Threo betaine

The normal preference for (Z) alkenes in reactions of non-stabilized phos-phoranes can be reversed by employing the Schlosser modification of the Wittig reaction (Scheme 6).19 Here, equilibration of the initially formed erythro and threo betaine intermediates is achieved by reaction with additional strong base, usually an alkyl lithium. The resulting betaine ylide then gives the (E) alkene on treatment with a proton source followed by potassium tert-butoxide. 

These conditions allow for the erythreo betaine to interconvert to the threo betaine... 

Thermodynamisch sind die threo-Betaine 335 stabiler. 1st der Zerfall 334 - -34 -4- 333 schneller als der Zerfall 334 - 336 und Phosphinoxid, so kann sich das Gleichgewicht zugunsten des threo-Betains 335 einstel-len und man erhalt iiberwiegend das trans-Olefin 337. Dies ist der Fall beim Arbeiten mit schwach nucleophilen Yliden (z.B. 34 mit R= C—Ri). 

This was accomplished by treating the putative betaine intermediate 9, generated from ylide 1 and aldehyde 3, with a strong base (PhLi or -BuLi) in ether/THF (1 1). This deprotonation afforded P-oxido ylide 56, also illustrated by 57. In a manner similar to the equilibration occurring in HWE vide supra), one can add an external electrophile which kinetically adds to the sterically less hindered face of 58. The resultant 59 can then undergo loss of 8 to produce 6, in a controlled equilibration of the erythro/threo betaines. 

The stereochemistry of the alkene product in Wittig reactions is thought to be influenced by the reversibility of formation of the isomeric threo and erythro oxaphosphetanes (or betaines) which undergo stereospecific loss of triphenyl-phosphine oxide to give the trans (E) and cis (Z) alkenes, respectively (Scheme 4). Factors that enhance the reversibility of this initial step favour the threo intermediate and hence the (E) alkene. Stabilized phosphoranes give a predominance of the (E) alkene while non-stabilized phosphoranes give the (Z) alkene. In general, stabilized phosphoranes react readily with aldehydes (see Protocol 4) while non-stabilized phosphoranes will react with aldehydes, hemiacetals (see Protocol 5) and ketones.2,3... 

Although lower yields (40%) were observed by Camps et al. (1971), they were improved (55-94%) by McKinley and Rakshys (1972). The separation of the insoluble polymer by-product (phosphine oxide) makes the isolation of the major alkene product very simple. The presence of lithium ion is known to lead to the formation of trans-alkenes because of the preferred complexation of the threo-form of the betaine. With the... 

Mechanistically, this variation is similar to the classical Wittig reaction. The only departure stems from the physico-chemical nature of the intermediates. The addition of ylide 34 to carbonyl compound 3 occurs as before to set up a mixture of erythro 35 and threo 37 adducts. Now the betaines are more acidic, which facilitates the interconversion of 35 and 37. Deprotonation of 35, in situ, produces 36. Kinetic protonation occurs from the least sterically hindered face, as shown in 38. With the equilibration to... 

In this context, one may also pay attention to the so-called "betaine-ylides" that act as key intermediates in stereocontrolled Wittig olefination reactions. They are generated from the ordinary adducts obtained by the combination of a phosphine ylide and an aldehyde in the presence of lithium bromide (or another soluble lithium salt). When the P-betaines are a-deprotonated with phenyllithium, the stereocenter at the phosphorus-adjacent carbon atom becomes configurationally mobile. In this way, erythro/threo mixtures can spontaneously convert into virtually pure /Areo-betaine ylides (p-lithiooxy ylides, P-oxido ylides). Reprotonation and subsequent elimination of triphenylphosphine oxide affords trans olefins, whereas a-substitution by electrophiles other than acids leads to branched alkenes exhibiting a well-defined stereochemistry "("three-dimensional"" Wittig reaction or SCOOPY method). ... 

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