Wittig reaction unstabilized

The first Wittig reaction with stabilized ylide TM 2.8d, available from a-bromoacetaldehyde, affords conjugated -alkene TM 2.8c. In the second Wittig reaction unstabilized ylide TM 2.8b forms a Z double bond in TM 2.8a. In the last step chemoselective reduction of the ester group to TM 2.8 is completed with complex hydride. 

The stereoselectivity of the Wittig reaction is believed to be the result of steric effects that develop as the ylide and carbonyl compound approach one another. The three phenyl substituents on phosphorus impose large steric demands that govern the formation of the diastereomeric adducts.240 Reactions of unstabilized phosphoranes are believed to proceed through an early TS, and steric factors usually make these reactions selective for the d.v-alkcnc.241 Ultimately, however, the precise stereoselectivity is dependent on a number of variables, including reactant structure, the base used for ylide formation, the presence of other ions, solvent, and temperature.242... 

The results of ab initio (HF and MP2) and MNDO-PM3 molecular modelling of the Wittig reaction of unstabilized (Me3P=CHMe), semistabilized (Me3P=CHC=CH) and stabilized (Me3P=CH-CN) ylides with ethanal have been compared with experimental findings. ... 

After these results had established the feasibility of generating and utilizing a carbohydrate phosphorane, the two systems that had been reported earlier were examined in order to determine if similar conditions would allow them to undergo the Wittig reaction. The ylide derived from phosphonium salt I condensed with both benz-aldehyde and U-chlorobenzaldehyde to produce good yields of olefinic products Villa and Vlllb. The ylide derived from phosphonium salt II also was successfully condensed with benzaldehyde, but the yield of IX was only 30 , presumably because of its extremely poor solubility even in an HMPA-THF solvent mixture. Both of these systems supported the tenet that it was possible to use unstabilized carbohydrate phosphoranes if the conditions are proper and if the g-oxygen is attached to the carbohydrate through another set of bonds. 

I hc key intermediates in the synthesis of the E- and the Z-isomers of capsaicin were the E and Z unsaturated esters shown below. By using a Wittig reaction with an unstabilized ylid it was possible to make the Z-isomer selectively, whilst the Julia olefination gave the -isomer. 

How can the Z selectivity in Wittig reactions of unstabilized ylids be explained We have a more complex situation in this reaction than we had for the other eliminations we considered, because we have two separate processes to consider formation of the oxaphosphetane and decomposition of the oxaphosphetane to the alkene. The elimination step is the easier one to explain—it is stereospecific, with the oxygen and phosphorus departing in a syn-periplanar transition state (as in the base-catalysed Peterson reaction). Addition of the ylid to the aldehyde can, in principle, produce two diastere-omers of the intermediate oxaphosphetane. Provided that this step is irreversible, then the stereospecificity of the elimination step means that the ratio of the final alkene geometrical isomers will reflect the stereoselectivity of this addition step. This is almost certainly the case when R is not conjugating or anion-stabilizing the syn diastereoisomer of the oxaphosphetane is formed preferentially, and the predominantly Z-alkene that results reflects this. The Z selective Wittig reaction therefore consists of a kinetically controlled stereoselective first step followed by a stereospecific elimination from this intermediate. 

The female silkworm moth attracts mates by producing a pheromone known as stabilized and unstabilized ylids, respectively, to control the stereochemistry of bombykol. Bombykol is an E.Zdiene, and in this synthesis (dating from 1977) the product, two successive Wittig reactions exploit the stereoselectivity obtained with... 

The first step is a simple Wittig reaction with an unstabilized ylid (Chapter 31), which we expect to favour the Z-alkene. It does but, as is common with Wittig reactions, an E/Z mixture is formed but not separated as both isomers eventually give the same compound. The reaction is kinetically controlled and the decomposition of the oxaphosphetane intermediate is in some ways like a fragmentation. 

The first is a Wittig reaction with an unstabilized ylid, the second a Julia reaction, and the last two are Peterson reactions under different conditions. Each reaction is described in detail in the chapter. The Wittig reaction is under kinetic control and is a stereospecifically cis elimination. In this case the product is the Z-alkene. 

Now a Wittig reaction with an unstabilized ylid selectively gives the Z-alkene. Note that molecules ol base are needed one to open the lactol, one to remove the proton from CO.H. one to make the ylid. 

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. 

Restrepo-Cossio, A. A., Cano, H., Mari, F., Gonzalez, C. A. Molecular modeling of the Wittig reaction. 6. Theoretical study of the mechanism of the Wittig reaction ab initio and MNDO-PM3 treatment of the reaction of unstabilized, semistabilized and stabilized ylides with acetaldehyde. Heteroatom Chem. 1997, 8, 557-569. 

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... 

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