Oxygen chiral ester approach

An alternative approach in the asymmetric catalysis in 1,3-dipole cycloaddition has been developed by Suga and coworkers. The achiral 1,3-dipole 106 was generated by intramolecular reaction of an Rh(ii) carbene complex with an ester carbonyl oxygen in the Rh2(OAc)4-catalyzed diazo decomposition of <9-methoxycarbonyl-o -diazoacetophenone 105 (Scheme 12). The asymmetric induction in the subsequent cycloaddition to G=G and G=N bond was achieved by chiral Lewis acid Sc(iii)-Pybox-/-Pr or Yb(iii)-Pybox-Ph, which can activate the dipolarophile through complexation. With this approach, up to 95% ee for G=0 bond addition and 96% ee for G=G bond addition have been obtained, respectively. ... 

Once the [3+2] mechanism was accepted as the operative one, to investigate the transition states associated with the formation of the osmate ester in a chiral system, one must take into account all of the different ways that an olefin can approach the catalyst. These different paths were classified according to the criteria shown in Fig. 12. The olefin binds to an axial and to an equatorial oxygen, providing three different families of reaction paths labeled as regions A, B and C. When the olefin has one substituent, it can be placed in four different orientations , which are labeled as I, II, III, IV. The... 

A variety of methods exists for the synthesis of optically active amino acids, including asymmetric synthesis [85-93] and classic and enzymatic resolutions [94-97], However, most of these methods are not applicable to the preparation of a,a-disubstituted amino acids due to poor stereoselectivity and lower activity at the a-carbon. Attempts to resolve the racemic 2-amino-2-ethylhexanoic acid and its ester through classic resolution failed. Several approaches for the asymmetric synthesis of the amino acid were evaluated, including alkylation of 2-aminobutyric acid using a camphor-based chiral auxiliary and chiral phase-transfer catalyst. A process based on Schollkopf s asymmetric synthesis was developed (Scheme 12) [98]. Formation of piperazinone 24 through dimerization of methyl (5 )-(+)-2-aminobutyrate (25) was followed by enolization and methylation to give (35.6S)-2,5-dimethoxy-3,6-diethyl-3.6-dihydropyrazine (26) (Scheme 12). This dihydropyrazine intermediate is unstable in air and can be oxidized by oxygen to pyrazine 27, which has been isolated as a major impurity. 

Yet another approach for differentiation of substituents at the lower rim involves directional bridging. The bridge can be placed at any position, however, in practice, the most convenient location is the lower rim oxygen atoms (Fig. 2.16e). For example such directional linkages composed of carboxamide [72] or ester [73] moieties were introduced by a cyclization reaction to give inherently chiral calixarene 60 possessing C2 symmetry. 

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