Amino acid-derived catalysts asymmetric protonation

Kobayashi et al. also applied the catalyst to asymmetric 1,4-addition reactions of azlactones with acrylates [66]. The active a-proton of the azlactone (5(4H)-oxazolone) skeleton showed a low pKa value compared to that of the alanine Schiff bases, because the anion formed is stabilized via enol formation and aromatization. After 1,4-addition reactions with acrylates, the 2-substituted glutamic acid derivatives formed could be obtained via hydrolysis using a weak acid. It was found that Pybox 3 prepared from alaninol derivatives was effective for this reaction. The desired products were obtained in good yields with good enantios-electivities. Several amino acid derivatives containing aUcyl chains in the a-position were screened, and the leucine derivative (R = Bu) showed the best enantio-selectivity in this reaction (Table 16, entry 8). 

A new kind of enantioselective [1,3]-proton transfer in aza-allylic systems was reported, namely, the N-benzylimines 30 were converted to the more thermodynamically favored N-benzylidene derivatives 31 as shown in Scheme 4. Among the chiral bases (i )-(-l-)-N,Ar-dimethyl-l-phenylethylamine, (li ,2S)-(-)-N-meth-ylephedrine, and (-)-cinchonidine employed as catalysts, only (-)-cinchonidine showed an asymmetric induction. A series of optically active 3-polyfluoroalkyl-P-amino acids 32, which are of great pharmaceutical interest, was prepared in 87 to 93% yields with ee s in the range of 15 to 36% [36]. 

Amino-derived BDPP (2,4-bis[diphenylphosphino]pentane) has been used in asymmetric hydrogenation catalysis [15-17] (cf. Sections 6.2 and 6.9). NMR analysis showed that a ten-fold excess of HBF4 is sufficient to protonate reversibly all four amino groups in the [Rh(diene)(BDPP)]BF4 complex. Recycling of the catalyst after enantioselective hydrogenation of dehydroamino acid derivatives in methanol is achieved by acidification with aqueous FIBF4 followed by extraction of the product with Et20. Immobilization of the protonated BDPP rhodium complex on a Nafion support has been studied as well [18]. 

Example 4.22 An axially chiral binaphthyl unit also characterizes chiral catalyst 41 for the asymmetric Mannich reaction presented in Scheme 4.53. The sufibnamido group acts as the proton donor to the imino N atom. Aldehydes are alkylated by an A-pam-methoxyphenyl (PMP) derivative of oxalaldehyde as an imino component. anft -Isomers of a-amino-y-keto acids TM 4.18a-e with (25,37 ) absolute configurations are obtained as the prevailing products with very high optical purity (Scheme 4.53) [37]. 

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