syn-Diastereoselective glycolate aldol addition reactions of an N(3)-(p-methoxyphenoxy)acetyloxazolidine-2-thione

Abstract

An N 3-(p-methoxyphenoxy)acetyloxazolidine-2-thione has been synthesized and employed in the glycolate asymmetric aldol addition reaction with aromatic and aliphatic aldehydes. The observed diastereoselectivies ranged from 62:38 to 80:20 when the reaction was conducted at-25 o C. The diastereoselectivities improved to 75:25 to 94:6 when the reaction was conducted at-78 o C. The absolute stereochemistry of the aldol adducts was determined by 1 H NMR spectroscopy and X-ray crystallography. The 1 H NMR spectra of the aldol adducts contained a signal (the -proton of the glycolate position of the aldol sidechain) that was highly deshielded.

Diastereoselective and Enantioselective Synthesis of α-p-Methoxyphenoxy-β-Lactones: Dependence on the Stereoelectronic Properties of the β-Hydroxy-α-p-Methoxyphenoxycarboxylic Acid Precursors

“…The initial work that had been carried out in the development of the ( S )-(+)-4-benzyl-1,3,-oxazolidine-2-thione-mediated asymmetric glycolate aldol reaction afforded products in good to high yield and diastereoselectivity. To improve the isolated yield and diastereoselection of the glycolate aldol reaction, the ( S )-(+)-4-phenyl-1,3,-oxazolidine-2-thione variant was prepared and applied in this research effort.…”

“…The isolated chemical yields ranged from 44 to 98%, and the stereochemistry of the isolated glycolate aldol addition products 22a–k was determined to be the syn -stereochemistry with the (2 S ,3 R )-configuration. The stereochemical assignment is based on the observed coupling constant between protons H a and H b , which ranged between 1.8 and 4.4 Hz …”

“…It is proposed that the origin of the stereochemical outcome was determined, in part, by a proposed Zimmerman–Traxler transition state between the titanium enolate of 221 and the coordinated aldehyde (Scheme ). , The proposed transition state for the formation of aldol adducts 22a–k is proposed to follow a pathway in which a chair-like transition state occurs between the preferred Z (O)-enolate of 21 with the aldehyde substrate. The placement of the aldehyde within the chair-like transition state 24 minimizes any interactions with the steric volume of the thione enolate Z (O)- 23 enolate.…”

Stereoselective Aldol Additions of Glycolic Acid and Its Derivatives

“…The oxazolidinone moiety of aldol adducts like those present in Tables 15-18 (Table 19) 119,141,142,147,[160][161][162][163] to the Cl 3 Ti enolates of the N-glycolyloxazolidinones (Table 17), providing syn-aldols with good diastereoselectivities. α-Chiral aldehydes react alike.…”

“…168 N-Acyloxazolidinethiones like the aldol adducts of Tables 19 and 20 are easily transformed into the corresponding esters, e.g. compound syn-115, 162 or Weinreb amides, e.g., the compound preceding the ketone anti-117 165 (Scheme 23).…”