Homo-Michael reaction

The first diastereoselective synthesis of methyl (3R,7R)-jasmonate is attributed to Gerhard Quinkert. [94] In the initial step, starting from bis-(8-phenyhnen-thyl) malonate, a vinylcydopropane is constructed. After removal of the chiral auxiliary, the cyclopentanone is built up by means of a domino homo-Michael reaction / Dieckmann cydisation. Attack of dimethyl pent-2-ynylmalonate leads to inversion at the stereogenic centre at the vinyl cyclopropane. After decarboxylation, the vinyl residue is transformed into an ester group and the triple bond hydrogenated with a Lindlar catalyst. 

Th is amounts formally to a homo-MIchael reaction, for which there Is abundant precedent In the literature concerning simple cyclo-propylcarbonyl compounds. [234]... 

T. Hiyama, Y. Morizawa, H. Yamamoto, H. Nozaki, Bull. Soc. Chem. pn. 54 (1981) 2151 (with organoaluminium compounds) E. J. Enholm, Z. J. Jia, J. Org. Chem. 62 (1997) 9159 (with organotin compounds) P. Herrington, M. A. Kerr, Tetrahedron Lett. 38 (1997) 5949 (lanthanoid-catalysed homo-Michael reactions). 

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... 

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>. 

In 2002, the Barbas group reported the first example of a self- Diels-Alder reaction or double Michael reaction of a,(3-unsaturated ketones providing access to acyl-substituted cyclohexanones. This reaction employed a combination of enamine and iminium ion chemistry, allowing for the HOMO and LUMO orbital to be raised and lowered respectively, promoting reactivity. Using L-proline, the ketone undergoes a self-Diels-Alder reaction, and produces access to exo.endo products in moderate yields and modest diastereoselectivities (Scheme 5.35). 

As mentioned, the applications of chiral secondary amines in domino processes have been numerous, mainly because of the dual mechanism of activation allowing easy incorporation of other reactions [7, 8]. The first of these processes involves an iminium-enarnine (Scheme 7.1a), and the second an enamine-iminium activation (Scheme 7.1b), both of which can be in operation in domino reactions involving Michael reactions. These modes of action rely on the lower energy lowest unoccupied molecular orbital (LUMO) for the iminium ion and a rise in the highest occupied molecular orbital (HOMO) energy for enamine activation, which are discussed in further detail in Chapter 10 of this book [9, 10]. In the... 

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. 

An attempt has also been made to form ring D from Sarett s ketone (67) by cyclizing 14,16-diketones to D-homo derivatives [761] (Scheme 69). On undergoing the Michael reaction in an anhydrous medium, the oxalyl and formyl derivatives (168) R = C02Et and R = H, respectively) of the initial ketone (67) formed, with the axial entry of the side chain, compounds with the 13q -configuration of the angular substituent (169) which shows the unsuitability of these products for the formation of 11,18-cyclohemiacetals. The cyclization of (169) under mild conditions gave the spirane derivatives... 

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. 

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. 

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... 

The Morita-Baylis-Hillman reaction is, in general, a carbon-carbon bondforming reaction of an a,(3-unsaturated compound with an aldehyde mediated by an organic nucleophilic base resulting in the formation of an allylic alcohol. Morita reported the use of a phosphine as catalyst and Baylis and Hillman used a tertiary amine. Variation of the electrophile to electron-deficient alkenes in a Michael-Michael elimination sequence leads to homo- and heterodimerisation and is known as the Rauhut-Currier reaction. The electrophilic aldehyde could be substituted by an imine or derivative in the aza-Morita-Baylis-Hillman reaction. Recently, there has been an increase in the use of this reaction for the construction of many different targets using many different amine derived catalysts. Scheme 2.2 shows a general view of this reaction and the accepted mechanism. ... 

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]. 

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