Michael additions of cyclohexanone

Michael addition of cyclohexanones to methyl vinyl ketone followed by intramolecular aldol condensation to afford six-membered a,(3-unsaturated ketones. 

Furthermore, to clarify the difference between task specific ionic hquids (or also called functionahzed ionic hquids) and chiral ionic hquids, one very successful example of a task specific ionic hquid 63 is presented in Scheme 65. This catalyst with a loading of 15 mol% under neat conditions gave up to 100% yield and 99% ee in the Michael addition of cyclohexanones to nitroolefms [179]. This catalyst belongs to the field of the prohne catalyzed reactions. 

A pyrrolidine-thiourea organocatalyst (69) facilitates Michael addition of cyclohexanone to both aryl and alkyl nitroalkenes with up to 98% de and ee 202 The bifunctional catalyst (69) can doubly hydrogen bond to the nitro group, leaving the chiral heterocycles positioned for cyclohexyl enamine formation over one face of the alkene. 

Cao CL, Ye MC, Sun XL, Tang Y (2006) Pyrrohdine-thiourea as a bifunctional organocatalyst Highly enantioselective michael addition of cyclohexanone to nitroolefins. Org Lett 8 2901... 

Table 7.14 Asymmetric Michael addition of cyclohexanone to P-nitrostyrene using ionic liquid-supported chiral pyrrolidines as a catalyst.

In 1953, chemists in Russia reported the asymmetric induction in the Michael addition of cyclohexanone and 2-methylcyclohexanone to acrylonitrile in the presence of optically active quartz coated with EtOLi,EtOK,or EtONa [37]. Maximum rotations of 0.07 and 0.157 were obtained, respectively. 

Scheme 2.11 Effect of the incorporation of achiral additive 29 in the 30-catalyzed enantioselective Michael addition of cyclohexanone to nitrostyrene.

Scheme 2.19 Enantioselective Michael addition of cyclohexanone to nitroalkenes using recyclable functionalized ionic liquids as catalysts.

Sugar-hased prolinamide 16m has also been employed as catalyst for the asymmetric Michael addition of cyclohexanones to p-nitroslyrenes. During optimisation of the reaction conditions, the authors found that the polarity of the solvent does not modify the yield or stereoselectivity, but the best ee was obtained under neat conditions at -20 °C. Ammonium ionic liquids 41a,b are also efficient organocatalysts for the asymmetric Michael addition of aldehydes to nitro-olefins giving the adducts with excellent yields and enantioselectivities and modest to high diastereoselectivities. 

Chen et al, designed and synthesised a series of chiral pyrrolidinyl-sulfamide derivatives, identifying 3j as an efficient bifunctional organocatalyst for the direct Michael addition of cyclohexanone to a wide range of nitrostyrenes. The desired Michael adducts were obtained in high chemical... 

Tang and coworkers" used bifunctional urea and thiourea-derived orga-nocatalysts (4a,b) for the Michael addition of cyclohexanone to nitro-olefins (Scheme 9.29). Using pyrrolidine-thiourea 4b afforded the desired y-nitroalkanes with high diastereo- and enantioselectivity under solvent-free conditions (up to 99 1 dr, 88-98% ee). Subsequently, Xiao and coworkers screened various bifunctional pyrrolidine-thiourea organocatalysts and identified 4c to be efficient at catalysing the Michael addition of various ketones to nitrostyrenes. Comparable results were observed (up to 99 1 dr and 99% ee) when the reactions were performed in both aqueous media and organic solvents. 

Scheme 9.29 Thiourea-derived organocatalysts for the Michael addition of cyclohexanone to nitro-olefins.

Scheme 11.16 Aqmametric Michael addition of cyclohexanone to nitroalkenes cata-tysed by proline-derived triamine 17.

In 2007 Sun and coworkers reported the use of the proline derived triamine 17 in the presence of weak acids as a highly stereoselective organocatalyst for the asymmetric Michael addition of cyclohexanone to nitroalkenes (Scheme 11.16). All selected aromatic nitroalkenes gave excellent yields and selectivities, with the exception of electron-deficient substrates (Ar = 4-CN-Ph, 4-N02-Ph), which also require much longer reaction times. 

Between 2009 and 2011, Peng and coworkers reported the asymmetric Michael addition of cyclohexanone and other carbonyl compounds to nitroalkenes, catalysed by different fra s-4-amino substituted proline derivatives (18-20, Scheme 11.17). The sulfonimide 18 gave very high yields and enantioselectivities, whereas the analogous polystyrene-supported... 

Scheme 2.31 Enantioselective organocatalytic Michael addition of cyclohexanones to chalcones...

A new class of organocatalyst, pyrroUdinyl-sulfamides (106), bearing strong hydrogen-bond donors, gives yields/dc/cc up to 96/98/95% in Michael additions of cyclohexanone to nitroalkenes. ... 

A BINAP-derived bifunctional thiophosphoramide gives >98% del>99% ee in Michael addition of cyclohexanones to both aryl- and alkyl-substituted nitroolefins. Imidazolylmethyl ketones undergo one-pot Michael-aldol cascade reactions with Q ,/3-unsaturated aldehydes in DCM at 20 °C using the simple organocatalyst, prolinol... 

A series of pyrrolidine catalysts has been investigated for the asymmetric Michael addition of cyclohexanone to nitroalkenes, which is the classical model commonly used. When an aminal-pyrrolidine, developed by Alexakis et al. was employed as an organocatalyst for the conjugate addition of cyclohexanone to nitrostyrene, it led quantitatively to the Michael product with 84% de and 87% ee (Scheme 1.48). Better stereoselectivities for this reaction were... 

Scheme 1.48 Michael additions of cyclohexanone to nitrostyrenes catalysed by various pyrrolidines.

In 2009, Peng et al. reported the synthesis of chiral 4-trifluoromethane-sulfonamidyl prolinol zerz-butyldiphenylsilyl ether and its highly efficient application as an organocatalyst for the Michael addition of cyclohexanone to various nitroalkenes, providing almost quantitative yields combined to... 

Scheme 1.51 Prolinamide cholic acid-catalysed Michael additions of cyclohexanone to nitroalkenes.

Benzoylthiourea-pyrrolidine (101), derived from L-proline, efficiently catalyses Michael addition of cyclohexanone to nitrostyrenes delee values of over 98/99% have 0 been achieved in the presence of 2,4-dichlorobenzoic acid as co-catalyst. 0... 

The L-proline-derived phosphinoxide (242) has been reported to catalyse the asymmetric Michael addition of cyclohexanone and other cyclic ketones to chalcones in Pr OH/Bu OH with <99% ee and up to >99 1 dr. NMR and ESI-MS spectroscopy shed some light on the mechanism. ... 

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