Stable oxaphosphetanes

The generally quite stable methylenephosphorane nevertheless resembles the short-lived highly reactive methyleneoxophosphorane. The oxaphosphetane intermediate 25 formed by -I- n2]-cycloaddition, which can only be isolated in exceptional cases21, is to be seen against the stable oxaphosphetanes of type 26, which can be photolyzed if suitably substituted or thermolyzed under drastic... 

E Selective Wittig reagents. The reaction of 1 with lithium in THF provides LiDBP, which on reaction with an alkyl halide (2 equiv.) and NaNH2 in THF gives a salt-free ylide such as 2 or 3, formed by reaction with ethyl iodide or butyl iodide, respectively. These ylides react readily with aldehydes at —78°, but the intermediate oxaphosphetanes are unusually stable and require temperatures of 70-110° for conversion to the phosphine oxide and the alkene, which is obtained in E/Z ratios of 6-124 1. Highest (E)-selectivity is observed with a-branched aldehydes. 

The stereochemical outcome of the Wittig reaction can depend on the presence or absence of lithium salts. This may be due to a betaine intermediate stabilized by lithium cation. A stable adduct of this type has now been observed during a Wittig reaction. When Ph3P=CH2 is treated with 2,2 -dipyridyl ketone, P NMR shows the formation of an oxaphosphetane (72) and addition of lithium bromide gives the chelation-stabilized betaine lithium adduct (73). 

The Wittig reaction is a very important method for olefin formation. The stereochemistry about the new carbon-carbon double bond is the Z (or less stable) isomer. This unusual stereoselectivity indicates that product formation is dominated by kinetic control during formation of the oxaphosphetane. 

By adding a strong base to the cold solution of the oxaphosphetane before it eliminates, die oxaphosphetane equilibrates to die more stable anti isomer and die E olefin is produced upon elimination. This so-called Schlosser modification in conjunction with the normal Wittig reaction enables either the Z or E isomer of the olefin to be prepared selectively. 

On the other hand the stability of 57 causes the reaction leading to a reversible oxaphosphetane where the isomers 63 and 65 can interconvert via the starting material. The stereoselectivity in this step is thermodynamically controlled. The more stable four-membered ring is anti 65, with the bulky groups on opposite sides of the ring. The product of this reaction after elimination of triphenylphosphine oxide is only the E-alkene 66. 

Oxaphosphetane (24) has been successfully isolated for the first time as stable crystals in the typical Wittig reaction of cyclopropylidenetriphenylphosphorane with activated carbonyl compounds.61 X-ray analysis of (24) showed that the phosphorus atom is at the centre of a slightly distorted trigonal bipyramidal structure. 

The unstable aspect of the ylid is the carbanion phosphonium salts are stable compounds so any substituent that stabilises the anion also stabilises the ylid and this reverses the stereoselectivity to favour the -alkene. Even benzylic ylids give -alkenes as in the reaction9 with the anthracene 37 that gives a good yield of crystalline 38 having a coupling constant between the two marked Hs of 17 Hz. One possible explanation is that the formation of the betaine or oxaphosphetane is reversible if the ylid is stabilised and only the faster of the two eliminations occurs to give the E -alkene. 

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. 

The transition state 16, however, does not give a real betain intermediate but directly an oxaphosphetane. The energy difference between the ( )- and the (Z)-transition state was 5 kJ/mol (C—C distance 200 pm) the ( )-oxaphosphetane was 5.4 kJ/mol more stable than the (Z)-isomer 7,9). The calculations thus confirm the preference to the formation of the oxaphosphetane instead of the betain as the intermediate, but cannot explain the favored ( -configuration of the ligands of the oxaphosphetane four-membered ring. 

The.l,2-A -oxaphosphetanes 58 and 68 can be considered stable intermediates of the Wittig reaction. Pyrolysis of the parent compounds yields the corresponding olefins and oxophosphoranes, respectively, which have been reported in several publications 204, 220, 221, 226). 

The tris-OHfp substituted oxaphosphetane 58g is thermally stable up to 190°C (225). 

The P—C bonds of 83 are essentially equivalent, suggesting contribution of polar forms. An extremely long P—O bond in contrast to 581 indicates open chain mesomeric structures, stable due to electron delocalization (60). At 125°C a Wittig reaction occurs, and 84 is formed (26). The same type of [2 + 2] cycloaddition has been found with a series of P-(chloro)alkylidene-phosphoranes. The oxaphosphetanes 83b-d thermally eliminate hydrogen chloride to yield vinyloxophosphoranes (165a). 

Protic solvents shift the alkene E)j Z) ratio in the direction of the (E)-form. The alkene [E)I Z) ratio of salt-free Wittig reactions is thus influenced not only by the electronic character of R, but also by the solvent and the stereochemistry of the formation of the 1,2-oxaphosphetane in the first rate-determining step. According to Eq. (5-48), the thermodynamically less stable (Z)-l,2-oxaphosphetane is formed in the first activation step. A conformational analysis of the activated complex leading to the 1,2-oxaphosphetane intermediate provides a reasonable explanation for this unexpected cis-selectivity [143, 556]. 

Currently accepted mechanism of the Wittig reaction of aldehydes with non-stabilized ylides involves the formation of oxaphosphetanes through a [2-I-2]-cycloaddition-like reaction . The oxaphosphetanes are thermally unstable and collapse to alkene and phosphine oxide below room temperature. Under salt-free conditions there is no formation of betaine intermediates. The salt-free ylides can be prepared by the reaction of phosphines with carbenes generated in situ. Vedejs etal proposed a puckered 4-centre cyclic transition state I for sy -oxaphosphetane and planar structure J for anff-oxaphosphetane. In general, the flnfi-oxaphosphetane J is more stable than the syn-oxaphosphetane I, and under equilibrium conditions (when stabilized ylides are used) the E-alkene product is favoured (Scheme 4.24). However, kinetic control conditions, which appear to dominate when non-stabilized ylides are used, would lead to Z-alkene. 

This is a Wittig reaction. The stable ylide is prepared from 29 prior to the reaction. Only the ketone reacts to form the corresponding olefin via the oxaphosphetane intermediate, as the Weinreb amide is not reactive enough. Owing to the use of a stable phosphonium ylide, only the product with the -configured double bond is obtained in 90 % yield ( /Z 99 1). 

The (Z)-stereoselectivity of salt-free Wittig olefmations leading to the thermodynamically less stable cA-alkenes has long been the subject of intense investigations. At one time, the olefmation was thought to proceed via an ionic stepwise process involving a zwitterionic betaine and a 1,2-oxaphosphetane intermediate. However, NMR spectroscopy studies revealed the oxaphosphetane as the only observed intermediate. ... 

Generally, oxaphosphetanes are thermodynamically unstable and fragment into alkenes and triphenylphosphine oxide. This elimination step is stereospecific with oxygen and phosphorus departing in a 5jn-periplanar mode to produce (Z)-alkenes, the driving force being formation of the very stable P = O bond (130-140 kcal/mol, 544-586 kJ/mol bond dissociation energy). 

The (E)- and (Z)-selectivity in HWE reactions is determined by a combination of the stereoselectivity in the initial carbon-carbon bond formation and the reversibility of the intermediate adducts. The ( )-selectivity has been explained by the formation of the thermodynamically more stable threo-a.dduct, which then decomposes via the oxaphosphetane intermediate to the ( )-olefin. The (Z)-selec-tivity has been attributed to the predominant formation of the erythro-adduct which collapses irreversibly via a transient oxaphosphetane intermediate to the (Z)-olefin. ... 

---