Michael addition reaction hetero

Biosynthetically, 125 is considered to be a dimer of 127, which itself could be an oxidation product of 126. The manner in which two avrainvillamide units are linked strongly indicates a dimerization mode that has not yet been described for indole alkaloids. Initiation of the dimerization by a hetero-Michael addition reaction sets the stage for the synthesis of 125. Until now, three syntheses of stephacidin B (all based on the dimerization of avrainvillamide) have been accomplished, by Myers et al. [55], Baran et al. [57, 58], and Williams et al. [59]. 

For a carbohydrate microarray, a glass slide is modified by the thiol group as solid support. Carbohydrates in the form of glycosylamines are converted into maleimide via a hydrocarbon tether chain and covalently bound to the glass surface by hetero-Michael addition reaction (Park and Shin, 2(X)2) between the thiol group and the maleimide moiety of the glycosyl derivative (Fignre 14.4C). 

In addition, we were able to extend the tandem hetero Michael addition/a-ester-enolate alkylation protocol by an intramolecular variant via a Michael-initiated ring closure (MIRC) reaction leading to diastereo- and enantiomerically pure trans-configured 2-amino-cycloalkanoic acids 30 (Scheme 1.1.7) [14c,d]. 

In a similar manner, Lu and Liu have more recently utilized the hetero-Michael addition of lithium propargylic alkoxides to alkylidene malonates in a synthesis of stereodefined allylidene tetrahydrofurans, based on the use of allylic chloride as coupling partner [98]. In this case, the cydization reaction is initiated by a catalytic amount of palladium salt [Pd(OAc)2] rather than by an organopalladium species as mentioned above. 

The reaction of 3-tosyloxy or 3-mesyloxy flavones (e.g., 361) with ammonia or primary amines has been shown to yield the corresponding 3-amino flavones (e.g., 362) in high yields (Scheme 55). The results can be rationalized through a hetero-Michael addition of the ammonia or primary amine followed by cyclization to form the aziridine... 

Crafts reactions, and oxidizing reagents like chlorine do not destroy this protection. The regeneration of the carbonyl functions has to be carried out with concentrated aqueous alkali and proceeds as a tandem hetero Michael addition/retro aldol reaction (Scheme 87). Although these drastic conditions set a limit to the general application of this protecting group, it has successfully been used in porphyrine total syn-theses. ... 

LiN(SiMe3)2 to form crixivan intermediate 4 [13]. The reactivity of bases may be dependent on the nature of the alkali metal portion of the base, as seen in the hetero-Michael additions shown in Figure 3.7 [14]. Phase-transfer catalyzed reactions (PTC) are often overlooked [15], and can provide safe, economic, and very productive alternatives to reactions using strong bases (see Figure 2.18). 

Nafion resins have been used not only for the opening of epoxides but also for their isomerization to aldehydes or ketones [137]. Various other rearrangements and isomerizations are catalyzed by this solid acid, in some cases with selectivities higher than those obtained with other solid catalysts [138-140]. Other reactions that have been studied include the Peterson methylenation of carbonyl compounds [141], hetero-Michael additions to unsaturated ketones [142], the Koch-type carbon-ylation of alcohols to form carboxylic acids [143], dimerization of a-methylstyrene [144], addition of carboxylic acids to olefins [145] and Diels-Alder reactions [146]. Notably, in most cases, reutilization of the catalyst is considered but only after an appropriate washing protocol to regenerate its acidity/activity. 

Compound (120) was prepared from 8,10-dihydrosweroside aglucone (32), which could be alkylated in aprotic solvent in the presence of a strong base to (33). However, under the same conditions, but in the absence of the alkylating agent, a sequence of four base-catalyzed reactions (dimerization by a vinylogous Michael addition, intramolecular aldolization, lactonization and cyclization by hetero Michael addition) gave the final product (120). Detailed analysis of its formation would exceed the frame of this paper [result to be published]. 

An alternative route allowed the generation of the C5 chiral center by hetero-Michael addition on cx,p-unsaturated Weinreb amide 54, which in turn could derived from aldehyde 52 through crotyltitanation and homologation (Scheme 12). Thus, crotyltitanation reaction of aldehyde 52 with (/f)-4 cleanly led to the syn-anti homoallylic alcohol 53. a, i-Unsaturated Weinreb amide 54 was obtained through a classical two-step sequence involving a Homer-Wads worth-Emmons olefination. Then, reaction of 54 with benzaldehyde mediated by potassium bis(trimethylsilyl)amide (KHMDS) afforded benzyli-dene 55 in 79% yield with an excellent diastereoselectivity (dr >95 5). After reduction to aldehyde 56, the last C1-C7 subunit was obtained in 32.7% overall yield for eight steps. 

Alternatively, C-ring formation has been achieved by connecting the atoms Cl 1 and C12 of the erythrinane core. This route principally involves the generation of angularly arylated hydroindoles, their N-alkylation with an appropriate C2-unit followed by the final cyclization step. Thus the hydroindole 93, accessible from 5-(nitromethyl)-l,3-benzodioxole (91) and the oxoheptenoic acid ester 92, has been reacted in a hetero Michael addition with phenyl vinylsulfoxide providing the required N-substimted precursor 94. The latter in turn has been cyclized in a Pummerer reaction to... 

Synthesis of chiral heterocycles by domino organocatalytic processes has also been intensively studied. In particular, various benzo-fused heterocycles, such as chiral chromans, " thiochromanes, hydro-quinolines, dihydropyranes, or thiopyranes were investigated. These organocatalytic sequence were typically initiated by a hetero-Michael addition of a sulfur, oiqrgen or nitrogen nucleophile, which triggers the formation of an enolate/enamine that adds to the ortho electrophile terminating the cascade reaction. An elimination step or an additional cyclisation step follows (Scheme 8.25). 

A solid-supported carbonate reagent was used to initiate the formation of 2H-l,4-benzoxazin-2-ones 303 from P-nitroacrylate 301 and 2-aminophenol 302 (Scheme 7.72) [154]. This hetero-Michael addition/intramolecular transesteri-fication/elimination of HN03/[l,3]-proton shift domino reaction proceeded in moderate to excellent yields. In another study, a series of various functionalized pyrrolo[l,2-r]pyrazines 305 were made synthetically available through the reaction of vinyl azides 304 and lH-2-pyrrolecarbaldehyde (Scheme 7.73). The deprotonated pyrrole initially reacts in a Michael manner with the vinyl azides, with nitrogen as... 

Oxa-Michael addition, like other hetero-Michael additions received much less attention from the scientific community compared to conventional Michael reactions, even though the potential products of such reactions are valuable intermediates. In addition, oxa-Michael reactions frequently enable an easy... 

Michael addition reactions (Hetero) Diels-Alder Aldol reactions Addition of ZnR2 to RCHO Formation of cyanohydrin Cross coupling... 

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