Bisoxazoline ligands

These processes could be performed in an enantioselective manner by addition of (-)-sparteine or bisoxazoline ligands in general the yields and ees were found to... 

Conjugate addition of iV-benzylhydroxylamine to pyrrolidinone cinnamate 101 catalysed by Mg(C104)2 and bisoxazoline ligand 103 gave the isoxazolidinone 102 in 80% yield and 96% ee . 

It is important to highlight that the regioselectiv-ity of nucleophilic addition in the above situation is entirely a result of unfavorable steric interactions between the bisoxazoline ligand and the r 3-allyl moiety. However, this is not the only means by which the regioselectivity may be influenced. As early as 1976, Faller and co-workers demonstrated... 

Chiral Lewis acid promoted atom transfer reaction (Kharasch reaction) of a-halo oxazolidinone imide 90 and 1-octene 92 has been reported by Porter et al. (Scheme 23) [78]. The enantioselective atom transfer utilizing Zn(OTf)2 and phenyl bisoxazoline ligand 93 as a chiral Lewis acid. The yields of the products, however, were quite low ranging from 5-15% and only moderate enantioselectivities were achieved (up to 40%). 

Arylation of activated double bonds with diazonium salts in the presence of copper catalysts is known as the Meerwin reaction. The reaction is postulated to either proceed through an organocopper intermediate or through a chlorine atom transfer from chiral CuCl complex to the a-acyl radical intermediate. Brunner and Doyle carried out the addition of mesityldiazonium tetrafluoroborate with methyl acrylate using catalytic amounts of a Cu(I)-bisoxazoline ligand complex and were able to obtain 19.5% ee for the product (data not shown) [79]. Since the mechanism of the Meerwin reaction is unclear, it is difficult to rationalize the low ee s obtained and to plan for further modifications. 

The high selectivity can be explained by the model shown in Scheme 25. Because of the steric bulk of the f-butyl groups of bisoxazoline ligand 96, reface cyclization (transition states 97 and 98) should be favored over si-face... 

Friestad and co-workers recently demonstrated that N-acyl hydrazones were excellent radical acceptors in the presence of a chiral Lewis acid [84], Valerolactam-derived hydrazone 117 proved to be the optimal substrate for enantioselective radical additions. Upon further optimization it was found that Cu(OTf )i and f-bulyl bisoxazoline ligand 96 gave the best yields and ee s (Scheme 31). Interestingly, a mixed solvent system (benzene dichloromethane in a 2 1 ratio, respectively) in the presence of molecular sieves (4 A) were necessary to achieve high yields and selectivities. 

A recent application of enantioselective conjugate radical additions was seen in the synthesis of (+)-ricciocarpins A and B [95]. The key step in the synthesis was an asymmetric addition of a functionalized radical precursor 141 to afford intermediate 142 (Scheme 37). A chiral catalyst screening revealed that Mgt and bisoxazoline ligand 19 was optimal for achieving... 

In a related study Porter et al. showed that a-bromo-y lactams 185 containing a pyridyl moiety can react with allyltrimethylsilane enantiose-lectively in the presence of chiral Lewis acids derived from zinc and 189 (Scheme 49) [142], In contrast to the above study, the ligand of choice for substrates 185 was found to be the bisoxazoline ligand 189. Excellent ee s were obtained in the presence of two equivalents of the chiral Lewis acid. Under substoichiometric amounts of the catalyst, lower selectivities were obtained. Different substituents on the pyridyl moiety were also examined although no predictable trend was observed. A trans octahedral model simi-... 

When the reaction is carried out with a racemic mixture of complexes, the product is a racemic mixture of the isotactic polymers. It was of interest to see what would happen if, after formation of a chiral block with one enantiomer of the bisoxazoline ligand, an equivalent of the other enantiomer was added. It was found that an excess of ligand changes the tacticity completely and the second block was syndiotactic In these diimine palladium complexes exchange of ligand is relatively fast and it can often be observed on the NMRtime scale as a broadening in the H NMR spectra. The process may well be associative. 

Undoubted, 2-haloaniline derivatives still maintain most vored precursor status for the preparation of the indole nucleus. Larock now reports the frill details of his examination of the asymmetric addition of IV-tosyl-2-iodoaniline (63) to allenes 64 (e.g. 1,2-undecadadiene) in the presence of palladium catafysts and chiral bisoxazoline ligand to afford chiral indolines 65 in up to 88% ee <99JOC7312>. Cook has utilized the palladhjm-catafyzed heteroannulation of iodoanilines with alkynes derivatized with the Schollkopf chiral auxiliary as a reliable route to optically active ring-A substituted tryptophans <99TL657>. 

Dagorne, S., Bellemin-Laponnaz, S. and Maisse-Francois, A. (2007) Metal complexes incorporating monoanionic bisoxazolinate ligands Synthesis, structures, reactivity and applications in asymmetric catalysis. Eur. J. Inorg. Chem., 913-925. 

Lowenthal and Masamune also reported that the copper complex bearing a bisoxazoline ligand 30 was an effective catalyst for aziridination of styrene (88% ee) (Scheme 6B.31) [76], However, Evans et al. later claimed that this result was not reproducible [75],... 

Another bisoxazoline ligand 31 was prepared from tartrate and applied to asymmetric aziridination. However, enantioselectivity observed was modest (Scheme 6B.33) [78], Bisaz-iridine ligand 32 was prepared, but its copper complex showed only modest enantioselectivity in the aziridination of styrene (Scheme 6B.34) [79],... 

Cu(II) and Sn(II) Bisoxazolinc Complexes. Evans has prepared and studied a family of Cu(II) complexes prepared from bisoxazoline ligands [8]. Utilizing these complexes a number of different addition reactions can be successfully conducted on pyruvate, benzyloxyacetalde-hyde, and glyoxylates. Whereas the focus of the work in the context of aldol addition reactions has been on the use of silyl ketene acetals (vide infra), the addition of ketone-derived enoxy silanes 8a-b with methyl pyruvate has been examined (Eq. 8B2.1). The additions of 8a-b proceed in the presence of 10 mol % Cu(II) catalyst at -78°C in CH2Cl2, affording adducts of acetophenone 9a and acetone 9b with 99% and 93% ee, respectively. 

Impressive advances in catalytic, enantioselective propionate aldol addition reactions have also been documented since 1992. Mikami has described a Ti(lV) catalyst readily prepared from BINOL and TiC O Pr. A propionate aldol addition process by Evans utilizes complexes prepared with bisoxazoline ligands and Sn(II) and Cu(II). In analogy to the acetate aldol... 

Several Lewis acids were investigated in enantioselective radical additions to cinnamoyl oxazolidone 59 using chiral bisoxazoline ligand. With Fe(NTf2)2 and fBu-BOX ligands, up to 80% ee were achieved (Scheme 8.26) [86], Selectivities up to 98% were obtained when Mg(NTf2)2 was used as the precatalyst. 

Heterocyclic products such as indolizidines and quinolizidine (Scheme 9.7) could also be obtained, as was shown by Takacs et al. for the synthesis of 5 in a stereoselective fashion applying a chiral bisoxazoline ligand [18]. The product was obtained in 65% yield with excellent diastereoselectivity and the enol ether was formed exclusively as the E-isomer. 

In addition to these commonplace substrates, only a few extraordinary educts have been used in iron-catalyzed DA reactions, such as the naphthoquinones investigated by Brimble and McEwen [75]. Whereas the application of FeCl3 and a chiral bisoxazoline ligand gave only a 25% yield and no chiral induction in the reaction of 2-acetyl-l,4-naphthoquinone with cyclopentadiene, the corresponding copper(II) triflate gave a 66% yield and moderate enantioselectivities (up to 50% ee). Another example was reported by Shibasaki s group in which the 2-alkoxy-l,3-butadiene 40... 

In this case a chiral bisoxazoline ligand was used S. Kanemasa, K. Adachi, H. Yamamoto, E. Wada, Bull. Chem. Soc.Jpn. 2000, 73, 681. 

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. 

Sibi and Chen [42] reported a related tandem intermolecular nucleophilic free-radical addition-trapping reaction of enoate 168 establishing chirality at both a and /(-centers with control over both absolute and relative stereochemistry (Scheme 9.30) using a Lewis acid catalyst and the bisoxazoline ligand 169. They observed... 

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