Asymmetric Michael additions with carbon-based

As a direct route for the constructing carbon-carbon bonds, catalytic asymmetric Michael additions with various carbon-based nucleophiles including malonic esters, cyanide, electron-deficient nitrile derivatives, a-nitroesters, nitroalkanes, Horner-Wadsworth-Emmons reagent, indoles, and silyl enol ethers have attracted considerable attention. 

Jenner investigated the kinetic pressure effect on some specific Michael and Henry reactions and found that the observed activation volumes of the Michael reaction between nitromethane and methyl vinyl ketone are largely dependent on the magnitude of the electrostriction effect, which is highest in the lanthanide-catalyzed reaction and lowest in the base-catalyzed version. In the latter case, the reverse reaction is insensitive to pressure.52 Recently, Kobayashi and co-workers reported a highly efficient Lewis-acid-catalyzed asymmetric Michael addition in water.53 A variety of unsaturated carbonyl derivatives gave selective Michael additions with a-nitrocycloalkanones in water, at room temperature without any added catalyst or in a very dilute aqueous solution of potassium carbonate (Eq. 10.24).54... 

The asymmetric Michael addition of active methylene or methyne compounds to electron deficient olefins, particularly a,P-unsaturated carbonyl compounds, represents a fundamental and useful approach to construct functionalized carbon frameworks [51]. The first successful, phase-transfer-catalyzed process was based on the use of well-designed chiral crown ethers 69 and 70 as catalyst. In the presence of 69, P-keto ester 65 was added to methyl vinyl ketone (MVK) in moderate yield but with virtually complete stereochemical control. In much the same way, crown 70 was shown to be effective for the reaction of methyl 2-phenylpropionate 67 with methyl acrylate, affording the Michael adduct 68 in 80% yield and 83% ee (Scheme 11.15) [52]. 

In the Michael-addition, a nucleophile Nu is added to the / -position of an a,fi-unsaturated acceptor A (Scheme 4.1) [1], The active nucleophile Nu is usually generated by deprotonation of the precursor NuH. Addition of Nu to a prochiral acceptor A generates a center of chirality at the / -carbon atom of the acceptor A. Furthermore, the reaction of the intermediate enolate anion with the electrophile E+ may generate a second center of chirality at the a-carbon atom of the acceptor. This mechanistic scheme implies that enantioface-differentiation in the addition to the yfi-carbon atom of the acceptor can be achieved in two ways (i) deprotonation of NuH with a chiral base results in the chiral ion pair I which can be expected to add to the acceptor asymmetrically and (ii) phase-transfer catalysis (PTC) in which deprotonation of NuH is achieved in one phase with an achiral base and the anion... 

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