Hetero Michael addition

Forsyth, C.J. Hao, J. Aiguade, J. (2001) Synthesis of the (-i-)-C26-C40 domain of the azaspiric acids by a novel double intramolecular hetero-Michael addition strategy. Angew. Che. Int. Ed. Engl., 40, 3663-7. 

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 use of heteroaryl vinyl sulfides and vinyl dithiocarbamates (166) as hetero-Michael addition acceptors has been described. Combined chelating and electron-withdrawing effects were postulated to stabilize the transient anionic species and allow smooth Michael-induced ring closure to produce C-glycosides (167).191... 

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... 

KF/AI2O3 catalyzed hetero-Michael addition of ethyl acrylate with pyrrole as weakly nucleophile gives ethyl pyrrol-l-yl)propanoate 145 in moderate yield <2005TL3279>. 

Scheme 16.6. Construction of the FGHI rings of azaspiracid-1 using a double intramolecular hetero-Michael addition (Forsyth 2001).

Nakamura, S., Inagaki, J., Kudo, M., Sugimoto, T, Ohara, K., Nakajima, M. and Hashimoto, S., 2002. Studies directed toward the total synthesis of pinnatoxin A synthesis of the 6,5,6-dispiroketal (BCD ring) system by double hemiketal formation/hetero-Michael addition strategy. Tetrahedron 58, 10353-10374. 

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. ... 

Enders, D., Bettray, W., Schankat, J., Wiedemann, J. Diastereo- and enantioselective synthesis of P-amino acids via SAMP hydrazones and hetero Michael addition using TMS-SAMP as a chiral equivalent of ammonia. Enantioselective Synthesis of/T-Amino Acids 1997,187-210. 

Enders, D. TMS-SAMP. Novel chiral hydrazine auxiliary for hetero-Michael additions and aza-Peterson olefinations. Acros Organics Acta 1995, 1, 37-38. 

Ramirez, M. A., Padron, J. M., Palazon, J. M., Martin, V. S. Stereocontrol led Synthesis of Cyclic Ethers by Intramolecular Hetero-Michael Addition. 6. A Computational Study of the Annelation to 2,3-Disubstituted Tetrahydropyrans. J. Org. Chem. 1997, 62, 4584 590. 

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). 

FIGURE 3.7. Hetero-Michael additions using moderately strong bases... 

Under thermal activation conditions, ester 161 reacts with benzylamine to give a mixture of a-amino-p,y-unsaturated ester 164 and amide 165, but under 1.1 GPa pressure ester 161 gives the spiro-aziridines 162 and 163 in high yield and good diastereoselectivity. These are part of an attractive class of compounds that are formed by hetero-Michael addition of amine onto the unsaturated ester 161, followed by intramolecular nucleophilic substitution of the bromine atom (Scheme 7.41). ... 

Takagi, R., Sasaoka, A., Kojima, S., and Ohkata, K., Stereoselectivity in the formation of 2,5-disubstituted tetrahydropyrans by intramolecular hetero-Michael addition, Heterocycles, 45, 2313, 1997. 

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. 

The hetero-Michael addition of 2,4-dihydropyrazol-3-one 422a-h to trichloro-acetaldimine derivatives 423a-h takes place best in apolar aprotic solvents and the... 

The hetero-Michael addition of 0-alkylthiocarbamates 85 to 1,2-diaza-l,3-butadienes 84 followed by cyclization of the adduct 86 provides a direct approach to 2-alkyliminothiazolines 88 <04SL1643>. 

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