Michael reductive

The heterocyclic spiro-oxindole moiety is found in a large number of alkaloids, which are important pharmaceutical compounds [44]. Several synthetic protocols are reported in the literature for the synthesis of these compounds [45]. Recently, Tao et al. [46] developed a direct asymmetric domino Michael/reduction/cychzation sequence for the construction of spiro[2H-pyran-3,4 -indohne] 99 from isatyhdene malononitrile 97 and acetone 98 in the presence of the chiral compound 100 (Scheme 9.20). 

Scheme 9.20 One-pot domino Michael/reduction/cyclization synthesis of spiro-oxindole.

To meet the needs of the advanced students, preparations have now been included to illustrate, for example, reduction by lithium aluminium hydride and by the Meerwein-Ponndorf-Verley method, oxidation by selenium dioxide and by periodate, the Michael, Hoesch, Leuckart and Doebner-Miller Reactions, the Knorr pyrrole and the Hantzsch collidine syntheses, various Free Radical reactions, the Pinacol-Pinacolone, Beckmann and Arbusov Rearrangements, and the Bart and the Meyer Reactions, together with many others. 

Mccrwein-Pormdorf-Verley reduction Michael reaction Oppenauer oxidation... 

Acetoxy-l,7-octadiene (40) is converted into l,7-octadien-3-one (124) by hydrolysis and oxidation. The most useful application of this enone 124 is bisannulation to form two fused six-membered ketonesfl 13], The Michael addition of 2-methyl-1,3-cyclopentanedione (125) to 124 and asymmetric aldol condensation using (5)-phenylalanine afford the optically active diketone 126. The terminal alkene is oxidi2ed with PdCl2-CuCl2-02 to give the methyl ketone 127 in 77% yield. Finally, reduction of the double bond and aldol condensation produce the important intermediate 128 of steroid synthesis in optically pure form[114]. 

The method was applied to the synthesis of (-t-)-l9-nortestosterone by the following sequence of reactions. Michael addition of the bisannulation reagent 124 to the optically active keto ester 129 and decarboxylation afforded 130, and subsequent aldol condensation gave 131. Selective Pd-catalyzed oxidation of the terminal double bond afforded the diketone 132 in 78% yield. Reduction of the double bond and aldol condensation gave ( + )-19-nortestosterone (133)[114]. 

Addition Reactions. The addition of nucleophiles to quinones is often an acid-catalyzed, Michael-type reductive process (7,43,44). The addition of benzenethiol to 1,4-benzoquinone (2) was studied by A. Michael for a better understanding of valence in organic chemistry (45). The presence of the reduced product thiophenyUiydroquinone (52), the cross-oxidation product 2-thiophenyl-1,4-benzoquinone [18232-03-6] (53), and multiple-addition products such as 2,5-(bis(thiophenyl)-l,4-benzoquinone [17058-53-6] (54) and 2,6-bis(thiophenyl)-l,4-benzoquinone [121194-11-4] (55), is typical ofmany such transformations. 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

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... 

The Y appendage of 2-cyclohexenone 191 cannot be directly disconnected by an alkylation transform. (y-Extended enolates derived from 2-cyclohexenones undergo alkylation a- rather than y- to the carbonyl group). However, 191 can be converted to 192 by application of the retro-Michael transform. The synthesis of 192 from methoxybenzene by way of the Birch reduction product 193 is straightforward. Another synthesis of 191 (free acid) is outlined in... 

Vinylogous amides undergo reduction with lithium aluminum hydride, by Michael addition of hydride and formation of an enolate, which can resist further reduction. Thus -aminoketones are usually produced (309, 563,564). However, the alternative selective reduction of the carbonyl group has also been claimed (555). 

At least two pathways have been proposed for the Nenitzescu reaction. The mechanism outlined below is generally accepted." Illustrated here is the indolization of the 1,4-benzoquinone (4) with ethyl 3-aminocrotonate (5). The mechanism consists of four stages (I) Michael addition of the carbon terminal of the enamine 5 to quinone 4 (II) Oxidation of the resulting hydroquinone 10 to the quinone 11 either by the starting quinone 4 or the quinonimmonium intermediate 13, which is generated at a later stage (HI) Cyclization of the quinone adduct 11, if in the cw-configuration, to the carbinolamine 12 or quinonimmonium intermediate 13 (IV) Reduction of the intermediates 12 or 13 to the 5-hydroxyindole 6 by the initial hydroquinone adduct 7 (or 8, 9,10). 

Thus, condensation of isoniazide with acetone at the basic nitrogen gives the corresponding Shiff base (8). Catalytic reduction affords the antidepressant, iproniazid (9). Addition of the same basic nitrogen to methyl acrylate by Michael condensation leads to the 3-amino ester (10). This is converted to the amide, nialamide (11), on heating with benzylamine. 

Aldol condensation of the methoxymethyl ether of m-methoxybenzaldehyde (83) with cyclohexanone affords the conjugated ketone 84. Michael addition of dimethyl amine leads to the ami noketone Reduction of the ketone... 

The Michael adclidon of a nitrogen-centered nucleophile to nitroalkenes affords compounds that may serve as precursors of vicinal chamines, since the nitro group can be reduced to an amino function by reduction The very convenient method for the preparation of 1,2-chamines is developed by the adchdon of O-ethyihydroxylamines to nitroalkenes followed by redncdon with H-, in the presence of PckC fEq 4 24 ... 

The Michael addition of nitro compounds to ct,fi-unsatiirated ketones or esters followed by reduction of the nitro to amino group is useful for the preparation of various heterocycles This is presented in Chapter 10 (Symhesis ofHatarocyclas). 

The hydrogenation in the presence of Pd/G is also effective for the d compounds to amines. The Michael addition of nitromethime to 2-alkenoic esters followed by catalytic hydrogenation using 10% Pd/G in acetic acid md hydrolysis is a convenient method for the preparation of 3-alkyl-4-aminobut moic acids, which are importimt y-amino acids for biological snidy fEq. 6.48. The reduction c m be carried out at room temperanire md atmospheric pressure. 

The Michael dclclidon of nitro ilkdnes to a,fi-unsdnirdted ketones gives Y-nitroketones, which re convetted into pyrroles by reduction of the nitro group with and PhSSPh fEq. 10.2. ... 

Battersby and coworkers have developed selective methods for total synthesis of chlorins on a model system, as shown in Scheme 10.15, in which the Michael addition of 5-f3-nittoethyl pyrrole to enone and reductive cyclizadon are used as key steps. "... 

The Michael addition of the carbanions derived from esters to nitroalkenes followed by reductive cycLizadon has been used extensively for the preparation of pyrrondin-3-ones fEq 1076 This strategy is used for synthesis of the carbaaole alkaloid staurosporine aglycon CK-352c ... 

After reduction of the nitro function of the porphyrin, the porphyrinamine intermediate can be reacted with z./l-unsaturated carbonyl compounds to yield porphyrins with a fused pyridine ring, which is formed by Michael addition, imine formation and dehydrogenation. 

In 1808, Sir Humphry Davy reported the production of Mg in the form of an amalgam by electrolytic reduction of its oxide using a Hg cathode. In 1828, the Fr scientist A. Bussy fused Mg chloride with metallic K and became the first to produce free metallic Mg. Michael Faraday, in 1833, was the first to produce free metallic Mg by electrolysis, using Mg chloride. For many years, however, the metal remained a laboratory curiosity. In 1886, manuf of Mg was undertaken on a production scale in Ger, using electrolysis of fused Mg chloride. Until 1915, Ger remained the sole producer of Mg. However, when a scarcity of Mg arose in the USA as a result of the Brit blockade of Ger in 1915, and the price of Mg soared from 1.65 to 5.00 per lb, three producers initiated operations and thus started a Mg industry in the USA. Subsequently, additional companies attempted production of Mg, but by 1920 only two producers remained — The Dow Chemical Co (one of the original three producers) and. the American Magnesium Corn. In 1927. the latter ceased production, and Dow continued to be the sole domestic producer until 1941. The source of Mg chloride was brine pumped from deep wells. In 1941, Dow put a plant into operation at Freeport, Texas, obtaining Mg chloride from sea-... 

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