Enantioselective Evans-Tishchenko Reduction of b-Hydroxyketone Catalyzed by Lithium Binaphtholate

Abstract

Lithium diphenylbinaphtholate catalyzed the enantioselective Evans-Tishchenko reduction of achiral β-hydroxyketones to afford monoacyl-protected 1,3-diols with high stereoselectivities. In the reaction of racemic β-hydroxyketones, kinetic optical resolution occurred in a highly stereoselective manner.

The Evans-Tishchenko Reaction: Scope and Applications

“…In some instances this product was accompanied by the undesired transesterification product 114 (cf., Section 2.1). One example of the kinetic resolution of a racemic α-methyl-β-hydroxy ketone 115 with the lithium binaphtholate catalyst 111 was also reported by Nakajima et al 5 Although attractive, these methods for the stereoselective generation of 1,3diol monoesters and kinetic resolution of racemic α-substituted β-hydroxy ketones clearly lack generality and a greater understanding of both the reaction mechanism and substrate scope are required before they can be widely adopted. In addition to the use of chiral BINOL-type ligands to induce asymmetry, a further intriguing possibility has been raised by recent reports of nickel catalysts with NHC ligands for related crossed-Tishchenko reactions.…”

“…Where the Evans-Tishchenko reaction results in ester products that are sterically crowded, Lewis acid catalysed transesterification between the two hydroxyl groups of the 1,3-anti diol may occur [5 → 6, Scheme 2 (c)]. 5,6 In addition, there is often a delicate interplay with a second pathway in which an epimerisation/Evans-Tishchenko reaction, 5,7 or alternatively a Lewis acid catalysed retroaldol/aldol-Tishchenko (RAAT) reaction takes place. 8 This latter pathway may result in the scrambling of the αstereocentre with the net generation of the thermodynamically favoured anti aldol adduct with 1,3-anti diol stereochemistry 9 [Scheme 2 (d)].…”

“…Chiral lithium binaphtholates have recently been shown to convert achiral βhydroxy ketones into the corresponding chiral 1,3-diol monoesters (Scheme 22). 5 Thus reaction of terminal β-hydroxy ketones 112 with benzaldehyde or pivaldehyde in the presence of 10 mol% of the lithium binaphtholate catalyst 111 (generated in situ) led to the corresponding products 113 in generally excellent yields (64-96%) and enantioselectivities (>83% ee). In some instances this product was accompanied by the undesired transesterification product 114 (cf., Section 2.1).…”

Lithium Binaphtholate-Catalyzed Michael Reaction of Malonates with Maleates and Its Application to the Enantioselective Synthesis of Tricarboxylic Acid Derivatives

“…Our group has reported enantioselective reactions catalyzed by metal binaphtholates. [24][25][26][27][28][29][30][31][32][33] Metal binaphtholates, [34][35][36][37][38][39][40][41][42][43][44][45] which are easily prepared from 2,2′-binaphthols (BINOLs) and metal bases, such as n BuLi or Grignard reagents, act as Brønsted bases to promote asymmetric reactions. Recently, we also reported the first example of the enantioselective Michael reaction of malonates to maleates, 46) affording tetracarboxylic acid esters as Michael adducts in high yields with high enantioselectivities.…”

Electrooxidative α-hydroxymethylation of ketones with dimethylformamide as the carbon source

“…β-Hydroxy ketones are widely found in natural products and bioactive molecules, 8 and serve as versatile synthetic intermediates and building blocks in organic synthesis. 9 Several methods for the synthesis of β-hydroxy ketones have been developed, such as aldol reaction, 10 a reduction of α,β-epoxy ketones, 10 b,c oxy-Michael addition of α,β-unsaturated ketones, 10 d,e photocatalytic oxygenation of cyclopropane derivatives, 10 f,g hydration of propargyl alcohol derivates, 10 h and coupling reaction of vinylarenes and alcohols. 10 i Traditionally, formaldehyde has been utilized as a one carbon linkage to construct β-hydroxy ketones with methyl ketones in an aldol reaction.…”