Oxaphosphetane decomposition

Phosphorous and oxygen form very strong bonds, driving the manner of oxaphosphetane decomposition... 

Several tests are available to determine whether equilibration of stereochemistry occurs in the course of oxaphosphetane decomposition (methods A-E, Scheme 7), but each method has some limitations. In method A, oxaphosphetane diastereomers are prepared independently by deprotonation of the )S-hydroxyphosphonium salts 27 or 28 with base (NaHMDS, NaNHj, KO-tert-Bu, etc.) (20). If each isomer affords a distinct oxaphosphetane 31 or 32 according to NMR analysis (usually, or H), then the solutions are warmed up to the decomposition temperature. Kinetic control is established if stereospecific conversion to the alkenes can be demonstrated from each diastereomer. A less rigorous version of this test is to perform the experiment only with isomer 27, the precursor of the cis-disubstituted oxaphosphetane 31 (21c). All known examples of significant (> 5%) stereochemical equilibration involve 31 and not the trans-disubstituted isomer 32 (20, 21c). A negative equilibration result with the cis diastereomer 31 can be assumed to apply to 32 as well. 

Both of the above teehniques can be reinforeed by erossover experiments (method C) (12-14,20,2Ic,22,23a). An excess of CIC H CHO (ArCHO) is added to the solution below the temperature for oxaphosphetane decomposition. If stereochemical equilibration occurs exclusively by a retro-Wittig process to give the ylide 33, then an excess of the crossover aldehyde must produee the crossover products. Since 33 would be intercepted by excess ArCHO faster than it can recombine with the original aldehyde, the conversion from one oxaphosphetane diastereomer into the other (i.e., from 31 to 32) by way of any retro-Wittig mechanism will be suppressed using method C. However, it is essential to prove that the oxaphosphetane has not already decomposed prior to the addition of the crossover aldehyde. Otherwise, there is the risk of a false-negative crossover result. 

Methods A, D, and E suffer from the inherent limitation that they deliberately generate a betaine as the precursor of the oxaphosphetane. Since there is no assurance that the reaction of an ylide with an aldehyde would involve the same ionic intermediate (19,21) these control experiments may provide opportunities for stereochemical equilibration that may not be available to the corresponding Wittig reactions. If the oxaphosphetane generated by methods A or E is stable enough to observe directly, then it is usually possible to distinguish between oxaphosphetane equilibration, betaine equilibration, and other mechanisms for loss of stereochemistry (21 c). However, this is not possible for oxaphosphetanes that contain unsaturated substituents at Cj because oxaphosphetane decomposition is fast at — 78°C (21c). In these examples, method A (like method D or E) can only establish an upper limit for equilibration of all of the conceivable intermediates betaines, betaine lithium halide adducts, oxaphosphetanes, and so on. 

By the same logic, it is unlikely that the stabilized ylide reactions can be influenced by stereochemical equilibration. It would be difficult for any equilibration process to compete with the exceptionally rapid oxaphosphetane decomposition step. Partial loss of stereochemistry does occur in some of the high-temperature control experiments at the betaine stage, as listed in Table 7, but oxaphosphetane decomposition takes place with retention of stereochemistry (Table 6, entries 18-21) (21c). 

The role of steric effects in explaining the prevalent formation of Z olefin from non-stabilized and keto-stabilized ylides has been highlighted. New insights into the second step of the Wittig reaction have been reported oxaphosphetane decomposition was found to take place in a single step via a polar transition state. 

Monocyclic Phosphoranes. - Further studies on the mechanism and stereochemistry of the Wittig reaction have been conducted by a combination of 1H, 13C and 3 P n.m.r.2k 25. The results show that at -18°C both ois and trans diastereomeric oxaphosphetans (e.g. 17 and 18) may be observed and their decomposition to alkenes monitored by n.m.r. Evidence was presented to suggest that during this process oxaphosphetan equilibration involving the siphoning of (17) into (18) occurred in competition with alkene formation. 

This accounts for the considerable discrepancy between the alkene Z/E ratio found on work-up and the initial oxaphosphetan ais/trans ratio. By approaching the problem from the starting point of the diastereomeric phosphonium salts (19) and (20), deprotonation studies and crossover experiments showed that the retro-Wittig reaction was only detectable with the erythreo isomer (19) via the cis-oxaphosphetan (17). Furthermore, it was shown that under lithium-salt-free conditions, mixtures of (19) and (20) exhibited stereochemical drift because of a synergistic effect (of undefined mechanism) between the oxaphosphetans (17) and (18) during their decomposition to alkenes. 

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. 

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

How can the Z selectivity in Wittig reactions of unstabilized ylids be explained We have a more complex situation in this reaction than we had for the other eliminations we considered, because we have two separate processes to consider formation of the oxaphosphetane and decomposition of the oxaphosphetane to the alkene. The elimination step is the easier one to explain—it is stereospecific, with the oxygen and phosphorus departing in a syn-periplanar transition state (as in the base-catalysed Peterson reaction). Addition of the ylid to the aldehyde can, in principle, produce two diastere-omers of the intermediate oxaphosphetane. Provided that this step is irreversible, then the stereospecificity of the elimination step means that the ratio of the final alkene geometrical isomers will reflect the stereoselectivity of this addition step. This is almost certainly the case when R is not conjugating or anion-stabilizing the syn diastereoisomer of the oxaphosphetane is formed preferentially, and the predominantly Z-alkene that results reflects this. The Z selective Wittig reaction therefore consists of a kinetically controlled stereoselective first step followed by a stereospecific elimination from this intermediate. 

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. 

Different behavior has been observed on heating dixoaphospholanes. With a few exceptions compounds bearing hydrogen on a carbon atom adjacent to phosphorus rearrange to 1,2-oxaphosphetanes (see Section III,A,5). At 160°C, 57d (X = Y = Z = Ph) dissociates into the starting materials (220). Compound 57g (X = Y = Z = OEt) loses one molecule of HFA at 165°C and forms several decomposition products (220)... 

Mechanism In early papers, Wittig described that the reaction proceeds with the formation of betaine, which collapsed to four-membered cyclic oxaphosphetane. Either of these two intermediates decomposes to form an alkene. The decomposition of oxaphosphetane... 

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