3-Oxido-ylides

Carbonyls. The stereochemistry of the Wittig olefin synthesis has been reviewed. /i-a/u-Stereoselective olefin synthesis via /3-oxido-ylides is possible only in the presence of soluble lithium salts. Protonation of jS-oxido-ylides prepared from salt-free ylides leads to mixtures of erythro-and r/jr o-betaines and hence to mixtures of cis- and rm/i5-olefins. 

The jS-oxido-ylides synthesis of trisubstituted olefins has also been applied to the synthesis of farnesol (127). The phosphonium salt (123) with the aldehyde (124) and formaldehyde gave the hydroxy farnesol derivative (125) which was transformed into farnesol (127) and into (126), a position isomer of Cj juvenile hormone. 

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). 

Unlike Wittig reagents, 1 reacts with epoxides to form a y-oxido ylide (b), which reacts with an aldehyde to form a /ran.v-homoallylic alcohol. 

A stereospecific total synthesis of prostaglandins E3 and F3, containing an additional double bond in this side chain, starts from the optically active phosphonium salt 161. In this synthesis the ( )-13-double bond and the 15-hydroxy function are generated simultaneously by condensation of the chiral bicyclic aldehyde 163 with the P-oxido ylide 162 obtained by treatment of 161 with methyllithium. The corresponding phosphonium salt S) +)-161, already possessing the (Z)-configurated A17-double bond of prostaglandins, was prepared from (S)(—)-tartaric acid 1351 (Scheme 29). 

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. 

Treatment of P-oxido ylides with electrophiles other than proton donors provides a route to stereospecific trisubstituted alkenes. For example, trapping the P-oxido phosphonium ylide B with formaldehyde (generated from paraformaldehyde) leads to dioxido phosphonium derivative D to yield, after elimination of triphenylphosphine oxide, the trisubstituted allylic alcohol... 

The stereospecificity of the j8-oxido-ylide synthesis using formaldehyde as one of the aldehyde components is dependent on the order of use of the aldehydes. Thus, starting from the ethylidenephosphorane, use of hexaldehyde and paraformaldehyde in that order gave almost pure isomer (22), while their use in the reverse order gave a mixture of the isomers (22) and (23) in the ratio 36 64. 

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

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. 

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-... 

Subsequent a deprotonation might conceivably involve an oxido ylide... 

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. 

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