A highly effective asymmetric synthesis of α-hydroxy acids by alkylation of chiral n-(benzyloxyacetyl)-trans-2,5-bis(methoxymethoxymethyl)pyrrolidine

✍ Scribed by Masayuki Enomoto; Yoshio Ito; Tsutomu Katsuki; Masaru Yamaguchi

• Publisher: Elsevier Science
• Year: 1985
• Tongue: French
• Weight: 169 KB
• Volume: 26
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)94889-5

✦ Synopsis

Alkylation of lithiated N-(benzyloxyacetyl)-trans-2,5-bis(methoxymethoxymethyl)pyrrolidine proceeded with high stereoselectivity (196% de) and subsequent transformations of the alkylated products gave synthetically useful o-benzyloxy acids or cr-hydroxy acids of high enantiomeric purity. a-Hydroxy acids which exist mostly in chiral forms, not only constitute an important class of biological substances but also serve as convenient building blocks for the synthesis of natural products. Asymmetric synthesis of the compounds has, thus, attracted considerable attention and methods of increasing effectiveness have been published in the last few years. 1) Recently, we developed a chiral auxiliary, w-2,5-bis(methoxymethoxymethyl)pyrrolidine, which was quite useful for cl-alkylation, 2) a-acylation, 3) and aldolization 4, of the corresponding amide enolates derived fraa simple carboxylic acids. Here, we wish to describe general and very effective asymmetric synthesis of a-hydroxy acids by using the same auxiliary through diastereoselective alkylation of its N-(benzyloxyacetyl) derivative (11, giving the highest de values so far reported in the asymmetric alkylation of glycolic acid derivatives. ia The snide (1J5) was lithiated in THF with n-BuLi 6) (1.6 mol dmm3 in hexane, 1.05 eq, at -78°C) or with LDA (0.7 mol dm -3 in THF, 1.05 eq, at -78°C and then at -2O"Cl, and the