Carbonyl ylides reaction mechanisms

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

The outcome of reactions involving carbonyl ylides is not always as easy to predict, as the examples in Table 4.20. Depending on the basicity of the intermediates, proton migrations might occur and unexpected results can be obtained. Two examples of such peculiar conversions and the proposed mechanisms are sketched in Figure 4.16. 

This unusual reaction involves the reductive dimerization of protected iodohy-drin (44) that produced a symmetrically substituted carbonyl ylide (48). The mechanism proposed for this interesting process involved initial reduction of the... 

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). 

The reaction mechanism proposed for the LiBr/NEta induced azomethine ylide cycloadditions to a,p-unsaturated carbonyl acceptors is illustrated in Scheme 11.10. The ( , )-ylides, reversibly generated from the imine esters, interact with acceptors under frontier orbital control, and the lithium atom of ylides coordinates with the carbonyl oxygen of the acceptors. Either through a direct cycloaddition (path a) or a sequence of Michael addition-intramolecular cyclization (path b), the cycloadducts are produced with endo- and regioselectivity. Path b is more likely, since in some cases Michael adducts are isolated. 

For clarification of the reaction mechanism, the rearrangements of cis- and trans-phenylvinyloxiranes have been investigated, to avoid the formation of dihydrooxepine. c/s-Dihydrofuran derivatives are formed by conrotational opening of the oxiranes through a carbonyl-ylide intermediate. 

Although the reaction mechanism depends upon the nature of the reacting anionic species (as illustrated in the scheme), a chelation between the lithium and the carbonyl oxygen of the dipolarophiles may be responsible for the exclusive regio- and endo selectivity. This chelation is so rigid that the high endo selectivity as well as the enhanced reactivity remains even when the a substituent of the ylide is a sterically bulky isopropyl group and the p substituent an olefinic methyl. On the other hand, the selectivity of cycloadditions of ylides 141 is very poor when the olefin dipolarophiles bear a noncarbonyl substituent (e.g., acrylonitrile) or when s-(rans-enones (e.g., 2-cyclopentenone) are used as dipolarophiles. 

Carbethoxycyclopropyltriphenylphosphonium fluoroborate (475) proves to be an excellent reagent for cycloalkenylation of carbonyl compounds. Reaction of p-kcio esters (as their sodium enolates) smoothly produces cyctopentene diesters (602) (equation 213). The mechanism can be most simply viewed as a nucleophilic attack of the enolate on the cyclopropane ring to produce a stabilized ylide, which rapidly cyclizes to the... 

The reactions of carbonyl compounds with benzyltrialkylstibonium ylides have been investigated (Scheme 9).39 The products are either benzyl alcohols (52) or mixtures of alkenes and epoxides depending on the base used to generate the ylide. A mechanism is suggested for the formation of (52). 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

The mechanism of the reaction between dimethyl diazomalonate with an excess of benzaldehyde has been shown to proceed via carbonyl ylide (57) 1 ylide undergoes either electrocyclic ring closure to (58) or further reaction... 

The reaction of phosphorus ylides with carbonyl compounds has developed into one of the most important methods for the synthesis of olefins the synthetic potential of the Wittig reaction has been described in a series of review articles [2-7]. Numerous other studies are concerned with the stereochemical course of the Wittig reaction (see Section C) and of the reaction mechanism (see Section D). 

The resonance form 5a accounts for the nucleophilic character of the ylide carbon atom. The reaction between ylide and carbonyl component can be regarded as nucleophilic attack of the ylide carbon atom on the carbonyl group (see Section D for a discussion of the reaction mechanism of the Wittig reaction). The reactivity, Le. the nucleophilicity of the ylide, on the one hand is influenced to a considerable extent by the character of the substituents and R, but, on the other hand, it is also influenced by the so-called stationary substituents on the phosphorus. 

The detection of oxaphosphetanes as relatively stable Wittig intermediates led to revision of the reaction mechanism theory. An asynchronous cycloaddition between ylide and carbonyl component was proposed for the oxaphosphetane formation a transition state resembling the starting material in the case of reactive ylides and a transition state resembling oxaphosphetane in the case of moderate and stable ylides can explain the different (E/Z)-selectivities of the different ylide types [44]. 

Despite the great synthetic utihty of diazocarbonyl compounds in the generation of carbonyl ylide intermediates, definitive mechanistic studies on the metal-catalyzed cycloaddition of carbonyl yhdes are scarce. Among the various metal catalysts, dirhodium(II) catalysts are the most effective and versatile for diazo decomposition. Because of the rapid catalytic tmnovers of these reactions, structural information about the intermediates is difficult to obtain. A reasonable mechanism can be rationahzed on the basis of product distribution, and especially on the basis of enantioselective outcome of various carbonyl yhde reactions [55-63]. 

In this section, we ll take a break from our survey of reaction mechanisms and focus instead on a class of intermediates, namely, carbanions. We will also discuss carbanion cognates such as enols, enolates, enamines, and ylides. As classic nucleophiles, carbanions react in highly characteristic ways, particularly via 8 2 displacements, as well as via other pathways (e.g., carbonyl addition and conjugate addition) we have discussed above. The material in this section will thus help you flesh out your understanding of what we have discussed so far. 

---