By Michael addition

The TT-allylpalladium complexes 241 formed from the ally carbonates 240 bearing an anion-stabilizing EWG are converted into the Pd complexes of TMM (trimethylenemethane) as reactive, dipolar intermediates 242 by intramolecular deprotonation with the alkoxide anion, and undergo [3 + 2] cycloaddition to give five-membered ring compounds 244 by Michael addition to an electron-deficient double bond and subsequent intramolecular allylation of the generated carbanion 243. This cycloaddition proceeds under neutral conditions, yielding the functionalized methylenecyclopentanes 244[148], The syn-... 

The synthesis of cyclohexenone derivatives by Michael addition followed by intramolec ular aldol condensation is called the Robinson annulation, after Sir Robert Robinson who popularized its use By annulatwn we mean the building of a ring onto some start mg molecule (The alternative spelling annelation is also often used)... 

A commercially important outlet in the fragrance industry is the methyl dihydrojasmonate [24851-98-7] (26) which is made by Michael addition of a malonate to 2-pentyl-2-cyclopenten-l-one [91791 -21 -8] (52) and which is used in perfumery for blossom fragrances, particularly jasmine (see Perfumes). 

Woodward s total synthesis of cephalosporin C begins with L-cysteine (48) which establishes the chiral center at C-7. The cis geometry at C-6,7 is achieved in intermediate (49) which is cyclized to (50) by treatment with triethylaluminum. The dihydrothiazine ring is constructed by Michael addition to the condensation product of trichloroethyl glyoxylate... 

Vinylogous amides undergo reduction with lithium aluminum hydride, by Michael addition of hydride and formation of an enolate, which can resist further reduction. Thus -aminoketones are usually produced (309, 563,564). However, the alternative selective reduction of the carbonyl group has also been claimed (555). 

Although a sulfhydryl group generally is not converted to an 5-phenyl thioether, the conversion can be accomplished through the use of a Pd-catalyzed arylation with an aryl iodide. Thiophenol can be used to introduce sulfur into molecules by simple displacement or by Michael additions, and thus, the phenyl group serves as a suitable protective group that can be removed by electrolysis (—2.7 V, DMF, R N X-). ... 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

As will be discussed in the next section, 1,5-pentanediones are obtained by Michael addition of acetophenones to chalcones. The addition and cyclization may be merged in one step (see Section II,C,2,g). When acetophenone was condensed with chalcone (74) in the presence of or of HC104, jS-phenylpropio-... 

The apparently loose structural requirements for antihista-iiiinic agents have already been alluded to. Thus, active compounds. ire obtained almost regardless of the nature of the atom that connects the side chain with the benzhydryl moiety. In fact, a methylene group, too, can also serve as the bridging group. Reaction of the aminoester, 95 (obtained by Michael addition of... 

Incorporation of a carbonyl group into the alkyl side chain also proved compatible with biologic activity. The key intermediate (76) is obtainable by Michael addition of the anion from diethyl malonate to methylvinyl ketone followed by ketalization with ethylene glycol. Condensation of 76 with hydrazobenzene leads to the pyrazolodione hydrolysis of the ketal group affords ketasone (78). ... 

The Michael addition of nih oalkanes to alkenes substituted with two elecbon-withdrawing groups at the a- and 3-positions provides a new method for the preparation of functionalized alkenes. Although reactions are not new, Ballini and coworkers have used this sbategy in the synthesis of polyfunctionalized unsaturated carbonyl derivatives by Michael addition of nih oalkanes to enediones as shown in Eqs. 7.124-7.126. Success of this type of reaction depends on the base and solvent. They have found that DBU in acetonihile is the method of choice for this puipose. This base-solvent system has been used widely in Michael additions of nitroalkanes to elechon-deficient alkenes (see Section 4.3, which discusses the Michael addition). ... 

After reduction of the nitro function of the porphyrin, the porphyrinamine intermediate can be reacted with z./l-unsaturated carbonyl compounds to yield porphyrins with a fused pyridine ring, which is formed by Michael addition, imine formation and dehydrogenation. 

The yield of the cyclization step under the influence of a metal template can be increased when the corresponding dialdehyde 19 of the tetrapyrrole 16 is used. The reaction sequence is initiated by insertion of palladium(II) or nickel(II) into the tetrapyrrole to give 20 followed by Michael addition of one acrylaldehyde side chain to the other yielding the macrotetracycle 21 from which in a retro-Michael reaction acetaldehyde is eliminated to give 22. 

Addition of dithioacids to electron-deficient monomers (MA, MMA, AN) proceeds by Michael addition to pul sulfur at the unsubslituted end of the double bond.479... 

An analogous cyclization to eventually form five-membered rings has also been observed for l-metalla-l,3,5-hexatrienes with an additional heteroatom within the chain, such as in the complexes 157. These are obtained by Michael additions of imines to alkynylcarbene complexes in good to excellent yields (reaction type F in Scheme 4), and their configurations were determined to be Z (>91%) in all cases. Upon warming in THF solution, complexes 157 underwent cyclization with reductive elimination to furnish 2Ff-pyrroles 158 in up to 97% yield (Scheme 34). With two cyclopropyl substituents at the terminus in... 

Key features of the cyclopropanation include the ylide acting as a mild base to isomerize the 1,2-dioxines into cis-y-hydroxy enones, followed by Michael addition of the ylide and last by cyclization of the intermediate enolate [35]. It must be noted that the trans-y-hydroxyenones do not give the cyclopropanation. 

Although the unsaturated nitrile oxides 124 can be prepared via the aldoxime route (see Scheme 8), the older procedure suffers from the disadvantage that a tenfold excess of allyl alcohol and two additional steps are required when compared to Scheme 15. Therefore, unsaturated nitro ether 123 that can be prepared by condensation of an aldehyde 120 and a nitro alkane followed by Michael addition of alcohol 122, was a useful precursor to nitrile oxide 124 [381. The nitrile oxide 124 spontaneously cyclized to ether 125. This procedure is particularly suitable for the synthesis of tetrahydrofurans (125a-h) and tetrahydropyrans (125i-k) possessing Ar substituents in 72-95% yield (Table 12). The seven-membered ether 1251 was obtained only in 30% yield on high dilution. The acetylenic nitro ether 126 underwent INOC reaction to provide the isoxazole 127. 

Example The lactone (8>, needed for a natural product synthesis, might be made from (6) via epoxide (7) and so a synthesis for (6) was required. Wittlg disconnection reveals a 1,5-dicarbonyl compound (9), best made by Michael addition of a substituted malonate (11) to enone (10). The enone was made by the simple but reliable Grignard route rather than risking a Mannich reaction of unknown regloselectivity. 

Amide disconnection reveals (18) and FGl (amino to nitro) gives (19) which could be made by Michael addition of nitro compound (16) to an acrylate ester.. lalys-ts... 

There are many possibilities and I shall simply analyse the published synthesis. Removal of the methyl group from (50) gives ketone (51) which can be made from enone (52) by Michael addition of an ethyl group. Unambiguous cross-condensation between enolisable (54) and reactive (53) gives (52). 

Fernandez, E.J., Gimeno, M.C., Jones, P.G., Laguna, A. and Olmos, E. (1997) Strong Activation of the Double Bond in (PPh2)2C CH2. Novel Synthesis of Gold (111) Methanide Complexes by Michael Addition Reactions. Organometallics, 16 (6), 1130-1136. 

Addition of nitromethane to benzaldehyde catalyzed by amine followed by Michael addition of DMM catalyzed by Ni complex Cross-linking of amine itself... 

P-Nitrosulfides, formed by Michael addition of allyl mercaptan to P-nitroenones, undergo either INOC or ISOC to give tetrahydrothiopheno[3,4-c] isoxazolines. In this case, stereoselectivity of ISOC is also better than that of INOC (Eq. 8.88).140... 

Dicarbonyl compounds can be converted into furans by methods other than the classical Feist- Benary method, the essential feature of which is alkylation by a haloketone or similar species. A curious variation is provided by the use of trichloronitroethene, Cl2C=CCIN02, which condenses with two moles of a 1,3-dicarbonyl compound by Michael addition followed by elimination of two chloride ions the third chloride is lost at the aroma-tization step so that, for example, methyl 3-oxobenzenepropanoate is converted into the nitrofuran 38."... 

In order to study the reactivity of the nitrogen atom in saccharidic OZT moieties Rollin and co-workers13,55 explored some standard reactions IV-acylation, IV-sulfonylation, IV-vinylsulfonylation by Michael addition, reductive elimination, conjugated addition and cycloaddition. 

Crosslinking of amine- or hydroxy-terminated PAMAM dendrimers using cyclic anhydride - amine or cyclic anhydride - hydroxy addition reactions was employed for preparation of crosslinked thin films of very low permeability [73], Polyanhydrides, such as maleic anhydride-methyl vinyl ether copolymers, were used as crosslinking components. In the case of amine-terminated PAMAM, crosslinking and chemical stability were further increased by imidization of the maleamic acid groups retro-Michael eliminations were followed by Michael additions to further crosslink the film. 

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