Cu /pybox complex

Landais has extended his desymmetrization of dienes from dihydroxylation approaches to a cyclopropanation reaction. A Cu-pybox complex provides the highest enantioselectivities and good diastereoselectivity in the asymmetric cyclopropanation of the silyl-substituted cyclopentadiene 210 ... 

Figure 13 Structure of an ir-PCP pincer complex and of a Cu-PyBox complex...

The aldehyde 157 was prepared according to the sequence in the synthesis of Evans total synthesis of callipeltoside A (Scheme 33) [75]. The vinylidene asymmetric Mukaiyama aldol reaction of a-oxy aldehyde 159 and silyl ketene acetal 160 catalyzed by Cu-pybox complex 161 [76] furnished 5-hydroxy-a, /l-unsaturated ester 162 in 95% ee, which was reduced to yield 157. 

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. 

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]. 

Similar to the CuOTf/PyBox system, the CuBr/QUINAP system also gave high enantioselectivities of the three component reactions to construct propargyl amines from aldehydes, amines, and alkynes (Scheme 5.6). In this system various aldehydes including aromatic aldehydes and aliphatic aldehydes could be used and a wide range of chiral propargyl amines were prepared in good yields and enantioselectivities. Mechanistic studies showed that the dimeric Cu/QUINAP complex is the catalytically active species that differs from the previous reaction. 

C2-symmetric bis(oxazolinyl)pyridine (pybox)-Cu (II) complex 27 has been shown to catalyze highly enantioselective Mukaiyaraa aldol reactions between (benzyloxy)acetaldehyde and silyl ketene acetals by Evans and co-workers as exemplified in Scheme 1-9 [38]. Here, the requirement for a chelating substituent on the aldehyde partner is critical to catalyst selectivity, as a-(terl-butyldimethylsil-oxy)acetaldehyde gave lower enantioselectivity (56% ee). In addition, P-(benzyl-oxy)propionaldehyde provided the racemic product, indicating a strict requirement for a five-membered catalyst-substrate chelate. 

Copper complexes of chiral Pybox (pyridine-2,6-bis(oxazoline))-type ligands have been found to catalyze the enantioselective alkynylation of imines [26]. Moreover, the resultant optically active propargylamines are important intermediates for the synthesis of a variety of nitrogen compounds [27], as well as being a common structural feature of many biologically active compounds and natural products. Portnoy prepared PS-supported chiral Pybox-copper complex 35 via a five-step solid-phase synthetic sequence [28]. Cu(l) complexes of the polymeric Pybox ligands were then used as catalysts for the asymmetric addition of phenylacetylene to imine 36, as shown in Scheme 3.11. tBu-Pybox gave the best enantioselectivity of 83% ee in the synthesis of 37. 

Schreiber and co-workers demonstrated that an indan (PyBox)-Cu(II) complex (140) was able to catalyze the P-3CR (Scheme 5.43) [86]. Nevertheless, the enantio-enriched Passerini adduct was obtained only when the chelating aldehyde was used as a reaction partner. 

Chiral Catalysts Containing Group 11 Metals (Cu, Ag, and Au). The most recent publications on the chiral copper catalysts are mainly dealing with those containing bis(oxazoline)-type ligands (Fig. 22). Cationic [Cu( Bu-BOX)] + complexes with OTf , [SbFe] , counterions catalyze Michael reactions, and various types of cycloadditions (292). Copper(II)-PYBOX complexes have been shown to catalyze enantioselective Mukaiyama aldol reactions (293). Similarly, bisoxa-zoline derivatives serve as ligands in the catalytic system prepared in situ from Cud) salts and are used for asymmetric peroxidation and enantioselective Meer-wein arylation of activated olefins (294). The copper-BOX-triflate complexes have found wide applications in cyclopropanation of alkenes (60), furans (295), and aziridination of alkenes (296). 

The use of chiral copper Lewis acids in enantioselective aldol processes has seen rapid development over the past 10 years. In particular, copper-catalyzed variants of the Mukaiyama aldol reaction received considerable attention in the years leading up to the new millennium. Evans and coworkers first demonstrated Cu(II)/pybox complex (59) as an efficient catalyst for highly enantioselective addition of a variety of silylketene acetals to aldehydes capable ofbidentate coordination (Scheme 17.12) [17]. In reactions utilizing silylketene acetals (61) and (63) with an additional stereoelement, diastereoselectivities and enantioselectivities were also high. A square pyramidal model (65), which has been further supported by a crystal structure of the complex, with the a-alkoxy aldehyde bound in a bidentate fashion accounts for the observed selectivity. 

C2-symmetric bis(oxazolinyl)pyridine (pybox)-Cu(II)-complexes have been shown to catalyze the enantioselective Mukaiyama aldol reaction between (benzyloxy)acetaldehyde and TMSOF in excellent yield, diastereo- and enantioselectivity (cqS )." ... 

Copper-bis oxazolidinone complex catalyzed the addition of alkyl and aromatic alkynes to the imine formed by the reaction of ethyl glyoxylate and p-anisidine, providing an easy access to chiral p,Y-alkynyl a-amino acids in good yields (61-80%) and enantioselectivities (66-74%) [38]. The presence of the two phenyl groups in the ligand was found to be crucial in the enantioselectivity enhancement and reduction of the reaction time, with aryl alkynes providing better results than alkyl acetylene derivatives [39]. Another type of Cu(II)-pybox complex led to excellent results in terms of enantioselectivities (28-93% yield, 81-98% ee) in the reaction of aliphatic alkynes with aldehydes and amines [40]. 

Figure 24. X-ray crystal structures of the [Cu((5, 5)-i-Pr-pybox)](H20)n]X2 complexes 267b and 267b along with selected bond lengths and angles. [Adapted from (197).]...

Allylic oxidation of a variety of cyclic alkenes with copper complexes of different pybox ligands (8) and with various peresters shows high enantioselectivity (80-96% ee). Use of phenylhydrazine as an additive and acetone as solvent accelerates the reaction. It has been suggested that the phenylhydrazone is responsible for the observed acceleration. Using EPR spectra, it has been shown that the Cu(II) species is reduced to Cu(I) by phenylhydrazine and phenylhydrazone. It has been found that the presence of a gem-diphenyl group at C(5) and a secondary or tertiary alkyl substituent at the chiral centre at C(4) of the oxazoline rings is crucial for high enantioselectivity. 

The use of (A,A)-/-Pr-pybox-Cu(OTf)2 complex as a catalyst preferentially produces the optically active syn-aldol... 

Shao, Chan, and coworkers have developed the first catalytic asymmetric synthesis of chiral p.y-alkynyl a-amino acid derivatives 404 in 61-80% yields and moderate enantioselectivities (66-74%), using ethyl glyoxylate 400, p-anisidine 401, and aliphatic or aromatic alkynes 402 (Scheme 6.60) [126]. This process is catalyzed by a catalyst system between Cu(I) triflate benzene complex and 10mol% of pybox catalyst 403. 

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