Other Michael Acceptors

Vinylsulfones have also been used as Michael acceptors suitable to be activated by H-bonding interactions with a cinchone-type catalyst. In particular. 

In the same context, an intramolecular Michael reaction involving a nitroalkane as Michael donor and a simple a,p-unsaturated ester as Michael acceptor has been reported using hydroquinidine-derived thiourea 72a as 

---

The stereochemical trends discussed above are not limited to a, yS-unsaturated carbonyl compounds other Michael acceptors such as nitroalkenes and unsaturated phosphane oxides display similar behavior. A representative example for the nitroalkene class of Michael acceptors is shown with substrate 70 in Scheme 6.13 [28]. The best results were thus obtained for arylcuprates. Other organocuprates were much less selective, which severely restricts their application in organic synthesis. 

Pyridines add to quinones in Michael-type reactions to give phenolbetaines (64). Many other Michael acceptors behave similarly, e.g. acrylate esters and acrylamides in the presence of acid yield quaternary ions py+CH2CH2COY. Pyridazine at room temperature with maleic anhydride gives the 2 1 adduct (65). 

A useful pyrrole synthesis depends upon the addition of the anion of p-toluenesulfonylmethyl isocyanide (TOSMIC) to a,(3-unsaturated ketones or other Michael acceptors (72TL5337) (Scheme 56). 

Conjugate additions of carbamates to a, P-unsaturated enones require - apart from metal halide - TMSC1 as a stoichiometric additive [96]. The addition of ethyl carbamate to cyclohexenone (41h) requires only 50mol% TMSC1, which was an exceptionally low amount compared with other Michael acceptors. With 10 mol% of the catalyst, the yield of 3-aminocyclohexenone derivative 66 was good (93%) [97], Aza-Michael reactions also proceed in aqueous media with good results if Co(II),... 

Later, in a collaborative work between Roland and Alexakis, it was found that the use of copper carboxylates as the copper source and Et20 as the solvent was critical to achieving high ee values (Eq. 30) [65]. In this study, several Ag/carbene complexes (20-24) were tested and found to produce significantly higher ee values than those in previous studies. Other Michael acceptors such... 

Several catalytic protocols have been developed for the 1,4-addition of silylcopper reagents to enones and other Michael acceptors. Lipshutz et al.183 treated phenyldimethylsilyllithium with dimethylzinc and used the silylzinc reagent PhMe2SiZnMe2Li thus formed as the nucleophile in copper-catalyzed 1,4-additions to various enones and enals, for instance, verbenone 248 which afforded the desired product 249 in almost quantitative yield (Equation (14)). Interestingly, the rather slow addition reaction is strongly accelerated by catalytic amounts of scandium triflate. 

Solid sodium sulphonate species 41 (Figure 43) impregnated with [dbim][SbF6] (25% wt) is itself capable to catalyse the 1,4-addition of several indole derivatives to methyl vinyl ketone (MVK) and other Michael acceptors in water (Figure 46)7 ... 

Other Michael acceptors than acrylonitrile have been investigated. For example, the Michael reaction of P-ketophosphonates with aryhnethylenemalonitriles in Et2O in the presence of piperidine produces 5-phosphonylated pyrans in good yields. 

Michael additions are among the most important organocatalytic transformations.The ability of prolinol silyl ethers to form enamines, diena-mines, trienamines or iminium ions makes them appealing in a number of chemical transformations based on addition of a nucleophile to an a,p-unsaturated carbonyl compound or other Michael acceptor. The first example of Michael addition catalysed by a prolinol silyl ether was published by Hayashi and coworkers. Aliphatic aldehydes added to a range of aryl-substituted nitroalkenes. Prolinol silyl ether Cla presumably formed chiral enamines with aldehydes. The F-anh-enamine was formed and it reacted with nitroalkene via an acyclic synclinal transition state, originally proposed... 

The catalyst Cla also efficiently mediated additions of aldehydes to other Michael acceptors. Cordova showed that the Michael addition of nonfunctionalised aldehydes to allq lidene malonates produced p-formyl-suhstituted malonates in high yields, diastereomeric and enantiomeric purities. The primary Michael adducts were also elaborated via reduction of the carbonyl function followed by spontaneous cyclisation to lactones (Scheme 8.4). 

Other Michael acceptors that were used in addition of aldehydes were vinyl sulfones. Zhu and Lu showed that the most efficient catalyst for this reaction was catalyst C2a with 3,5-bis(trifluoromethyl)phenyl groups (Scheme 8.5). It provided the corresponding products in high yields, with good to high diastereomeric and high enantiomeric purities. Palomo and coworkers also came to the same conclusion. They also extended the scope of the addition to E-a-ethoxycarbonyl vinyl sulfones. 

Conjugate Addition of Activated Methylenes to Other Michael Acceptors... 

Other Michael Acceptors, other Michael acceptors such as malei-mides [27], vinyl phosphonates [28], alkylidine malonates [29], ethyl 2-(dithox-yphosphoryl)acrylate [30], a-keto-a,(3-unsaturated esters [31], -Y-keto a, 3-unsaturated esters [32], and a,(3-unsaturated thiol esters [33] were also applicable in the enantioselective Michael reactions with aldehydes (Scheme 5.15). 

This organocatalyst and the corresponding trifluoromethyl-substituted derivative have been applied by Zhu and Lu to the asymmetric Michael reaction of aldehydes with other Michael acceptors, such as vinyl sulfones, providing the corresponding Michael products with exceptional enantioselectivities and excellent yields (Scheme 1 A) In order to make this methodology more useful, the authors extended its scope to 2-aryl-substituted vinyl sulfones as acceptors, which yielded the corresponding Michael products in excellent yields, good diastereoselectivities and nearly perfect enantioselectivities, as shown in Scheme 1.4. 

Monomer Synthesis. The synthesis of NVF derivative monomers is straightforward. Michael addition of NVF to an alkyl or substituted alkyl (meth)acrylate or other Michael acceptor is the core of the process (Scheme 1). The reaction can be catalyzed using common strong bases such as sodium or lithium methoxide. The reaction initiates at ambient temperature and is strongly exothermic. 

Variable results were observed with other Michael acceptors. Addition to methyl methacrylate was successful using metal hydrides (sodium was faster than calcium) or butyl lithium, while addition to crotonate or maleate esters failed in our hands. NVF reacted violently with acrolein, resulting in polymers. 

Other Michael acceptors have also been tested in the enantioselective conjugate addition of triorganoaluminum reagents. These mainly include activated substrates such as nitro-olefins and nitro-acrylates, 1,1 -dicarbonyl enones and... 

---