Michael addition process

Scheme 2.124. Domino elimination/twofold Michael addition process.

A retro-Michael addition process leading to an aminomethyl-dihydrodipyridopyra-zine analogue was described by Guillaumet and coworkers in the context of prepar-... 

Compound 388 is an acylating agent for electron-deficient alkenes, in a Michael addition process. It is formed by treating molybdenum hexacarbonyl with an organolithium compound, followed by quenching the intermediate 387 with boron trifluoride (equation 104). The structure of 388 (R = Ph) can be elucidated by NMR spectroscopy. Other examples of enantioselective and diastereoselective Michael-type additions involving lithium-containing intermediates in the presence of chiral additives can be found elsewhere in the literature . 

The a, jfl-unsaturated component for a Michael reaction may be formed in situ by an initial Knoevenagel reaction. An example is provided by the formation of tetraethyl propane-1,1,3,3-tetracarboxylate (14) from formaldehyde and diethyl malonate in the presence of diethylamine. Diethyl methylenemalonate (13) is first formed by the simple Knoevenagel reaction and this is followed by the Michael addition process. 

Convenient reagent equivalents could be a nitroalkane (for the acyl anion syn-thon, p. 627), and acrolein or an acrylic ester (for the carbocation). The reaction would then be a Michael addition process (Section 5.11.6, p. 681), followed by functional group modification (e.g. C—N02 to 0=0, p. 599, and CHO to C02H, p. 667). 

The Aspidosperma family of indole alkaloids has inspired many synthetic strategies for the construction of their pentacyclic framework of the parent compound aspidospermidine (366), since the initial clinical success of two derivatives, vinblastine (10) and vincristine, as anticancer agents. The alkaloids such as (-)-rhazinal (369) and (-)-rhazinilam (6) have been identified as novel leads for the development of new generation anticancer agents [10,11]. Bis-lactams (-)-leucunolam (370) and (-t-)-epi-leucunolam (371) have bio-genetic and structural relationships with these compounds [236]. Recently, enantioselective or racemic total syntheses of some of the these natural product were achieved. One successful synthesis was the preparation of the tricyclic ketone 365, an advanced intermediate in the synthesis of aspidospermidine (366), from pyrrole (1) (Scheme 76) [14]. The key step is the construction of the indolizidine 360, which represents the first example of the equivalent intramolecular Michael addition process [14,237,238]. The DIBAL-H mediated reduction product was subject to mesylation under the Crossland-... 

Reaction of 3-bromo-7-azabicyclo[2.2.1]hepta-2,5-dienecarhoxylic esters 1229 with 2-amino- or 2-aminomethyl-anilines 1230 produces r-5-(benzimidazol-2-yl)pyrroline-2-acetic acid esters 1231 from a double Michael addition process. Substituents on the nitrogen atoms or in the aromatic ring are tolerated as long as they do not strongly reduce the nucleophilicity of the nitrogen atoms (Scheme 307) <2005S2357>. 

Conjugate additions. Formation of P-aminonitriles and 1,5-dicarbonyl compounds by the Michael addition processes are mediated by InC. ... 

In the Michael addition to 26, Connor and Ross reported the isolation of the cis counterpart 11 besides the main tram acid 27 [63]. Later, there was no mention of the formation of the cis product [40, 41]. The present author has repeated the Michael addition process several times, but has never observed the presence of c/s-2-ACPC. 

This type of acyclic nucleoside could be prepared by a Michael addition process. Thus, when 2-amino-6-chloropurine was reacted with 485, and 8 1 mixture of the N-9 (486) and N-7 cyclopropylpurines was produced. When the chloroethylidene malonate was used, the ratio became 40 1. Catalytic hydrogenation of 486 in presence of base effected both dehalogenation and 1,2-cyclopropane bond fission to provide 487. Its reduction and acetylation gave Famciclovir 488 (91EUP420559 92TL4609). 

Transition metal enolate complexes have been prepared with most or all transition metals, and the enolate ligands have been shown to adopt a variety of bonding modes. Bofli early and late transition metal enolate complexes are intermediates in a number of important catalytic processes. Early transition metal enolates are important intermediates in asymmetric aldol reactions that exploit the Lewis acidic character of early metals. Late transition metal enolates are intermediates in aldol and Michael addition processes, -Saegusa oxidations,Heck-type processes, catalytic asymmetric conjugate additions, - and cross coupling of enolate nucleophiles. - ... 

An intramolecular retro-Michael/Michael addition process can also cause racemization. For example, the thioester of 3-aryl-4,5-dihydroisoxazol-5-ylacetic acid can be hydrolysed by lipase in the presence of amine, giving the corresponding acid with 98% ee quantitatively (Scheme 5.39) [112]. Equihbrium between the enol(ate) and the enone/oxime anion intermediates has been proposed to explain this reaction. 

As a Lewis Acid. CuCl induces photoreaction of conjugated enones with sUyl enol ethers through a Michael addition process, addition of amines to unactivated nitriles" and... 

Collard, S. and Keep, A. (2003) Synthesis of 3-substituted isoindolin-l-ones via a palladium-catalysed 3-component carbonylation/amination/Michael addition process. Tetrahedron Letters, 44, 7441-7443. 

Formulate a detailed mechanism for the Michael addition process just depicted. Why is the base required in only catal3rtic amounts ... 

Tian and Lin disclosed a Rh(III)-catalyzed arylative cyclization reaction of 1,6-enynes with JV-(pivaloyloxy)benzamides for the synthesis of a new type of tetracyclic isoquinolones 76 in quantitative yields [39]. Product formation fully depends on the O-substituted JV-hydroxybenzamide substrate. For example, treatment of A/ -(pivaloyloxy)benzamide with 1,6-enynes in the presence of acetone afforded polycycUc products 76 by a Michael addition process (Eq. (5.74)), whereas the treatment of A/ -(methoxy)benzamide did not afford the Michael addition product. 

Another example of the use of thiourea catalysts in total synthesis was reported by You and coworkers, who obtained (-)-mesembrine by means of an organocata-lyzed aza-Michael addition process (Scheme 44.8) [86]. The crucial step in this route is based on a previous study of the desymmetrization of cydohexadienones performed by the same research group [87]. On this occasion, the difficult task of controlling the sterically congested chiral arylated quaternary carbon center was... 

Wang et al. [53] have reported the synthesis of a new primary-secondary diamine catalyst containing a long alkyl chain and its application to the Michael addition of malonates to a,b-unsaturated ketones in water which was not successful earlier. This asymmetric Michael addition process was found to be effective... 

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