Oxaphosphetanes olefination

Reaction of an alkyltriphenylphosphorane in tetrahydrofuran with an aldehyde produces the oxaphosphetane B, which can be further treated with 1 eq. of 3-butyllithium to form the P-oxidophosphonium ylide C. This ylide can in turn react with another aldehyde, for instance, paraformaldehyde to give, after work-up, the trisubstituted olefin D. 

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

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... 

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. 

The Wittig reaction is a very important method for olefin formation. The stereochemistry about the new carbon-carbon double bond is the Z (or less stable) isomer. This unusual stereoselectivity indicates that product formation is dominated by kinetic control during formation of the oxaphosphetane. 

By adding a strong base to the cold solution of the oxaphosphetane before it eliminates, die oxaphosphetane equilibrates to die more stable anti isomer and die E olefin is produced upon elimination. This so-called Schlosser modification in conjunction with the normal Wittig reaction enables either the Z or E isomer of the olefin to be prepared selectively. 

With phosphorus ylides as used for the Wittig Reaction, the phosphorus atom forms a strong double bond with oxygen. This leads the mechanism in a different direction, to effect olefination instead of epoxidation through intermediate oxaphosphetanes. 

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. 4.44. syn-Selective eliminations from oxaphosphetanes in Wittig olefinations with unstabilized (upper row gives ris-olefin) and stabilized P-ylides (bottom row gives trans-olefin). 

Protic solvents or the addition of proton-active compounds after oxaphosphetane formation shift the stereoselectivity of the reaction in the direction of the ( )-form. If the Wittig reaction is carried out in C2HsOD or if the oxaphosphetane solution, prepared at —75 °C in an aprotic solvent, is treated with deuterated ethanol, then deuterium is incorporated in high yield into the ( )-olefm formed, and the degree of deuterium labelling of the coexisting (Z)-olefin is lower. On the basis of these findings the mechanism discussed below has been established (Scheme 5). 

A syn-elimination of Ph2MeP=0 and simultaneous stereoselective olefin formation from an oxaphosphetane are shown in Figure 4.40 (note that this oxaphosphetane is... 

You will learn about the reaction of a-metallated phosphonic add esters with aldehydes in Section 9.4. This reaction also seems to give a fraus-configured oxaphosphetane (Figure 4.41). A. vyu-selective /3-elimination by a [2+2]-cycloreversion of a compound containing a P=0 double bond follows this compound is (EtO)2 P(=0)0. The second elimination product is an olefin. It is predominantly or exclusively traus-configured. 

One has a detailed conception of the mechanism of the Wittig reaction (Figure 9.7). 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 olefin. This decomposition takes place stereoselectively (cf. Figure 4.39) A cfs-disubstituted oxaphosphetane reacts exclusively to give a cw-olefin, whereas a trans-disubstituted oxaphosphetane gives only a trans-olefin. In other words, stereospecificity occurs in a pair of decomposition reactions of this type. 

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

Semistabilized ylides generally react with aldehydes to form mixtures of cis- and fnms-oxaphosphetanes before the decomposition to the olefin starts. Therefore, stere-ogenic reactions of ylides of this type usually give olefin mixtures regardless of whether the work is carried out salt-free or not. 

On the other hand, stabilized ylides react with aldehydes almost exclusively via trans-oxaphosphetanes. Initially, a small portion of the cw-isomer may still be produced. However, all the heterocyclic material isomerizes very rapidly to the fnms-configured, four-membered ring through an especially pronounced stereochemical drift. Only after this point does the [2+2]-cycloreversion start. It leads to triphenylphosphine oxide and an acceptor-substituted fnms-configured olefin. This frara-selectivity can be used, for example, in the C2 extension of aldehydes to /ran.v-con figured aj8-unsaturated esters (Figure 9.11) or in the fnms-selective synthesis of polyenes such as /1-carotene (Figure 9.12). 

It would thus be possible that first both the alkoxide A and its diastereomer D form unselectively but reversibly from the phosphonate ion and the aldehyde. Then an irreversible cyclization of the alkoxide A would give the fnms-oxaphosphetane B. The alkoxide D would also gradually be converted into the fnms-oxaphosphetane B through the equilibrium D . starting materials . A. In summary, in this explanation one would deal with the productive formation of an alkoxide intermediate A finally leading to the olefin and with the vain formation of an alkoxide intermediate D which cannot react further to an olefin. 

Structure 1 of oxaphosphetane is taken as proved. Ylid 5 or 4 as an intermediate stage on the way starting at educts R3P + Hal —CH2 —R was generated as a precursor of the structure 1 betaine 7, which is produced by fast splitting of oxaphosphetanes by for instance lithium halides [59] can be considered as a successor of the systeme 1 in the opposite direction to the olefin route. 

The.l,2-A -oxaphosphetanes 58 and 68 can be considered stable intermediates of the Wittig reaction. Pyrolysis of the parent compounds yields the corresponding olefins and oxophosphoranes, respectively, which have been reported in several publications 204, 220, 221, 226). 

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. ... 

For the reaction of labile ylides with aldehydes, the formation of cis-oxaphosphetanes is favored, unless lithium ion-containing bases are used. The four-membered ring system of cis-39 dissociates in a [2+2]-cycloreversion and forms triphenyl phosphonium oxide and the desired olefin Z-13. Using labile ylides in Wittig reactions that contain no electron-withdrawing group except the phosphonium moiety, leads predominantly to the formation of c/ -oxaphosphetanes. Hence, Z-olefins are typically formed with > 90 % selectivity. ... 

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). 

Schlosser Modification. Almost pure tran -olefins are obtained from nonstabilized ylides by the Schlosser modification of the Wittig reaction (Wittig-Schlosser reaction). For example, treatment of the (cij )-oxaphosphetane intermediate A with n-BuLi or PhLi at -78 °C results in lithiation of the acidic proton adjacent to phosphoras to produce the P"Oxido phosphonium ylide B. Protonation of B with f-BuOH leads to the trans-1,2-disubstituted alkene C. 

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