Reverse Wittig reactions

In the reversible Wittig reaction, triphenylarsine oxide reacted with electron-deficient acetylene derivatives to form stable ylides. Thus triphenylarsine oxide reacted readily with methyl propiolate, ethyl phenylpropiolate, dimethyl acetylenedicarboxylate, and hexafluoro-2-butyne as well as dicyanoacetylene to give arsonium ylides (12). The reaction temperatures required ranged from -70°C in the case of dicyanoacetylene to 130°C in the case of ethyl phenylpropiolate (15). 

E. Vedjs, T. Fleck and S. Hara, Evidence against reversible Wittig reaction of stabilised ylide high... 

REDUCTIVE DEOXYGENATION OF ALCOHOLS AND KETONES N,N,N ,N -Tctramethyldiamldophosphorochloridate. REFORMATSKY REACTION Ethyl Ui-chloroacetate. Lithium diisopropylamide. REVERSE WITTIG REACTION Triphenyl-aisine oxide. 

Triphenylarsine oxide reacts with a number of electrophilic acetylenes having electron-withdrawing substituents in what are, in effect, reverse-Wittig reactions, thereby providing stable arsonium ylides (equation 31) Reaction is presumably initiated by Michael-type reaction of the oxide with the alkyne, as exemplified in equation 32. As would be expected from such a mechanism, use of an unsymmetric alkyne, as in the foregoing example, results in virtually regiospecific attack by the oxide to give the product shown. 

Reverse Wittig reactions,1 Dicyanoacetylene reacts with triphenylphosphine oxide in benzene at 160° to give triphenylphosphoranylideneoxalacetonitrile (1) in 78% yield by way of the intermediates formulated. 

In addition to its other properties, interest in the potential use of the vasodilative properties of prostaglandin El, alprostadil ( ), has led to several conceptually different syntheses.For this purpose, the classic Corey process has to be modified by reversing the order of addition of the side chains to allow for convenient removal of the unwanted double bond in the upper side chain. For example, Corey lactone is protected with dihydropyran (acid catalysis), reduced to the lactol with diisobutyaluminum hydride, and then subjected to the usual Wittig reaction to give intermediate This is... 

A. Preparation.—The first reverse Wittig olefin synthesis has been reported. Triphenylphosphine oxide and dicyanoacetylene at 160 °C gave the stable ylide (1 78%) the reaction was reversed at 300 °C. No comparable reaction was observed with a variety of other activated acetylenes but tri phenyl arsine oxide gave the corresponding stable arsoranes with dicyanoacetylene (— 70 °C), methyl propiolate, hexafluorobut-2-yne, dimethyl acetylene dicarboxylate, and ethyl phenylpropiolate (130 °C). 

In 2004, Whittlesey and Williams demonstrated that the reversible C-H activation of Ru-NHC complexes (e.g. 32a, Scheme 13.14) provides an effective manifold for tandem dehydrogenation/Wittig reaction/hydrogenation of alcohols, thus generating alkanes from alcohols and phosphorus ylides [56]. 

In practice, however, the annulation does not take place because the aldol condensation is essentially a reversible reaction and strain between the two cyclopentane rings shifts the equilibrium towards the reactants rather than towards the products. In order to overcome this difficulty, the synthetic scheme was substantially modified and 3-acetoxy-2-ethoxypropene (4) was used as the umpoled C3 fragment and the aldol condensation was substituted by a Wittig reaction, as... 

The second synthesis of 654 and 655 makes use350,351 of the Wittig reaction. The (methylthio)methyl ether 656 is converted into the chloromethyl ether 657, which reacts with triphenylphosphine to yield a crystalline phosphonium salt (658). Reaction of 658 with phenyllithium gives a phosphorane, treatment of which with acryl-aldehyde leads to ethers 654 and 655 in —50% yield. Pure trtms-diene 654 was obtained352 in a reversed way consisting in preparation of a sugar ether acrylaldehyde (660) by replacement of the p-tolylsulfonyl group in 659, followed by reaction of 660 with methylenetriphenyl-phosphorane. 

Vitamin A acid, especially used in the treatment of acne for some years, can also be obtained by Wittig reaction. Thus, olefination of phosphorane 506, with y-formyl-crotonic ester 509 as well as the reversed Wittig olefination, i.e. the conversion of aldehyde 511 and ylide 512 yields the ester 510 of vitamin A acid 255), according to Scheme 86. 

This C - H activation event is reversible, and is required to achieve catalytic turnover [62], A series of alcohols, mostly secondary benzylic examples, have been oxidized using this catalyst. The catalytic activity does not match that of the Ir examples described above, but it has been used in several tandem reactions that feature both dehydrogenation and hydrogenation steps to achieve interesting transformations. One example is a tandem alcohol oxidation/Wittig reaction/alkene hydrogenation sequence (Scheme 9) [61,62],... 

Stereogenic Wittig reactions of nonstabilized ylides of the structure Ph3P+—CH —R2 have been studied in-depth in many instances. They give the cis-configured oxaphosphetane rapidly, with the rate constant kcis, and reversibly (Figure 9.7). On the other hand, the same nonstabilized ylide produces the /ran.v-oxaphosphetane slowly, with the rate constant ktrans, and irreversibly. The primary product of the [2+2]-cycloaddition of a nonstabilized P ylide to a substituted aldehyde is therefore a cis-oxaphosphetane. Why this is so has not been ascertained despite the numerous suggestions about details of the mechanism which have been made. 

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... 

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. 

Total synthesis of pyranicin by Takahashi et al. used a Sml2-mediated reductive free radical reaction to constmct the desired cw-THP ring 223 (Scheme 10-37). The stereochemistry of hydroxyl on the THP ring was reversed by an intramolecular Sn2 substitution, giving the lactone 224. A Wittig reaction between 225 and known aldehyde 110 furnished the skeleton of the target. 

There are essentially three different types of transition metal carbene complexes featuring three different types of carbene ligands. They have all been named after their first discoverers Fischer carbenes [27-29], Schrock carbenes [30,31] and WanzUck-Arduengo carbenes (see Figure 1.1). The latter, also known as N-heterocycUc carbenes (NHC), should actually be named after three people Ofele [2] and Wanzlick [3], who independently synthesised their first transition metal complexes in 1968, and Arduengo [1] who reported the first free and stable NHC in 1991. Fischer carbene complexes have an electrophilic carbene carbon atom [32] that can be attacked by a Lewis base. The Schrock carbene complex has a reversed reactivity. The Schrock carbene complex is usually employed in olefin metathesis (Grubbs catalyst) or as an alternative to phosphorus ylides in the Wittig reaction [33]. 

The generation of an ylide from a phosphine oxide and an alkyne is of interest because it represents the reversal of the known intramolecular Wittig reaction of acylated alkylidenephosphoranes. ... 

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