Atropisomeric C2-symmetric

The dione 214 upon treatment with hydrazine afforded 215, which was converted into 2,2 -bis(bromomethyl)-3,3 -biquinazoline-4,4 -dione 217 (Scheme 47) via 216. The racemic 1,2,5-triazepine ( )-53 was obtained from 217 by reaction with aqueous ammonia in THF. The enantiomerically pure (—)-53 was formed by refluxing ( )-53 with (+)-CSA (camphorsulfonic acid) <1999CC1991>. It is interesting that this work is the first nonracemic example of a C2-symmetric bis-heterocycle, which is atropisomeric by virtue of retarded rotation around an N-N bond. 

As unique C2-symmetric transition metal complexes, the atropisomeric (Rp,Rp)-2,2 -bi([2]paracyclo[2]-5,8-quinolinophane) (52) and (Rp,Rp)-1,1 -bi([2]paracyclo [2]-5,8-isoquinolinophane) (53) were prepared from (/ p)-4-amino- and (Rp)-4-carboxy-[2.2]paracyclophanes, respectively. The CD spectra of 52 and 53 were significantly different from each other (Fig. 14) [60]. The bisquinoline moieties are in almost planar orientation in 2,2 -isomer 52 and the origin of chirality is ascrib-able primarily to the paracyclophane structure. In contrast, the main source of chirality in l,l -isomer 53 is the distorted bisquinoline chromophores (i.e., the axial chirality). 

When coordinated to the metal, the chiral ligand plays an important role in the control of enantioselectivity during the course of the catalysis reaction. These ligands can contain chirality in the backbone (e.g.. CHIRAPHOS, 1), at the phosphorus atom (e.g., DIP AMP, 2), or atropisomerically from C2 symmetric axial configurations (e.g., BINAP, 3). Typically, most chiral ligands possess di-phenylphosphine moieties (Figure 1). 

If ethylbromoacetate is replaced in the alkylation reaction by /-butylbromoace-tate, the residues R are bulky enough to hinder not only the rotation around the Ar-Ar bonds but also around the Ar-CH2 Ar bonds. This means the diphenylmethane subunits become asymmetric (atropisomeric), too. In addition to a C2 symmetric derivative now also an asymmetric (Ci) derivative exists for the / ,/ , 5/5,5,/ configuration of the biphenyl units (see Figure 6). Both diastereomers could be isolated in pure form and converted by transesterification into the same (C2 symmetrical) hexamethylester which was also obtained from the hexaethylester. 

With the purposes of structure simplification and reactivity enhancement, further optimization led to a series of catalysts of the type 36-38 by replacing the rigid and highly lipophilic binaphthyl moiety with flexible and more polar straight-chain alkyl groups (Figure 12.9) [68-70]. In addition, the modification of the electronic and steric properties of atropisomeric biphenyl backbone could lead to the development of new, efficient C2-symmetric chiral phase-transfer catalysts 39 [71], 40 [72], and 41 [73] with conformationally fixed biaryl unit core, which were found to be quite effective for the asymmetric alkylation reactions. 

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