Michael addition metal catalysis

Addition of HCN to unsaturated compounds is often the easiest and most economical method of making organonitnles. An early synthesis of acrylonitrile involved the addition of HCN to acetylene. The addition of HCN to aldehydes and ketones is readily accompHshed with simple base catalysis, as is the addition of HCN to activated olefins (Michael addition). However, the addition of HCN to unactivated olefins and the regioselective addition to dienes is best accompHshed with a transition-metal catalyst, as illustrated by DuPont s adiponitrile process (6—9). 

During the coverage period of this chapter, reviews have appeared on the following topics reactions of electrophiles with polyfluorinated alkenes, the mechanisms of intramolecular hydroacylation and hydrosilylation, Prins reaction (reviewed and redefined), synthesis of esters of /3-amino acids by Michael addition of amines and metal amides to esters of a,/3-unsaturated carboxylic acids," the 1,4-addition of benzotriazole-stabilized carbanions to Michael acceptors, control of asymmetry in Michael additions via the use of nucleophiles bearing chiral centres, a-unsaturated systems with the chirality at the y-position, and the presence of chiral ligands or other chiral mediators, syntheses of carbo- and hetero-cyclic compounds via Michael addition of enolates and activated phenols, respectively, to o ,jS-unsaturated nitriles, and transition metal catalysis of the Michael addition of 1,3-dicarbonyl compounds. ... 

Our own group is also involved in the development of domino multicomponent reactions for the synthesis of heterocycles of both pharmacologic and synthetic interest [156]. In particular, we recently reported a totally regioselective and metal-free Michael addition-initiated three-component substrate directed route to polysubstituted pyridines from 1,3-dicarbonyls. Thus, the direct condensation of 1,3-diketones, (3-ketoesters, or p-ketoamides with a,p-unsaturated aldehydes or ketones with a synthetic equivalent of ammonia, under heterogeneous catalysis by 4 A molecular sieves, provided the desired heterocycles after in situ oxidation (Scheme 56) [157]. A mechanistic study demonstrated that the first step of the sequence was a molecular sieves-promoted Michael addition between the 1,3-dicarbonyl and the cx,p-unsaturated carbonyl compound. The corresponding 1,5-dicarbonyl adduct then reacts with the ammonia source leading to a DHP derivative, which is spontaneously converted to the aromatized product. 

The advancements in supramolecular catalysis are not limited to transitions-metal catalyzed reactions. Clarke and coworkers recently reported the preparation of a library of organocatalysts and their application in the asymmetric Michael addition of ketones to nitroalkenes [37]. They proposed use of a supramolecular catalyst formed... 

Enolase type activity is displayed in the efficient supramolecular catalysis of H/D exchange in malonate and pyruvate bound to macrocyclic polyamines [5.32]. Other processes that have been studied comprise for instance the catalysis of nucleophilic aromatic substitution by macrotricyclic quaternary ammonium receptors of type 21 [5.33], the asymmetric catalysis of Michael additions [5.34], the selective functionalization of doubly bound dicarboxylic acids [5.35] or the activation of reactions on substituted crown ethers by complexed metal ions [5.36]. 

Aziridines can add to carbon—carbon multiple bonds. Elevated temperature and alkali metal catalysis are required in the case of nonpolarized double bonds (193—195). On the other hand, the addition of aziridines onto the conjugated polarized double or triple bonds of a,p-unsaturated nitriles (196—199), ketones (197,200), esters (201—205), amides (197), sulfones (206—209), or quinones (210—212) in a Michael addition-type reaction frequendy proceeds even at room temperature without a catalyst. The adducts obtained from the reaction of aziridines with a,p-unsaturated ketones, eg, 4-aziridinyl-2-butanone [503-12-8] from 3-buten-2-one, can be converted to 1,3-substituted pyrrolidines by subsequent ring opening with acyl chlorides and alkaline cyclization (213). 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Table 5) [28], and heteroatom Diels-Alder reactions (Sch. 50) [79,80] but no X-ray structure had ever been reported for it or for the 3,3 -disubstituted derivatives which were first introduced as an asymmetric Claisen catalyst [24-27]. Although compound 435 was found not to induce any reaction between cyclohexenone and phosphonate 425 under the standard conditions for catalyst 428, consistent with the proposed equilibrium of species 394, 431, 432, 433, and 434 is the finding that catalysis of the reactions between cyclohexenone or cyclopentenone and phosphonate 425 with a 2 1 mixture of 434 (M = Li) and 435 gave only the Michael adducts 426 and 427 in 96 % ee and 92 % ee, respectively. Because 394 and 432 are inactive catalysts and 434 results in much lower induction and some 1,2-adduct, it was proposed that the active catalyst in the Michael addition of phosphonate 425 to cyclohexenone was the species 431 resulting from association of ALB catalyst with a metal alkoxide. It was proposed that the stereochemical determining step involved intramolecular transfer of the enolate of 425 to the coordinated cyclohexenone in species 436. 

Reaction of Aniline with Organic Functional Groups. In the absence of catalysis by enzymes or metals, aniline undergoes nucleophilic addition reactions to quinone and other carbonyl groups in humic substances to form both heterocyclic and nonheterocyclic condensation products (9). In aqueous solution, aniline undergoes 1,4-addition (Michael addition) to both 1,2- and 1,4-quinones (10-14). The reaction of aniline with 1,4-benzoquinone, from the oxidation of hydroquinone, and with 4-methyl-1,2-quinone, from the oxidation of 4-methylcatechol, are illustrated here. 

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

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