Wittig alkene synthesis

A fifth category must be mentioned even though it may have no direct relevance to Wittig alkene synthesis. This is the equilibration of anti betaines under lithium-free conditions that was encountered in early attempts to design control experiments [Speziale and Bissing (12) and Trippett and Jones (13)]. As already discussed, strong evidence is now available that the... 

Dondoni et al. prepared a 1-hydroxyethylene peptide using a thiazole-aldehyde synthesis starting from an amino acid.[38] The aldehyde is converted into an alkanoate by Wittig alkenation and reduction of the double bond (Scheme 18). Then, removal of the tert-bu-tyldimethylsilyl group gives the unsubstituted lactone. In the last step, the lactone is alkylated using the method reported by Kleinman and co-workers. 20 ... 

In a similar manner, alkynes can undergo sequential carbometallation reactions, previously illustrated in equation (32).136 It is possible to combine carbocupration of alkynes with the use of a Michael acceptor as electrophile when that electrophile is a vinylphosphonium salt, carbocupration can be coupled to Wittig alkenation to result in a stereospecific synthesis of dienes via a one-pot, four-component, four carbon-carbon bond-forming reaction sequence.302... 

Reviews have featured epoxidation, cyclopropanation, aziridination, olefination, and rearrangement reactions of asymmetric ylides 66 non-phosphorus stabilized carbanions in alkene synthesis 67 phosphorus ylides and related compounds 68 the Wittig reaction 69,70 and [2,3]-Wittig rearrangement of a-phosphonylated sulfonium and ammonium ylides.71 Reactions of carbanions with electrophilic reagents, including alkylation and Wittig-Homer olefination reactions, have been discussed with reference to Hammett per correlations.72... 

Silicon-based alkene synthesis is used much less than the analogous phosphorus-based Wittig reaction. In some cases, however, the silicon-based method has proved superior to the phosphorus-based chemistry. For example, a Wittig reaction failed to methylenate the hindered ketone shown in Equation... 

Fig. 11.10. Wittig-Horner synthesis of alkenes with stereogenic C=C double bond via condensation of lithiated phosphine oxides B <-> B with aldehydes. In the two-step reaction the initially formed addition products syn- and anti-D are protonated and the resulting alcohols syn- and anti-C are isolated and separated the suitable diastere-omer is then stereoselectively converted into the desired alkene isomer. The one-step reaction leads to the same alkene in a cis,trans mixture.

The nucleophilic addition of the a-lithiated alkyldiphenylphosphine oxide B to the carbonyl group of an aldehyde at the beginning of a Wittig-Horner reaction results in the phos-phorylated lithium alkoxide D. If the alkene synthesis is carried out in a single step, the Li of the intermediate D is, without workup, reversibly replaced by K by adding potassium-ferf-butoxide. In this way, the phosphorylated potassium alkoxide F is made available. Only in F... 

Fig. 11.11. Wittig-Horner synthesis of stereouniform alkenes via ketophosphine oxide B. The reaction proceeds via its Felkin-Anh-selective or chelate-controlled reduction to form the syn-configured hydroxyphosphine oxides D and the anti-configured hydroxyphosphine oxides E. D and E continue to react—after deprotonation with KO-tert-Bu—via a syn-elimination to give the trans- and cis-alkene, respectively. R1 in the formula A-C corresponds to a primary (prim-alkyl) or a secondary alkyl residue (sec-altyl).

When the Wittig reaction was introduced (Chapter 14) we saw it simply as an alkene synthesis. Now if we look at one group of Wittig reagents, those derived from a-halo-carbonyl compounds, we can see that they behave as specific enol equivalents in making unsaturated carbonyl compounds. 

Wittig reaction (Section 19.11) a general method of alkene synthesis by treatment of a ketone or aldehyde with an alkylidenetriphenylphosphorane. 

The Wittig alkenation has found widespread application in synthetic organic chemistry, and numerous papers and reviews have detailed the progress of the Wittig reaction. A principal advantage of alkene synthesis by the Wittig reaction is that the location of the double bond is absolutely fixed in contrast to the mixture often produced by alcohol dehydration. With simple substituted ylides Z-alkenes are favoured. 

An advantage in using the Wittig reaction over other elimination methods to synthesize alkenes is that you always know the location of the double bond. Whereas other methods of alkene synthesis often give a mixture of constitutional isomers, the Wittig reaction always gives a single constitutional isomer. 

Table 2 Alkene Synthesis Via (Fluoren-9-ylidene)methane Probase-Promoted Wittig Reaction...

The use of anions derived from a phosphine oxide (132) or a diethyl phosphonate (133) to form al-kenes was originally described by Homer.Although these papers laid the foundations for the use of phosphoryl-stabiliz carbanions for alkene synthesis, it was not until Wadsworth and Emmons published a more detailed account of the general applicability of the reaction that phosphonates bet e widely used. Since the work of Wadsworth and Emmons was significant and crucial to the acceptance of this methodology, the reaction of a phosphonate caibanion with a carbonyl derivative to form an alkene is referred to as a Homer-Wadsworth-Emmons reaction (abbreviated HWE). The phosphine oxide variation of the Wittig alkenation is called the Homer reaction. 

This methodology has been applied to the synthesis of oudemansins by Kallmerten. In this example, the Wittig alkenation gave mixtures of ( )- and (Z)-products, as well as epimerizing the ether position. These problems were solved by acylating the phosphine oxide (239) and carrying out reduction and... 

The Peterson olefination is a connective alkene synthesis and represents a useful alternative to the Wittig reaction. The precursors for the Peterson olefination are 3-hydroxy-alkyltrimethylsilanes which undergo P-elimination of trimethylsilanol under basic or acidic conditions to furnish stereodefined alkenes. This olefination method is especially valuable for the preparation of terminal and exo-cyc ic double bonds and for the methylenation of hindered ketones where the Wittig reaction is problematic. Also, the... 

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