Michael addition Homer-Wadsworth-Emmons

Among the selected examples, we can cite the remarkable Hayashi s syntheses of (-)-oseltamivir [94] and ABT-341 [95] both catalyzed by diphenylprolinol silyl ether (R)-124 (Scheme 2.69). In both cases, a highly substituted cyclohexane moiety B (obtained via an asymmetric Michael addition and a domino Michael reaction/Homer-Wadsworth-Emmons... 

In addition to the use of elemental fluorine 63 and DAST 64, Miyake and Kitazume (2003) demonstrated the introduction of fluorine into a series of small organic compounds via trifluoromethylation of carbonyl compounds (Table 7), Michael addition (Scheme 20a), and Homer-Wadsworth-Emmons (Scheme 20b) reactions. 

An interesting approach to the central eight-membered ring of ceroplastol I is based on an intramo-lecnlar Homer-Wadsworth-Emmons reaction employing a diethyl 7-formylalkylphosphonate. The C-7 aldehyde, protected as a 1,3-dioxolane, is obtained in 20% yield by a Michael addition of an alkenyllithium to 2-(diethoxyphosphinyl)cyclopentenone in THF at -78°C. Hydrolysis of the acetal nsing HjO and TsOH in reflnxing acetone yields 89% of the phosphonylated ketoaldehyde (Scheme, 5.56). ... 

The same strategy has been used to prepare trans bicyclic enones. The protected C5 phosphonylated aldehyde is obtained in 84% yield by a CuBr SMe2-mediated Michael addition of the Grignard reagent derived from 4-chlorobutyraldehyde diethyl acetal to a 5-phosphonylated 2,3-dihydro-4-pyridone in THF. Subsequent room-temperature hydrolysis of the acetal using aqueous oxalic acid in THF affords a near-quantitative yield of the crude aldehyde, which undergoes an intramolecular Homer-Wadsworth-Emmons reaction under treatment with Et3N/LiCl in THF at room temperature (89%). ... 

The use of diethyl l-(ethoxycarbonyl)vinylphosphonate is based on Michael addition of anionic nucleophiles to the double bond to produce stabilized phosphonate anions capable of undergoing subsequent alkenylation reaction with aldehydes or ketones by a Homer-Wadsworth-Emmons process (Scheme 8.27)." 2 " "... 

Oxygen and nitrogen nucleophiles add to diethyl l-(ethoxycarbonyl)vinylphosphonate to generate the formation of various fused heterocyclic compounds. Thus, A -carbapcncrns are readily prepared by the Michael addition of A-lithio-4-vinylazetidin-2-one to diethyl l-(ethoxycarbo-nyl)vinylphosphonate followed by ozonolysis of the adduct and subsequent treatment of the generated aldehyde by intramolecular Homer Wadsworth-Emmons reaction (Scheme 8.28). ... 

The pivotal step associated with our approach to compounds 31-34 was an organocatalysed, enantioselective and intramolecular Michael addition reaction of the nucleophilic C-2 carbon of a pyrrole to an iV-tethered a,p-unsaturated aldehyde residue and thereby estabhshing the required CD-ring system. Full details of the reaction sequence are shown in Scheme 4 and this involves initial reaction of the potassium salt, 35, of pyrrole with butyrolactone (36) to give, after acidic workup, compound 37 (60-90%). Conversion of this last species into the corresponding Weinreb amide 38 (87%) followed by its reaction with ethylmagnesium bromide then afforded the ethyl ketone 39 (95%) that was subjected to standard Homer-Wadsworth-Emmons (HWE) conditions and thereby generating the... 

The utility of aqueous [ C2]acetaldehyde is illustrated by its Homer-Wadsworth-Emmons olefmation with diethyl (cyanomethyl)phosphonate under phase transfer conditions to give [3,4- C2]crotonitrile (16) in 83% radiochemical yield. Subsequent Michael addition of a-aminonitrile 17 produced the masked y-ketoacid derivative IS (Figure 8.6), which served as a key intermediate in the synthesis of [ " C2]C1930 (19). For the TiCLi-promoted aldol reaction with the propiophenone derivative 20, however, the use of anhydrous [ 2] acetaldehyde was essential. The reaction proceeded with excellent stereoselectivity, providing exclusively the racemic syn-diastereomers 21. Subsequent... 

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