Base-catalyzed Michael-type addition

The base-catalyzed Michael—type addition of active hydrogen compounds to activated double bonds is generally performed under homogeneous conditions and lays therefore at the borderline of the scope of this paper, even if it has been sometimes carried out under typical phase transfer conditions. However, considering that the catalysts promoting phase transfer reactions, i.e. ammonium salts, amines and crown ethers, are generally active in the Michael addition, the reported reactions will be discussed here in some details also for the reasons mentioned in the introduction. 

Iron(II) templates 1 based on a [(t/ -Cp )Fe] core have been employed for the successful synthesis of 1,4,7-triphosphacyclononane derivatives 2 from a range of appropriately functionalized coordinated diphosphines and monophosphines (Scheme 12.1). 1,2-Diphosphinoethane or (2-phosphinoethyl)phenylphos-phine undergo a base-catalyzed Michael-type addition to trivinylphosphine,... 

A further frequent complication is that acetylenic esters undergo base and acid-catalyzed self-condensation on standing under normal laboratory conditions, and they will add methanol or similar nucleophiles in Michael-type addition reactions (cf. 4 and 6). Such products are almost invariably present in reaction mixtures obtained from heterocycles. A short account of these products is included as their early recognition in a new investigation can save much time. 

The 1 1 addition of RPH2 to a vinylphosphonate (Equation 4a) proceeds effectively under base-catalyzed conditions in contrast to the 1 1 addition of RPH2 to a vinylphosphine (Equation 3). This point can be related to the basicity of the anions involved as intermediates in the Michael-type addition of phosphorus-hydrogen compounds to vinyl-phosphorus derivatives (12). 

Abstract Cascade reactions involving a transition metal-promoted step and a Michael-type addition process have emerged as a powerful tool to construct cyclic and polycyclic structures. In this review, recent advances in this field are presented. The first part is related to cycloaddition reactions based on zwitterionic jr-allylPd complexes. The second part deals with Michael initiated metal-catalyzed cyclofunctionalization reactions of unactivated C C jt-bonds. Parts three and four feature reactions where an initial Michael addition reaction is followed by either a coupling reaction or an electrophilic trapping. Part five is devoted to Michael terminated reactions. 

Alkali-exchanged mesoporous molecular sieves are suitable solid base catalysts for the conversion of bulky molecules which cannot access the pores of zeolites. For example, Na- and Cs-exchanged MCM-41 were active catalysts for the Knoevenagel condensation of benzaldehyde with ethyl cyanoacetate (pKa=10.7) but low conversions were observed with the less acidic diethyl malonate (pKa=13.3) [123]. Similarly, Na-MCM-41 catalyzed the aldol condensation of several bulky ketones with benzaldehyde, including the example depicted in Fig. 2.38, in which a flavonone is obtained by subsequent intramolecular Michael-type addition [123]. 

A number of alkylation reactions, Michael-type additions, and base-catalyzed rearrangements have been previously reported for Reissert compounds. These reactions appear to proceed through the conjugate... 

Asymmetric Michael Reactions. Asymmetric induction has been observed in Michael-type addition reactions that are catalyzed by chiral amines. The Ai-benzyl fluoride salt of quinine has been particularly successful since the fluoride ion serves as a base and the aminium ion as a source of chirality. Drastic improvements in optical purity (1-23%) have resulted by changing from quinine to the N-benzyl fluoride salt (eq 11). ... 

The Knoevenagel condensation is a base-catalyzed aldol-type reaction, and the exact mechanism depends on the substrates and the type of catalyst used. The first proposal for the mechanism was set forth by A.C.O. Hann and A. Lapworth Hann-Lapworth mechanism) In 1904." When tertiary amines are used as catalysts, the formation of a p-hydroxydlcarbonyl Intermediate is expected, which undergoes dehydration to afford the product. On the other hand, when secondary or primary amines are used as catalyst, the aldehyde and the amine condense to form an Imlnlum salt that then reacts with the enolate. Finally, a 1,2-ellmlnatlon gives rise to the desired a,p-unsaturated dicarbonyl or related compounds. The final product may undergo a Michael addition with the excess enolate to give a bis adduct. 

Allyl vinyl ethers have also been obtained by elimination reactions, e.g., intramolecular bromo-etherification/base-catalyzed hydrogen bromide elimination164 166( 0r the phenylseleno etherifi-cation/selenoxide elimination reaction158 167. Tertiary allylic alcohols have been vinylated by a Michael-type addition to a vinyl sulfoxide followed by elimination of benzenesulfenic acid168. 

While base-catalyzed Michael additions of Schiff s bases of the type Me3CCH = NCH2C02Me are known to be catalyzed by NEt3 and DBU [129], the ratio of Michael adduct to cycloaddition product formed in the reaction depended on the presence of lithium ion [130]. By contrast, the pro-azaphosphatrane bases induce a clean Michael addition of the imine with various a, -unsaturated compounds in the absence of lithium ion [127]. 

Several transition metal-based Lewis acid catalysts such as FeCls, CrCls, SnCU, or A1(03S0Ci2H25 )s were shown to be highly effective for aza-type Michael additions of amines such as indoles and pyrroles to a,/ -unsaturated compounds in aqueous solution. Addition of thiols to a,/ -unsaturated ketones in water was also catalyzed by SDS or /3-cyclodextrin. There is also a single report on the stereoselectivity of base-catalyzed Michael additions of thiols to nitro-olefins, where moderate diastereoselectivities were obtained (Scheme 8.13). 

For those substrates more susceptible to nucleophilic attack (e.g., polyhalo alkenes and alkenes of the type C=C—Z), it is better to carry out the reaction in basic solution, where the attacking species is RO . The reactions with C=C—Z are of the Michael type, and OR goes to the side away from the Z. Since triple bonds are more susceptible to nucleophilic attack than double bonds, it might be expected that bases would catalyze addition to triple bonds particularly well. This is the case, and enol ethers and acetals can be produced by this reaction. Because enol ethers are more susceptible than triple bonds to electrophilic attack, the addition of alcohols to enol ethers can also be catalyzed by acids. " One utilization of this reaction involves the compound dihydropyran... 

The majority of the Michael-type conjugate additions are promoted by amine-based catalysts and proceed via an enamine or iminium intermediate species. Subsequently, Jprgensen et al. [43] explored the aza-Michael addition of hydra-zones to cyclic enones catalyzed by Cinchona alkaloids. Although the reaction proceeds under pyrrolidine catalysis via iminium activation of the enone, and also with NEtj via hydrazone activation, both methods do not confer enantioselectivity to the reaction. Under a Cinchona alkaloid screen, quinine 3 was identified as an effective aza-Michael catalyst to give 92% yield and 1 3.5 er (Scheme 4). 

However, more interesting from an application point of view are silylation reactions which introduce new functions into the materials. These can be created either directly or in subsequent further steps after silylation. Most simple is the direct conversion of the silica to a basic material by reaction, for instance, with 3-aminopropyltriethoxysilane [17]. Also two-step processes have been employed to synthesize basic materials, where first chloropropyl groups are anchored to the surface with subsequent conversion of the chloro group into an amine. In order to remove the residual, unreacted silanol groups, a second silylation with hexamethyldisilazane can be used. Such materials were found to be reasonably active in different base-catalyzed reactions, such as Knoevenagel condensations and Michael additions. A survey of the catalyzed reactions and the types of modification used can be found in Ref. [5]. 

Ito and Sawamura showed that the use of rhodium and palladium in the presence of the TRAP-type ligand generates an effective catalyst combination for the reaction of an allyl carbonate with a cyanopropionamide [128]. The palladium-TRAP complex is proposed to generate a cationic Jt-allyl species. In addition, a rhodium-TRAP species complexes the cyano group of the nucleophile and induces formation of the enolate. Reaction of the enolate with the Tt-complex in assembly I generates the observed product. Scheme 45. The notion that enoliza-tion is caused by complexation to the cyano group is based on previous results in the enantioselective rhodium-catalyzed Michael addition. 

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