Unstabilized ylides

Enaminone 128 (Scheme 33) is obtained, together with an isomeric indo-lizine derivative, by flash vacuum thermolysis of aminomethylene Meldrum s acid derivative through intermediate ketene and delocalized azomethine ylide (85TL833). The thermally induced cyclization of semi-cyclic dienamines to afford, for instance, tricyclic 129 is also believed to start with an azomethine ylide (97JOC7744) the p-chlorophenyl substituent is essential for the reaction. Unstabilized ylide 130, on the other hand, is generated from pipecolinic acid and /1-phenylcinnamaldehyde by the decarboxylation method target base 131 is formed by 1,7-electrocycliza-tion and [l,5]-hydrogen shift (99J(P1)2605). 

To explain this phenomenon, there are two seperate processes to consider. The first and most important one for this reason is the formation of the oxaphosphetane. The addition of the ylide to the aldehyde can, in principle, produce two isomers with either a Z or E substituted double bond. The following elimination step is stereospecific, with the oxygen and phosphorus departing in a syn-periplanar transition state. With unstabilized ylides the syn diastereomer of the oxaphosphetane similar to 61 is formed preferentially. This step is kinetically controlled and therefore irreversible, and predominantly the Z-alkene 62 that results reflects this. 

The stereoselectivity of the Willi reaction depends strongly on both the structure of the ylide and the reaction conditions. The broadest generalization is that unstabilized ylides give predominantly the Z-alkene while stabilized ylides form mainly the -alkene (see Chapter 9). In this case the stabilized ylide 49 is generated by reaction of cthyl-2-bromopropionate 48 with tributylphosphine followed by addition of NEtj. This solution is added to a solution of the aldehyde and yields in a 2 1 (E/Z) ratio 56 % of 50 together with 26 % of the Z-isoraer. The isomers are separable by flash chromatography. 

Other examples of stereoselective additions of sulfoxonium methylide (2) to chiral aldehydes are shown in equations (8), - (9) and (10). At present, no one model is able to account for all of these results. Equations (lOa) and (lOb) show the effect of a nitrogen protecting group on the stereoselectivity of addition of unstabilized ylide (1) to a-amino acid derived aldehydes. The major products of... 

Dimethylsulfonium Methylide. Methylation of dimethylsulfide with methyl iodide produces trimethylsulfonium iodide. The positive charge on sulfur enhances the acidity of the methyl protons so that treatment of the sulfonium salt with a base converts it to dimethylsulfonium methylide. This unstabilized ylide should be used immediately after its preparation. 

Mari, F., Lahti, P. M., McEwen, W. E. Molecular modeling of the Wittig reaction. 3. Atheoretical study of the Wittig olefination reaction MNDO-PM3 treatment of the Wittig half-reaction of unstabilized ylides with aldehydes. J. Am. Chem. Soc. 1992, 114, 813-821. 

The unstabilized ylide, derived from triphenylphosphonium methyl bromide, is a reagent for introducing terminal olefins. Homologues of the methyl derivative deliver Z-alkenes. See section 5.2.11 for the Wittig reaction. 

The latest proposal by Vedejs (3d) is that the Wittig reaction proceeds via a concerted but asynchronous puckered 4-center cycloaddition pathway in which the stereoselectivity is determined by multiple steric effects and varying degrees of rehybridization at the phosphorus atom in the transition state. At present, there is not definitive evidence to prove that the reaction must proceed in this manner. Recent MNDO-PM3 computations by us (7,8) and somewhat related MNDO computations by Yamataka et al, (9) do not support the puckered 4-center cycloaddition hypothesis for the reactions of unstabilized ylides with aldehydes (3d), Instead, the MNDO-PM3 computations indicate that such Wittig reactions proceed through an essentially planar transition state (TS) with respect to the four central atoms, P-C-C-O. This process is... 

C. Wittig Reaction with Unstabilized Ylides Followed by Cyclization... 

The stereoselectivity of the Wittig reaction depends on the structure of the ylide. Ylides can be divided into two types Stabilized ylides have a group, such as a carbonyl group, that can share the carbanion s negative charge unstabilized ylides do not have such a group. 

Stabilized ylides form primarily E isomers, and unstabilized ylides form primarily Z isomers. 

An aldehyde or a ketone reacts with a phosphonium ylide in a Wittig reaction to form an alkene. A Wittig reaction is a concerted [2 + 2] cycloaddition reaction it is completely regioselective. Stabilized ylides form primarily E isomers unstabilized ylides form primarily Z isomers. 

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