Synthesis of Enantiopure γ‐Lactones via a RuPHOX‐Ru Catalyzed Asymmetric Hydrogenation of γ‐Keto Acids

Abstract

A RuPHOXÀRu catalyzed asymmetric hydrogenation of g-keto acids has been developed, affording the corresponding enantiopure g-lactones in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 10000 S/C) under the indicated reaction conditions and the resulting products can be transformed to several enantiopure building blocks, biologically active compounds and enantiopure drugs.

Selective Asymmetric Hydrogenation of Four-Membered Exo-α,β-Unsaturated Cyclobutanones Using RuPHOX–Ru as a Catalyst

“…We have previously developed a readily accessible chiral ruthenocenyl P,P,N,N-ligand, RuPHOX, which has shown promising asymmetric catalytic behavior in several asymmetric reactions . In particular, its Ru complex, RuPHOX–Ru, has been successfully applied in the asymmetric hydrogenation of many types of substrates containing CC and/or CO double bonds . Herein, we disclose an efficient and mild RuPHOX–Ru-catalyzed selective asymmetric hydrogenation of the CO double bond of four-membered exo -α,β-unsaturated cyclobutanones.…”

Reducing Challenges in Organic Synthesis with Stereoselective Hydrogenation and Tandem Catalysis

“…Other reports by Zhan and Zhou have used chiral Ru and Ir complexes, respectively, to effect similar hydrogenation/lactonization of γ-keto acids with high enantioselectivities. 136,137 Lastly, enzymatic approaches have also been reported. Gotor and Borowiecki have demonstrated stereodivergent enzyme-catalyzed AH/cyclizations of γ-keto esters, giving both enantiomers of the corresponding lactone, depending upon the enzyme chosen.…”

“…This Lewis acid-catalyzed process is free of transition metals and provides good yields for a number of aryl-substituted γ-keto acids. Other reports by Zhan and Zhou have used chiral Ru and Ir complexes, respectively, to effect similar hydrogenation/lactonization of γ-keto acids with high enantio­selectivities. , Lastly, enzymatic approaches have also been reported. Gotor and Borowiecki have demonstrated stereodivergent enzyme-catalyzed AH/cyclizations of γ-keto esters, giving both enantiomers of the corresponding lactone, depending upon the enzyme chosen. , Collectively, these reports demonstrate clever design of hydrogenation conditions to solve synthetic challenges.…”

Glyoxylic Acid: A Carboxyl Group‐Assisted Metal‐Free Decarboxylative Reaction Toward Propargylamines

“…Despite the remarkable achievements that have been made in the decarboxylative coupling [9] and carboxyl group-directed functionalization of carboxylic acids [10] (Scheme 1A), the available routes for enhancing the reactivity of the reaction through a carboxyl group-assisted process are still underdeveloped. [11] Among them, the well-known report is the multicomponent Petasis reaction of a glyoxylic acid, an amine, and a boronic acid where the carboxyl group can activate the boronic acid followed by the migration of boronate substituent (Scheme 1c). [12] Meanwhile, glyoxylic acid has been exploited for the synthesis of 3-amino-1,4-enynes [13a] and polysubstituted butenolides [13b] through transition-metal-catalyzed tandem glyoxylic acid-amine-alkyne coupling process.…”