Intermolecular reactions asymmetric

The development of catalytic asymmetric reactions is one of the major areas of research in the field of organic chemistry. So far, a number of chiral catalysts have been reported, and some of them have exhibited a much higher catalytic efficiency than enzymes, which are natural catalysts.111 Most of the synthetic asymmetric catalysts, however, show limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activate only one side of the substrate in an intermolecular reaction, whereas the latter can not only activate both sides of the substrate but can also control the orientation of the substrate. If this kind of synergistic cooperation can be realized in synthetic asymmetric catalysis, the concept will open up a new field in asymmetric synthesis, and a wide range of applications may well ensure. In this review we would like to discuss two types of asymmetric two-center catalysis promoted by complexes showing Lewis acidity and Bronsted basicity and/or Lewis acidity and Lewis basicity.121... 

The virtue of performing the PKR in an enantioselective manner has been extensively elaborated during the last decade. As a result, different powerful procedures were developed, spanning both auxiliary-based approaches and catalytic asymmetric reactions. For instance, the use of chiral N-oxides was reported by Kerr et al., who examined the effect of the chiral brucine N-oxide in the intermolecular PKR of propargylic alcohols and norbornadiene [59]. Under optimized conditions, ee values up to 78% at - 60 °C have been obtained (Eq. 10). Chiral sparteine N-oxides are also able to induce chirality, but the observed enantioselectivity was comparatively lower [60]. 

Brase reported an intramolecular asymmetric Heck-intermolecular Heck cascade reaction of l,3-bis(enolnonaflates) 131 to the highly congested bicyclic compound 132 [122] (Scheme 5). Although the level of asymmetric induction is low (up to 52% ee), this result shows that the concept of two leaving groups in the desymmetrization reaction can be applied. 

Scheme 13 The best (and almost unique) example of an asymmetric catalytic intermolecular PK-type reaction...

The ability of rhodium or copper complexes to promote carbene formation allows the study of asymmetric reactions with chiral ligands attached to the metal centre. Some highly enantioselective transformations are possible in certain cases. For example, the lactone 101 was formed with high optical purity using the complex [Rh2(5S-MEPY)4] (4.79). In the absence of competing intramolecular reactions, intermolecular C—H insertion is possible and such reactions are also amenable to asymmetric induction. Thus, high enantioselectivity in the insertion into a C—H bond of cyclohexane has been reported (4.80). 

The remainder of this section will focus on the different ways carbopalladation has been used to consuuct natural products. First, Sect. B will consider intermolecular cases. Then, Sect. C will discuss innamolecular carbopalladation showing the potential of the reaction to create small, medium, or large rings. Finally, domino reactions, cycloiso-merizations of enynes, and asymmetric reactions will be highlighted. 

The scope of this chapter does not allow nor attempt a comprehensive account of all developed processes to date. A detailed summary, in particular of aldol, Mannich, or ot-functionalisation reactions, can be found in excellent reviews written on the topic." Barbas and List reported an asymmetric, direct, intermolecular aldol reaction of acetones and aldehydes (Scheme 5.4), presumably via enamine formation of proline and acetone. As compared to its metal-catalysed alternatives, no preformation of the respective enolate is required, a mode of action that mimics metal-free aldolase enzymes. ... 

Organocatalysed aldol reaction has been extensively studied after being rediscovered in 2000 when List et al. developed the first proline-catalysed asymmetric direct intermolecular reaction. The aldol process is defined as the reaction of two carbonyl compounds to produce p-hydrojq carbonyl derivatives, and many combinations of starting compounds could be envisaged, but the most studied are summarised in Scheme 6.1. 

The first asymmetric direct intermolecular aldol reaction catalyzed by L-proline was disclosed by List, Lemer, and Barbas III in 2000 [5]. Other amino acids possessing secondary amine groups were also screened but at best exhibited the same activity [14]. Both functional groups present on an amino acid are essential for good catalytic activity. Additionally, enantioselectivity is dependent on the distance between the amino and carboxylic groups, with (3-amino acids exhibiting lower enantioselectiv-ities [8f, 15]. 

Abstract The present work describes a comprehensive review of the functionalization of cyclopropyl C-H bonds via transition-metal catalysis. Compared to the enormous number of publications related to direct sp and sp bond transformations in the last two decades, the first full account of direct cyclopropyl C(sp )-H bond functionalization was only disclosed in 2011. Both intra- and intermolecular transformations are detailed in the review, including asymmetric reactions. In addition, mechanistic aspects of various Pd-catalyzed cyclopropane functionalizations are discussed. 

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