Michael acceptors unsaturated nitro compounds

The Michael reaction occurs with a variety of a,/3-unsaturated carbonyl compounds, not just conjugated ketones. Unsaturated aldehydes, esters, thio-esters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor component in Michael reactions (Table 23.1). Similarly, a variety of different donors can be used, including /3-diketones, /3-keto esters, malonic esters, /3-keto nitriles, and nitro compounds. 

Acceptor-substituted alkenes that are employed as substrates in Michael additions include a./l-unsaturated ketones (for example, see Figure 10.59), a,/3-unsaturated esters (Figure 10.60), and a,/3-unsaturatcd nitriles (Figure 10.61). The corresponding reaction products are bifunctional compounds with C=0 and/or C=N bonds in positions 1 and 5. Analogous reaction conditions allow Michael additions to vinyl sulfones or nitroalkenes. These reactions lead to sulfones and nitro compounds that carry a C=0 and/or a O N bond at the C4 carbon. 

Other motifs can be eliminated besides sulfonyls in order to introduce an unsaturation. Nitrogen dioxide is a good leaving group in a radical sense and, since nitroolefins are excellent Michael acceptors, it is easy to prepare /3-nitro xanthates by conjugate addition of a xanthate salt. Exposure of these compounds to an equivalent amount of lauroyl peroxide furnishes the corres-... 

A wide variety of Michael acceptors have been reacted with sulfoxonium methylides, e.g. a,p-unsaturated ketones, nitriles, sulfones, sulfonamides and nitro compounds, to give good yields of the corresponding cyclopropane derivatives.1,2a Steric hindrance may decrease the rate of reaction but need not prevent reaction for example, the very hindered compound 4,6,6-trimethyl-3-hepten-2one (61) reacts with dimethylsulfoxonium methylide (33) to give the cyclopropane (62) (Scheme 24). 

NaBHj/NiC or Raney nickel, the menthyloxy group is removed with NaBH /KOH to give 3,4-disubstituted butyrolactones with a high diastereo- and enantioselectivity (Figure 7.69). Corey and Houpis [1458] have described asymmetric Michael reactions of ketone enolates with a 2-thiophenyl crotonate of 8-phenmenthol. Chirality has also been introduced on the amino group of 2-ami-nomethyiacrylates to perform the asymmetric addition of the anion of the tert-Bu ester of cyclopentanecarboxylate [1459], More important developments have been reported with chiral a,p-unsaturated sulfoxides and nitro compounds as Michael acceptors (see below). 

The term Michael addition has been used to describe 1,4- (conjugate) additions of a variety of nucleophiles including organometallics, heteroatom nucleophiles such as sulfides and amines, enolates, and allylic organometals to so-called Michael acceptors such as a,p-unsaturated aldehydes, ketones, esters, nitriles, sulfoxides, and nitro compounds. Here, the term is restricted to the classical Michael reaction, which employs resonance-stabilized anions such as enolates and azaenolates, but a few examples of enamines are also included because of the close mechanistic similarities. 

The Michael reaction occurs with a variety of a,/3-unsaturated carbonyl compounds, not just conjugated ketones. Unsaturated aldehydes, esters, thioesters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor... 

S.2.3.2. 0L, -Unsaturatecl Aldehydes as Acceptors. As an alternative strategy for the synthesis of y-nitro aldehyde compounds, the asymmetric Michael addition of nitroalkanes to a,(3-unsaturated aldehydes was also investigated in recent years. Due to the high reactivity of aldehydes, the competitive 1,2-addition reaction is the major limitation for the development of such a reaction. Disubstituted prolinol silyl ether derivatives [72] proved to be effective catalysts to tackle this synthetic challenge, and excellent results were obtained with 7 in the presence of acid or base additive (Scheme 5.35). 

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