Trisoxazolines

Pseudo-C3-symmetrical trisoxazoline copper(II) complexes prove to be excellent catalysts in the Friedel-Crafts alkylation of indoles with alkylidene malonates (Eq. 7.13). Water tolerance of chiral catalyst trisoxazoline/Cu(OTf)2 was examined, and it was found that the addition of up to 200 equivalents of water relative to the catalyst in /,vo-butyl... 

Nucleophilic attack at the 5-position of an oxazoline normally proceeds under acidic conditions. For example, in their total synthesis of thiangazole, Wipf and coworkers used thiolacetic acid to convert the trisoxazoline 337 to the S-protected cysteine derivative 338 that was further elaborated to thiangazole through aminol-... 

Several pseudo-C3-symmetric homo- and hetero-trisoxazolines have been developed and applied successfully in the asymmetric Michael-type alkylation of indoles with alkylidene malonates. The C3-symmetric trisoxazoline 121a-copper(C104)2 -6H20 complex, as a catalyst, is an air- and water-stable compound (Scheme 34) [108-110]. 

Enantioselective cycloadditions of nitrones with alkylidene malonates were catalyzed by the complex of Go(ll) with trisoxazoline 528. The cycloaddition was reversible and the diastereoselectivity could be controlled by reaction temperature. For example, A, C-diphenyl nitrone and diethyl 2-benzylidenemalonate reacted at —40°C under kinetic control, affording mainly the m-adduct 530, but at 0°C the thermodynamically more stable /ra r-isomer 529 was the major product (Equation 85) <20040L1677>. 

The enantiopure C3 symmetric trisoxazoline 173 proved to be a suitable supporting ligand for scandium-catalyzed olefin polymerization whilst invoking sufficient stereocontrol over the substrate to induce a high level of tacticity in the polymer microstructure <05AG(E)1668>. 

The complex of Co(II) with trisoxazoline 76 catalysed the 1,3-DC between a variety of nitrones and alkylidene malonates to give the corresponding isoxazolidines with both high enantio- and diastereoselectivity. The cycloaddition was reversibile and the endo/exo selectivity could be effectively controlled by reaction temperature. For example, 66 and 73 reacted in the presence of catalytic amounts of Co(C104)2 6H20 (5 mol%) and 76 (3.3 mol%) at -40 °C under kinetic control affording mainly the cis isoxazolidine 74, but at 0 °C the thermodinamically more stable trans isomer 75 was the major product <04OL1677>. 

Chiral trisoxazolines in asymmetric catalysis and molecular recognition 05CSR664. 

Sterically hindered trisoxazoline (TOX) ligands, such as 165, were exploited in Cu(II)-catalyzed enantioselective intramolecular Cannizzaro reactions of aryl and alkyl glyoxals with alcohols (13JA16849). 

Oxazolines are nowadays essential ligands in asymmetric catalysis and also important synthons for stereoselective synthesis [8]. The success of the Cj-symmetric bis(oxazolines) ( BOX ) and pyridine-bis(oxazolines) ( Pybox ) discovered in the early 1990s has established them as a privileged class of ligands [9]. In contrast, the development and application of trisoxazolines lagged behind for a long time. Katsuki and collaborators [10] reported the first example of a chiral trisoxazoline in 1995 and their use in the allylic oxidation of alkenes (Kharasch-Sosnovsky reaction), as well as the enantioselective addition of diethylzinc to aldehydes. 

The results obtained were promising, though, ultimately, not superior to those of the well-established C2-symmetric BOX systems. However, a class of non-Cg-symmetrical trisoxazolines was developed by Zhou and Tang [11] and successfully employed in a range of highly enantioselective catalytic transformations. 

Scheme 15.1 Modular assembly of trisoxazoline ligands by reaction of the metal-lated bisoxazolines with 2-bromooxazoline derivatives. This allows the synthesis of Cj-chiral ligands (A), the inversion of one...

Trisox as a Bidentate Ligand Chiral Trisoxazolines in Copper(ll) Lewis Acid Catalysis and Palladium-Catalyzed Asymmetric Allylic Substitutions... 

Pfaltz and coworkers [29] had previously investigated the allylic alkylation of l,3-diphenylprop-2-enyl acetate with dimethyl malonate as nucleophile (in the presence of A/ ,0-bis(trimethylsilyl)acetamide, BSA) with the well-established BOX ligands as stereodirecting ligands, and this particular system therefore provided the point of reference for the catalytic study at hand (Table 15.3, entry 1) [28]. Under the reaction conditions displayed in Scheme 15.4, the trisoxazoline-based catalysts generally induce a better enantioselectivity compared to their BOX analogs, and this behavior appears to be independent of the substituent, as shown in Table 15.3. 

Catalysis In a Tea Bag" with Dendrimer-lmmobilized Bis- and Trisoxazoline Copper Catalysts... 

The reason for the different behaviors of the two dendrimer catalysts was thought to be primarily the markedly lower activity of the trisoxazoline derivative compared to BOX-derived system, the probable origin of which has been discussed above. This necessitated increased reaction times for each cycle, leading to higher levels of metal ion leaching as well as the modification of the membrane structure due to its exposure to trifluoroethanol at 40 C. 

In 2007, Kang et al. improved the method conducted by Sibi and coworkers by maintaining the diastereoselectivity of the reaction of which Kerr and coworkers had originally reported, as well as maintaining excellent enantioselectivity with monosubstituted cyclopropane diesters [26]. This was achieved with the trisoxazoline Ugand as shown in Scheme 10.29. 

Figure 4.30 Carbosilane dendrimers bound bis- and trisoxazolines for the Cu-catalyzed asymmetric hydrazination and Henry reactions.

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