C2-symmetric bisoxazolines,

Chiral C2-symmetric bisoxazoline-copper(II) complexes [30, 31] were introduced as catalysts for cycloaddition and ene reactions of glyoxylates with dienes [9] leading to intense activity in the use of these catalyst for different cycloaddition reactions. 

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

Scheme 3. C2-symmetric bisoxazoline 3 in allylic oxidation according to Pfaltz.

After the initial successful application of C2-symmetric bisoxazolines, other oxazo-line-based ligands were also employed. Andrus developed biaryl bisoxazolines 4 with both axial and central chirality [25], Compared to the C2-symmetric bisoxazolines, however, these ligands were less successful in the oxidation of simple cyclic olefins (for cyclopentene 78 % yield, 73 % ee at -20 °C with tert-butyl-p-nitrobenzoate). 

The C2-symmetric bisoxazolinate 175 formed complexes with lanthanides for the catalysis of enantioselective intramolecular hydroamination /cyclization <03JA14768>. 

C2-Symmetric Bisoxazolines as Ligands in Asymmetric Catalysis. Methylenebis(oxazolines) such as (1), (3), and (5) are patterned after the semicorrins, which have been successfully employed as ligands in enantioselective Cu-catalyzed cy-clopropanations and other reactions (see (IS,9S)-I,9-Bis [(t-butyl)dimethylsilyloxy]methyl- 5-cyanosemico rrin). The potential of bisoxazoline ligands of this type, which has been recog-... 

Evans has studied the asymmetric catalysis of carbon-carbon bond forming reactions with C2 symmetric bisoxazoline-Cu(II) complexes [18, 19J. The (+)-NLE observed in asymmetric aldol reactions catalyzed by the bis(oxazolinyl)pyridine... 

Evans has recently reported the use of structurally well-defined Sn(II) Lewis acids 119 and 120 (Fig. 9)for the enantioselective aldol addition reactions of a-heterosubstituted substrates [83]. These complexes are easily assembled from Sn(OTf)2 and C2-symmetric bisoxazoline Hgands 124 and 126 (Fig. 10). The facile synthesis of these ligands commences with optically active 1,2-amino alcohols 122, which are themselves readily available from the corresponding a-amino acids 121 [84, 85]. The Sn(II) bis(oxazoHne) complexes were shown to function optimally as catalysts for enantioselective aldol addition reactions with aldehydes and ketone substrates that are suited to putatively chelate the Lewis acid. For example, using 10 mol % of 119, thioacetate and thiopropionate derived silyl ketene acetals add at -78 °C in CH2CI2 to glyoxaldehyde to give hydroxy diesters 130 in superb yields and enantioselectivities as well as diastereo-selectivities (Eq. 12). The process represents an unusual example wherein 2,3-anti-aldol adducts are obtained in a stereoselective manner. 

The enantioselective copolymerization of styrenes and CO has also been achieved (Scheme 12). Using bidentate pyridine-imine ligands (26), Sen synthesized optically active styrene and 4-methylstyrene copolymers [80]. Based on a microstructural analysis, a 36% ee for olefin insertion was reported. Brookhart employed a C2-symmetrical bisoxazoline complex (27) to produce styrene-based... 

Figure 6.20. (a) Acryloyloxazolidinone in bidentate coordination. strain favors the s-cis conformation, (b) Cycloaddition of Ci-symmetric bisoxazoline-magnesium complex [206]. (c) Cycloaddition of C2-symmetric bisoxazoline-copper complex [205]. (d) Rationale for the different topicities of the bisoxazoline complexes, even though both ligands have the same absolute configuration. The dienophile is awn in the plane of the paper, and the favored approach is from the direction of the viewer. 

The chemistry is a development of earlier methodology. [17] The organolithium additions to A-aryl imines 18, are promoted by C2-symmetric bisoxazoline (BOX) ligands, [18] e.g. 20, or (-)-sparteine [19] 21 (Scheme 4) with high asymmetric induction. 

In 1994 Denmark and coworkers reported a major advance in the asymmetric addition of organolithium reagents to imines using bisoxazolines as ligands (e.g., 19, Scheme 7) excellent yields and high levels of ee were observed [29,30]. C2-Symmetric bisoxazolines have been widely used as ligands in asymmetric... 

Complexes 24, 25, and 26 aU possess two neutral and two anionic ligands, respectively, and they are included in this section although they do not have halide ligands. Each of C2-symmetric bisoxazoline complexes 24 and 25 has two tiifluoroacetate ligands and is a good catalyst for asymmetric Wacker-type cyclization. Complex 26, applied to the asymmetric Fujiwara-Moritani reaction, is a rare example of having anionic chelate... 

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. 

Double lithiation of bisoxazoline 314 is possible with either s-BuLi or f-BuLi, and each base gives different planar diastereoselectivity. Double lithiation with i-BuLi, quenching the dianion with ClPPh2, leads to the C2-symmetric bisphosphine 315 as the... 

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... 

Many other chiral copper catalysts have been reported, most of them being derived from C2-symmetrical bidentate nitrogen ligands [13, 27]. Some ligands such as the bipyridine derivatives 14 [60, 61, 62], the diamine 15 [63] and the bis(azaferrocene) 16 [64] are capable to induce high ees, but none of them can compete so far with chiral bisoxazolines in terms of high selectivity combined with effectiveness, general applicability and ease of preparation. 

In 2006, Pfaltz et al. demonstrated that boron-bridged anionic bisoxazoline C2-symmetric ligands could be successfully employed in the copper(II)-catalysed benzoylation of pyridyl alcohols, providing selectivity factors of up to 125 [36]. In... 

Reactions of A-tosyliminophenyliodinanes (PhI=NTs) as nitrene source with alkenes in the presence of chiral ligands also present a valuable method to achieve asymmetric aziridination reactions. Cinnamate esters 73 yield enantiomeric aziridinate products in good selectivities on reaction with chiral bisoxazolines 23 and Al-tosyliminophenyliodinanes in the presence of copper salts (Scheme 29) [87]. Biaryl Schiff bases 74 can also be used as ligands in the enantioselective aziridination of ciimamate esters, chromenes and st5renes [88]. Chiral C2-symmetric salen-type ligands 75 were also found to be highly effective for the... 

Evans studied a family of Cu- and Sc-catalyzed enantioselective conjugate addition processes in the presence of C2-symmetric chiral bisoxazoline... 

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