Diastereoselectivity reactions, nitroaldol reaction

Scheme 6.170 Suggested transitions states for the anti-diastereoselective Henry (nitroaldol) reaction promoted by (R,R)-catalyst 186 (TS 1) and its (S,S)-isomer 183 (TS 2) to demonstrate the match/mismatch relationship between guanidine-thiourea catalyst and (S)-a-aldehyde.

Scheme 6.171 Product range of the 186-catalyzed anti-diastereoselective Henry (nitroaldol) reaction of a-chiral aldehydes with nitromethane.

Diastereoselective Catalytic Nitroaldol Reaction Starting from Chiral Aldehydes... 

H. Sasai, T. Tokunaga, S. Watanabe, T. Suzuki, N. Itoh, M. Shibasaki, Efficient Diastereoselective and Enantiose-lective Nitroaldol Reactions from Prochiral Starting MaterialsStUtilization of La-Li-6,6 -Disubstituted BINOL Complexes as Asymmetric CatalystsUtJ. Org Chem 1995, 60, 7388-7389. 

Use of an organocatalyst in a highly diastereoselective nitroaldol reaction was reported by the Corey group in the synthesis of 123 [128]. This compound is a key building block in the synthesis of the HIV-protease inhibitor amprenavir. The alkaloid-based fluoride salt, 122, was used as an efficient chiral phase-transfer catalyst (this type of catalyst was developed by the same group [129-131]) and led to formation of the (2R,3S) diastereomer (2H,3S)-123 in 86% yield and with a diastereo-meric ratio of d.r. = 17 1 (Scheme 6.53) [128], It is worthy of note that a much... 

Nitroaldol reactions of enantiomerically pure a-amino aldehydes with nitromethane using a catalytic amount of LLB were found to proceed in a highly diastereoselective manner.35 The adducts (3-amino-2-hydroxy-l-nitro derivatives) are attractive intermediates for the synthesis of unnatural erythro-amino-2-hydroxy acids, which are important components of several biologically active compounds. As an example, the promising HIV-protease inhibitor KNI-272 (65)36 37... 

LLB-type catalysts were also able to promote diastereoselective and enantioselective nitroaldol reactions starting from substituted nitroalkanes. In preliminary work, however, LLB itself gave unsatisfactory results in terms of both diastereoselectivity (syn/anti ratio 63 37 to 77 23) and enantioselectivity (<78% ee).32 To address the problem of modest enantio- and diastereoselectivities with... 

Figure 21. Proposed transition states of diastereoselective and enantioselective nitroaldol reactions.

The results from the analysis indicated that nitroaldol intermediate 461 was resolved by crystallization from the dynamic system (36 possible diastereomers). This shows the advantage of DSR using diastereoselective crystallization technique to identify the optimal constituent from large and diverse dynamic systems in one-pot processes. After the resolution process, the reaction conditions of the single nitroaldol reaction of 4-pyridinecarboxyaldehyde 451 was further optimized in... 

With more effective asymmetric catalysts in hand, we next applied the most efficient catalysts 27 and 28 to diastereoselective nitroaldol reactions. We were very pleased to find that high syn selectivity and enantioselectivity were always obtained by use of 3.3 mol % catalyst [58]. Representative results are listed in Table 14. 

Highly diastereoselective nitroaldol reactions <2003TL8681> and Lewis acid-catalyzed reactions with furan derivatives <2000PAG1589> on enantiopure glyoxylic acid derivative 586 (R = H, X = 0) were performed. 

Keywords HeterobimetaUic lanthanoid catalysts. Asymmetric nitroaldol reaction, Henry reaction, Enantioselective and diastereoselective reactions, syn-Selectivity... 

First encouraging results for a stereoselective synthesis in general were reported by Seebach in 1982, who investigated the syn/anti-diastereoselectivity starting from achiral aldehydes and nitroalkanes [4,5]. Barrett et al. examined the influence of nonchiral Lewis acids on the syn/anti diastereoselectivity [6]. Stoichiometric amounts of an enantiomerically pure aldehyde were used in a di-astereoselective reaction with 3-nitropropionate by Hanessian et al. [7]. However, an approach to enantioselective synthesis of nitroalcohols via the route of the asymmetric Henry reaction could not be carried out until almost one hundred years after the discovery of the nitroaldol reaction. 

A further example of a diastereoselective nitroaldol reaction using heterobimetallic lanthanoid complexes as catalysts was recently reported by Okamoto et... 

Schemes. Diastereoselective nitroaldol reaction as key step in the synthesis of erythro-AHPA 34...

Scheme 9. Catalytic diastereoselective nitroaldol reaction promoted by the LPB type catalyst...

A further example of a diastereoselective nitroaldol reaction using heterobimetallic lanthanoid complexes as catalysts was recently reported by Okamoto et al. [18] in connection with a novel approach to lc/.,24( R)-dihydroxyvitamin D3... 

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