Alkylation bisoxazoline with

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 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. 

An enantioselective nitro-Mannich reaction of alkyl- and aryl-benzylimines gives /3-nitroamines in high ee, using a chiral copper(II)-bisoxazoline catalyst, with the products affording 1,2-diamines by reduction.30... 

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],... 

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. 

Analogous alkylations with unsaturated ketones can also be effected with silica-supported benzenesul-fonic acid sodium salt or, with some stereoselectivity, using a chiral imidazolidinone organo-catalyst. Optical induction can also be achieved in the addition of indole to alkyhdene malonates using bisoxazoline copper(II) complexes. ... 

Chiral bisoxazoline associated with palladium is a very efficient organometallic catalyst for the asymmetric allylic alkylation of allylic acetates and carbonates, allowing the formation of carbon-carbon as well as carbon-heteroatom bond in enantiomeric excesses higher than 95%.[1,2] However one of the problems in organometallic homogeneous catalysis is the separation of the catalyst, often toxic and very expensive, from the product(s) of the reaction. Very recently, a chiral fluorous bisoxazoline (Figure 3.1) has been shown to be an efficient ligand in the... 

The synthesis of chiral fluorous bisoxazolines is very easy to reproduce. This ligand in association with palladium is an efficient catalyst for the asymmetric catalytic alkylation of l,3-diphenylprop-2-enyl acetate with various carbonucleophiles. Table 3.2 gives some examples of such allylic alkylation. 

Chiral polycyclic indoles are ubiquitous and important ring systems found in many bioactive alkaloids and pharmaceuticals. Various methods have been developed for the efficient construction of the polycyclic indole derivatives. Recently, an unprecedented approach to a wide range of diverse, enantioenriched 2,3-dihydro-lH-pyrrolo[l,2-a]indoles 75 was demonstrated by Chen, Xiao, and co-workers. In the presence of 5 mol% Cu(OTf)2 and 5 mol% commercially available bisoxazoline 76 in toluene at 0 °C, the AFC alkylation/N-hemiacetalization cascade reaction of substituted indoles with P,y-unsaturated a-keto esters 74 occurred smoothly to afford products 75 in high yields with excellent diastereo- and enantioselectivity (Table 6.9). 

Recently, the Jia group reported AFC alkylation reactions of p,p-disub-stituted nitroalkenes with indoles. The AFC alkylation of indoles with p-CFa-p-disubstituted nitroalkenes 148 and acyclic a-substituted-p-nitroacry-lates 149 was achieved by using Ni(Cl04)2/bisoxazoline 147 complex as a catalyst, affording indoles bearing an all-carbon quaternary stereogenic center in good yields with excellent enantioselectivity (up to 97% ee) (Scheme 6.67). ... 

Scheme 6.67 Ni(Cl04)2/bisoxazoline 147 complex catalyzed AFC alkylation of indoles with P-CFj-p-disubstituted nitroalkenes 148 and acyclic a-substituted-P-nitroacrylates 149 reported by Jia.

Friedel-Crafts Alkylation. The Pr-bisoxazoline-Cu(OTf)2 system is an efficient catalyst in Friedel-Crafts alkylation of indole (eq 17) with arylidene malonates. Using 10 mol of Cu(OTf)2 in FBuOH, the 5-enantiomer was obtained in yields ranging from 50 to 94% and with 97% ee (eq 17, R = H, Ri = Et). The opposite enantiomer was obtained at 0°C by using CH2CI2 or 1,1,2,2-tetrachloroethane as solvent, in up to 78% ee. The Cu(OTf)2-Pr-bisoxazoline system also proved to be efficient for the asymmetric Friedel-Crafts reaction of indole derivatives with arylidene mal-onates. 

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