Bisoxazolines ligands

An enormous variety of ligands have been applied to AAA, too many to mention. We will mention only two more groups of ligands, bisoxazolines and PHOX ligands. Bisoxazolines have been studied and reviewed by Pfaltz [8], They are also C2 symmetric bidentate ligands (Fig. 13.13) and the R-group can be easily varied to search for optimal rates and ee s. 

Keywords Aziridine, Dilmine ligands, Bisoxazoline, Copper... 

The cationic aqua complexes prepared from traws-chelating tridentate ligand, R,R-DBFOX/Ph, and various transition metal(II) perchlorates induce absolute enantio-selectivity in the Diels-Alder reactions of cyclopentadiene with 3-alkenoyl-2-oxazoli-dinone dienophiles. Unlike other bisoxazoline type complex catalysts [38, 43-54], the J ,J -DBFOX/Ph complex of Ni(C104)2-6H20, which has an octahedral structure with three aqua ligands, is isolable and can be stored in air for months without loss of catalytic activity. Iron(II), cobalt(II), copper(II), and zinc(II) complexes are similarly active. 

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... 

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

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. 

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 . 

Takacs has reported the cyclization of tu-enedienes catalyzed by an iron(0) complex that is generated in situ through the reduction of iron(m) tris(acetylacetonate) with triethylaluminum in the presence of a ligand such as 2,2 -bipyridine or bisoxazoline (Scheme 100). The 1,4-diene cycloadducts are obtained in very good yields.366... 

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. 

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-... 

An effective group of ligands for obtaining isotactic polymer are C2 symmetric bisoxazolines [68], Since C2v symmetric ligands gave syndiotactic... 

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