Synthesis of α-Hydroxyacetophenones

A general method for the preparation of α-hydroxyacetophenones is presented. Functionalized arylmagnesium species are transmetalated to the corresponding arylzinc intermediates, which undergo Cu­(I)-catalyzed reaction with acetoxyacetyl chloride. Acidic hydrolysis of the acetate group releases the target α-hydroxyacetophenones with minimal production of undesired polymeric degradates that are often observed under alternative conditions

Correction to “Application of Machine Learning and Reaction Optimization for the Iterative Improvement of Enantioselectivity of Cinchona-Derived Phase Transfer Catalysts”

Correction to “Application of Machine Learning and Reaction Optimization for the Iterative Improvement of Enantioselectivity of Cinchona-Derived Phase Transfer Catalysts

Enantioselective Synthesis of Hemiaminals via Pd-Catalyzed C–N Coupling with Chiral Bisphosphine Mono-oxides

A novel approach to hemiaminal synthesis via palladium-catalyzed C–N coupling with chiral bisphosphine mono-oxides is described. This efficient new method exhibits a broad scope, provides a highly efficient synthesis of HCV drug candidate elbasvir, and has been applied to the synthesis of chiral <i>N,N</i>-acetals

Process Development of C–N Cross-Coupling and Enantioselective Biocatalytic Reactions for the Asymmetric Synthesis of Niraparib

Process development of the synthesis of the orally active poly­(ADP-ribose)­polymerase inhibitor niraparib is described. Two new asymmetric routes are reported, which converge on a high-yielding, regioselective, copper-catalyzed <i>N</i>-arylation of an indazole derivative as the late-stage fragment coupling step. Novel transaminase-mediated dynamic kinetic resolutions of racemic aldehyde surrogates provided enantioselective syntheses of the 3-aryl-piperidine coupling partner. Conversion of the C–N cross-coupling product to the final API was achieved by deprotection and salt metathesis to isolate the desired crystalline salt form

Enantioselective Synthesis of 4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) via Enzymatic Desymmetrization

An enantioselective synthesis of the potent anti-HIV nucleoside EFdA is presented. Key features of stereocontrol include construction of the fully substituted 4′-carbon via a biocatalytic desymmetrization of 2-hydroxy-2-((tri­iso­propyl­silyl)­ethynyl)­propane-1,3-diyl diacetate and a Noyori-type asymmetric transfer hydrogenation to control the stereochemistry of the 3′-hydroxyl bearing carbon. The discovery of a selective crystallization of an <i>N</i>-silyl nucleoside intermediate enabled isolation of the desired β-anomer from the glycosylation step