ABSTRACT
The dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation has been developed as a technique for the highly stereoselective construction of structurally diverse ß-substituted-α-hydroxy carboxylic acid derivatives. Through the development of a privileged m-terphenylsulfonamide for (arene)RuCl(monosulfonamide) complexes with a high affinity for selective α-keto ester reduction, excellent levels of chemo-, diastereo-, and enantiocontrol can be realized in the reduction of ß-aryl- and ß-chloro-α-keto esters.
Subject(s)
Esters/chemistry , Glycolates/chemical synthesis , Ketones/chemistry , Thermodynamics , Glycolates/chemistry , Hydrogenation , Kinetics , Molecular Conformation , StereoisomerismABSTRACT
The dynamic kinetic resolution of ß-aryl α-keto esters has been accomplished using a newly designed (arene)RuCl(monosulfonamide) transfer hydrogenation catalyst. This dynamic process generates three contiguous stereocenters with remarkable diastereoselectivity through a reduction/lactonization sequence. The resulting enantioenriched, densely functionalized γ-butyrolactones are of high synthetic utility, as highlighted by several secondary derivatizations.
Subject(s)
4-Butyrolactone/chemistry , Ketones/chemistry , 4-Butyrolactone/chemical synthesis , Catalysis , Esters/chemical synthesis , Esters/chemistry , Hydrogenation , Ketones/chemical synthesis , Kinetics , StereoisomerismABSTRACT
This Perspective describes the discovery and development of silyl glyoxylates, a new family of conjunctive reagents for use in multicomponent coupling reactions. The selection of the nucleophilic and electrophilic components determines whether the silyl glyoxylate reagent will function as a synthetic equivalent to the dipolar glycolic acid synthon, the glyoxylate anion synthon, or the α-keto ester homoenolate synthon. The ability to select for any of these reaction modes has translated to excellent structural diversity in the derived three- and four-component coupling adducts. Preliminary findings on the development of catalytic reactions using these reagents are detailed, as are the design and discovery of new reactions directed toward particular functional group arrays embedded within bioactive natural products.
Subject(s)
Glyoxylates/chemistry , Indicators and Reagents/chemistry , Organosilicon Compounds/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
A simple and efficient method for the preparation of ß-stereogenic α-keto esters is described using a copper(II)-catalyzed aerobic deacylation of substituted acetoacetate esters. The substrates for the title process arise from catalytic, enantioselective conjugate additions and alkylation reactions of acetoacetate esters. The mild conditions do not induce racemization of the incipient enolizable α-keto ester. The reaction is tolerant of esters, certain ketones, ketals, and nitro groups and utilizes inexpensive, readily available materials.
Subject(s)
Acetoacetates/chemistry , Copper/chemistry , Esters/chemical synthesis , Glyoxylates/chemistry , Acylation , Alkylation , Anions/chemistry , Catalysis , Epoxy Compounds/chemistry , Oxygen/chemistry , StereoisomerismABSTRACT
Beta-silyloxy-alpha-keto esters are prepared through a cyanide-catalyzed benzoin-type reaction with silyl glyoxylates and aldehydes. The products undergo a dynamic kinetic resolution to provide enantioenriched orthogonally protected alcohols and can be converted to the corresponding beta-silyloxy-alpha-amino esters.