Michael functions adduct

Secondary nitro compounds can be converted into carbanions in similar fashion. Interesting highly functionalized adducts (46) were prepared by addition to levoglucosene (45) (equation 17)59. Mixtures of diastereomeric adducts were generally formed60. The adduct from nitromethane undergoes double Michael addition followed by aldol condensation to afford the novel adduct 47. 

The most impressive result of the catalytic Michael-aldol cascade is the kinetic resolution of the racemic cyclopentenone 458 shown in Sch. 64. The reaction is performed with 10 mol % (S)-ALB to give the tandem Michael-aldol adduct 459 in 97 % ee and 75 % yield based on malonate 390f. Asymmetric induction in 459 was measured after dehydration of the hydroxyl group, as was done for 451. Clearly, this demonstrates the viability of this new asymmetric strategy for the synthesis of a variety of fully functionalized prostaglandins. 

As has already been mentioned, the low reactivity of enamine nucleophiles needs a highly electrophilic Michael acceptor for the reaction to proceed with good conversions in an acceptable time. In this context, the Michael reaction of aldehydes and ketones with nitroalkenes can be regarded as one of the most studied transformations in which the enamine activation concept has been applied. This reaction furnishes highly functionalized adducts with remarkable potential in organic synthesis, due to the synthetic versatility of the nitro group and the presence of the carbonyl moiety from the donor reagent. 

The aldehyde or ketone functionalities in the Michael adducts are restored by ozonolysis of the hydrazone moiety resulting in am/-3,4-disubstituted-5-oxoalkanoates 1. 

The application of 3-aminopropyl phosphine (3) [41,46] as a building block for incorporation into -COOH functionalized frameworks provides an excellent example of the utility of preformed primary phosphine frameworks (Scheme 8) [46]. The reactions involved Michael addition of ferf-butyl acrylate to malonic acid dimethyl ester to produce the intermediate adduct, 2-methoxycarbonyl-pentanedioc acid 5-ferf-butyl ester 1-methyl ester, which upon treatment with trifluro-acetic acid (TFA) produced the corresponding diester acid,2-methoxy-carbonyl-pentanedioic acid 1-methyl ester, in near quantitative yield. It is remarkable to note that the reaction of NH2(CH2)3PH2 (3) with the diester acid is highly selective as the -COOH group remained unattacked whereas the reaction occurred smoothly and selectively at the -COOMe groups to pro-... 

Yamamoto s group recently published a highly enantioselective chiral amine-catalyzed domino O-nitroso aldol/Michael reaction of 2-268 and 2-269 (Scheme 2.63) [141]. As products, the formal Diels-Alder adducts 2-271 were obtained with >98% 66, which is probably due to the selective attack of an enamine, temporarily formed from amine 2-270 and enone 2-268, onto the nitroso functionality. 

Aliphatic compounds containing terminal gem-dinitro functionality form adducts with Michael acceptors.Of particular interest is the reaction of a,a,o),a)-tetranitroalkanes with Michael acceptors. ° Most a, o, y, y-tetranitroalkanes will react with two equivalents of Michael acceptor to form bis-adducts, like in the case of 1,1,4,4-tetranitrobutane, which reacts with two equivalents of methyl vinyl ketone, methyl acrylate, acrylonitrile etc. ° The influence of steric effects becomes apparent with a,a,y,Y-tetranitroalkanes, like 1,1,3,3-tetranitropropane, which can form either mono-adducts or bis-adducts depending on the Michael acceptor used 1,1,3,3-tetranitropropane will only react with one equivalent of methyl acrylate and the sole product of this reaction is methyl 4,4,6,6-tetranitrohexanoate. °... 

Phenylsulfonyl-1,3-dienes are versatile synthetic intermediates. They can participate in cycloaddition reactions and Michael-type additions leading to adducts which can be further functionalized. In the latter case the resulting allylic sulfone can be functionalized by electrophiles, nucleophiles, or both (Figure 1). 

In the presence of thiourea catalyst 122, the authors converted various (hetero) aromatic and aliphatic trons-P-nitroalkenes with dimethyl malonate to the desired (S)-configured Michael adducts 1-8. The reaction occurred at low 122-loading (2-5 mol%) in toluene at -20 to 20 °C and furnished very good yields (88-95%) and ee values (75-99%) for the respective products (Scheme 6.120). The dependency of the catalytic efficiency and selectivity on both the presence of the (thio) urea functionality and the relative stereochemistry at the key stereogenic centers C8/C9 suggested bifunctional catalysis, that is, a quinuclidine-moiety-assisted generation of the deprotonated malonate nucleophile and its asymmetric addition to the (thio)urea-bound nitroalkene Michael acceptor [279]. 

The hrst step in the preparation of the antidepressant maprotiline (33-5) takes advantage of the acidity of anthrone protons for incorporation of the side chain. Thus treatment of (30-1) with ethyl acrylate and a relatively mild base leads to the Michael adduct saponihcation of the ester group gives the corresponding acid (33-1). The ketone group is then reduced by means of zinc and ammonium hydroxide. Dehydration of the hrst-formed alcohol under acidic conditions leads to the formation of fully aromatic anthracene (33-2). Diels-Alder addition of ethylene under high pressure leads to the addition across the 9,10 positions and the formation of the central 2,2,2-bicyclooctyl moiety (33-3). The hnal steps involve the construction of the typical antidepressant side chain. The acid in (33-3) is thus converted to an acid chloride and that function reacted with methylamine to form the amide (33-4). Reduction to a secondary amine completes the synthesis of (33-5) [33]. 

The addition to a, -unsaturated esters is usually difficult. However, under appropriate conditions, the 1,4-addition of diorganozincs to enoates is possiblc As mentioned above, Michael-addition reactions can also be catalyzed by Ni(II) salts . The 1,4-addition of functionalized organozinc iodides to enones in the presence of Ni(acac)2, a diamine as ligand and TMSCl provides, after hydrolysis, the Michael adducts in satisfactory yields . 

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