Stereoselective Total Synthesis of (−)-(2S,4R)-3′-Methoxyl Citreochlorol: Preparation and Use of New Proline-Based Auxiliary for Asymmetric Acetate Aldol Reaction

Abstract

The first stereoselective total synthesis of (−)-(2S,4R)-3′-methoxy citreochlorol and (−)-(2S,4S)-3′-methoxy citreochlorol is demonstrated. A proline-based imidazolidinone was synthesized and used as chiral auxiliary for asymmetric acetate aldol reaction to generate initial chirality in the targeted molecule. Geminal dichloromethane functionality was introduced by the addition of in situ generated dichloromethyllithium to Weinreb’s amide functional group.

A copper-catalyzed four-component reaction of arylcyclopropanes, nitriles, carboxylic acids and N-fluorobenzenesulfonimide: facile synthesis of imide derivatives

“…Imides are commonly occurring in natural products and pharmacologically active compounds 7 and have been widely applied in polymer chemistry 8 as well as in organic synthesis. 9 Therefore, their synthesis has evolved into one of the important topics in modern synthesis, resulting in numerous methods, including condensation of amides and carboxylic acid derivatives (such as carboxylic acids, carboxylic acid salts, acyl chlorides, esters, etc.…”

Ligand‐Enabled NiII‐Catalyzed Hydroxylarylation of Alkenes with Molecular Oxygen

“…(±)‐3′‐Methoxyl citreochlorol, [14a–b] a bioactive molecule against several human pathogenic microorganisms like E. coli and S. aureus, was prepared in 23 % total yield from 7 p within 3 steps by using current method as the key step (Scheme 3a). Notably, the previous preparation of (−)‐3′‐methoxyl citreochilorol requires 8 steps [14a] or 9 steps, [14b] respectively. In addition, the tea catechin metabolites M4, which could inhibit the growth of a panel of immortalized and malignant human cell lines, [13c] was also efficiently synthesized in 30 % total yield from 7 v within 3 steps via sequential nickel‐catalyzed hydroxylarylation, lactonation, and demethylation (Scheme 3b), while the previous synthetic route requires 7 steps with lower efficiency [14d]…”

“…To further demonstrate the synthetic utility of this newly developed methodology, the efficient synthesis of (±)‐3′‐methoxyl citreochilorol and tea catechin metabolites M4 were carried out. (±)‐3′‐Methoxyl citreochlorol, [14a–b] a bioactive molecule against several human pathogenic microorganisms like E. coli and S. aureus, was prepared in 23 % total yield from 7 p within 3 steps by using current method as the key step (Scheme 3a). Notably, the previous preparation of (−)‐3′‐methoxyl citreochilorol requires 8 steps [14a] or 9 steps, [14b] respectively.…”

Phosphonium Ion-Tethered Secondary Amines for Chemospecific 5-Enolexo Aldol Condensations of 6-Ketoaldehydes

“…As part of our efforts to develop novel proline-based catalysts and ligands, we successfully prepared catalyst 1 from proline using a straightforward six-step process with a 49% overall yield (Scheme ). We anticipated that the oxophilic phosphonium ion within catalyst 1 would enhance selectivity by stabilizing intermediate transition states through Coulombic interactions between phosphonium and carbonyl oxygen. Importantly, these proline derivatives with methylphosphonium ion substitution had not previously been reported …”