Enantioselective reactions examples

A number of oxazaphospholidines (69) have found use as ligands in the preparation of chiral catalyst systems which promote a variety of enantioselective reactions. Examples include the use of palladium complexes for the asymmetric carbonylation of a-methylbenzyl bromide <880M59>,... 

Another important example of an enantioselective reaction mediated by a chiral catalyst is the hydrogenation of 3-substituted 2-acetamidoacrylic acid derivatives. 

In recent years, several modifications of the Darzens condensation have been reported. Similar to the aldol reaction, the majority of the work reported has been directed toward diastereo- and enantioselective processes. In fact, when the aldol reaction is highly stereoselective, or when the aldol product can be isolated, useful quantities of the required glycidic ester can be obtained. Recent reports have demonstrated that diastereomeric enolate components can provide stereoselectivity in the reaction examples include the camphor-derived substrate 26, in situ generated a-bromo-A -... 

Because ketones are generally less reactive than aldehydes, cycloaddition reaction of ketones should be expected to be more difficult to achieve. This is well reflected in the few reported catalytic enantioselective cycloaddition reactions of ketones compared with the many successful examples on the enantioselective reaction of aldehydes. Before our investigations of catalytic enantioselective cycloaddition reactions of activated ketones [43] there was probably only one example reported of such a reaction by Jankowski et al. using the menthoxyaluminum catalyst 34 and the chiral lanthanide catalyst 16, where the highest enantiomeric excess of the cycloaddition product 33 was 15% for the reaction of ketomalonate 32 with 1-methoxy-l,3-butadiene 5e catalyzed by 34, as outlined in Scheme 4.26 [16]. 

Accordingly, cyclic nitronates can be a useful synthetic equivalent of functionalized nitrile oxides, while reaction examples are quite limited. Thus, 2-isoxazoline N-oxide and 5,6-dihydro-4H-l,2-oxazine N-oxide, as five- and six-membered cyclic nitronates, were generated in-situ by dehydroiodination of 3-iodo-l-nitropropane and 4-iodo-l-nitrobutane with triethylamine and trapped with monosubstituted alkenes to give 5-substituted 3-(2-hydroxyethyl)isoxazolines and 2-phenylperhydro-l,2-oxazino[2,3-fe]isoxazole, respectively (Scheme 7.26) [72b]. Upon treatment with a catalytic amount of trifluoroacetic acid, the perhydro-l,2-oxazino[2,3-fe]isoxazole was quantitatively converted into the corresponding 2-isoxazoline. Since a method for catalyzed enantioselective nitrone cycloadditions was established and cyclic nitronates should behave like cyclic nitrones in reactivity, there would be a good chance to attain catalyzed enantioselective formation of 2-isoxazolines via nitronate cycloadditions. 

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. 

As can be seen from the above examples, the decarboxylation reaction can be said to generate carbanion-equivalent, which is capable of undergoing the enantioselective reactions not only with a proton but also with a carbon electrophile in an aqueous medium. In the future extension of this field, this characteristic point should be utilized for the design of the unique reactions. 

The asymmetric nickel-catalyzed hydroalumination of prochiral terminal alkenes using adducts of BujAl and chiral amines was reported in 1981 [74], Among the different amines investigated, (-)-N,N-dimethylmenthylamine (DMMA) gave the best enantioselectivities. For example, reaction of 2,3,3-trimethyl-l-butene (39) at room temperature with 0.33 equiv. of the DMMA/iBu3Al adduct in the presence of 0.6 mol% of Ni(mesal)2 gave, after oxidation of the intermediate organoaluminum compounds, 2,3,3-trimethyl-l-butanol 40 in 76% yield and 27% ee (Scheme 2-19). 

The highly ordered cyclic TS of the D-A reaction permits design of diastereo-or enantioselective reactions. (See Section 2.4 of Part A to review the principles of diastereoselectivity and enantioselectivity.) One way to achieve this is to install a chiral auxiliary.80 The cycloaddition proceeds to give two diastereomeric products that can be separated and purified. Because of the lower temperature required and the greater stereoselectivity observed in Lewis acid-catalyzed reactions, the best diastereoselectivity is observed in catalyzed reactions. Several chiral auxiliaries that are capable of high levels of diastereoselectivity have been developed. Chiral esters and amides of acrylic acid are particularly useful because the auxiliary can be recovered by hydrolysis of the purified adduct to give the enantiomerically pure carboxylic acid. Early examples involved acryloyl esters of chiral alcohols, including lactates and mandelates. Esters of the lactone of 2,4-dihydroxy-3,3-dimethylbutanoic acid (pantolactone) have also proven useful. 

As in intermolecular reactions, enantioselectivity can be achieved in IMDA additions by use of chiral components. For example, the dioxolane ring in 5 and 6 results in TS structures that lead to enantioselective reactions.130 The chirality in the dioxolane ring is reflected in the respective TSs, both of which have an endo orientation of the carbonyl group. 

Enantioselective Reactions of Organocopper Reagents. Several methods have been developed for achieving enantioselectivity with organocopper reagents. Chiral auxiliaries can be used for example, oxazolidinone auxiliaries have been utilized in conjugate additions. The outcome of these reactions can be predicted on the basis of steric control of reactant approach, as for other applications of the oxazolidinone auxiliaries. 

In a related study, the same group investigated molybdenum-catalyzed alkylations in solution and on a solid phase [35], demonstrating that microwave irradiation could also be applied to highly enantioselective reactions (Scheme 7.15). For these examples, commercially available and stable molybdenum hexacarbonyl [Mo(CO)6] was used to generate the catalytic system in situ. The reactions in solution provided good yields (see Scheme 6.50). In contrast, the conversion rates for the solid-phase examples were rather poor. However, the enantioselectivity was excellent (>99% ee) for both the solution and solid-phase reactions. 

Chiral manganese complexes have been used to perform the enantioselective amidation of saturated C-H bonds.256-258,262 Cationic Mn(salen) 107 showed good catalytic activity and moderate enantioselectivity. Typical examples are shown in Equations (86)-(88). High enantioselectivity of 89% ee was obtained in the reaction of 1,1-dimethylindan (Equation (88)).258 Chiral manganese(m) porphyrin 106 was used in the enantioselective amidation as well nevertheless, the best enantioselectivity was only 54% (Equation (89)).256,257... 

Alkylative aldol reactions with aryl- or vinylboron reagents are also catalyzed by rhodium complexes.404 4043 4041 Equations (54) and (55) show examples of enantioselective reactions. 

Acetylenic esters react with arylboron reagents in the presence of rhodium diphosphine catalyst to give cyclic ketones.409 Equation (61) shows an example which may involve ortfe-metallation and ketone formation. A catalytic, enantioselective reaction was also achieved (Equation (62)). These processes presumably involve unprecedented addition of organorhodium species to the ester carbonyl group. 

The BINAP-Ru(II)-catalyzed enantioselective hydrogenation of f>-keto esters is used for the synthesis of a wide range of important natural and man-made compounds [1-4, 48] some examples of these are listed in Figure 32.10, wherein chiral centers created by the enantioselective reaction are labeled with R or S. 

Chemical catalysts for transfer hydrogenation have been known for many decades [2e]. The most commonly used are heterogeneous catalysts such as Pd/C, or Raney Ni, which are able to mediate for example the reduction of alkenes by dehydrogenation of an alkane present in high concentration. Cyclohexene, cyclo-hexadiene and dihydronaphthalene are commonly used as hydrogen donors since the byproducts are aromatic and therefore more difficult to reduce. The heterogeneous reaction is useful for simple non-chiral reductions, but attempts at the enantioselective reaction have failed because the mechanism seems to occur via a radical (two-proton and two-electron) mechanism that makes it unsuitable for enantioselective reactions [2 c]. 

The Lewis acid catalyst 53 is now referred to as the Narasaka catalyst. This catalyst can be generated in situ from the reaction of dichlorodiisopropoxy-titanium and a diol chiral ligand derived from tartaric acid. This compound can also catalyze [2+2] cycloaddition reactions with high enantioselectivity. For example, as depicted in Scheme 5-20, in the reaction of alkenes bearing al-kylthio groups (ketene dithioacetals, alkenyl sulfides, and alkynyl sulfides) with electron-deficient olefins, the corresponding cyclobutane or methylenecyclobu-tene derivatives can be obtained in high enantiomeric excess.18... 

Asymmetric aza Diels-Alder reactions provide a useful route to optically active heterocyclics such as piperidines and tetrahydroquinolines.45 Although successful examples of diastereoselective approaches had been reported as early as 10 years ago,46 only recently have enantioselective reactions been accomplished.47 For example, the reaction of chiral amine-derived aromatic imine 115 with Brassard s diene 116 gives adduct 117 with up to 95% diaster-eoselectivity (Scheme 5-37).48... 

R)-product. Although there is still room for further improvement of the enantioselectivity, this first example of an enantioselective reaction with a,(S-unsaturated ketones reveals the potential of acylzirconocene chlorides as unmasked acyl anion donors. 

This method was later applied to samarium diiodide initiated reactions [26] and to tita-nocene-catalyzed pinacol couplings [27]. The first examples of enantioselective reactions using Me3SiCl as a mediator for catalysis have very recently been reported by Cozzi et al., as shown in Scheme 12.14 [28]. 

---