Synthesis of Yb Complexes with Amino‐Acid‐Armed Ligands for Direct Asymmetric Tandem Aldol Reduction Reactions

Abstract

A synthetic route to a series of C 2 -symmetric chiral ligands armed with selectively protected amino acids have been developed with the aim to study the potential of the corresponding Yb(III) complexes for enantioselective direct aldol reactions. These ligands, which contain chiral bis(ester) or bis(amide) moieties, were readily prepared in enantiomerically pure form by the reaction of (S,S)-hydrobenzoin or (S,S)-diphenylethylenediamine with various chiral amino acids. In this article, the asymmetric aldol-reduction reaction leading to 1,3-diols (known as the aldol-Tishchenko reaction) has been performed with an elaborated family of ligands. This unique tandem reaction was catalysed by chiral [a] 5553 Yb complexes that promote both the aldol reaction of unactivated carbonyl compounds and the Evans-Tishchenko reduction of the aldol intermediates. 1,3-anti-Diols with three stereogenic centers have been isolated as a result of the condensation of aliphatic ketones with aromatic aldehydes with up to 64 % ee. Additional detailed investigations of the nature of the binding of both class of ligands have also been carried out with high-resolution 1 H-, 13 C-, and 14 N-NMR techniques.(5554 Scheme 2. Asymmetric aldol-Tishchenko reaction promoted by the ligand 1-Yb complex.

Electrochemical formal homocoupling of sec-alcohols

“…Reductive coupling of carbonyl compounds known as pinacol coupling would be a powerful method to construct vic-1,2-diol scaffolds through C-C bond formation [1,2]. Such scaffolds are widely utilized as versatile building blocks in the synthesis of biologically active compounds [3][4][5][6][7], chiral auxiliaries [8,9], and chiral ligands [10][11][12][13]. Traditional pinacol coupling reactions are performed with a stoichiometric or even excess amount of low-valent metal reductants, such as Al, Ti, V, Zn, and Sm (Scheme 1a).…”

Crystallizing Fats? Development of a Scalable, Chromatography-Free Synthesis of Cationic Lipids

“…Commonly used conditions for the coupling of N , N -dimethylglycine 6 with secondary amines employ carbodiimides or uronium-based reagents . Evaluation of mixed anhydride conditions for the reaction between 6 and 3-MSA 2 , for which limited precedent exists, showed pivaloyl chloride (PivCl) was superior to isobutyl chloroformate for the amide bond formation, particularly since PivCl performed well in either EtOAc or THF (Table ). Poor results were obtained using Vilsmeier conditions to generate the corresponding acid chloride of 6 .…”