Wittig reagent synthesis

In view of the synthetic importance of dicarbonvl compounds surprisingly little has been done, apart from carotene synthesis, on dialkenylation with Wittig reagents. However, from the few examples reported one may conclude, that no special problems are involved. Benzocyclobutanedione was converted by two equivalents of methoxycarbonylmethylidenetri-phenylphosphorane to the corresponding diene in 85% yield (M. P. Cava, 1960). 

In the course of a synthesis of ( )-nootkatone the keto-ester (148) with ethylidenetriphenylphosphorane gave the cyclohexanone (149), a Dieckmann condensation having occurred under the basic conditions. Among other natural products synthesized using Wittig reagents are... 

Synthesis of the amino-triazole derivative (43) was performed in the authors laboratory by Pati et al. [52] (Scheme 7). Substituted benzyl bromide was reacted with triphenylphosphine to produce the phosphonium bromide starting material, 44. The Wittig reagent, obtained by treatment with sodium hydride, was reacted with 3,4,5-trimethoxybenzaldehyde 18 to generate the nitro-stilbene 45 in good yields. The alkyne 46 was obtained by bromination of the stilbene, followed by didehydrobromination. Compound 46 was then reacted under thermal conditions with benzyl azides... 

The relation of the heteroatomic lone pair to the common double bond in matters relating to -electron mobility has long been accepted as a theoretically sound one.1 Because of a general lack of synthetic methodology, however, representation in the area of -excessive heterocycles was, until recently (early part of the past decade), limited to the long-known five-membered systems pyrrole, furan, and thiophene. In fact, it was not until the late 1960 s that well-developed synthetic procedures, such as (i) condensation with properly constructed Wittig reagents and (ii) the use of synthetic pericyclization, were successfully applied to the synthesis of the various substances now known. 

The /3-lactam carbonyl group transformations have been utilized successfully in the synthesis of azetidine derivatives. The reduction of the carbonyl group in azetidin-2-ones yielding azetidine derivatives is described in Section 2.01.2.8.10. Treatment of jV-BOC-protected 4-(trifluoromethyl)azetidin-2-one 229 with a stabilized Wittig reagent yielded the azetidines 28 and 230 (Equation 61) <20030L4101>. 

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. 

The rest of the synthesis (Scheme 13) is completely stereospecific and most of the steps are known (20). The bicyclic acid was oxidatively decarboxylated with lead tetraacetate and copper acetate (21). The resulting enone was alkylated with methyllithium giving a single crystalline allylic tertiary alcohol. This compound was cleaved with osmium tetroxide and sodium periodate. Inverse addition of the Wittig reagent effected methylenation in 85% yield. Finally, the acid was reduced with lithium aluminum hydride to grandisol. 

Polymer-supported Wittig reagents have recently been developed as an extension to the traditional reagents.29 For example, polystyryldiphenylphosphine has been developed in an attempt to replace the use of triphenylphosphine in the preparation of phosphoranes (see Protocol 1). The hope is that these polymer-bound regents will overcome the practical problem of removing the triphenylphosphine oxide by-product formed in Wittig reactions. Polymer supported phosphonates and Wittig substrates have also been prepared for use in solid phase synthesis and combinatorial chemistry.30... 

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