Enantioselective reactions reaction coordinates

To achieve catalytic enantioselective cycloaddition reactions of carbonyl compounds, coordination of a chiral Lewis acid to the carbonyl functionality is necessary. This coordination activates the substrate and provides the chiral environment that forces the approach of a diene to the substrate from the less sterically hindered face, introducing enantioselectivity into the reaction. 

Some of the developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds have origin in Diels-Alder chemistry, where many of the catalysts have been applied. This is valid for catalysts which enable monodentate coordination of the carbonyl functionality, such as the chiral aluminum and boron complexes. New chiral catalysts for cycloaddition reactions of carbonyl compounds have, however, also been developed. 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

In contrast to 1, isomeric p-nitrophenyl nicotinate shows almost no catalysis. Thus, it is clear that substrate coordination to the metal ion complex plays the critical role for an enormous rate enhancement. The lipophilic ester (R = C5Hn) also undergoes a large rate enhancement indicating the importance of substrate binding into the micellar phase by hydrophobic interaction. A large rate enhancement can also be seen in lipophilic esters which lack the metal coordination site as given below with the enantioselective micellar reactions (Table 9, 10). 

Abstract In general, asymmetric catalysts are based on the combination of a chiral organic ligand and a metal ion. Here we show that future research should also focus on complexes in which the chirality resides only at the metal center, as the result of a given topology of coordination of achiral ligands to the metal ion. Here we make a brief presentation of the methods available for preparing such compounds as well as the very few examples of enantioselective reactions catalyzed by chiral-at-metal complexes. 

Metal-assisted enantioselective catalytic reactions are one of the most important areas in organic chemistry [1-3]. They require the appropriate design and the preparation of chiral transition metal complexes, a field also of major importance in modern synthetic chemistry. These complexes are selected on both their ability to catalyze a given reaction and their potential as asymmetric inducers. To fulfill the first function, it is absolutely required that the catalysts display accessible metal coordination sites where reactants can bind since activation would result from a direct interaction between the metal ion... 

Schematic plots of the internal energy versus the reaction coordinate for both primary and secondary insertions and for generic aspecific, syndiospecific, and isospecific model complexes are sketched in Figures 1.11 a,b, and c, respectively. The minima at the centers and at the ends of the energy curves correspond to alkene-free intermediates, including a growing chain with n and n + 1 monomeric units, respectively. Movements from the central minima toward the left and the right correspond to possible reaction pathways leading to primary and secondary insertions, respectively. For the enantioselective complexes the reaction pathways for monomer enantiofaces being...

In 1998 the groups of Jprgensen and Helmchen reported the preparation of the chiral silyl cationic salt 2 (Scheme 3) [30]. This was the first time that a chiral silyl cation was used as a catalyst in an enantioselective reaction, hi order to ensure that the silyl salt had a high reactivity, the almost chemically inert and non-coordinating anions tetrakis[pentafluorophenyl]borate [TPFPB] and tetrakis[3,5-bis (trifluor-omethyl)phenyl]borate [TFPB] were chosen as counter anions. 

The distinction between enantio- and diastereoselectivity in a reaction is usually, but not generally, evident. Clearly, an enantioselective reaction must proceed via diastereomeric transition states and often diastereomeric intermediates can be demonstrated. In order to narrow the overlap area as far as possible it is demanded that a diastercoselective reaction must yield covalent diastereomers, as distinct from salts, coordination compounds etc., as reaction products. 

The high level of stereocontrol in the formation of complexes 25 and 27 suggests that compounds of this type may be useful as chiral catalysts. Indeed, several examples of enantioselective catalytic reactions carried out with half-sandwich complexes have been published recently [23, 25]. However, it seemed desirable to have access to complexes of the [21 Ru(solv)2] type, which have two easily removable solvent molecules coordinated to the central metal, in order to provide coordination sites for a substrate to be transformed. Although the chloride ligand could be easily removed from 23 and 25 all attempts to strip off the PPhs were unsuccessful. Therefore a new reaction scheme was developed which precluded the use of phosphine ligands, and the bis (acetonitrile) complex 28 could be obtained in a multi-step protocol via the T1 salt T1 21 (Scheme 1.5.12) [26]. 

An enantioselective Strecker reaction involving Brpnsted acid catalysis uses a BINOL-phosphoric acid, which affords ees up to 93% in hydrocyanations of aromatic aldimines in toluene at -40 °C.67 The asymmetric induction processes in the stereoselective synthesis of both optically active cis- and trans-l-amino-2-hydroxycyclohexane-l -carboxylic acids via a Strecker reaction have been investigated.68 A 2-pyridylsulfonyl group has been used as a novel stereocontroller in a Strecker-type process ees up to 94% are suggested to arise from the ability of a chiral Lewis acid to coordinate to one of the sulfonyl (g)... 

In one of the earliest reports on enantioselective radical reactions, chiral Lewis acid mediated conjugate addition followed by enantioselective H-atom transfer a to a carbonyl was reported by Sato and co-workers (Scheme 3) [22], The single point binding chiral aluminum complex presumably coordinates to the carbonyl oxygen of the lactone as shown in 10. The strong Lewis acidity of the aluminum complex activates the substrate 7 to nucleophilic conjugate addition, which is followed by an enantioselective H-atom transfer from BuaSnH in a chiral environment provided by BINOL ligand in 8. Only 28% ee was observed for product 9. 

Although these enantioselective photoreactions are limited to amide or salt derived from achiral acid and chiral amine, one enantioselective photoisomerization reaction of cobaloxime coordinated with chiral axial ligands such as 1-methylpropylamine, l-(l-naphthyl)ethylamine, and 2-phenylglycinol has been reported. For example, finely powdered (2-cyanoethyl)cobaloxime (60), suspended in liquid paraffin and spread onto a Petri dish, was irradiated to give (S)-(-)-61 of about 80% ee after displacement of the chiral auxiliary of the complex with pyridine [32],... 

According to the hypothetical catalytic cycle (Figure 36), the lanthanum atom is believed to function as a Lewis acid and a lithium binaphthoxide moiety as a Brpnsted base. The nature of the coordination of the aldehyde appears to be of first importance. This coordination provides activation of the aldehyde for reaction with the hypothetical LLB-enolate (II) (which on the basis of pKa values can be present at most in low concentration), and also controls of the orientation of the aldehyde for enantioselective reaction. A H NMR study also supports the existence of the coordination between aldehydes and the lanthanum cation.89... 

Controlling the coordination of palladium intermediates with silver salts was the key to developing highly diastereo- and enantioselective Heck reactions.58 For example, the presence of silver phosphate in the key cyclization step during the synthesis of various alkaloids reversed the stereochemistry at the newly created spiro center (Scheme 10.33).59... 

The Shibasaki cychzation of mc.vo-cyclohexa-1,4-dienes in the presence of a chiral palladium complex and silver carbonate in l-methyl-2-pyrrolidinone is probably the first example of an enantioselective Heck reaction (Scheme 10.34).60 The enantiomeric excess could be slightly improved by replacing the chiral phosphine ligand BINAP with the corresponding less coordinating arsine ligand, as well as replacing silver carbonate with silver phosphate.61,62... 

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