Direct asymmetric aldol-Tishchenko reaction of aliphatic ketones catalyzed by syn-aminoalcohol–Yb(iii) complexes

Abstract

The asymmetric direct aldol condensation of aldehydes with ethyl- and propylketones is catalyzed by syn-alpha-aminoalcohol-Yb(OTf)3 complexes, yielding the anti-1,3-diol monoesters with high diastereocontrol and good enantioselectivity. Three adjacent stereogenic centers are created in a simultaneous aldol condensation and Evans-Tishchenko reduction in an acyclic system.

Chiral Ytterbium Complex‐Catalyzed Direct Asymmetric Aldol‐Tishchenko Reaction: Synthesis of anti‐1,3‐Diols

“…Our initial aim was to identify the best suited chiral ligand in terms of both reaction conversion and enantioselection. An initial study21 revealed that ephedrine‐type aminoalcohols 1 are the most promising candidates for further optimization of the aldol‐Tishchenko condensation. While ligands containing an unprotected amino function, that is, norephedrine ( 1 a ) and ephedrine ( 1 b ) were simply unpromising.…”

“…A syn orientation of the hydroxy and amino substituents in the ligand turned out to be essential for both the reactivity and selectivity of the catalyst composed of the ephedrine ligand and ytterbium triflate 21. Thus, (1 S ,2 S )‐ N ‐methylpseudoephedrine was not suitable as a ligand, due to the inconvenient orientation of the substituents.…”

Comparative Study of Regioselective Synthesis of β-Aminoalcohols under Solventless Conditions Catalyzed by Sulfated Zirconia and SZ/MCM-41

“…The classical approach for the synthesis of β-aminoalcohols, involving nucleophilic opening of epoxides by amines requires heat treatment and requires an excess of amine. Several catalysts have been utilized in these reactions: montmorillonite [16], Ti(o-i-Pr) 4 [17], SmI 2 , [18] basic metal amides, [19] SmCl 3 [20], metal triflates such as Sn(OTf) 2 , Cu(OTf) 2 , LiOTf and Yb(OTf) 3 [21], ammonium decatungstocerate (IV) [22], RuCl 3 [23], zirconium (IV) chloride [24], cyclodextrins [25] and also CeCl 3 [26], silica-gel [27], alumina [28], ionic liquids [29], water [30] We have successfully used sulfated zirconia for Biginelli condensation reactions, [35] for the Paal Knorr reaction in the synthesis of tetrahydroindolone derivatives [36] and for the acylal protection and deprotection reactions [37]. In this paper we have synthesized, characterized and evaluated sulfated zirconia and SZ/MCM-41 in the oxirane opening with amines to obtain β-aminoalcohols under mild, solventless conditions.…”

Facile Coupling of Aldehydes with Alcohols: An Evolved Tishchenko Process for the Preparation of Unsymmetrical Esters

“…The Tishchenko reaction, which involves the dimerization of an aldehyde to produce the corresponding ester [Scheme Equation (1)], has been known for over a century and has served as a highly efficient and waste‐free method for the production of ester compounds Nevertheless, it has not been accepted as a common approach for the selective synthesis of unsymmetrical esters . In the cross‐coupling reactions of two different aldehydes, it is a challenge to selectively obtain a single unsymmetrical ester out of four possible products [Scheme , Equation (2)] . Previous efforts have employed steric/electronic discrepancies, reaction rate differences, and special ortho substituents to promote crossed Tishchenko reactions between different aldehydes .…”

“…[12] In the cross-coupling reactions of two different aldehydes, it is a challenge to selectively obtain a single unsymmetrical ester out of four possible products [Scheme 1, Equation (2)]. [13][14][15][16][17][18] Previous efforts have employed steric/electronic discrepancies, reaction rate differences, and special ortho substituents to promote crossed Tishchenko reactions between different aldehydes. [19][20][21][22][23] For instance, using Ni 0 /N-heterocyclic carbene (NHC) complexes in the reaction of CyCHO (Cy = cyclohexyl) with PhCHO can afford the cross-coupled unsymmetrical ester CyCOOCH 2 Ph in high yields under mild conditions.…”