Pybox

Evans et al. reported that the his(oxazolinyl)pyridine (pybox) complex of copper(II) 17 is a selective catalyst of Diels-Alder reactions between a-bromoacrolein or methacrolein and cydopentadiene affording the adducts in high enantioselectivity [23] (Scheme 1.30). Selection of the counter-ion is important to achieve a satisfactory reaction rate and enantioselectivity, and [Cu(pyhox)](ShFg)2 gave the best result. This catalyst is also effective for the Diels-Alder reaction of acrylate dieno-philes (vide infra). 

Evans s bis(oxazolinyl)pyridine (pybox) complex 17, which is effective for the Diels-Alder reaction of a-bromoacrolein and methacrolein (Section 2.1), is also a suitable catalyst for the Diels-Alder reaction of acrylate dienophiles [23] (Scheme 1.33). In the presence of 5 mol% of the Cu((l )-pybox)(SbF5)2 catalyst with a benzyl substituent, tert-butyl acrylate reacts with cyclopentadiene to give the adduct in good optical purity (92% ee). Methyl acrylate and phenyl acrylate underwent cycloadditions with lower selectivities. 

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... 

Jacobsen developed a method employing (pybox)YbCl3 for TMSCN addition to meso-epoxides (Scheme 7.22) [46] with enantioselectivities as high as 92%. Unfortunately, the practical utility of this method is limited because low temperatures must be maintained for very long reaction times (up to seven days). This reaction displayed a second-order dependence on catalyst concentration and a positive nonlinear effect, suggesting a cooperative bimetallic mechanism analogous to that proposed for (salen)Cr-catalyzed ARO reactions (Scheme 7.5). 

Davies [30] studied the PyBOx-induced conformational effects by testing several ligands sterically hindered on the oxazoUne moieties (Scheme 11, structures 18 and 19). However, these new ligands gave poorer results in terms of yields and enantioselectivities than ligand 16 for the Ru-catalyzed cyclopropanation reaction, indicating unfavorable steric interactions between styrene and the carbene complex. 

Cornejo et al. [65] reported the first immobihzation of pyridine-bis(oxa-zoline) chiral hgands and the use of the corresponding solid ruthenium complex in the model cyclopropanation test. They synthesized vinyl-PyBOx, the vinyl functionahty being introduced in the fourth position of the pyridine ring. This monomer was further homo- or copolymerized in the presence of styrene and divinylbenzene. The corresponding ruthenium catalysts proved... 

Ghosh et al. [70] reviewed a few years ago the utihty of C2-symmetric chiral bis(oxazoline)-metal complexes for catalytic asymmetric synthesis, and they reserved an important place for Diels-Alder and related transformations. Bis(oxazoline) copper(II)triflate derivatives have been indeed described by Evans et al. as effective catalysts for the asymmetric Diels-Alder reaction [71]. The bis(oxazoline) Ugand 54 allowed the Diels-Alder transformation of two-point binding N-acylimide dienophiles with good yields, good diastereos-electivities (in favor of the endo diastereoisomer) and excellent ee values (up to 99%) [72]. These substrates represent the standard test for new catalysts development. To widen the use of Lewis acidic chiral Cu(ll) complexes, Evans et al. prepared and tested bis(oxazoHnyl)pyridine (PyBOx, structure 55, Scheme 26) as ligand [73]. 

Several groups have reported the use of rare earth complexes as catalysts for asymmetric Diels-Alder reaction. Qian and Wang described thus the preparation and use of Yb complexes chelated by Pr-PyBOx to successfully achieve the hetero-Diels-Alder reaction of methyl glyoxylate with Danishefsky s diene in 77% ee and 73% yield (Scheme 37) [98]. 

Fukuzawa et al. [99] found analogous scandium(III)triflate/ Pr-PyBOx complex as efficient catalyst for the asymmetric Diels-Alder reaction between cyclopentadiene or acyclic dienes and acyl-l,3-oxazohdin-2-ones with up to 90% ee. They latter described the same reaction in super critical CO2 in the presence of MSdA [ 100] that proceeded more rapidly than in CH2CI2 leading to the expected product with analogous selectivity. 

Desimoni et al. [101] further investigated the influence of the variation of the lanthanide and of the PyBOx ligand (bearing a Pr- or Ph-substituent with the same configuration) on the enantioselectivity of the Diels-Alder test... 

Evans and Wu have prepared complexes derived from PyBOx ligands and samarium or gadolinium triflates that were efficient for the Diels-Alder reaction between various quinones and dienes [102] (see Scheme 38 for an example). 

In 2004, ruthenium-catalysed asymmetric cyclopropanations of styrene derivatives with diazoesters were also performed by Masson et al., using chiral 2,6-bis(thiazolines)pyridines. These ligands were prepared from dithioesters and commercially available enantiopure 2-aminoalcohols. When the cyclopropanation of styrene with diazoethylacetate was performed with these ligands in the presence of ruthenium, enantioselectivities of up to 85% ee were obtained (Scheme 6.6). The scope of this methodology was extended to various styrene derivatives and to isopropyl diazomethylphosphonate with good yields and enantioselectivities. The comparative evaluation of enantiocontrol for cyclopropanation of styrene with chiral ruthenium-bis(oxazolines), Ru-Pybox, and chiral ruthenium-bis(thiazolines), Ru-thia-Pybox, have shown many similarities with, in some cases, good enantiomeric excesses. The modification... 

Favorable results have also been achieved using PyBOX type catalysts. Acryloyl and crotonoyloxazolidinones gave 80-95% yields, 90-98% e.e., and more than 9 1 endo-diaslereoseleclivity in reactions with /V-phenylbenzylidene nitrones.159... 

Nishiyama et al. introduced a new catalyst, the chiral tr<2 i -RuCl2(Pybox-i-Pr)(ethylene) complex (91), which showed for the first time both enantio- and diastereoselectivity (trans-selectivity) at excellent levels in the reactions of terminal olefins (Scheme 66).251-253 With 4-substituted Ru(Pybox-i-Pr) complexes (92), they studied the substituent effect on enantioselectivity... 

It has been widely accepted that the carbene-transfer reaction using a diazo compound and a transition metal complex proceeds via the corresponding metal carbenoid species. Nishiyama et al. characterized spectroscopically the structure of the carbenoid intermediate that underwent the desired cyclopropanation with high enantio- and diastereoselectivity, derived from (91).254,255 They also isolated a stable dicarbonylcarbene complex and demonstrated by X-ray analysis that the carbene moiety of the complex was almost parallel in the Cl—Ru—Cl plane and perpendicular to the pybox plane (vide infra).255 These results suggest that the rate-determining step of metal-catalyzed cyclopropanation is not carbenoid formation, but the carbene-transfer reaction.254... 

The Ru(Pybox- -Pr) complex (91), which induces high trans- and enantioselectivity in intermolecular cyclopropanation, has also been applied to the cyclization of allyl diazoacetates (Scheme 80) 252 The enantioselectivity observed depends largely on the susbstitution pattern of the allyl moiety. 

Cycloaddition reactions of alkenes DIO with nitrones were also catalyzed by Yb(OTf)3, by Sc(OTf)3 (795), by chiral 2,6-bis(4R-trialkylsiloxymethyl-oxazolinyl)pyridine/Ni(II) (pybox) (Fig. 2.43) (796a), and by chiral bis(2-oxazolinyl)xanthene (xabox) (Fig. 2.44) (796b). 

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