Homer-Wadsworth-Emmons chemistry

This is true for both cyclization options however, in the Homer-Wadsworth-Emmons chemistry, the cephem 29 is isolated before conversion into 30. 

Homer-Wadsworth-Emmons chemistry to generate an alkenylphosphonate intermediate that was reduced to generate the alkylphosphonate species. Normally, phosphonate fragments are introduced into the 5 -position using Michaelis-Arbuzov or MichaeUs-Becker chemistry however, this route is an attractive alternative since it avoided the high temperatures typically required for Michaelis-Arbuzov chemistry and it also eliminated the... 

In isotope chemistry the label can be introduced with the acyl group or with the electrophile, or both. Apphcations of these options are exemplified in Figures 11.37 and 11.38. In most cases only singly or doubly labeled products are needed, but it is obvious that two or more labels can be incorporated via each reaction partner, leading to products containing larger numbers of labels. Examples of multiply labeled intermediates prepared via Homer-Wadsworth-Emmons chemistry are discussed in Section 11.3.10. 

The instability of 4-(4 -chlorophenyl)-2-butenoic acid led to an alternative strategy for the preparation of (35) (Scheme 6) [18]. The protocol involved Homer-Wadsworth-Emmons-type chemistry, initially acylating with diethoxy-phosphorylacetyl chloride before treatment with lithium diisopropylamide and 4-chlorophenylacetaldehyde. 

Similarly, 29 can be formed by the Homer-Wadsworth-Emmons modihcation of the Wittig reaction via the phosphonate 28 rather than the phosphorns ylide 27. In this case, the iodo compound mixture 26 is treated with trimethyl phosphite. Cyclization reqnires the nse of lithinm chloride/Hunig s base, ° and cyclization proceeds smoothly at room temperature in similar yield to the Wittig chemistry. Details of this process with isolation and characterization of the intermediates 26, 27, and 29 can be fonnd in a recently pnblished world patent application." Yields for the conversion of 24 into 27 are -77% overall cyclization yield from 27 to 29 is -85%. 

Methyl 3-C-allyl-4,6-0-benzylidene-3-deoxy-a-D-glucopyranoside has been used as a common starting material for preparing annulated sugars involving intramolecular Homer-Wadsworth-Emmons reactions. Thus successive reaction of the allyl derivative with osmium tetroxide, lithium dimethylmethylphosphonate, Dess-Martin periodane then potassium carbonate furnished 51. Whereas successive reaction of the allyl derivative with borane-THF, PCC oxidation, lithium dimethylmethylphosphonate, Dess-Martin periodane then potassium carbonate afforded 52. Analogous chemistry was also performed on methyl 2-C-allyl-4,6-0-benzylidene-2-deoxy-a-D-allopyranoside. ... 

Keywords Aldehydes, Bestmann-Ohira reagent [diethyl(diazomethyl)phosphonate], diazomethyl sulfone, cesium carbonate, potassium hydroxide, copper(I) iodide, ethanol, room temperature, Homer-Wadsworth-Emmons (HWE) reaction, click chemistry, cycloaddition, phosphonates, one-pot synthesis, phosphonylpyrazoles, sulfonylpyrazols... 

Various [l- C]carboxylic acids have been prepared by carboxylation of carbanions stabilized by -I or -M substituents. The examples in Figure 5.7 have been selected here as prototypes, since they are of strategic interest. Deprotonation of diethyl methylphos-phonate (18 with n-BuLi followed by [ CJcarboxylation and esterification with diazoethane provided triethyl phosphonoll- Clacetate (19) in an overall radiochemical yield of 62%. Compound 19 has been widely exploited for chain extensions by a labeled two-carbon unit via its alkenylation reaction with carbonyl compounds (Homer-Wadsworth-Emmons reaction). Similarly, reaction of alkyl halides, tosylates or carbonyl compounds with LiC = CH or LiC=CH H2NCH2CH2NH2 followed by deprotonation and [ C]carboxylation of the resulting terminal alkynes has been used as a strategic tool for the incorporation of a labeled three-carbon unit, as exemphfied in a steroid platform (20 to 21). This chemistry provides outcomes complementary to those using [ C2]acetylene (Chapter 8, Section 5.1). Finally, the [ CJcarboxylation of lithiated dimethylsulfide provided an alkylthio[l- C]acetic acid 22 and thence a functionalized 2-alkylthio[l- C]ethyl derivative 23 useful, in this case, for elaboration into e.p. 

Muscone (40) is a sex pheromone of the musk deer and a chemical component of cosmetics. A 12-member library of racemic muscone analogs was synthesized by Nicolaou et al.," who anployed a cyclorelease method on solid support to form the macrocycle scaffold (Figure 11.17). A phosphonate-functionalized resin loaded on encoded SMART microreactors 36 was coupled to olelinic esters 35 to form the p-ketophosphonates 37. Sorting and cross olefin metathesis of 37 with two alkenols followed by oxidation with Dess-Martin reagent gave aldehydes 38. An intramolecular ketophosphonate-aldehyde condensation (Homer-Emmons-Wadsworth reaction) of 38 caused smooth cyclorelease of macrocyclic enones 39. Parallel solution-phase chemistry completed the sequence. 

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