Copper bisoxazoline-derived complex

Bernadi and Scolastico, and later Evans in a more effective manner, indicated that the enantioselective addition reaction using silyl enol ethers can be catalyzed by Lewis acidic copper(II) cation complexes derived from bisoxazolines [38-40]. In the presence of the copper complex (S,S)-14 (10 mol %), silyl enol ethers derived from thioesters add to alkylidenemalonates or 2-alkenoyloxazo-lidone in high ees (Scheme 12). Bernadi, Scolastico, and Seebach employed a titanium complex derived from TADDOL for the addition of silyl enol ethers to nitroalkenes or 2-cyclopentenone [41-43], although these are stoichiometric reactions. 

The SbFe-derived complex 134 is approximately 20 times more reactive than its triflate analogue 66. The use of copper as the metal allows a well-defined catalyst with (distorted) square-planar geometry, and analysis of the catalyst-substrate complex 135 allows the prediction that the diene component will approach from the less hindered Re face of the dienophile (note that the dienophile adopts the s-cis conformation). The bisoxazoline ligand has C2-symmetry and this is beneficial as it reduces the number of competing diastereomeric transition states. 

The first Lewis acid-catalyzed exo and enantioselective cycloaddition of azome-thine imines with pyrazolidinone acrylates 147 was developed by Sibi in 2008 [54]. By using in situ formed copper(II)/bisoxazoline 25 complex as the catalyst, cycloadducts 149 derived from a variety of azomethine imines 148 were prepared in good to high yields with moderate to good exo selectivity and high enantioselectivity (Scheme 2.38). 

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 use of catalyst 187 or 188 (see Sch. 43) in cycloadditions requires anhydrous conditions. Recently, several practical alternatives for this requirement have been reported. Evans has shown that the easily manipulated aquo complex prepared from 187 and water can be dehydrated to the active catalyst in the reaction vessel by addition of molecular sieves, without any loss of reactivity or selectivity [87]. Copper(II) perchlorate is available commercially as a hexahydrate. Ghosh and co-workers have reported that a complex 207 prepared from an aminoindanol-derived bisoxazoline and Cu(C104)2 6H2O is an excellent Lewis acid in Diels-Alder reactions (Sch. 46). It is interesting to note that the generally sluggish reactions with oxazolidinone croto-nates proceed with very high selectivity at room temperature [88]. 

Some new combinations of chiral ligands with different Lewis acids have been lately evaluated in catalytic asymmetric 1,3-DC reactions of nitrones. When the complex derived from copper(II) triflate and bis(oxazoline) 72 was used as chiral catalyst in the cycloaddition of nitrone 66 and crotonate 68, both endo and exo isomers were obtained with very high enantioselectivities (7 3 dr > 99% ee). In this reaction, the presence of molecular sieves 4 A (MS) was crucial as in their absence the nitrone decomposed and almost no cycloadduct was obtained <04TL9581>. Sibi et al. found that square planar complexes derived from copper triflate and some chiral bisoxazolines favour the COZ-exo approach in the 1,3-DC of nitrone... 

Starting from an optically active dimer, tetramer, or octamer of 2,3-dihy-droxynaphthalene derivatives, Tsubaki and co-workers realized the synthesis of numerous optically active oligonaphthalene products by second-order asymmetric transformation under amine-copper conditions (Scheme 3.17). On the other hand, Okamoto and co-workers achieved asymmetric oxidative coupling polymerization (AOCP) reactions to synthesize poly(2,3-dihy-droxy-l,4-naphthylene) derivatives (Scheme 3.18). The starting materials of AOCP reactions can be either partially protected tetrahydroxybinaphthale-nes or 2,3-dihydroxynaphthalene. The chiral Cu complexes ligated by (-)-sparteine or bisoxazolines were identified as suitable catalysts for these reactions. However, the enantioselectivity attained in these AOCP reactions was estimated to be low. 

Yu and Luo et al. reported a catalytic enantioselective benzylic C(sp )-H functionalization of 207 via a [l,5]-hydride transfer/cyclization sequence with the chiral complex of copper(II) and side-armed bisoxazoline 209 as catalyst, which provided tetrahydronaphthalene derivatives 208 in moderate to high yield with up to 69 % ee (Scheme 79). 

Very recently a number of additional copper complexes with chirality derived from sources other than bisoxazoline ligands have been reported for application in enantioselective nitroaldol reactions [46]. Of particular interest was an application of iminopyridine ligand (161) in a Cu(II)-catalyzed nitroaldol reaction, Pedro and CO workers reported efficient addition of (154) to o-anisaldehyde (160) with good enantioselectivity (Scheme 17.33) [47]. 

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