Enantioselective activation

The idea of enantioselective activation was first reported by Mikami and Matsukawa111 for carbonyl-ene reactions. Using an additional catalytic amount of (R)-BINOL or (/ )-5.5 -dichloro-4,4, 6,fi -tctramcthyl biphenyl as the chiral activator, (R)-ene products were obtained in high ee when a catalyst system consisting of rac-BINOL and Ti(OPri)4 was employed for the enantioselective carbonyl ene reaction of glyoxylate (Scheme 8-54). Amazingly, racemic BINOL can also be used in this system as an activator for the (R)-BINOL-Ti catalyst, affording an enhanced level of enantioselectivity (96% ee). 

Sharpless et al. coined the word ligand-accelerated catalysis (LAC), which means the construction of an active chiral catalyst from an achiral precatalyst via ligand exchange with a chiral ligand. By contrast, a combinatorial library approach in which an achiral pre-catalyst combined with several chiral ligand components (L, L, —) may selectively assemble in the presence of several chiral activators (A, A, —) into the most catalytically active and enantioselective activated catalyst (ML A" ) (Scheme 8.16). ... 

These data and considerations on structural features of substrates have suggested the hypothesis that a readily reachable reactive site is embedded within a spacious pocket of the enantioselective nitrile hydratase, while the amidase comprises a relatively deep-buried and size-limited enantioselective active site. This hypothesis has been supported by the results obtained studying the biotransformations of differently configured 2,2-dimethyl-3-arylcyclopropanecarbonitriles catalyzed by... 

Asymmetric Ene Reaction. The enantioselective activation of carbonyl groups with the chiral aluminum reagent also enabled the asymmetric ene reaction of electron-deficient aldehydes with various alkenes (eq 3). In the presence of powdered 4 X molecular sieves, the chiral aluminum reagent can be utilized as a catalyst without loss of enantioselectivity. 

The best combination of chiral ligands and activators can easily be found out in an efficient way by super high throughput screening (SHTS) employing CO-HPLC with achiral stationary phase for affording the most enantioselective activated catalyst to give excellent yields and enantioselectivities. 

Smart Self-Assembly into the Most Enantioselective Activated Catalyst... 

Based on the concept of the diastereoseiective activation of carbonyl groups with MAD or MAT, the bulky, chiral organoaluminum reagent, (/ )-BINAL or (5)-BINAL has been devised for enantioselective activation of carbonyl groups. 

Fig. 2) Effective catalysts, reaction conditions, enantioselectivity, activity, and productivity...

The chiral oxygenophilic organoaluminum catalyst 12 bearing such a sterically hindered chiral auxiliary unit may form a stable 1 1 complex with benzaldehyde, allowing enantioselective activation of the carbonyl moiety as illustrated in Fig. 1. Then the diene 10a would approach benzaldehyde with an endo alignment of the aldehyde phenyl residue and 10a in order to minimize the steric... 

Harada et al. have found that the presence of traces of aluminium or Al-compounds in Ni catalysts are unfavorable for enantioselective activity. Therefore the use of Ni catalyst prepared by... 

Table 4.14. Catalytic and enantioselective activities of Raney Cu-Ru, Cu and Ru catalysts in the hydrogenation of ethyl acetoacetate (according to Kuznetsova et al.

The asymmetric synthesis of cyclopropanes has attracted continual efforts in organic synthesis, due to their relevance in natural products and biologically active compounds. The prevalent methods employed include halomethylmetal mediated processes in the presence of chiral auxiliaries/catalysts (Simmons-Smith-type reactions), transition-metal-catalyzed decomposition of diazoalkanes, Michael-induced ring closures, or asymmetric metalations [8-10,46], However, the asymmetric preparation of unfunctionahzed cyclopropanes remains relatively undisclosed. The enantioselective activation of unactivated C-H bonds via transition-metal catalysis is an area of active research in organic chemistry [47-49]. Recently, a few groups investigated the enantioselective synthesis of cyclopropanes by direct functionalization reactions. 

ABSTRACT. With the aid of selected examples an overview is given of the development trends in highly discriminative reactions using novel Lewis acid catalysts. 1) Bulky organoaluminum reagent, methylaluminum 3,3 -bis(triphenylsilyl)-l,r-bi-2-naphthoxide, has been successfully utilized for enantioselective activation of carbonyl moiety. 2) A novel reactivity of acyloxyborane derivatives and their usefulness in organic synthesis is demonstrated. As an example, asymmetric Diels-Alder reaction catalyzed by new acyloxyboranes derived from chiral acids is described. 

Among several terpene derived chiral ketones examined, 3-d-bromocamphor was found to be most satisfactory and 3d-bromocamphor is responsible for the generation of (S)-catalyst. Combination of the racemic catalyst and chiral ketone in a 1 1 ratio gave a better results, suggesting that decomplexation of one enantiomeric organoaluminum reagent and the chiral ketone is more readily facilitated by the addition of aldehyde, thereby allowing the enantioselective activation of the aldehyde for the asymmetric hetero-Diels-Alder reaction. 

Pan S, Matsuo Y, Endo K, Shibata T (2012) Cationic iridium-catalyzed enantioselective activation of secondary sp C-H bond adjacent to nitrogen atom. Tetrahedron 68 9009-9015... 

Terada, M. Soga, K. Momiyama, N. Enantioselective Activation of Aldehydes by Chiral Phosphoric Acid Catalysts in an Aza-Ene-Type Reaction between Glyoxate and Enecarbamate. Angew. Chem. Int. Ed. 2008, 47, 4122-4175. 

Seiser T, CramerN (2010) Rhodium(I)-catalyzed enantioselective activation of cyclobutanols formation of cyclohexane derivatives with quaternary stereogenic centers. Chem-Eur J 16(11) 3383-3391. doi 10.1002/chem.200903225... 

Another example is provided by Simonneaux et al. with macroporous optically active polymers (not obtained through anodic oxidation) bearing chiral porphyrins. These systems showed efficient catalytic and enantioselective activity for sulphide oxidations and epoxidation reactions [70, 71]. 

Charette et al. examined a Rh(ll)-carboxylate catalyst with four amino acid derived M-phthaloyl ligands [129]. This catalyst has seen widespread use, for example in the cyclopropanation of alkenes with diazo compounds. Depending on the orientation of these ligands (up or down), four different symmetries are possible. Previous studies were unable to clarify which is the enantioselectively active one (Scheme 15). 

---