Oxaphosphetane intermediates

The Wittig reaction is one that IS still undergoing mech anistic investigation An other possibility is that the oxaphosphetane intermedi ate IS formed by a two step process rather than the one step process shown in Figure 17 13... 

Betaine precipitates have been isolated in certain Wittig reactions, but these are betaine-lithium halide adducts, and might just as well have been formed from the oxaphosphetane as from a true betaine. However, there is one report of an observed betaine lithium salt during the course of a Wittig reaction. In contrast, there is much evidence for the presence of the oxaphosphetane intermediates, at least... 

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 generally quite stable methylenephosphorane nevertheless resembles the short-lived highly reactive methyleneoxophosphorane. The oxaphosphetane intermediate 25 formed by -I- n2]-cycloaddition, which can only be isolated in exceptional cases21, is to be seen against the stable oxaphosphetanes of type 26, which can be photolyzed if suitably substituted or thermolyzed under drastic... 

Calculations on two Wittig reactants, alkylidenetriphenylphosphorane (a non-stabilized ylid) and its benzylidene analogue (a semi-stabilized one), have been used to identify the origin of the product selectivities for the two classes. A planar transition state gives a trani-oxaphosphetane intermediate, while a puckered one leads to cis-. These two transition states were favoured by the semi- and un-stabilized reactants, respectively. 

In the first step a Wittig reaction" is used to transform the aldehyde into a terminal olefin. This requires initial preparation of a quaternary phosphonium salt. The latter is then deprotonated with sodium amide to give phosphorus ylide 46, which after nucleophilic attack on aldehyde 12 leads to the oxaphosphetane intermediate 47. This intermediate in turn decomposes into olefin 48 and triphenylphosphine oxide. 

Quantum mechanical calculations in the gas phase and DMSO solution at different temperatures can highlight the hazards of standard 0 K gas-phase calculations.259 For the Wittig reaction, a small barrier in the potential energy curve is transformed into a significant entropic barrier in the free energy profile, and the formally neutral oxaphosphetane intermediate is displaced in favour of the zwitterionic betaine in the presence of DMSO. 

Ring opening of cz s-2,3-dimethyloxirane by triphenylphosphine has been modeled using the B3LYP functional with the 6—3lG(d) basis set.43 The calculations suggest that the first step of the reaction is an SN2 process with simultaneous C-C bond rotation giving an oxaphosphetane intermediate that decomposes to the frans-alkene no betaine intermediate is formed. 

The acid-catalyzed Peterson olefination is presumably an E2-elimination, that is, a one-step reaction. On the other hand, the base-induced Peterson olefination probably takes place via an intermediate. In all probability, this intermediate is a four-membered heterocycle with a pentavalent, negatively charged Si atom. This heterocycle probably decomposes by a [2+2]-cycloreversion just like the oxaphosphetane intermediate of the Wittig reaction (Section 4.7.3). 

Fig. 4.46. A Het /Het2 elimination from the presumed oxaphosphetane intermediate of a Homer-Wadsworth-Emmons reaction.

Ylids can be isolated, but are usually used in reactions immediately they are formed. They are nucleophilic species that will attack the carbonyl groups of aldehydes or ketones, generating the four-membered ring oxaphosphetane intermediates. Oxaphosphetanes are unstable they undergo elimination to give an alkene (65% yield for this particular example) with a phosphine oxide as a byproduct. The phosphorus-oxygen double bond is extremely strong and it is this that drives the whole reaction forward. 

The first step is a simple Wittig reaction with an unstabilized ylid (Chapter 31), which we expect to favour the Z-alkene. It does but, as is common with Wittig reactions, an E/Z mixture is formed but not separated as both isomers eventually give the same compound. The reaction is kinetically controlled and the decomposition of the oxaphosphetane intermediate is in some ways like a fragmentation. 

Protic solvents shift the alkene E)j Z) ratio in the direction of the (E)-form. The alkene [E)I Z) ratio of salt-free Wittig reactions is thus influenced not only by the electronic character of R, but also by the solvent and the stereochemistry of the formation of the 1,2-oxaphosphetane in the first rate-determining step. According to Eq. (5-48), the thermodynamically less stable (Z)-l,2-oxaphosphetane is formed in the first activation step. A conformational analysis of the activated complex leading to the 1,2-oxaphosphetane intermediate provides a reasonable explanation for this unexpected cis-selectivity [143, 556]. 

Keglevich et al. have reported a series of papers on the mechanistic aspects of what they term inverse Wittig reactions , i.e. the preparation of phosphoranes from the [2-f2] cycloadditions of phosphine oxides and acetylenedicar-boxylates, an example of which is given in Scheme 1. A raft of spectroscopic and structural evidence, coupled with theoretical calaculations, indicate that these reactions proceed via oxaphosphetane intermediates (16). ... 

A review on the chemistry of thio derivatives of trivalent phosphorus acids which covers the literature to 1986, includes a section on pentaco-ordinate phosphorus compounds derived from addition to a-diketones and unsaturated systems activated to nucleophilic attack by electron withdrawing groups. Chemical bonding in hypervalent molecules has been discussed and qualitative bonding concepts developed to supersede the dsp and d sp models. A review on the mechanism and stereochemistry of the Wittig olefination reaction inevitably includes a discussion of the equilibrium between betaine and 1,2-oxaphosphetane intermediates. A correction has been published to reference 19 of Chapter 2 in SPR14, Vol.21, concerning the Mitsunobu Reaction. ... 

In the first step a Wittig transformation is performed. The a-position of the phosphonium salt 12 is C,H-acidic, and therefore the strong base NaHMDS abstracts a proton forming the labile ylide 38. This ylide is a carbon nucleophile, which attacks the ketone moiety of Segment B (7) forming the oxaphosphetane intermediates cw-39 and trans-39. The mode of action is thought to proceed via a [2+2]-cycloaddition. 

This is a Wittig reaction. The stable ylide is prepared from 29 prior to the reaction. Only the ketone reacts to form the corresponding olefin via the oxaphosphetane intermediate, as the Weinreb amide is not reactive enough. Owing to the use of a stable phosphonium ylide, only the product with the -configured double bond is obtained in 90 % yield ( /Z 99 1). 

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