Peptide Catalyzed Asymmetric Conjugate Addition Reactions of Aldehydes to Nitroethylene—A Convenient Entry into γ²-Amino Acids

Abstract

The peptide H-D-Pro-Pro-Glu-NH2 is a highly effective catalyst for conjugate addition reactions between aldehydes and nitroethylene. Only 1 mol % of H-d-Pro-Pro-Glu-NH2 and a 1.5-fold excess of aldehyde with respect to nitroethylene suffice to obtain gamma-nitroaldehydes and, after reduction, monosubstituted gamma-nitroalcohols in excellent yields and optical purities. The products can be readily converted into gamma2-amino acids, thereby opening an effective direct entry into this important class of compounds.

Synthesis of γ‐Aminobutyric Acid Analogs

“…(R)-and (S)-4-Amino-3-methylbutanoic acids (41) (Scheme 14.9) were synthesized in a stereodivergent route via an initial enantioselective hydrolysis of dimethyl 3-methylglutarate (37) to give methyl (R)-3-methylglutarate (38) with pig liver esterase (PLE). Conversion of the ester group to an amide (39) by ammonolysis and subsequent Hoffmann rearrangement gives (R)-4-amino-3-methylbutanoic acid (R)- (41).…”

“…The reactions, catalyzed by either proline containing peptides [38], or (S)-diphenylprolinol silyl ether (34) (Scheme 14.8) [39], afford (36) in high yield (95%) and enantioselectivity (>95% e.e. ), after reduction with NaBH 4 .…”

“…Jones oxidation of the aldehyde, reduction of the nitro group, and protection of the resulting amine affords the protected amino acids (19d, e, g and k-n) in high overall yield [39]. The use of the peptide catalyst produces compounds with the opposite stereochemistry to those produced by (S)-(34) [38]. The addition of bromoacetonitrile to the dianions of carboxylic acids has been reported as a two-step process to afford a-substituted amino acids.…”

Structure‐Reactivity Studies of Simple 4‐Hydroxyprolinamide Organocatalysts in the Asymmetric Michael Addition Reaction of Aldehydes to Nitroolefins

“…[6] The most efficient catalyst reported to date is the tripeptide 8 described by Wennemers. [7] This catalyst is highly efficient at levels of only 0.1-0.2 mol%, even with the nitroalkene in excess, giving high yields and selectivities for a range of aldehydes and nitroalkenes. The usefulness of the products from these reactions resides in the potential for further reaction or the transformation of both the nitro and carbonyl functionalities.…”

Exploiting the benefits of continuous-flow processing for the development of novel sustainable catalytic procedures

“…First, the effect of the exchange of the C-terminal amino acid from aspartic acid to the homologous glutamic acid (bearing an additional methylene group on the acidic side-chain) was examined. 132 H-D-Pro-Pro-Glu-NH-resin was synthetized on PS-MBHA with a loading of 0.64 mmol g -1 (59). In the 1,4-addition of propanal to BNS under the previously optimized reaction conditions, catalyst 59 furnished comparable diastereo-and enantioselectivities to 58, but lower yield (Table 10, entries 1 and 2).…”