ChemInform Abstract: Asymmetric Reactions Using C2‐Symmetrically 2,5‐Disubstituted Pyrrolidines as Chiral Auxiliaries

Abstract

Newly introduced trans-2, 5-bis (methoxymethyl) -and trans-2, 5-bis (methoxymethoxymethyl) -pyrrolidines were found to be highly effective chiral auxiliaries in asymmetric reactions of their N-acylated compounds.Alkylation of the lithium enolates derived from these amides proceeded with high diastereoface selectivity (> 95 % de) for various combinations of reactants. The enolates were also acylated diastreoselectively (> 96 % de) and the resulting 2-alkyl-3-oxo amides were reduced stereoselectively (> 96 % de) to syn-or anti-2-alkyl-3-hydroxy amides by Zn (BH4) 2 or by KBEt3H, respectively.The aldol condensation of the amide enolate with aldehydes proceeded with high diastereo and diastereoface selectivities, when the corresponding zirconium enolates were used. Zirconium enolates derived from (E) -alkenyloxyacetyl amides, exhibited high level of syn-diastereo and diastereoface selectivities in their [2, 3] Wittig rearrangement reaction. Zirconium mediated [2, 3] Wittig rearrangement of (E) -alkenyloxyacetic acid esters was also performed with syn-diastereoselectivity, high level of chirality transfer, and exclusive formation of (Z) -double bond.Thus, very effective and generally applicable asymmetric syntheses of α-alkyl, α-hydroxy, and α-amino acids, syn-and anti-2-alkyl-3-hydroxy acids, 4-unsaturated 3-alkyl-2-hydroxy acids, and acids bearing a quaternary α-carbon atom have been established.Some of these asymmetric reactions were applied to the synthesis of natural products.