Oxido-ylides reactions

VI. Oxido Ylide Reactions Modification of Oxaphosphetane Stereochemistry... 

A variety of anionic ylides reacts with high E selectivity with the reversal-prone aromatic aldehydes. On the other hand, aliphatic aldehyde adducts are more resistant to Li -induced betaine equilibration. The y-oxido ylides appear to have the optimal substitution pattern for betaine reversal, and these reagents afford useful ( )-alkene selectivity with aliphatic as well as aromatic aldehydes, results that are tabulated later. Only the aromatic aldehyde example (Table 7, entry 4) has been studied in depth, but it seems safe to conclude that all of the E-selective y-oxido ylide reactions are dominated by betaine reversal (23b). Other anionic ylides react with aliphatic aldehydes to give lower, less predictable ( )-alkene selectivity (for example. Table 7, entry 5 42 58 Z E). 

VI. OXIDO YLIDE REACTIONS MODIFICATION OF OXAPHOSPHETANE STEREOCHEMISTRY... 

All of the oxido ylide reactions demand the presence of at least one equivalent of lithium halide. This requirement is most easily satisfied when the starting alkylidenetriphenylphosphorane is generated by the conventional butyllithium method from phosphonium salts in THF. Thus, Maryanoff et al. (22a) treated Ph3P C4Hg Br" sequentially with butyllithium, benzaldehyde, butyllithium, and acid to give 60 (R = phenyl replace Me by propyl) con-... 

An extension of this method can be used to prepare allylic alcohols. Instead of being protonated, the (3-oxido ylide is allowed to react with formaldehyde. The (J-oxido ylide and formaldehyde react to give, on warming, an allylic alcohol. Entry 12 is an example of this reaction. The reaction is valuable for the stereoselective synthesis of Z-allylic alcohols from aldehydes.245... 

Miscellaneous Reactions.- The Schlosser-Wittig reaction of ylide (209) with aldehyde (208) and treatment of the intermediate 6-oxido ylide with perchloryl fluoride has been used to construct the 13-fluoro unit (210) in a total synthesis of (+)-13-fluoroprosta-... 

The reaction of 1 with 2 equiv. of an aldehyde produces a tranv-allylic alcohol (3) by way of a /1-oxido ylide a (equation I). 

Finally, an example of fluorination of the C = P bond has been reported." Reaction of the /1-oxido ylide 22 with gaseous perchloryl fluoride at — 35 C gives the fluoroalkenes 23A and B in 12 and 45 % yield, respectively. Alkene 23B is an intermediate in the synthesis of (-F)-13-fluoroprostaglandin methyl ester, a compound with antifertility and muscle-stimulating effects. 

Schlosser, M., Coffinet, D. SCOOPY [a-substitution plus carbonyl olefinatlon via P-oxido phosphorus ylides] reactions. Regioselectivity of alkenol synthesis. Synthesis 1972, 575-576. 

There are some additional potential complications with the control experiments. Loss of stereochemistry in method D can be due to product equilibration induced by the phosphine additive as already mentioned. Furthermore, equilibration in method A or E can occur because of competing (reversible) (x-deprotonation to give the oxido ylide 38 or the derived hydroxy ylide 39 (21c). The latter problem can usually 1% avoided by lowering the temperature or by using a weaker base for the deprotonation of the )5-hydroxyphosphonium salt 27 or 28 (21c). Nevertheless, positive equilibration results cannot be attributed to retro-Wittig reaction unless (1) crossover is also demonstrated or (2) labeling results can rule out the intervention of 38 or 39. 

Schlosser Synthesis of (E)-alkenes. In contrast to the first two examples, this process does not involve equilibration of stereoisomers. The Schlosser method establishes stereochemistry in a kinetically controlled quenching reaction of an oxido ylide with acid. 

It is likely that the ( )-alkene selective reactions of anionic ylides are due to equlibration of the betaine lithium halide adduct as discussed earlier. However, the balance is delicate and small structural changes can have surprising consequences. Thus, Corey s stereospecific trisubstituted alkene synthesis via /3-oxido ylides (Table 10) is clearly under dominant kinetic control, even though lithium ion is present and aromatic aldehydes can be used as the substrates (54,55). The only obvious difference between the intermediates of Table 10 and oxido ylide examples such as entry 11 in Table 21 is that the latter must decompose via a disubstituted oxaphosphetane while the stereospecific reactions in Table 10 involve trisubstituted analogues. Apparently, the higher degree of oxaphosphetane substitution favors decomposition relative to equilibration. There are few easy and safe generalizations in this field. Each system must be evaluated in detail before rationales can be recommended. 

The addition of a second equivalent of a strong base, usually an alkyllithium, to reactions of non-stabilized ylides facilitates the formation of the -alkene (Scheme 1.3). The resulting ) -oxido ylide is then quenched with add under kinetic control to afford the -alkene. This sequence is known as the Schlosser modification [14-16]. Lithium bases must be employed here since the presence of lithium ions is required to convert the oxaphosphetane 3 into the more addic betaine. 

The reaction of nonstabilized ylides with aldehydes can be induced to yield E-alkenes with high stereoselectivity by a procedure known as the Schlosser modification of the Wittig reaction. In this procedure, the ylide is generated as a lithium halide complex and allowed to react with an aldehyde at low temperature, presumably forming a mixture of diastereomeric betaine-lithium halide complexes. At the temperature at which the addition is carried out, fragmentation to an alkene and triphenylphosphine oxide does not occur. This complex is then treated with an equivalent of strong base such as phenyllithium to form a )8-oxido ylide. Addition of r-butyl alcohol protonates the P-oxido ylide stereoselectively to give the more... 

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). ... 

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. 

The stereoisomeric mixture of -hydroxyalkyl selenides resulting from the reaction of the a-selenoalkyllithium and the carbonyl compound has been often cleanly and easily separated into its constituents by liquid chromatography on silica gel (Schemes 124,133,134, and 170 172).200.206.222,226,229,258 59 jj,jg has, therefore, allowed the synthesis of each of the two stereoisomers of various di- and tri-substituted alkenes (Schemes 124,170 and 171 Scheme 172, a) and epoxides (Scheme 124 Scheme 172, b), which are otherwise obtained as intractable mixtures of stereoisomers through the conventional phosphorus or sulfur ylide methods. Last but not least, 2-lithio-2-methylselenopropane can be used as the precursor of various compounds bearing gem dimethyl substituted carbons, such as squalene, oxido-squalene, lanosterol and cholesterol. Use of commercially available perdeuterated or Ci or — 2 acetone allows the straightforward synthesis of the corresponding labelled compounds... 

Schlosser, M., Christmann, K. F., Piskala, A. Olefinatlon reactions with phosphorus ylides. II. P-Oxido phosphorus ylides in the presence and absence of soluble alkaline metal salts. Chem. Ber. 1970, 103, 2814-2820. 

In the case of the sulfur analogues, the reaction of sulfiir ylides with carbonyl compounds, known as the Corey-Chaykovsky reaction, is a well-established procedure for the synthesis of oxiranes This reaction is usually considered to involve the formation of an a/ift -betaine (205) followed by a back side attack of an oxido anion on the p-carbon. (Scheme 3.29)... 

Instead of protonation, the P-oxidoylide can be scavenged by other electrophiles such as aldehydes or methyl iodide to give a-substituted betaines. Trisubstituted olefins are obtained directly in this manner. The designation substitution + carbonyl olefination via p-oxido phosphonium ylides (SCOOPY) has been proposed for this reaction [19,33]. 

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