Hydroxy acid modifying reagent

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

The direction of enantio-differentiation (the predominant enantiomer R or S, to be produced) is decided by two factors. One factor is the configuration of the chiral structure, that is, if the catalyst modified with (S)-glutamic acid [(S)-Glu-MRNi] produces (R)-MHB from MAA, then (R)-Glu-MRNi produces (S)-MHB (2). The other factor is the nature of X. That is, when the amino acid or hydroxy acid with the same configuration is used as the modifying reagent, the configurations of the predominant products are enantiomers of each other in most cases. For example, (S)-aspartic acid-MRNi produces (R)-MHB and (S)-malic acid-MRNi produces (S)-MHB (19). 

The degree of EDA is governed by the nature of the substituent (R). The effect of R is observed often in opposite directions between amino acid MRNi and hydroxy acid MRNi. For example, the increase in bulkiness of R increases the EDA of amino acid-MRNi but decreases that of hydroxy acid MRNi as shown in Fig. 3 (77, 72). An increase (decrease) in electron density at the chiral center of the modifying reagent increases (decreases) the EDA of amino acid-MRNi and decreases (increases) the EDA of hydroxy acid-MRNi as shown in Table 111 (52a). 

Since RNi contains a large amount of aluminum and 2-hydroxy acid is a strong chelating reagent, one difference between RNi and RNiA could be ascribed to their difference in aluminum contents. Table XII (49) shows the correlation between the aluminum content and the EDA of those catalysts modified with tartaric acid. The aluminum content of RNi was decreased by pretreatment with hydroxy acid. Moreover, reduced nickel prepared from NiO (HNi-1) gives an effective modified catalyst and its pretreatment with hydroxyacid does not affect its EDA. 

Fig. 18. Effect of modifying pH on the adsorption amount of modifying reagent and EDA of 2-hydroxy-3-phenylpropionic acid-MRNi. (O) amount of modifying reagent ( ) EDA of MRNi. Modifying condition 0 C. Reaction conditions MAA (neat), 60 C, 80 kg/cm2.

The absorption modes of (S)-3-phenyl-2-hydroxypropionic acid, (S)-3-phenyl-2-aminopropionic acid, and (S)-alanine adsorbed on a nickel plate or RNi were studied by Suetaka s group (71, 72). From the measurement of infrared (IR) dichroism in the reflection spectrum, the molecular orientation of the modifying reagent was deduced. Figures 19-21 show molecular orientations of (S)-2-hydroxy-3-phenylpropionic acid on a nickel plate and (R)-alanines on RNis modified at 5° and 100°C, respectively. 

Some of the versions of the mixed anhydride technique discussed may involve components other than a-hydroxy acids. Therefore, the resultant products cannot be considered as main-chain modified peptidomimetics. However, on many grounds these methods are of general importance in depsipeptide synthesis. For example the classical peptide reagent isobutyl chloroformate appears to be suitable for ester bond formation through the corresponding mixed anhydride with Boc- or Z-protected amino acids and the Thr (3-hydroxy group in the synthesis of a number of natural peptide lactones.145 7 ... 

Systematic studies on the enantioselective heterogeneous catalytic hydrogenation of carbonyl compounds were carried out by Izumi using Raney nickel modified with various chiral reagents. Hydroxy acids or amino acids were used for the modification of the nickel catalyst, and (-i-)-tartaric acid (2R,3R)... 

The chiral allylboration reagents employed by Itsuno et al. in this study were prepared by mixing triallylborane (1 equiv) with the appropriate chiral modifier in THE A variety of chiral modifiers, including chiral diols 47 and 48, chiral hydroxy acid 49, N-sulfonylated amino acid 50, and M-sulfonylamino alcohols 51--54 was evaluated (Scheme 21). The chiral modifiers 47-54 used in this study could be prepared easily and efficiently, and were easily recovered and recycled. 

---