Maleimides, Michael addition acceptors

Tan also found that guanidine 21, acting as a base to activate the o [3], X [3] tautomers of diaryl phosphine oxides, catalyzes the asymmetric phospha-Michael reachon of aryl nitroalkenes (Scheme 5.42) [76]. He later employed 21 to realize highly enantioselective Michael additions of dithiomalonate and 3-keto thioesters with a range of acceptors, including maleimides, cyclic enones, furanone, and acyclic 1,4-dicarbonylbutenes [77]. 

Scheme 4.44 Enantioselective Michael addition using maleimide as Michael acceptor.

From the various conjugate addition reactions of nucleophiles to a,p-unsaturated carbonyl compounds, the use of maleimides as the Michael acceptor deserves special mention. Xue and coworkers developed a highly sustainable protocol for the Michael addition of a,a-disubstituted aldehydes to maleimides (Scheme 19.52). Remarkably, using 1 mol% of the simple bifunctional thiourea catalyst 46 and water as additive, the reaction proceeded smoothly to afford oc-branched succinimides in high yields and with... 

S.2.2.3. a, -Unsaturated Sulfones, Malononitriles, and Maleimides as Acceptors, Base on their previous achievements on the asymmetric Michael addition of aldehydes [24], Lu and co-workers [55] developed the first enantiose-lective conjugate addition of cyclic ketones to vinyl sulfone catalyzed by a primary amine 57 (Scheme 5.28). Various cyclic ketones could be applied, affording the corresponding adducts in good yields and with high to excellent enantioselectivities. However, linear ketones were not suitable substrates for this catalytic system. Performing the desulfonylation procedure on a-substituted ketones and in combination... 

Tan and co-workers reported the Michael reactions of di-thiomalonates and P-keto-thioesters to a range of acceptors, including maleimides, cyclic enones, furanones and acyclic dioxobutenes [129]. Unlike dimethyl malonate, additions with acidic thioesters proceeded in higher yields, and overall better enantioselectivities (Scheme 74). 

An example of a tandem [4 + 2]/1,4-conjugate addition/ [3 + 2] consecutive cycloaddition has been reported by Grigg and coworkers (Scheme 16.5) [33]. In this maneuver, diene 17, maleimide 18, and Michael acceptor 20 are combined and heated to 80 °C, whereupon the [4 + 2] cycloaddition provides an isolable adduct 19. However, if the temperature is raised to 140 °C (qualifies as a change of conditions), the 1,4-addition to the electron-poor olefin 20 provides intermediate dipole 21, which undergoes intramolecular [3 + 2] cycloaddition to form the final product 22. Although Grigg and coworkers provide several examples with variations of 17 and 20, no further illustration of such a tandem [4 + 2]/ [3 + 2] process has been reported. 

Maleimides (350) can also serve as Michael acceptors in the addition of a-substituted isocyanoacetates C=N-CH(R )C02R. When catalysed by (352), the reaction proceeds in xylenes at 15 C and affords adducts (353) with <99 1 dr and <98% ee ... 

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