Michael amines/phosphines

Davis introduced some complimentary strategies for the synthesis of functional ionic liquids, by the inclusion of functional group (FG) to the cationic skeleton, in his review (Davis, 2004). The called "task-specific ionic liquids" have been synthesized, for example, by N-alkylation of alkyl halides covalently linked to FG with appropriate Lewis bases (e.g., imidazole, amine, phosphine, and sulfide Scheme 2a), accompanied by the anion metathesis to realize ionic liquids. One of other strategies is to use Michael reaction of alkyl vinyl ketones linked to FG with tertiary cations, as in Scheme 2b (Wasserscheid et al., 2003). It is noteworthy that this facile one-pot reaction dispenses with the need for a further anion metathesis step and are free from haUde-containing by-product. 

Scheme 2. Schematic synthetic routes of functional ionic liquids by (a) N-alkylation reaction (Davis, 2004) and (b) Michael addition reaction (Wasserscheid et al, 2003) to form ionic liquids of functional cations, and (c) the addition of acidic group to form ionic liquids of functional anion. A blank sphere represents a Lewis base such as imidazole, amine, phosphine, and sulfide, while a sphere with a plus sign represents the corresponding cation.

Substituted allyl alcohols can be prepared on insoluble supports under mild conditions using the Baylis-Hillman reaction (Figure 7.2). In this reaction, an acrylate is treated with a nucleophilic tertiary amine (typically DABCO) or a phosphine in the presence of an aldehyde. Reversible Michael addition of the amine to the acrylate leads to an ester enolate, which then reacts with the aldehyde. The resulting allyl alcohols are valuable intermediates for the preparation of substituted carboxylic acids [43,44],... 

MB) by the base can result in dye loss. Addition of the activator to the monomer in a Michael reaction, particularly critical for the sulfinate activators (43), can lead to loss of activator. A third, less well-characterized process, can also occur in addition to these two dominant deactivation processes. The interaction of some activators, for example, phosphines (19) and amines, with certain dyes result in the formation of complexes (80-83). The complexes generally absorb at shorter wavelengths than the dye, and can complicate the system photochemistry as well as induce deleterious ground state chemistry. 

The Morita-Baylis-Hillman reaction and its aza-variant - the reaction of an electron-deficient alkene with an aldehyde (MBH) or an imine (aza-MBH) - provide a convenient route to highly functionalized allylic alcohols and amines. This reaction is catalyzed by simple amines or phosphines, which can react as a Michael donor with an electron-deficient alkene, generating an enolate intermediate. This intermediate in turn undergoes the aldol or Mannich reaction with electrophilic C=0 or C=N bonds, respectively, to deliver allylic alcohols and amines. 

Enolates, generated by Michael addition reactions of a,p-unsaturated esters or ketones, can add to aldehydes. If the Michael addition is carried out with a tertiary amine (or phosphine) then this is referred to as the Baylis-Hillman reaction. Typically, an amine such as l,4-diazabicyclo[2.2.2]octane (DABCO) is used. After the aldol reaction, the tertiary amine is eliminated and it can therefore be used as a catalyst (1.61). The reaction is somewhat slow (requiring several days), but rates may be enhanced with other amines such as quinuclidine or quinidine derivatives, the latter effecting asymmetric reaction with high levels of selectivity. ... 

In addition, they carried out enantioselective Michael-type hydroamination of the alkenoyl-A-oxazolidinone 26 with aniline and obtained the chiral amine 27 with 93 % ee. Furthermore, they reported hydroamination of dihydrofuran (28) and 2,3-dihydropyran (30). Reaction of dihydrofioran (28) with morpholine proceeded at room temperature to give 2-aminotetrahydrofuran 29 regioselectively in high yield. Hydroamination of 2,3-dihydropyran (30) with morpholine proceeded at 80 "C to give 2-morpholinotetrahydropyran (31). For this hydroamination, phosphine-free... 

The Morita-Baylis-Hillman reaction is, in general, a carbon-carbon bondforming reaction of an a,(3-unsaturated compound with an aldehyde mediated by an organic nucleophilic base resulting in the formation of an allylic alcohol. Morita reported the use of a phosphine as catalyst and Baylis and Hillman used a tertiary amine. Variation of the electrophile to electron-deficient alkenes in a Michael-Michael elimination sequence leads to homo- and heterodimerisation and is known as the Rauhut-Currier reaction. The electrophilic aldehyde could be substituted by an imine or derivative in the aza-Morita-Baylis-Hillman reaction. Recently, there has been an increase in the use of this reaction for the construction of many different targets using many different amine derived catalysts. Scheme 2.2 shows a general view of this reaction and the accepted mechanism. ... 

Subsequently, the highly enantioselective Michael addition of malonates and 1,2,4-triazole to cyclic and acyclic enones, as well as the first phospha-Michael reaction of cyclic enones and diaryl phosphine oxides was reported using a similar catalyst.In 2012, Huang, Wang and coworkers demonstrated that primary amine-thiourea 39 can efficiently catalyse the... 

A combined system of PhjP and a cinchonidine-derived primary amine has been identified as an ideal catalyst for the Michael addition of aliphatic aldehydes to iV-aryl maleimides (with <99% ee). Mechanistic investigation, involving UV-vis, fluoreseenee emission (FL), NMR, circular dichroism (CD), and ESI-MS, revealed the existenee of the molecular assembly of phosphine and amine (248) with an arene-arene staeking, which is believed to play the key role ... 

The Painter group developed another approach to tetramates (e.g., 320) that involved the reductive amination of y-oxobutenoates (e.g., 319) in the presence of primary amines (Scheme 81 2002S869). Unsaturated dicarbonyl 319 was prepared in three steps by the phosphine-catalyzed Michael addition of benzyl alcohol to butynoate 318, desilylation, and oxidation of the resulting primary alcohol with 2-iodoxybenzoic acid (IBX). Treatment of 319 with tert-butylamine followed by sodium borohydride gives the O-benzyl tetramate 320 via a reductive amination—lactamization. 

The new phosphine amine ligand (486) has been developed for the Cu-catalysed Michael addition of vinyl alanes R2A1C(R )C=CR R to A-substituted-2,3-dehydro-4-piperidones. The reaction gave the expected products with <97% ee ... 

Apart from base catalysis, Michael addition of thiols can also be performed using nucleophUic catalysis. Primary and secondary amines and certain phosphines are the most commonly used catalysts. Nucleophile mediated thiol-Michael addition reactions have extensively been studied. The nucleophiles attack the Michael acceptors to generate a carbanion, which abstracts protons from thiols to generate thiolate anions, which in turn propagate the reaction (Scheme 1.16) [56]. NucleophUicity of the catalyst plays a crucial role in the kinetics of the nucleophile-based thiol-Michael addition reactions, as stronger the nucleophile, more easily the thiolate anion will be generated. 

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