The ylid mechanism

Unlike the three fundamental mechanisms of olefin formation already outlined, the a -ji (or ylid) mechanism is only applicable to elimination from onium salts . The base abstracts an alpha hydrogen from the leaving group to form an ylid which subsequently acts as an internal base and abstracts the beta hydrogen atom, viz. 

The ylid mechanism was first postulated to account for the presence of iodobenzene among the reaction products when elimination from isopropyl-dimethyl(iodomethyl)ammonium ion was induced by phenyl lithium , viz- 

An E2 reaction would have produced benzene. Under the same conditions it was suggested that eliminations from isopropyltrimethylammonium ion followed the same route. 

Subsequent work revealed that the ylid mechanism was induced by metal alkyls and aryls but not by metal alkoxides and amides . Stereochemical evidence was cited, metal alkyls giving more c/s-cyclooctene and metal amides and alkoxides more trans-cyclooctene for elimination from cyclo-octyltrimethylammonium ion (49). Elimination from cyclooctyldimcthyl-(bromomethyl)ammonium ion with methyl lithium gave the same predominance of the c(i-cyclooctene. 

Five- and six-membered alicyclic ammonium ions, (50) below, undergo facile elimination under the normal conditions of the Hofmann reaction 

---

However, under somewhat different conditions (aqueous acetonitrile at 85°), no evidence for the free carbonium ion could be found (Bethell et al., 1965). Moreover, the invariance of the product proportions when water is replaced by deuterium oxide, coupled with the observation of a large tritium isotope effect on the formation of diphenylmethanol, is consistent only with the ylid mechanism (equation 21) (Bethell et al., 1969). For reaction of diarylmethylenes with alcohols, substantial hydrogen-isotope effects are observed, consistent with both equations 21 and 22. 

In this situation of a slow methyl ylid formation and fast rearrangement, the ylid mechanism is not distinct from a concerted mechanism and perhaps is less favorable. The following mechanism, which does not involve a free ylid, was then proposed for the formation of 7 95>. 

It is noted that a nitrogen ylid has been invoked in the Hofmann elimination reaction (sec. 2.9.C.i). 4 This ylid mechanism is highly questionable for many substrates that proceed via 3-elimination with a coordinated hydroxide.In those cases, removal of the hydrogen directly by hydroxide appears more likely. The ylid mechanism probably operates when PhLi is used as a base and when there is steric inhibition of the usual (3-elimination process. 

A more elegant and convincing demonstration of the ylid mechanism is accomplished by tracer studies. In the ylid mechanism, the trimethylamine produced contains one deuterium atom per molecule if the beta hydrogen atom is labelled in the substrate (47), whereas the E2 mechanism yields unlabelled material. Analysis by mass spectroscopy or nuclear magnetic resonance affords a convenient diagnosis of mechanism. Tracer studies confirm the absence of the ylid mechanism for the Hofmann reactions of a series of quaternary ammonium salts (51) , (52) . 

Entropy considerations may favour the concerted process as the rotation of the trimethylammonium group is restricted during the ylid mechanism. 

A useful guide to the ylid mechanism should be provided by the activation entropy. In a reaction following the E2 mechanism, in attaining the transition state in polar solvents a reduction in solvation of the ammonium ion occurs. 

As a finale to this work, it would be worthwhile completely to exclude the admittedly unlikely possibility of the ylid mechanism as the explanation of... 

In neutral and alkaline media, the rate of exchange at the 3 and 6 position of 4-aminopyridazine is independent of acidity but decreases markedly when the media become more acidic. This was interpreted in terms of a rate-determining removal of the 6-proton by deuteroxide ion to give the ylid (XXIV), which reacts with deuterium oxide in a fast step. A similar result for the 3 and 6 positions of py-ridazin-4-one suggests the same mechanism. For reaction at the 5 position, the rate-acidity profile indicated reaction on the free base as did that for the 5 position of pyridazin-3-one, though the appearance of a maximum in the rate at — HQ = 0.8 was anomalous and suggested incursion of a further mechanism. 

From Azides and x-Acylphosphorus ylids Addition of azides to a-acylphosphorus ylids takes place at room temperature in dichloromethane or at 80°C in benzene, giving triazolines from which a phosphine oxide is spontaneously eliminated. " The ylids exist almost exclusively in the cis-enolate configuration, and a mechanism involving concerted 1,3-dipolar addition has been proposed (Scheme 12) on the basis that there is a low entropy of activation for the reaction, and that the reaction rate is insensitive to changes in solvent polarity. ... 

Essentially the same mechanism is likely to be involved in an electrochemical version of the Stevens rearrangement. The mechanism of this reaction is not known with certainty however, it is known to be intramolecular and to involve deprotonation of quaternary ammonium salts to give nitrogen ylids which rapidly rearrange. The scheme set out in Scheme 9 is therefore entirety plausible. 

If an allyl halide is used as the quaternizing agent, an intramolecular 1,5-cyclization of the ylid may take place. In this way, various dihydro-indolizines, which are prone to oxidation and thus difficult to prepare, have been made.67 The probable mechanism is shown in Scheme 9. 

Reaction intermediates can be detected by reaction monitoring (i.e. analyses at several reaction times), and their presence may be inferred or even observed more readily at low temperatures. In a Wittig reaction, the ylid 32 in Scheme 2.13 was produced from ethyl-triphenylphosphonium bromide and butyl lithium, and reacted with a small excess of cyclohexanone in THF at —70°C the initial product, the oxaphosphetane 33, was identified by 31P NMR and converted to the alkene product and triphenylphosphine oxide (34) above — 15°C (see also Chapter 9). These results provide relatively direct experimental evidence for the mechanism shown in Scheme 2.13 [23]. 

The mechanism for the formation of the alkene is open to discussion especially as there is no agreement on the source of the stereoselectivity.5 We suggest that the carbanion end of the ylid... 

However, internal cycloaddition fails to give an adduct when an ethylenic moiety is linked to the ylid precursor. Even a styrene does not give any adduct and a diamine is obtained instead (note that in this instance zinc chloride was used instead of lithium fluoride). The same result is observed starting from the corresponding phenyl derivative, i.e., from /V-benzyl-/V-(methoxy methyl)trimethylsilylmethylamine. The proposed mechanism involves demethox-ylation under the action of the Lewis acid to form cation, K, which adds to the ylid to give the ethylenediamine framework.219... 

A quite different heterolytic mechanism has been put forward for the reaction of diphenylmethylene with alcohols to form diphenylmethyl alkyl ethers (Kirmse, 1963). The ability of alcohols to suppress the reaction of the photolytically generated carbene with oxygen increased with increasing acidity of the alcohol. When sodium azide was present, the ylids of diphenylmethyl azide and alkyl ether were close to those obtained by solvolysis of diphenylmethyl chloride under the same conditions. Equation (22) is a plausible formulation of the reaction. 

This question is the subject of much debate, because the mechanism by which the oxaphosphetane is formed is not entirely understood. One possible explanation relies on rules of Orbital symmetry, which you will meet in Chapters 35 and 36—we need not explain them in detail here but suffice it to say that there is good reason to believe that, if the ylid and carbonyl compound react... 

The attacks of heterocyclic A -oxides, e.g. of pyridine, quinoline, isoquinoline, phenanthridine, etc., on activated alkynes (RC CR R = R = COOMe R = Ph, R = COOEt R = Ph, R = CN) pose similar problems . An acyclic intermediate has been postulated but is rarely detected. Some of the possibilities are illustrated in equation (126) . If the open intermediate is formed, then the paths to the ylid and the 2-substituted quinoline in equation (126) seem simple enough, but several possible mechanisms can lead to the 3-substituted products . Other workers regard the reaction of the nitrone (or azomethine oxide) with alkyne as simple cycloadditions - which yield 2,3-dihydro-l,2-oxazoles since these are often unstable, only decomposition products may be found (equation 127). The construction of the indolizine skeleton initiated by a similar process has been reviewed (equation 128). ... 

Formally, the insertion of a carbene(oid) into the 2,3-doubIe bond of the thiophene ring should result in the formation of the 2-thiabicyclo [3.1.0] hex-3-ene ring system. Copper(II)-catalyzed reaction of thiophene with diazomethane results in the formation of 24 (R = H) in modest yield (63TL1047). Analogously, the reaction of thiophene with ethyl diazoacetate yields 24 (R = COjEt) (22LA154). Although these reactions appear to be simple carbene insertion reactions, it is probable that this simple mechanism is not in operation. Rather, the cyclopropane derivatives 24 probably result from the initial formation of the ylid (e.g., 18), which subsequently rearranges. 

An a hydrogen is obviously necessary in order for the ylid to be formed. This type of mechanism is called a, p elimination, since a p hydrogen is removed by the a carbon. The mechanism has been confirmed by labeling experiments similar to those described at 17-7, " and by isolation of the intermediate ylids. An important synthetic difference between this and most instances of 17-7 is that syn-elimination is observed here and anti-elimination in 17-7, so products of opposite configuration are formed when the alkene exhibits cis-trans isomerism. 

---