Michael and related reactions

Surprisingly, the catalytic potential of proline (1) in asymmetric aldol reactions was not explored further until recently. List et al. reported pioneering studies in 2000 on intermolecular aldol reactions [14, 15]. For example, acetone can be added to a variety of aldehydes, affording the corresponding aldols in excellent yields and enantiomeric purity. The example of iso-butyraldehyde as acceptor is shown in Scheme 1.4. In this example, the product aldol 13 was obtained in 97% isolated yield and with 96% ee [14, 15]. The remarkable chemo- and enantioselectivity observed by List et al. triggered massive further research activity in proline-catalyzed aldol, Mannich, Michael, and related reactions. In the same year, MacMillan et al. reported that the phenylalanine-derived secondary amine 5 catalyzes the Diels-Alder reaction of a,/>-un saturated aldehydes with enantioselectivity up to 94% (Scheme 1.4) [16]. This initial report by MacMillan et al. was followed by numerous further applications of the catalyst 5 and related secondary amines. 

Tin(II) Enolates in the Aldol, Michael, and Related Reactions Teruaki Mukaiyama and Shu Kobayashi... 

Such important processes as alkylation of arylacetonitriles, cyclopentadiene hydrocarbons, aldehydes and ketones, esters, sulfo-nes etc., condensation of carbanions with aldehydes and ketones, the Knoevenagel, Darzens, Michael and related reactions as well as many reactions involving sulfonium and phosphonium ylides have been successfully carried out under these conditions. 

Wittig, Michael, and Related Reactions.—Carbanions generated under PTC conditions can undergo reactions other than alkylation, and an amount of interest has been shown in adapting the Wittig reaction (Equation 3), and related processes. 

Methacryhc acid and its ester derivatives are Ctfjy -unsaturated carbonyl compounds and exhibit the reactivity typical of this class of compounds, ie, Michael and Michael-type conjugate addition reactions and a variety of cycloaddition and related reactions. Although less reactive than the corresponding acrylates as the result of the electron-donating effect and the steric hindrance of the a-methyl group, methacrylates readily undergo a wide variety of reactions and are valuable intermediates in many synthetic procedures. 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

Surprisingly, little follow-up work on this idea of small molecule asymmetric catalysis appeared for the next 25 years. In the late 1980s, Agami reported the asymmetric intramolecular aldol reaction of acyclic diketones with (S)-proline as the catalyst. It was not nntil the twenty-first centnry, however, when this notion of organocatalysts became fnlly exploited. List and Barbas ° pioneered enam-ines as catalysts for aldol and Mannich and related reactions. MacMillan has developed a variety of imininm-based catalysts prodncing large asymmetric indnction for Diels-Alder chemistry, Friedel-Crafts alkylations, Mnkaiyama-Michael and cyclopropanation " reactions. 

Domino Sf /Michael Addition and Related Reactions llll... 

The Claisen reaction The crossed Claisen and related reactions The Dieckmann reaction The Michael reaction The Robinson annulation... 

Since the discovery of proline-catalyzed enantioselective aldol reactions, an extensive research program to explore chiral secondary amine catalysts has been pursued. Several polymer-supported chiral amines have been synthesized for aldol, Mannich, and related reactions. Polystyrene is a popular solid phase for use in place of silica gel in the proline-based organocatalysis. In contrast, silica gel displays a slightly acidic character and has a hydrogen-bond donor or acceptor, which may change the catalytic activity and chiral space of the organocatalyst. Flow enantioselective aldol [158-161], Mannich [162], Michael [163], and related reactions... 

For Aldol and Related Reactions. The TMSI/(TMS)2NH combination can be used for the synthesis of polycyclic cyclobutane derivatives by tandem intramolecular Michael-aldol reaction. TMSI-induced diastereoselective synthesis of tetrahy-dropyranones by a tandem Knoevenagel-Michael reaction, has also been developed. More recently, the facile synthesis of a,a bis(substituted benzylidene)cycloalkanones has been reported, using TMSI (in situ generated) mediated cross-aldol condensations (eq 53). ... 

Chiral Ca-, Sr-, and Ba-Catalyzed Asymmetric Direct-Type Aldol, Michael, Mannich, and Related Reactions... 

Recent progress in asymmetric direct-type aldol, Michael, Mannich, and related reactions using chiral Ca, Sr, and Ba catalysts was summarized in this chapter. Ca, Sr, and Ba are very attractive, because they are abundant and ubiquitous elements... 

Organocatalysis and Related Reactions [Michael-Initiated Ring-Closure (MIRC) Reactions]... 

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