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 (BH
4)
2 or by KBEt
3H, 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.
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