme 21). However, when a sterically demanding, electron-withdrawing, trimethylsilyl group is present as a substituent on the ylidic carbon (108c) then no metallation was observed, possibly because ortho-metallation is strongly dependent upon pre-coordination of the lithium ion to the ylide function. 

Fretz has prepared a L-phenylalanine derivative substituted with a keto-ylide (149). The ylide function of 149 acts as a stable precursor to a vicinal tricarbonyl moiety which is readily obtained by oxidation of the phosphoranylidene group with oxone. Ylide 149 has been utilized in the solid-phase synthesis of peptides containing the vicinal tricarbonyl moiety. ... 

Double deprotonation of the bisphosphonium salt 4 by triethylethylidenephosphorane does not afford a product with two terminal ylide functions but an unsymmetrical carbodiphos-phorane 5. The formation of cyclopropyl[(methyldiphenylphosphoranylidene)methylene]-diphenylphosphorane (5) occurs via nucleophilic attack of a terminal ylide function at the adjacent phosphonium center in the primary ylide intermediate." ... 

The synthesis of (46) (Table 6) has been achieved by exploiting the high reactivity of the azomethine ylide functionality of 1,4,8-triazapentalenes (207) towards DMAD <78TL1291>. The cycloaddition will occur at the azomethinimine ylide function of (207) when the reaction at the azomethine ylide moiety of (207) is deliberately hindered, for example, by benzocondensation. On treatment with ddq, (46) Anally affords (208) (Scheme 21). 

Further details have appeared of the condensation of the dimethylsulphoxonium ylide (23 R = H or Me) with aP-unsaturated carbonyl compounds, which were discussed in an earlier Report. In the attempted alkylation of the ylide (24) with phenacyl bromide the ylide functions solely as a base, trans-l,2,3-tribenzoylcyclo-propane being the sole product formed in high yield. ... 

These iodonium ylides function as carbene and nitrene transfer agents. Carbene transfer typically requires a transition-metal catalyst. A few uncatalyzed reactions, however, have been documented, such as the following remarkably stereospecific transformations of (Z)-and ( )-hept-3-ene ... 

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