Semi-stabilized ylides

With non-stabilized ylides ( R = H or Me) and numerous saturated or unsaturated aldehydes and ketones the Wittig reaction ( i ix) gives the corresponding dithianes 7 in good yields (70-93 %) The autoxidation of these ylides gives the expected products 8 and 9. The semi-stabilized ylides (R1= 0) react only with a reactive aldehyde. 

To explain the enantioselectivity obtained with semi-stabilized ylides (e.g., benzyl-substituted ylides), the same factors as for the epoxidation reactions discussed earlier should be considered (see Section 10.2.1.10). The enantioselectivity is controlled in the initial, non-reversible, betaine formation step. As before, controlling which lone pair reacts with the metallocarbene and which conformer of the ylide forms are the first two requirements. The transition state for antibetaine formation arises via a head-on or cisoid approach and, as in epoxidation, face selectivity is well controlled. The syn-betaine is predicted to be formed via a head-to-tail or transoid approach in which Coulombic interactions play no part. Enantioselectivity in cis-aziridine formation was more varied. Formation of the minor enantiomer in both cases is attributed to a lack of complete control of the conformation of the ylide rather than to poor facial control for imine approach. For stabilized ylides (e.g., ester-stabilized ylides), the enantioselectivity is controlled in the ring-closure step and moderate enantioselectivities have been achieved thus far. Due to differences in the stereocontrolling step for different types of ylides, it is likely that different sulfides will need to be designed to achieve high stereocontrol for the different types of ylides. 

Ylide type non-stabilized ylide semi-stabilized ylide stabilized ylide... 

Comparison of stable, reactive and semi-stabilized ylides. 666... 

If there are electron-withdrawing substituents conjugated with the ylidic carbon atom, further dipolar structures such as 4 and 5 may make major contributions to the overall structure. Delocalization of the charge in this way frequently leads to the ylides being isolable. Such ylides are commonly described as stable ylides in this context stable is, in effect, a synonym for isolable. Many ylides are not, however, isolable, because of their high reactivity, in particular their very ready hydrolysis. In this article such ylides are called reactive ylides. Some other ylides, notably benzylylides, have reactivity intermediate between those ylides which are obviously stable or obviously reactive. They are described as semi-stabilized ylides. 

Initial studies of solvent effects, on the reactions of triarylarsonium benzoylylides with p-nitrobenzaldehyde in N, A-dimethylformamide, dimethyl sulphoxide or methanol, indicated little solvent effect in these cases" ", but later studies of the more finely balanced reactions of semi-stabilized ylides have provided examples of strong influences due to the effect of different base and solvent when the ylide is generated in the presence of a carbonyl compound ". Thus, when benzyltriphenylarsonium bromide or p-chloroben-zyltriphenylarsonium bromide were treated with sodium hydride in benzene in the presence of a variety of p-substituted benzaldehydes the products were alkenes, but if sodium ethoxide in ethanol was used the isolated products were epoxides ". Likewise, when triphenylarsonium benzylylide was generated by phenyllithium in the presence of either benzaldehyde or acetaldehyde, the preponderant product was the epoxide whereas use of sodium amide as base provided mostly the alkene . Similar results were obtained when an allyltriphenylarsonium salt was deprotonated using different hexamethyldisilaz-... 

However, choice of appropriate base and solvent can, in the case of less stabilized ylides, have an effect on both the product distribution and on the stereospecificity of the product. More detailed analysis is desirable, but it seems likely that, at least in the case of semi-stabilized ylides and possibly for others also, control over the product can be achieved by suitable choice of the substituents on arsenic, and of the solvent and base, thus making a valuable addition to the organic chemist s synthetic armoury. 

A single sulfonium ylide is beUeved to be formed as alkylation of oxathiane 3a gave the equatorial sulfonium salt exclusively [29]. Ylide conformation has been studied by X-ray, NMR, and computation [30]. All of these studies indicate that the preferred conformation of sulfur yUdes is one in which the filled orbital on the ylide carbon is orthogonal to the lone pair on sulfur. The barrier to rotation around the C-S bond of the semi-stabilized ylide, dimethylsulfonium fluorenide, has been found to be 42 1.0 kJmol [30]. This impHes that the ylide will adopt conformations 6a and 6b and that these will be in rapid equilibrium at room temperature. Of these two, conformation 6b will be favored as 6a suffers from... 

Intermediate between the reactive and the stable ylides, there is the group of so-called moderate or semi-stable ylides. In this case, the ylide carbon atom bears a vinyl, aryl, alkynyl or halogen substituent. The nucleophilicity of the semi-stabilized ylide is further decreased or increased by electron acceptors or donors on the vinyl or aryl group. 

Phosphonium salts that bear substituted vinyl groups on the a-carbon atom are the usual precursors of semi-stabilized ylides in carotenoid synthesis. Alkali metal alkoxides, generally as a solution in the corresponding alcohol, are frequently the bases of choice. A two-phase system is also sometimes employed, e.g. dichloromethane/aqueous NaOH solution (see Section F). 

Stabilized and semi-stabilized ylides can also be produced under virtually neutral conditions by using oxiranes as proton acceptors [18]. This has a precondition that the anion of the phosphonium salt is a halide, since epoxide and phosphonium halide are in equilibrium with ylide and the corresponding halohydrin. The technique is particularly advantageous if base-labile functionalities are present. 

Usually, the semi-stabilized ylides are produced in the presence of the carbonyl component and are immediately scavenged by this to form the olefin. 

The highly stereoselective conversion of the a-haloylides 6 into the 1-alkenyl halides 7 is a remarkable and rare example of the specific synthesis of (Zj-olefms from semi-stabilized ylides. 

In the case of Wittig reactions between alkenyl-substituted, i.e. semi-stabilized, ylides and aliphatic aldehydes, the f j-content could be substantially increased under salt-free conditions when a stationary phenyl group on the phosphorus was replaced by a methyl or alkenyl group [37]. 

In an interesting new approach, the f /Zj-selectivity of Wittig reactions of semi-stabilized ylides was successfully influenced by host molecules. Triphenylbenzylphosphonium bromides with different substituents were reacted with aromatic aldehydes in the presence of cyclodextrins. For the same Wittig reaction, in a polar-aprotic medium (DMF), an increase in the (Zj-selectivity from 57% to 92% was observed and in ethanol an increase in the ( J-selectivity from 67% to 80% was observed [38]. 

DFT calculations have been used to obtain mechanistic insights into the reaction of sulfur ylides PhHC (S+Me2) with dienals and enones by identifying all key transition states and intermediates along the reaction pathway for the 1,2-, 1,4-, and 1,6-nucleophilic attacks at PhCH=CHCH=CHCH=0 and for the 1,2- and 1,4-attacks at MeCH=CHCOMe. The final outcome of the reaction with both substrates has been found to be decided by the interplay between kinetic and thermodynamic factors. Thus, addition of a semi-stabilized ylide to conjugated carbonyl compounds prefers the 1,4-pathway under thermodynamic conditions, in consonance with the experimental reports. However, the formation of epoxides via a 1,2-addition pathway is equally competitive and could be favoured under kinetic conditions. The 2,3-trans cyclo-propanecarbaldehyde is the major product of the 1,4-addition pathway. The enone also prefers the 1,4-addition. ... 

Selenylated 1,3-dienes have been accessed via Wittig and related reactions, starting from a-phenylselenyl a,p-unsaturated aldehydes. With non- or semi-stabilized ylides, the reaction mainly leads to the formation of the IZ diastereomer. Due to steric instability, isomerization could yield the more stable E diastereomer. Expectedly, when stabilized ylides are involved in the reaction, the C1=C2 double bond configuration of the product is mainly E (Scheme 95) [189]. 

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