Unstabilized ylids

I hc key intermediates in the synthesis of the E- and the Z-isomers of capsaicin were the E and Z unsaturated esters shown below. By using a Wittig reaction with an unstabilized ylid it was possible to make the Z-isomer selectively, whilst the Julia olefination gave the -isomer. 

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 female silkworm moth attracts mates by producing a pheromone known as stabilized and unstabilized ylids, respectively, to control the stereochemistry of bombykol. Bombykol is an E.Zdiene, and in this synthesis (dating from 1977) the product, two successive Wittig reactions exploit the stereoselectivity obtained with... 

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. 

Why does the stabilized ylid prefer to react with the double bond In order to understand this, let s consider first the reaction of a simple, unstabilized ylid with an unsaturated ketone. The enone 1 has two electrophilic sites, but from Chapters 10 and 23, in which we discussed the regioselectivity of j attack of nucleophiles on Michael acceptors like this, you would expect that direct 1,2-attack on the i ketone is the faster reaction. This step is irreversible, and subsequent displacement of the sulfide i leaving group by the alkoxide produces an epoxide. It s unimportant whether a cyclopropane prod- uct would have been more stable ihe epoxide forms faster and is therefore the kinetic product. 

Wittig, with a stabilized ylid, gives the -enal (A). The second, with an unstabilized ylid, i Z-alkene, and the final structure is an ,Z-diene. 

The first is a Wittig reaction with an unstabilized ylid, the second a Julia reaction, and the last two are Peterson reactions under different conditions. Each reaction is described in detail in the chapter. The Wittig reaction is under kinetic control and is a stereospecifically cis elimination. In this case the product is the Z-alkene. 

Now a Wittig reaction with an unstabilized ylid selectively gives the Z-alkene. Note that molecules ol base are needed one to open the lactol, one to remove the proton from CO.H. one to make the ylid. 

So why is there a change to E stereoselectivity when the ylid is stabilized Again, the details are still unclear, and there are several possible explanations. Here we give one which is gaining ground, supported by recent experimental and computational evidence. It seems that, as with unstabilized ylids, the stereochemistry of the alkene product is determined by the stereochemistry of the intermediate oxaphosphetane, which with stabilized ylids must be anti. 

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