Nitroalkanes Michael condensations

An elegant extension of this approach is the combination of the nitroalkanes to ketone reaction with prior EGB-catalysed Michael condensation involving nitronate anions. Azobenzene works well as the catalyst probase and the condensation and... 

Michael condensations, together with the Diels-Alder cycloaddition and the aldol reactions, are the most powerful and useful bond-fonning reactions in synthetic organic chemistry. Like the nitro-aldol (Henry) additions, nitroalkanes are particularly appropriate reagents in Michael reactions they act as a-hydrogen donors. Nitroalkanes react easily with typical Michael acceptors such as a,p-unsaturated aldehydes or ketones under base or Lewis acid catalysis. ... 

Jorgensen used p-ketoesters with a,p-unsaturated aldehydes for the construction of optically active 5-(triallq7lsilyl)cyclohex-2-enones. These compounds served as suitable starting material for other syntheses. Enders developed a domino nitroalkane-Michael addition/aldol condensation. This process provided an efficient asymmetric synthesis of trisubstituted... 

Enders et al. [54] developed an asymmetric organocatalytic domino reaction of y-nitroketones 83 and enals. The reaction, catalyzed by compound VII, renders the final cyclohexene 84 via a Michael-Aldol cascade reaction followed by dehydration, with moderate yields and diastereoselectivities and good enantioselectivities (Scheme 10.23). Two years later, the same research group reported a related reaction starting from 2-(nitromethyl)benzaldehyde [55]. The reaction proceeds via a domino nitroalkane-Michael-aldol condensation reaction that leads to the final 3,4-dihydronaphthalenes in excellent yields and enantioselectivities. 

The dialdehydes from periodate oxidation of methyl 4,6-0-benzylidene-a-and -p-D-glucopyranoside reacted with appropriate Wittig reagents to give such dienes as (400) that afforded cyclized products [e.g. (401)] with nitromethane by a double Michael condensation, whereas only one of the olefinic linkages was attacked, without cyclization, with ethyl cyanoacetate and malononitrile. Details of the reactions of these dialdehydes with nitroalkanes (see Vol. 8, p. 108), ethyl cyanoacetate (see VoL 8, p. IlOX and other carbanions to give various branched-chain heptoseptanosides have also been reported. ... 

Lubineau and Aug reported the beneficial effect of using water as the solvent in the Michael addition of nitroalkanes to methyl vinyl ketone under neutral conditions. Moreover, addition of glucose or saccharose increased the rate of the reaction. Various nitroalkanes were condensed with different electrophilic alkenes in NaOH (0.025-0.1 m), without any added organic solvent, affording the corresponding adducts with moderate to good yields when a catalytic amoimt of cetyltrimethylammonium chloride (CTACl) was used (Scheme 8.12). ... 

Since aliphatic nitroalkanes are active methylene compounds, these may be used as starting materials for the preparation of more complex products by typical reactions of methylene compounds such as alkylations, aldol condensations, Michael condensations, and Mannich reactions. 

This catalytic cascade was first realized using propanal, nitrostyrene and cinnamaldehyde in the presence of catalytic amounts of (9TMS-protected diphenylprolinol ((.S )-71,20 mol%), which is capable of catalyzing each step of this triple cascade. In the first step, the catalyst (S)-71 activates component A by enamine formation, which then selectively adds to the nitroalkene B in a Michael-type reaction (Hayashi et al. 2005). The following hydrolysis liberates the catalyst, which is now able to form the iminium ion of the a, 3-unsaturated aldehyde C to accomplish in the second step the conjugate addition of the nitroalkane (Prieto et al. 2005). In the subsequent third step, a further enamine reactivity of the proposed intermediate leads to an intramolecular aldol condensation. Hydrolysis returns the catalyst for further cycles and releases the desired tetrasubstituted cyclohexene carbaldehyde 72 (Fig. 8) (Enders and Hiittl 2006). 

The process mechanism as shown in Figure 2.23 consists of an initial activation of the aldehyde (66) by the catalyst [(5)-67] with the formation of the corresponding chiral enamine, which then, selectively, adds to nitroalkene (65) in a Michael-type reaction. The following hydrolysis liberates the catalyst, which forms the iminium ion of the a,(3-unsaturated aldehyde (62) to accomplish the conjugate addition with the nitroalkane A. In the third step, another enamine activation of the intermediate B leads to an intramolecular aldol condensation via C. Finally, the hydrolysis of it returns the catalyst and releases the desired chiral tetra-substituted cyclohexene carbaldehyde (68). 

Dinitroalkanes, obtained by condensation of nitroalkane Mannich base with other nitroalkanes or by Michael addition of nitroalkanes to nitroalkenes give 1,3-diones only when a secondary amine is used as base however, yields are moderate (- 40%). 

Condensations. Alumina promotes the formation of a-hydroxyphosphonate esters from aromatic aldehydes and dialkyl phosphonates, and the adducts are converted to a-aminophosphonate esters on reaction with ammonia. A solvent-free synthesis of a-nitro ketones comprises mixing nitroalkanes, aldehydes, and neutral alumina and oxidizing the adducts with wet, alumina-supported CrOj (15 examples, 68-86%). The Knoevenagel reaction, the Michael addition of nitromethane to gcm-diactivated alkenes, and the formation of iminothiazolines from thioureas and a-halo ketones are readily effected with alumina under microwave irradiation. 

Alumina can be impregnated with potassium fluoride, creating a solid, basic catalyst [145]. This solid has a wide range of catalytic applications involving elimination, condensation and addition reactions. Included in this group are the Michael additions of nitroalkanes to a, 3-unsaturated carbonyls (equation 4.35) [80]. 

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