Bisoxazolines chiral

Bayardon and Sinou have reported the synthesis of chiral bisoxazolines, which also proved to be active ligands in the asymmetric allylic alkylation of l,3-diphenylprop-2-enyl acetate, as well as cyclopropanation, allylic oxidations and Diels-Alder reactions. [62] The ligands do not have a fluorine content greater than 60 wt% and so are not entirely preferentially soluble in fluorous solvents, which may lead to a significant ligand loss in the reaction system and in fact, all recycling attempts were unsuccessful. However, the catalytic results achieved were comparable with those obtained with their non-fluorous analogues. 

Chiral bisoxazolines (box) ligands have been attached to a polyethylene glycol (PEG) matrix 25.24 The supported ligands were tested on a variety of reactions for their enantioselectivity. The carbonyl-ene reaction between a-methyl styrene or methylene cyclohexane (26, Equation (15)) and ethylglyoxalate 12 afforded the corresponding ene adduct 27 in 96% and 91% yield and 95% and 85% ee, respectively. 

Figure 12.24. Chiral bisoxazoline complexes giving chiral 4-tBu-styrene/CO copolymers...

Under oxidation conditions, a C—C double bond can be functionalized by either two alkoxycarbonyl groups or one alkoxycarbonyl group and one heteroatom. As shown in Scheme 4.14, two ester groups are successfully introduced to styrene in an enantioselective manner, producing a phenylsuccinic ester using a Pd/MeO-BIPHEP complex. mcw-Diols are converted into cyclic ethers in an asymmetric manner when catalyzed by Pd/chiral bisoxazoline. Intramolecular aminopallada-tion followed by carbomethoxylation gives an cyclic amino ester in moderate ee when catalyzed by a Pd/bis(isoxazoline) complex. " ... 

Chiral dirhodium(II) carboxamidates are preferred for intramolecular cyclopropanation of allylic and homoallylic diazoacetates (Eq. 2). The catalyst of choice is Rh2(MEPY)4 when R " and R are H, but Rh2(MPPIM)4 gives the highest selectivities when these substituents are alkyl or aryl. Representative examples of the applications of these catalysts are listed in Scheme 15.1 according to the cyclopropane synthesized. Use of the catalyst with mirror image chirality produces the enantiomeric cyclopropane with the same enantiomeric excess [33]. Enantioselectivities fall off to a level of 40-70% ee when n is increased beyond 2 and up to 8 (Eq. 2) [32], and in these cases the use of the chiral bisoxazoline-copper complexes is advantageous. 

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>. 

Takacs, J.M., Hrvatin, P.M., Atkins, J.M., Reddy, D.S. and Clark, J.L. (2005) The selective formation of neutral, heteroleptic zinc(ll) complexes via self-discrimination of chiral bisoxazoline racemates and pseudoracemates. New J. Chem., 29, 263—265 Atkins, J.M., Moteki, S.A., DiMagno, S.G. and Takacs, J.M. (2006) Single enantiomer, chiral donor—acceptor metal complexes from bisoxazoline pseudoracemates. Org. Lett., 8 (13), 2759-2762. 

Encouraged by the excellent enantioselectivity in the conjugate radical addition, Sibi et al. further investigated the Michael addition of O-benzylhydroxylamine to pyrazol-derived croto-namides catalyzed by chiral bisoxazoline 30-MgBr2 complex (Scheme 8D.17) [38]. Good-to-high enantioselectivity (up to 95% ee) was achieved with 10 mol % of the catalyst. The trajectory... 

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. 

An enantioselective reaction also occurs in a system in which the alkene itself does not contain any chiral auxiliary, but a chiral ligand is used in combination with a Lewis acid. In the following example, a chiral bisoxazoline (BOX) ligand is successfully employed together with zinc triflate as a Lewis acid to achieve an enantiomeric excess as high as 90% (Scheme 6.21) [37]. 

Oxidative homo-coupling of enolates from acyl oxazolidinones to give the corresponding dimers can be achieved in the presence of oxidants. Titanium and ytterbium enolates of 252 were coupled in the presence of a chiral diol or chiral bisoxazoline in the presence of ferrocenium cation 254 (Scheme 63) [166]. The amount of the meso dimer varied with the chiral ligand with a maximum of 5 1. TADDOL 172 performed best providing a 76% ee for the meso product. Ytterbium enolate gave a low ee of 34% with the same ligand. 

Finally, the best enantioselectivity with this system was obtained by using cop-per(II) acetate, with propionic acid as additive, and by conducting the reaction at lower temperatures (70 %, 57 % ee) [20]. Later, the use of an azanorbornane add, which was a bicyclic analog of proline, resulted in better activity and enantioselectivity (65 % ee) [21], In the same year, Pfaltz reported the use of chiral bisoxazoline 3 in the enantioselective copper-catalyzed acyloxylation reaction (Scheme 3) [22], Although long reaction times were required, the enantioselectivity achieved with... 

Aryl iodides 590 react with nona-1,2-diene in the presence of a palladium catalyst and a chiral bisoxazoline ligand to afford isochromans 591 in good yield with moderate enantioselectivity (Equation 244) <1999JOC7312>. 

A palladium-catalyzed asymmetric annulation of the allene 1133 with 2-iodobenzoic acids proceeds in the presence of a chiral bisoxazoline ligand to afford 4-methylenedihydroisocoumarins in good yield and enantiomeric excess (Equation 440) <1999JOC7312>. 

The catalytic enantioselective addition of aromatic C - H bonds to alkenes would provide a simple and attractive method for the formation of optically active aryl substituted compounds from easily available starting materials. The first catalytic, highly enantioselective Michael addition of indoles was reported by Jorgensen and coworkers. The reactions used a,fl-unsaturated a-ketoesters and alkylidene malonates as Michael acceptors catalyzed by the chiral bisoxazoline (BOX)-metal(II) complexes as described in Scheme 27 [98,99]. 

The enantioselective alkylation of indoles catalyzed by C2-symmetric chiral bisoxazoline-metal complexes 90 encouraged many groups to develop superior asymmetric catalysts which are cheap, accessible, air-stable and water-tolerant. Other analogs of the bisoxazoline-metal complex 90 as chiral catalysts and new Michael acceptors have also been studied. The enantioselective alkylations of indole derivatives with of-hydroxy enones using Cu(II)-bis(oxazoline) catalysts 93 and 94 provided the adducts in good yields... 

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],... 

Diastereotopic differentiation of two leaving groups has been achieved for the first time by the reaction of (dichloromethyl)borates with BuLi in the presence of Yb(OTf)3 and the chiral bisoxazoline ligand 203.108 As shown in Figure 51, pinacol dichloromethyl boronate (204) gave 205 in up to 88% ee. The reaction can be said to be catalytic, as the use of 0.5 equiv. of chiral ligand 203 and 0.2 equiv. of Yb(OTf )3 provided 205 in 55% ee and 86% yield. 

Highly diastereoselective alkyl radical addition to Oppolzer s camphorsultam derivative (33) of oxime provides enantiomerically pure a-alkyl-a-amino acid derivative (34) at — 78 °C by the same method as shown in eq. 10.16. Moreover, enantioselective tandem radical 1,2-difunctionalization of cinnamamide (35) can be carried out with high stereoselectivity, using the chelation manner of the cinnamamide and a chiral bisoxazoline ligand on Mgl2, as shown in eq. 10.17. 

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