Cyclizations 1,2-oxaphosphetanes

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

Olefination Reactions Involving Phosphonium Ylides. The synthetic potential of phosphonium ylides was developed initially by G. Wittig and his associates at the University of Heidelberg. The reaction of a phosphonium ylide with an aldehyde or ketone introduces a carbon-carbon double bond in place of the carbonyl bond. The mechanism originally proposed involves an addition of the nucleophilic ylide carbon to the carbonyl group to form a dipolar intermediate (a betaine), followed by elimination of a phosphine oxide. The elimination is presumed to occur after formation of a four-membered oxaphosphetane intermediate. An alternative mechanism proposes direct formation of the oxaphosphetane by a cycloaddition reaction.236 There have been several computational studies that find the oxaphosphetane structure to be an intermediate.237 Oxaphosphetane intermediates have been observed by NMR studies at low temperature.238 Betaine intermediates have been observed only under special conditions that retard the cyclization and elimination steps.239... 

Structure 3 is the intermediate oxyanion adduct. TS2 is the structure leading to cyclization of the oxyanion to the oxaphosphetane. Structure 4a is the oxaphosphetane, and the computation shows only a small barrier for its conversion to product. 

The first spirophosphorane with an azaphosphetidine ring 63 was prepared from the intramolecular cyclization and dehydration of phosphane oxides with DEAD/PPh3 <1996AGE1096, 1996PS489>. Dissolution of 63 in [r/8]-toluene led to some isomerization to the pseudorotamer 64, where the electronegative nitrogen occupies the equatorial position (Scheme 32). Such rotamers were previously unknown for the analogous oxaphosphetanes. 

Why trans-selectivity occurs is not known because of the lack of detailed knowledge about the mechanism. Perhaps the reason is that only the alkoxide A is cyclized to the more stable ira 5-oxaphosphetane shown. This is conceivable because the diastereomeric alkoxide (D in Figure 11.13) should cyclize comparatively slowly to the less stable cw-oxaphosphetane E if product development control were to occur in this step. It would thus be possible that both the alkoxide A and its diastereomer D form unselectively, but reversibly, from the phosphonate ion and the aldehyde. Then an irreversible cyclization of the alkoxide A would give the trans-oxaphosphetane B. The alkoxide D would also gradually be converted into the trans-oxaphosphetane B through the equilibrium D starting materials A. 

Like other strong nucleophiles, triphenylphosphine attacks and opens epoxides. The initial product (a betaine) quickly cyclizes to an oxaphosphetane that collapses to an alkene and triphenylphosphine oxide. 

The zwitterionic phosphorus betaine intermediates from the reaction of conjugated azoalkenes with triphenylphosphine selectively undergo cyclization to four-membered 1,2-oxaphosphetane intermediates. From them 4-unsubstituted-5-alkoxypyrazoles have been obtained through loss of a triphenylphosphine oxide molecule [92T1707]. This behaviour is in full agreement with a typical Wittig reaction (Scheme 10). 

Nucleophilic addition of the organoUthium species to the ketone gives an intermediate adduct which is still a phosphonium ylide. Protonation of this ylide on the carbon atom gives the alkoxy-phosphonium species which cyclizes to the oxaphosphetane. Elimination of triphenylphosphine oxide gives the alkene 9. See Scheme 2.78 and E. J. Corey, J. Kang and K. Kyler, Tetrahedron Lett., 26 (1985), 555. 

Oxaphosphetanes from semi-stable ylides have been detected spectroscopically only in the special case of the dibenzophosphole group [43]. Naked betaines, i.e. those that are not complexed with metal ions, have not been found because they cyclize too rapidly for detection by NMR [6]. 

Ab initio calculations (RHF/6-31 -I- G ) have revealed that the Homer-Wadsworth-Emmons (HWE) reaction of acetaldehyde with the lithium enolate derived from trimethyl phosphonoacetate occurs by a sequence of carbonyl addition, oxaphosphetane formation, pseudorotation, P-C bond cleavage, and then O-C bond cleavage. The transxis alkene ratio (97.5 2.5) is a direct consequence of competitive formation of the corresponding oxaphosphetanes in the rate-determining cyclization step. 

The mechanism of the HWE reaction is closely related to that of the Wittig reaction. It is generally accepted that the addition of the phosphonate-stabilized carbanion to the aldehyde gives a mixture of erythro and threo isomeric p-oxido phosphonates under reversible conditions (Scheme 35) [156-160]. The erythro and threo intermediates cyclize to form cis- and trans-oxaphosphetanes, rapid elimination of which affords Z- and -aIkenes, respectively. It should be pointed out that the decomposition of the p-oxido phosphonate intermediate requires an electron-withdrawing group (e.g., ester, acyl, amide, cyano, sulfonyl, vinyl, or aryl) a to the phosphonate moiety. Otherwise, the final product is a p-hydroxy phosphonate... 

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