Michael-cyclisation reaction

These reaction conditions were also applied to the domino Michael/cyclisation reactions of other nucleophiles, such as 4-hydroxy-6-methyl-2-pyrone 43, 4-hydroxycoumarin 44, and 3-hydroxyperinaphthenone 45, as shown in Scheme l. hlF By reaction with variously substituted l-(alk-2-enoyl)-4-bromo-3,5-dimethylpyrazoles, these compounds afforded the corresponding chiral domino products 46a-c, 46d-h, and 47, respectively. These products arose from domino Michael/cyclisation reactions and were obtained in moderate to good yields and with good to high enantioselectivities of up to 98% ee. 

Scheme 2.35 Domino Michael/cyclisation reaction of dimedone with l-(2-cro-tonoyl)-3,5-dimethylpyrazoles catalysed by an in situ generated (i ,i )-DBFOX-Ph nickel catalyst.

Scheme 2.39 Domino Michael/cyclisation reaction of cyclic 1,3-dicarbonyl compounds with p,y-unsaturated a-keto esters catalysed by an in situ generated iV,iV -dioxide nickel catalyst.

Scheme 4.5 Domino Michael/cyclisation reaction of dimedone with l-(2-crotonoyl)-3,5-dimethylpyrazoles.

Scheme 4.7 Domino Michael/cyclisation reactions of enols with l-(alk-2-enoyl)-4-bromo-3,5-dimethylpyrazoles.

Scheme 2.3 Domino Michael-cyclisation reactions catalysed by a combination of a chiral cinchona alkaloid-derived primary amine and a chiral phosphoric acid.

Cooperative catalysis using cinchona alkaloid derivatives in combination with metals such as silver have also been widely developed. On the basis of this concept, Escolano et al. have disclosed an enantioselective domino Michael-cyclisation reaction. This formal [3 + 2] cycloaddition occurred between isocyanoacetates and enones in the presence of a combination of a chiral hifunctional cinchona alkaloid, such as cupreine, and AgNOs to provide the corresponding chiral 2,3-dihydropyrroles in low to high yields and... 

Domino Michael-cyclisation reaction catalysed by chiral cinchona alkaloid catalysis and silver catalysis. 

Standard cyclisation methodology was used to access the cyclic monophosphinic acid derivative 78 by reaction of ammonium phosphonate and ethyldiisopropylamine, followed by the addition of chlorotrimethylsilane, with 2,2 -bis (bromomethyl)-l,l -biphenyl. Silane reduction of 78 gave the secondary phosphine. The secondary phosphine borane complex 79 could be used in alkylation or Michael addition reactions. For example the Michael adduct 80 was produced in high yield by treatment of 78 with a NaH suspension in THF followed by the addition of diethylvinylphosphonate . 

Quite often these cyclisation reactions happen spontaneously after some other normal reaction. Carry out the normal Michael reaction between these two compounds and then see if you can predict what cyclisation will... 

The kinetic control approach to constructing the CD-spiroacetal segment envisaged a hetero-Michael cyclisation of the dihydropyrone 28 (derived from 26 by sequential oxidation to the P-diketone, PMB removal and cyclisation to provide the D-ring), where axial attack might be favoured (Scheme 7). In practice, treatment of 28 with DBU led to installation of the C-ring via hetero-Michael reaction, with a small preference (60 40) for formation of the desired spiroacetal 29 over 30. Despite the modest selectivity observed in this mode of spiroacetal formation, the endeavour highlighted an important new means for... 

The intramolecular carbon-carbon bond-forming reactions considered in this section are based on the aldol condensation (see Section 5.18.2, p. 799), the Claisen-Schmidt reaction (see Section 6.12.2, p. 1032), the Claisen ester condensation (see Section 5.14.3, p. 736), and the Claisen reaction (see Section 6.12.2, p. 1032). Since these carbonyl addition reactions are reversible, the methods of synthesis are most successful for the formation of the thermodynamically stable five- and six-membered ring systems. The preparation of the starting materials for some of these cyclisation reactions further illustrates the utility of the Michael reaction (see Section, 5.11.6, p. 681). 

If an unsaturated aldehyde was combined with a 1,3-dinitro compound, chiral cyclohexanes were formed by a nitro-Michael/Heniy reaction sequence. Miehael addition followed by double Heniy reaction also led to ehiral eyelohexane derivatives. In another application of the Henry re-aetion, Hayashi used nitroalkenes with pentane-l,5-dial (generated in situ) to form ehiral eyelohexane carboxaldehydes. Chiral cyclopentanes were also eonstrueted in another manner. Enamine-mediated Michael addition of aldehydes to 5-iodo-l-nitropent-l-ene led to an intermediate enamine, which underwent intramoleeular cyclisation via iodide displacement. ... 

A short and highly diastereoselective synthesis of tetrahydropyran-4-ones was recently reported hy the group of Tong. Reductive 1,2-oxazoline N-O cleavage in 71 with Sml2 followed by acid-catalysed 6-e do-trig oxa-Michael cyclisation of the crude product furnished q n-tetrahydropyran-4-one 72 (Scheme 25). Extended reaction times resulted in improved yields and diastereoselectivities, presumably due to a retro-oxa-Michael/ oxa-Michael isomerisation. The total synthesis of ( )-diospongin Awas completed in a 20% overall yield. 

Scheme 1.35 Silylated biphenylprolinol-catalysed domino Michael addition-cyclisation reactions.

Scheme 2.22 Three-component domino Michael-Mannich-cyclisation reaction catalysed by a combination of chiral diphenylprolinol triethylsilyl ether and a chiral thiourea.

Michael-cross-benzoin cyclisation reaction afforded the corresponding chiral polyfunctionalised cyclopentanones bearing three contiguous stereocentres in good yields, moderate to excellent diastereoselectivities of up to 98% de, and good to high enantioselectivities of up to 96% ee, as shown in Scheme 2.31. 

Scheme 2.31 Tandem Michael-cross-benzoin cyclisation reaction catalysed by a chiral diarylprolinol trimethylsilyl ether and an Af-heterocyclic carbene.

Scheme 7.61 Tandem Michael-acetalisation-cyclisation reaction catalysed by chiral amine catal) is and gold catalysis.

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