Mechanism of the Wittig reaction

The [2+2]-cycloaddition between the mentioned reaction partners to form an oxaphosphetane is not only stereogenic hut frequently also exhibits a considerable degree of stereoselectivity. The latter is more precisely called simple diastereoselectivity. 

By simple diastereoselectivity we mean the occurrence of diastereoselectivity when bond formation between the C atom of a C=X double bond and the C atom of a C=Y double bond establishes a stereocenter at each of these C atoms. 

The simple diastereoselectivity of the formation of oxaphosphetanes depends mainly on which ylide type from Table 11.1 is used. 

11 Conversion of Phosphorus- or Sulfur-Stabilized C Nucleophiles with Carbonyl Compounds 

Under salt-free conditions, the cw-oxaphosphetanes formed from nonstabilized ylides can be kept from participating in the stereochemical drift and left intact until they decompose to give the alkene in the terminating step. This alkene is then a pure ci.s-isomer. In other words, salt-free Wittig reactions of nonstabilized ylides represent a stereoselective synthesis of cis-alkenes. 

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To understand the mechanism of the Wittig reaction we need to examine the struc... 

To understand the mechanism of the Wittig reaction, we need to exanine the structure and properties of ylides. Ylides are neutral molecules that have two oppositely... 

Active Figure 19.13 MECHANISM The mechanism of the Wittig reaction between a phosphorus ylide and an aldehyde or ketone to yield an alkene. Sign in at www.thomsonedu.com fo see a simulation based on this figure and to take a short Quiz. 

The notable increases in theoretical studies of ylides and their reactions reflects similar developments throughout organic chemistry. The renewed interest in the mechanism of the Wittig reaction have continued, but in spite of several years of considerable effort from a number of respected research groups a fully satisfactory explanation is still some way off. 

E. Vedjs and C.F. Marth, Mechanism of the Wittig reaction the role of substituents at phosphorus,... 

Scheme 2.13 Mechanism of the Wittig reaction examined by NMR at low temperatures.

We have a fairly detailed knowledge of the mechanism of the Wittig reaction (Figure 11.3). It starts with a one-step [2+2]-cycloaddition of the ylide to the aldehyde. This leads to a heterocycle called an oxaphosphetane. The oxaphosphetane decomposes in the second step—which is a one-step [2+2]-cycloreversion—to give triphenylphosphine oxide and an alkene. This decomposition takes place stereoselectively (cf. Figure 4.44) a cw-disubstituted oxaphosphetane reacts exclusively to give a cis-alkene, whereas a fraws-disubstituted oxaphosphetane gives only a trans-alkene. The reaction is stereospecific. 

Fig. 11.3. Mechanism of the Wittig reaction. kcjs is the rate constant for the formation of the cis-oxaphosphetane, kmns is the rate constant for the formation of the trans-oxaphosphetane, and kdrjft is the rate constant for the isomerization of cis- to turns-configured oxaphosphetane, which is called "stereochemical drift."...

The mechanism of the Wittig reaction of phosphoranes with carbonyl compounds has fascinated chemists and remains a matter of discussion. Though the sulfur equivalent is very much less used, this reaction is known... 

Because the geometry of the 9-double bond was not clear at that time, Corey et al. 75> tried to prepare the (Z)-9-isomer as well as the ( )-9-isomer of leukotriene-A (78 and 86). In the synthesis of the former isomer the tribenzoyl derivative of D-(—)-ribose (79) was converted in 8 stepy into the optically active epoxyaldehyde 71 and the latter to 72. 72 was olefmated with ylide 82, generated by treatment of the corresponding phosphonium mesylate with lithium diisopropylamide in THF/ HMPA75) (Scheme 15). In the first olefination step 72+82- 78, however, similar to the first method, a A9-isomer mixture was formed. The loss of (Z)-selectivity of the Wittig reaction is due to the use of conjugated unsaturated, i.e. moderate ylides of type 82, and had to be expected because of the mechanism of the Wittig reaction (see Sect. 2). 

Mechanism of the Wittig reaction. Test yourself on the concepts in this figure at OrganicChemistryNow. 

Phosphorus Ylides 18.2 Mechanism of the Wittig Reaction (page 760)... 

The final stages follow the mechanism of the Wittig reaction you met in Chapter 14 you see them as a special case of dehydration made favourable by the formation of a phosphine oxide as well as an unsaturated carbonyl compound. 

Scheme 4.22 Mechanism of the Wittig reaction of non-stabilized ylides under salt-free conditions...

Currently accepted mechanism of the Wittig reaction of aldehydes with non-stabilized ylides involves the formation of oxaphosphetanes through a [2-I-2]-cycloaddition-like reaction . The oxaphosphetanes are thermally unstable and collapse to alkene and phosphine oxide below room temperature. Under salt-free conditions there is no formation of betaine intermediates. The salt-free ylides can be prepared by the reaction of phosphines with carbenes generated in situ. Vedejs etal proposed a puckered 4-centre cyclic transition state I for sy -oxaphosphetane and planar structure J for anff-oxaphosphetane. In general, the flnfi-oxaphosphetane J is more stable than the syn-oxaphosphetane I, and under equilibrium conditions (when stabilized ylides are used) the E-alkene product is favoured (Scheme 4.24). However, kinetic control conditions, which appear to dominate when non-stabilized ylides are used, would lead to Z-alkene. 

The currently accepted mechanism of the Wittig reaction involves two steps. Like other nucleophiles, the Wittig reagent attacks an electrophilic carbonyl carbon, but then the initial addition adduct undergoes elimination to form an alkene. Mechanism 21.4 is drawn using Ph3P=CH2. 

Four-membered oxaphosphetan rings are, of course, an integral feature of the mechanism of the Wittig reaction whidi has again received an exhaustive treatment during the year. " The first two papers by Vedejs et argue that kinetic (not equilibrium) factors are dominant in Wittig... 

Reports of the use of the Wittig and related methods in synthesis have, if anything, increased and many of these include useful innovations. New results and speculation on the mechanism of the Wittig reaction continue to be published by groups with well established reputations in the area. There has been a substantial increase in the number of reports of the use of iminophosphoranes in synthesis, especially those of heterocycles. 

Phe mechanism of the Wittig reaction between a phosphorus ylide and a ketone or aldehyde to yield an alkene. 

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