Homo-Michael additions

Addition of halogens and pseudohalogens to the cyclopropylthiocarbene chromium complexes 122 affords the 1,4-dihalo-1-phenylthio-l-alkenes 123 stereoselectively [65]. Electrophilic halogen is likely to activate the carbene complexes, followed by the homo-Michael addition of halide anion. (Scheme 44)... 

Therefore acceptor cyclopropanes 1 will be ring opened by nucleophiles N to provide products like 2 (homo Michael addition) as depicted in Eq. 1. On the other hand, electrophiles E+ cleave donor activated cyclopropanes 3 affording adducts 4 or 5 which demonstrates that the cyclopropane serves as a homoenolate equivalent in this sequence (Eq. 2). Seebach consequently classified these methods as umpolung with the cyclopropane trick 4. ... 

Most frequently, cuprates or other C-nucleophiles are employed in homo-Michael additions which often serve as the basic reactions for constructing natural product skeletons The preparation of optically active compounds also profits from this type of... 

The preceding sections have shown that cyclopropanes with electron-withdrawing groups are very susceptible to the cleavage of the proximal bond by S- and O-nucleophiles. Thus, C-nucleophiles can be expected to react in a similar fashion and give rise to the formation of homo-Michael addition products. 

The cyanide anion is a powerful nucleophile. When methyl 2-oxobicyclo[3.1.0]hexane-l-carboxylate (1) was treated with sodium cyanide in dimethylsulfoxide, the 3-cyanomethylpen-tanone derivative 2 was obtained in 69% yield.With 2-hydroxy-2-methylpropanenitrile in methanol, dimethyl 3-cyanomethylhexane-l,4-dioate (3) was isolated as the sole product. Its formation involved nucleophilic opening of both rings by a homo-Michael addition and the reversal of an ester condensation. 

The maleimide group can undergo a variety of chemical reactions. The reactivity of the double bond is a consequence of the electron withdrawing nature of the two adjacent carbonyl groups which create a very electron-deficient double bond, and therefore is susceptible to homo- and copolymerizations. Such polymerizations may be induced by free radicals or anions. Nucleophiles such as primary and secondary amines, phenates, thiophenates, carboxylates, etc. may react via the classical Michael addition mechanism. The maleimide group furthermore is a very reactive dienophile and can therefore be employed in a variety of Diels Alder reactions. Bisdienes such as divinylbenzene, bis(vinylbenzyl) compounds, bis(propenylphenoxy) compounds and bis(benzocyclobutenes) are very attractive Diels Alder comonomers and therefore some are used as constituents for BMI resin formulations. An important chemical reaction of the maleimide group is the ENE reaction with allylphenyl compounds. The most attractive comonomer of this family is DABA particularly when tough bismaleimide resins are desired. 

HOMOCONJUGATE ADDITION, 66 Homo-Michael acceptor, 69 Hydrogen peroxide-acetonitrile, 63 4-Hydroxy-2-butanone, 93... 

HOMOCONJUGATE ADDITION, 60, 66 Homo-Michael acceptor, 60, 69 Hydrazine hydrate, 61, 17 Hydrazine monohydrate [7803-57-8], 61, 17 HYDROC1NN AM ALDEHYDE, a-METHYL-, 61,82... 

Reaction of monosubstituted hydrazines with the readily available spirocyclic cyclo-propanedicarboxylates (163) gives 1-substituted l,4,5,6-tetrahydropyridazin-3(2/i)-ones (164) in a one-pot reaction (Scheme 123). Initial attack is thought to be a homo-Michael type of addition by the substituted hydrazine nitrogen decarboxylation occurs under the reaction conditions. The formation of the alternative pyridazinone (165) by attack of the unsubstituted hydrazino nitrogen was only observed (<5%) with (4-chloro-2-methylphenyl)hydrazine <93H(36)219>. 

Another pioneer in the Diels-Alder reactions of vinylpyrroles was Noland, who also developed the reactions of vinylindoles to yield carbazoles. Some examples of the former are shown in Scheme 2 (equations 1 and 2) [4-7], Jones and his colleagues were equally active in this cycloaddition chemistry of vinylpyrroles (equations 3 and 4) [8-12], These workers measured the rates of the reaction between 1-methyl-2-vinylpyrrole and seven dienophiles, with maleic anhydride being 4800 to 50,000 times more reactive than the other dienophiles (DMAD, maleonitrile, fumaronitrile, dimethyl maleate, methyl acrylate, and acrylonitrile) [8], In a clever tactic to thwart the formation of dihydroindoles, Jones used an excess of methyl propio-late to convert the initial adduct to a second Diels-Alder cycloadduct that subsequently loses ethene by a retro-Diels-Alder reaction to afford the dimethyl 1-methyl (phenyl)-4,7-dicarboxylates (equation 4). The reactions are concerted and were consistent with FMO calculations (HOMO[vinylpyrrole]-LUMO[alkene]). The yields are 54% to 81%, but attempts to dehydrogenate the tetrahydroindole products to indoles were unsuccessful. 2-Vinylpyrrole itself undergoes Michael additions and polymerization with these dienophiles. Domingo, Jones, and coworkers subsequently... 

The double bond of the itialeimide is very reactive. Grundschober first reported their homo and copolymerization which can be achieved by simply heating the monomer to temperature between 150-400°C. It can also undergo a chain extension reaction with primary and secondary amino compounds, known as Michael addition, which is used to synthesize a well-known commercial resin, Kerimid 601 of Rhone Poulenc, by reacting 4,4 - bismaleimidodiphenylmethane with methylene dianiline to form a po1yaminobisma1eimide[9]. 

Scheme 9.10 Thiol-Michael addition on exo-ONBEs and their use homo and copolymerization via ROMP [49].

We decided to evaluate our hypothesis with readily available substrates having a tethered enone to the starting aldehyde in order to maximize the chances of bond formation (Scheme 18) [141]. After screening for reactimi conditicms, we found that the use of 10 mol% of azolium salt 7 in the presence of DBU was the most efficient combination to promote the reaction and afford 3,4-dihydrocoumarins structures in high yield. The reaction was performed in acetonitrile at low cmicentration to prevent homo-aldol coupling. In this process, acylation of the alkoxide followed by intramolecular Michael addition was a plausible pathway, but it was ruled out after subjecting the acylated substrate to the reaction conditimis, which was found to be mneactive. 

The reaction of 2,5-anhydro-3,4-0-isopropyIidene-DL-allose (450) (see Vol. 9, p. 22) with ethyl triphenylphosphoranylidene pyruvate at 90 °C gave the internal Michael-addition product (451) via the a)S-unsaturated ketoester formed in the Wittig reaction. Homo-C-nucleosides (452) containing 6-azauracil or 4-hydroxy-5-carboxamidopyrazole were elaborated from (451). Details of an earlier synthesis of the racemic hemiacetal (454), a precursor of carbocyclic C-nucleosides, have been published, together with an improved synthesis of (454) via the lactone (453) part of this route is outlined in Scheme 87. Condensation of the lactone... 

The [3+2] cycloaddition reaction with indoles developed by Kerr and co workers led to the belief that cyclopropanes had a very similar reactivity to a,p-unsaturated carbonyl moieties in their ability to react with nucleophiles in a homo-Michael type addition. Hence, the use of substituted cyclopropanes as precursors for cycloaddition reactions has become very popular due to their ability to undergo ring-opening while in the presence of a Lewis acid. 

A variety of a-spirolactones and lactams from 2-diazo-l,3-dicarbonyl compounds, (homo)allylic alcohols or amines and acrylic derivatives, in a single synthetic operation by a Wolff rearrangement/a-oxo ketene trapping/cross metathesis/ intramolecular Michael addition sequence has been obtained by Boddaert et al. (2011). 

The cycloaddition of azides to multiple -ir-bonds is an old and widely used reaction. Organic azides are well known to behave as 1,3-dipoles in thermal cycloaddition reactions.178 The first example of this reaction was observed by Michael in 1893.179 Since then the addition of azide to carbon-carbon double and triple bonds has become the most important synthetic route to 1,2,3-triazoles, -triazolines and their derivatives.180-184 The cycloadditions of simple organic azides with electron-rich dipolarophiles are LUMO controlled.3 Since the larger terminal coefficients are on the unsubstituted nitrogen in the azide and unsubstituted terminus in the dipolarophiles, the 5-substituted A2-triazolines are favored, in agreement with experiment.185-187 Reactions with electron-deficient dipolarophiles are HOMO controlled, and... 

Another route to the synthesis of aldosterone using D-homo derivatives as intermediates has been studied by SzpilfogePs group [738-742] (Scheme 67). The formylation of ketone (67) and its use in the Michael reaction with the participation of acrolein led to the dialdehyde (140), which was selectively acetylated at C21 and oxidized at Cjg to give the lactone (141). The subsequent path of the synthesis consisted in the addition of a side chain at C14 by reaction with ethoxyethynyllithium in this case, the use of ethoxyethynylmagnesium bromide led to products containing halogen. 

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