Michael’s reaction

Mononitro, C.H.NOand Dinitrocrotonic Acid, C H N-O,. derivs were not found in Beil or in CA thru 1961 Derivs of 4,4-Dinitrocrotonic Acid or 4,4-Dinitrobutene-2-oic Acid were prepd from nitroform by the Michael s reaction in non-alka-line media (Ref)... 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

A reaction related to the Michael addition reactions of enamines to unsaturated esters, which leads to S-ketoesters, is the reaction with 1-carb-ethoxy-l-cyanocyclopropane (318). This gives access to ketones substituted with the next higher homologous acid chain. 

Feringa s group has demonstrated that cyclopentene-3,5-dione monoacetals as 2-47 can also be successfully applied as substrates in an asymmetric three-component domino Michael/aldol reaction with dialkyl zinc reagents 2-48 and aromatic aldehydes 2-49 [17]. In the presence of 2 mol% of the in-sitw-generated enantiomeri-cally pure catalyst Cu(OTf)2/phosphoramidite 2-54, the cyclopentanone derivatives 2-51 were formed nearly exclusively in good yields and with high ee-values (Scheme 2.11). 

Ley SV, Baxendale IR (2002b) New tools and concepts for modern organic synthesis. Nat Rev Drug Disc 1 573-586 Ley S V, Massi A (2000) J Comb Chem Polymer supported reagents in synthesis preparation of bicyclo[2.2.2]octane derivatives via tandem michael addition reactions and subsequent combinatorial decoration. 2 104—107 Ley SV, Schucht O, Thomas AW, Murray PJ (1999) Synthesis of the alkaloids ( )-oxomaritidine and ( )-epimaritidine using an orchestrated multi-step sequence of polymer supported reagents. J Chem Soc Perkin Trans 1 1251— 1252... 

Other reactions involving the addition of carbanions are reactions like Perkin s reaction, Claisen condensation, benzilic acid rearrangement and Michael addition. 

An accessory proposal was Arthur Michael s hypothesis that many reactions proceed by addition, for example, a polymerization of acetaldehyde (CH3CH = O) in the presence of bases (OH) to an aldol (CH3CHOHCH2CHO), with subsequent loss of water to form crotonaldehyde (CH3CH = CHCHO). Michael, educated in America, Germany, and France, made use of Kekule s idea that two molecules may form a "polymolecule" or molecular compound, which, in turn breaks up to yield the final products.33 Lachman expressed fairly standard misgivings about this proposal of an intermediary and transition form "If we are going to explain reactions by means of addition products which we do not or cannot isolate, our explanation loses its definiteness. It becomes simply a possible explanation, and its conclusions are by no means binding."34... 

In the Michael addition reaction of (S )-phenylethylamine and L-alanine isopropyl ester to [Pg.444]

The stereochemical outcome of the Michael addition reaction with substituted starting materials depends on the geometry of the Q, /S-unsaturated carbonyl compound as well as the enolate geometry a stereoselective synthesis is... 

Before the blowpipe on charcoal it melts in a strong heat, turns white. on the surface, and deposits a fixed sublimate of binoxide of tin round the assay. After roasting, it affords, with the usual fluxes, the peculiar reactions of iron and copper, and a brittle globnleof the latter metal on fluxing, with soda and borax. Nitric acid decomposes it, dissolving the iron and copper, and leaving a deposit of sulphur and of bin-oxide of tin. The following analyses indicate the composition of a few samples of this ore samples A and b from Hucl Bock . 0 from St. Michael s Mount, and d from Zinnwald —... 

The resulting tetraethyl ester on hydrolysis and decarboxylation yields propane-1, 2,3-tricarboxylic acid.155 In this example the malonate anion is generated by using one molar proportion of sodium ethoxide this is Michael s original method. However, these conditions sometimes lead to competing side reactions and the formation of abnormal reaction products. Better yields of the required product are often obtained with small amounts of sodium ethoxide (the so-called catalytic method) or in the presence of a secondary amine (e.g. diethyl-amine, see below). 

When the 5-position of the pyrrole ring is substituted, as in 1,5-dimethyl-2-vinylpyrrole 242, or when there is a substituent on the TV-ring (Ph) as in compound 20b, the Michael type reaction is sterically inhibited at the 5-position. A 1 2 adduct, 243, was formed as a result of an initial [4 + 2]-cycloaddition followed by a further ene reaction with a second molecule of DEAZD [85JCR(S)12]. 

Significant rate acceleration of metal-catalysed Michael addition reactions of fi-dicarbonyls to a,/S-enones in water was observed upon addition of dibasic ligands. Ytterbium triflate and TMEDA was the most effective combination leading to a nearly 20-fold faster reaction than in the absence of ligand.148... 

Trialkylammonium salts of the N-unsubstituted tetrazoles 231 are equally applicable as substrates in reactions both with haloalkyls and unsaturated compounds. These reactions, as already mentioned, lead mainly to formation of Nz-isomers. For instance, the reaction of 5-phenyltetrazole triethylammonium salt 231 (generated in situ from 5-phenyltetrazole and triethylamine) in acetonitrile with y-bromobutyronitrile (alkylation) or with acrylonitrile (Michael s method) afforded the corresponding Nz-substituted derivatives 254 and 255 in acceptable yields (Scheme 26) <2002CHE986>. 

In contrast with previous reports, Sodeoka s reaction conditions were applicable to a variety of /8-ketoesters (Scheme 2) [5]. With the Pd aqua complex 3, the Michael adducts were obtained in high yield with high enantioselectivity. For example, the reaction of the /8-ketoester 4 with less reactive /3-substituted enones such as 3-penten-2-one proceeded smoothly to give 5 in 99 % ee. In this reaction, catalytic asymmetric construction of the highly crowded vicinal tertiary and quaternary carbon centers was achieved in one step. Furthermore, the reaction of 1,3-diketones with enones was successfully performed, and the desired triketone 6 was obtained in good yield and with 90 % ee. In contrast, conventional basic conditions (tertiary amines, alkoxides, or ammonium hydroxides) gave complex mixtures, probably because of the instability, under the basic conditions, of the triketone produced. This result clearly indicates that the reaction using the Pd aqua complex 3 is quite mild. 

The resulting chiral organometallic materials were used as catalysts in the Michael addition reaction of methyl vinyl ketone to (R/S)-ethyl a-iso-cyanopropionate, and after 24 h a conversion of 63% was obtained as compared to 80% conversion observed for the covalently immobilized [PtI(NCN-COOK)]. As for the latter, no chirality transfer was observed (see Sect. 2). 

It is interesting that Walden s work (Ingold, 1953) on substitution reactions and Michael s work on addition-elimination appeared at the same time. By 1912, Frankland could sense that trans processes and the Walden inversion (equations 4b, d) were related, and an underlying explanation would eventually be found for both. 

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