Wittig reaction alkene synthesis

To use the Wittig reaction in synthesis, you must be able to determine what carbonyl compound and Wittig reagent are needed to prepare a given compound—that is, you must work backwards, in the retrosynthetic direction. There can be two different Wittig routes to a given alkene, but one is often preferred on steric grounds. 

Wittig reaction (Section 17 12) Method for the synthesis of alkenes by the reaction of an aldehyde or a ketone with a phosphorus yhde... 

With a regioselectivity opposite to that of the Zaitsev rule, the Hofmann elimination is sometimes used in synthesis to prepare alkenes not accessible by dehydrohalo-genation of alkyl halides. This application decreased in importance once the Wittig reaction (Section 17.12) becfflrre established as a synthetic method. Similarly, most of the analytical applications of Hofmann elimination have been replaced by spectroscopic methods. 

The Peterson oleflnation presents a valuable alternative to the Wittig reaction. It has the advantage to allow for a simple control of the alkene geometry. Its applicability in synthesis depends on the availability of the required silanes.2... 

The (Horner-)Wadsworth-Emmons reaction generally is superior to the Wittig reaction, and has found application in many cases for the synthesis of a ,/3-unsaturated esters, a ,/3-unsaturated ketones and other conjugated systems. Yields are often better then with the original Wittig procedure. However the Wadsworth-Emmons method is not suitable for the preparation of alkenes with simple, non-stabilizing alkyl substituents. 

With respect to the carbonyl substrate, a variety of additional functional groups is tolerated, e.g. ester, ether, halogen. With compounds that contain an ester as well as a keto or aldehyde function, the latter usually reacts preferentially. Due to its mild reaction conditions the Wittig reaction is an important method for the synthesis of sensitive alkenes, as for example highly unsaturated compounds like the carotinoid 17 shown above. 

Intermediates 18 and 19 are comparable in complexity and complementary in reactivity. Treatment of a solution of phosphonium iodide 19 in DMSO at 25 °C with several equivalents of sodium hydride produces a deep red phosphorous ylide which couples smoothly with aldehyde 18 to give cis alkene 17 accompanied by 20 % of the undesired trans olefin (see Scheme 6a). This reaction is an example of the familiar Wittig reaction,17 a most powerful carbon-carbon bond forming process in organic synthesis. 

With a-monosubstituted ylides the oxidation results in the formation of alkenes (by subsequent Wittig reaction on the intermediate aldehyde). A recent example of such synthesis is found in the preparation of all-(Z)-cyclododecate-traene by oxidation of the appropriate bis-ylide [33]. It must be pointed out that an approach of the same macrocycle based on ring closing metathesis was found ineffective. 

For the synthesis of alkenes, the Wittig and Horner-Wadsworth-Emmons reactions have become important tools. Triphenylphosphine that is used in the Wittig reaction can be immobilized either on the polymer or can be used in solution for solid-phase chemistry (Scheme 3.18). The Horner-Wadsworth-Emmons reaction for example is used for the synthesis of aldehyde building blocks [261]. 

Snider and colleagues have developed the sequential ene reaction/thia-[2,3]-Wittig reaction which provide appropriately functionalized product 152 at allylic position on simple alkene 150 in two steps involving intermediate 151 (equation 87) . Thia-[2,3]-Wittig rearrangement was often utilized as a key step of natural product synthesis. Masaki and colleagues have demonstrated that the potassium enolate thia-[2,3]-rearrangement of aUyl sulfide 153 to 154 is useful for the synthesis of terpenoid diol component 155 of the pheromonal secretion of the queen butterfly (equation 88) . 

Buchanan et al. (48) reported a new route to the synthesis of the chiral hydroxy-pyrrolidines 234 and 238 from D-erythrose (230) via an intramolecular cycloaddition of an azide with an alkene (Scheme 9.48). Wittig reaction of the acetonide 230 with (carbethoxyethylene)triphenylphosphorane gave the ( ) and (Z) alkenes 231 and 232. On conversion into the triflate followed by its reaction with KN3, the ( ) isomer 231 allowed the isolation of the triazoline 234 in 68% overall yield, which on treatment with sodium ethoxide afforded the diazo ester 235 in 86% yield. 

Pearson and Lin (52) developed an elegant approach to the synthesis of optically active ( )-swainsonine (247) from isopropylidene-D-erythrose (242) (Scheme 9.52). Wittig reaction of the acetonide 242 led to the (Z) alkene 252 in 86% yield. The chloro alcohol 252 was converted to the azide 253 in 76% yield, which subsequently underwent 1,3-dipolar cycloaddition, isomerization and hydroboration-oxidation to give the indolizidine 255 in 70% overall yield. Cleavage of the acetonide unit in 255 using 6 N HCl gave the target molecule 247 in 85% yield. 

The synthesis of alkenes through the Wittig reaction has generated an impressive understanding of the chemistry of organophosphorus compounds. The generated car-banions stabilized by a phosphoryl moiety can be considered as ylide anions, and the... 

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