Bases for preparation of Ylides? (Wittig Rxn)

[SpicyBrown]

SWIM is interested in the Wittig reaction and some of it's potential uses. Recall that an alkyl halide is reacted with PPh3, then treated with base to remove a hydrogen and leave a neutral compound. The problem for SWIM lies in the final step of Ylide preparation, the removal of a hydrogen from the carbon neighboring the phosphorous atom to create the neutral compound for carrying out the Wittig reaction with.

All literature SWIM has read thus far (which, admittedly, isn't a whole lot, few text books and what-not) indicates that Butyllithium or Potassium tert-Butoxide must be used to accomplish this. BuLi is right out of the question for SWIM, and KtOBu could prove to be a bitch as well, although Antoncho's find for OTC alkoxides isn't too bad looking.

SWIM's question is, would something like Sodium Hydride be capable of removing the slightly acidic hydrogen neighboring the phosphorous?

SpicyBrown

[hermanroempp]

You could try lithium ethanolate or even plain sodium hydroxide.
In "Gattermann-Wieland: Die Praxis des organischen Chemikers, 43. ed., de Gruyter, 1982", lithium ethanolate, dissolved in absolute ethanol is used for the synthesis of 1,4-diphenyl-1,3-butadiene from cinnamyl-triphenylphosphonium chloride and benzaldehyde. Yield of the raw product is 50-60% of the theory, after recrystallization a mere 32%.
Sodium hydroxide in water (yep, right, w a t e r!) is used for the preparation of the ylene methoxycarbonylmethylene-triphenylphosphorane from methoxycarbonylmethyltriphenylphosphonium bromide. The ylene is isolated in 85% yield before it is converted to m-nitrocinnamic acid methyl ester with m-nitrobenzaldehyde by refluxing in benzene. Yield of the m-nitrocinnamic ester is 65% after crystallization from methanol.
Quidquid agis, prudenter agas et respice finem!

[Aurelius]

using ptc conditions with chloroform, water, NaOH, benzaldehyde and the proper phophonium chloride, propenylbenzene can be obtained in reasonable yeilds.

[SpicyBrown]

Nice! Thank you hermanroempp.

using ptc conditions with chloroform, water, NaOH, benzaldehyde and the proper phophonium chloride, propenylbenzene can be obtained in reasonable yeilds.

This is right along the lines of what SWIM was thinking. Do you have any refs for that?

SpicyBrown

[b159510]

I have seen references for using NaH to form the ylide. From experience, to form the ylide using NaOH, the proton must be at least as acidic as a hydrogen in the benzylic position. NaOH will not deprotonate the methyl group of something like methyltriphenylphosphonium bromide. Compare the pKa of the phosphonium salt to the pKa of the protonated base to see what will work. You can see why butyllithium is a much more effective base, its conjugate acid has a pKa around 50, where the conjugate acid of NaOH would be around 15. Back to the Primitive

[PrimoPyro]

Why make propenylbenzene when you can make P2P with the same mechanism?

https://www.thevespiary.org/rhodium/Rhodium/chemistry/phenylacetone.html#ylide

                                                  PrimoPyro

[Aurelius]

Hey PrimoPyro, you're right about the formation of P2P, it's just that your ref has already been mentioned and documented.  aurelius' is still a "new" idea.  however, aurelius has no refs to back up the claim, an analogous reaction was run with good yeilds (80%+) and besides, aurelius' prof. said it would work so, nah.

[Aurelius]

forgot to mention, aurelius has access to the phos chloride necessary for the propenyl synth, and not the P2P synth. that's the main reason.
and aliquat 336 was the PTC for those interested.
(the benzyl ammonium chlorides also work well)

[Rhodium]

A New Generation of Ylide by Use of Activated Magnesium
Yanchang Shen and Ming Qi

Synthetic Communications, 27(24), 4319-4325 (1997)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/mg-ylide.pdf)

Abstract
A new method for the generation of ylide under neutral condition by use of activated magnesium is described and it would be expected to be used in the synthesis of alkenes in base sensitive substrates.

Olefination of carbonyl compounds is one of the most useful methods and has been found widespread application in synthetic organic chemistry, particularly for the synthesis of natural products. The Wittig reaction is a well known methods for achieving olefination in which a base is necessary to convert the phosphonium salts into the ylides and many kinds of bases have been chosen. But in the base sensitive substrates the Wittig reaction was unsuccessful. Therefore to develop an effective method for the generation of ylide under neutral condition would be valuable. It has been reported that a variety of metals such as zinc, cadmium, mercury can be used in the dehalogenation of halophosphonium salts to generate the ylides. However, to the best of our knowledge, dehydrohalogenation of phosphonium salts by metal to generate the ylides has not been reported previously. We now wish to report a new method for the generation of ylide under neutral condition by use of magnesium activated by iodine.

The reaction sequence is as follows:

Ph₃P⁺CH₂E X^- --Mg/I₂--> Ph₃P=CHE --RCHO--> RCH=CHE

ln this reaction a catalytic amount of iodine is necessary to be added. Otherwise the reaction time should be longer and the yield was low. Therefore the role of iodine may be to activate the magnesium.

It is noteworthy that the characteristic feature of this reaction is no base is needed and the reaction is of wide scope. The aldehydes may be aliphatic, aromatic or heterocyclic.

Thus, this new method for the generation of ylide would be expected to be used in the synthesis of alkenes in base sensitive substrate, particularly in the synthesis of natural products with base sensitive moiety.

General Procedure for the Preparation of Substituted Alkenes

Magnesium chips (0.5 mmol), several crystals of iodine, and phosphonium halide (1.1 mmol) were added in turn with stirring to a solution of dried N,N-dimethylformamide (1.5 ml) and aldehyde (1.0 mmol) at 20°C under nitrogen.

The reaction mixture was stirred and heated at 120°C for several hours (see Table 1). After cooling, 20 ml of water was added and the mixture was extracted with petroleum ether (60-90°C). The organic layer was washed with saturated sodium chloride solution and dried. Evaporation of the solvent gave a residue which was purified by chromatography eluting with petroleum ether (bp 60-90°C)-ethyl acetate (95:5 v/v) to give the product alkene (~70-90%).