Pyridine-2,6-bisoxazoline

In 1997 the application of two different chiral ytterbium catalysts, 55 and 56 for the 1,3-dipolar cycloaddition reaction was reported almost simultaneously by two independent research groups [82, 83], In both works it was observed that the achiral Yb(OTf)3 and Sc(OTf)3 salts catalyze the 1,3-dipolar cycloaddition between nitrones 1 and alkenoyloxazolidinones 19 with endo selectivity. In the first study 20 mol% of the Yb(OTf)2-pyridine-bisoxazoline complex 55 was applied as the catalyst for reactions of a number of derivatives of 1 and 19. The reactions led to endo-selective 1,3-dipolar cycloadditions giving products with enantioselectivities of up to 73% ee (Scheme 6.38) [82]. In the other report Kobayashi et al. described a... 

A chiral pyridine-bisoxazoline ( PYBOX ) ligand has been combined with indium (III) triflate to produce an enantioselective catalyst for allylation of a wide variety of aldehydes in ionic liquids 183 ees of >90% were obtained, and extraction and reuse of the catalyst-ionic liquid combination saw this figure hold up to >80% on the fourth recycle. 

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

New 4-substituted phenyl(bisoxazoline) ligands (PHEBOX ligands) have been com-plexed with rhodium and examined as enantioselective catalysts of the reductive aldol of acrylates and aldehydes.160 The results have been compared with the corresponding pyridine-centred (PYBOX) ligand complexes. 

The additions of indoles to ethenetricarboxylates as Michael acceptors in the presence of copper(II) complexes (10%) of chiral bisoxazolines (97-100) under mild conditions gave the alkylated products in high yield and up to 96% ee [101]. The observed enantioselectivity could be explained by secondary orbital interaction on approach of indole to the less hindered side of the 102-Cu(II)-ligand complex. The chiral ligands 97-99 of the catalyst gave similar ee%. The phenyl derivative 100 produced inferior results compared to 97-99, while (S,S)-2,6-bis(4-isopropyl-2-oxazoline-2-yl)pyridine (101) gave no reaction (Scheme 29) [56]. The enantioselective alkylation of indoles with arylidene malonates catalyzed by z-Pr-bisoxazoline-Cu(OTf)2 was also reported [102],... 

The oxo-HDA reaction of 2-carbonyl derivatives of pyridine 1-oxide with electron-rich dienes catalysed by bisoxazoline Cu(II) complexes proceeds by a Mukaiyama-aldol route and affords dihydropyran-4-ones 33 in good yield and excellent enantioselectivity <07JOC240>. 

Evans has studied the asymmetric catalysis of carbon-carbon bond forming reactions with C2 symmetric bisoxazoline-Cu(II) complexes [18, 19J. The (+)-NLE observed in asymmetric aldol reactions catalyzed by the bis(oxazolinyl)pyridine... 

Miura and coworkers showed that the reaction could also be carried out using catalytic amounts of Cul in the presence of pyridine (95JOC4999). Asymmetric reactions were reported to occur with chiral bisoxazoline ligands producing p-lactams with moderate (40-68%) enantiomeric excesses. Use of an oxazolidinone with a chiral auxiliary appended to the alkyne also provided enantiomerically pure products (02TL5499). In all of these latter reports, mixtures of cis and irons lactam isomers were obtained in which the trans-product predominates. It was also shown that the c/s-isomer could easily be converted to the trans-product when exposed to base. 

The enantioselective copolymerization of styrenes and CO has also been achieved (Scheme 12). Using bidentate pyridine-imine ligands (26), Sen synthesized optically active styrene and 4-methylstyrene copolymers [80]. Based on a microstructural analysis, a 36% ee for olefin insertion was reported. Brookhart employed a C2-symmetrical bisoxazoline complex (27) to produce styrene-based... 

Chiral bisoxazolines were also used in the formation of a-substituted y-lactams (Eq. 7) [11]. Selectivity is controlled by the bidentate coordination of the chiral Lewis acid to the lactam carbonyl and the pyridine moiety. The combination of Zn(OTf)2 and ligand 19 proved to be the most effective combination, allowing for selectivities of up to >99% ee to be reached at -78 °C with 2 equivalents of chiral Lewis acid. Warming to -20 °C only decreased the enantioselectivity to 95% ee. Conversely, the use of substoichiometric amounts of chiral Lewis acid (20 mol%) substantially decreased the enantiomeric excess to 81% at —20°C. A trans octahedral model (21) is proposed to account for the sense of stereoinduction. 

The same group had earlier described the use of bisoxazoline ligands for nickel catalyzed fluorination reactions of 1,3-dicarbonyl compounds, [39] which was also observed for an elaborate 2-oxazolinyl pyridine ligand bearing an axially chiral methylenylamine in 6-position [40]. 

Cobalt(II) complexes with the chiral AA -dioxides (140a,b) have been reported to catalyse the cascade 1,5-hydride transfer and cyclization of (144) to afford tetrahy-droquinolines (145) in <90% ee. A plausible mechanism was proposed to account for the origin of the activation and asymmetric induction. a,/3-Enones decorated with the pyridine A-oxide chelating unit (146) have been shown to undergo a Michael addition of malonates, catalysed by a complex generated from (TfO)2Zn and the bisoxazoline ligand (147) with <96% ee ... 

An enantioselective process of this reaction has been developed by replacing the phenanthroline ligand with a chiral bisoxazoline or pyridine-oxazoline ligand (30,47,50). For example, the reaction of diene 35 catalyzed by palladium... 

A Cu-Box complex supported on monolith (51) was developed for the enantio-selective cydopropanation of ethyl diazoacetate. The flow reactions using (51) provided an increase in enantioselectivities of about 20% relative to those for the homogenous batch process (Scheme 7.38) [142]. Pyridine-oxazolidine based monoliths (52) and (53), whose central metals were Ru and Cu, respectively, were also developed [143,144]. Mesoporous silica was utilized as a support for the Cu-Box complex for asymmetric cydopropanation in a flow reador. Aza(bisoxazoline) was easily immobilized on siliceous mesocellular foam MCF) microparticles, which are... 

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