Catalytic Enantioselective Protonation of Monofluorinated Silyl Enol Ethers towards Chiral α‐Fluoroketones

Described herein is an organocatalytic enantioselective protonation of monofluorinated silyl enol ethers, affording an array of optically active α‐secondary α‐fluoroketones in good to high yields and enantioselectivities, under the catalysis of bifunctional cinchonidine derived squaramide C4 . It represents a rare example of facile synthesis of enantioenriched α‐secondary α‐fluoroketones. With D₂O as the deuterium source and MeOD as the solvent, the first highly enantioselective preparation of chiral α‐deuterated α‐fluoroketones in >92% deuteration is developed.     

Chiral Zinc(II)‐Catalyzed Enantioselective Tandem α‐Alkenyl Addition/Proton Shift Reaction of Silyl Enol Ethers with Ketimines

A new catalytic asymmetric tandem α‐alkenyl addition/proton shift reaction of silyl enol ethers with ketimines was serendipitously discovered in the presence of chiral N,N′‐dioxide/Zn^II complexes. The proton shift preferentially proceeded instead of a silyl shift after α‐alkenyl addition of silyl enol ether to the ketimine. A wide range of β‐amino silyl enol ethers were synthesized in high yields with good to excellent ee values. Control experiments suggest that the Mukaiyama–Mannich reaction and tandem α‐alkenyl addition/proton shift reaction are competitive reactions in the current catalytic system. The obtained β‐amino silyl enol ethers were easily transformed into β‐fluoroamines containing two vicinal tetrasubstituted carbon centers.     

Catalytic Enantioselective Synthesis of α‐Chiral Azaheteroaryl Ethylamines by Asymmetric Protonation

The direct enantioselective synthesis of chiral azaheteroaryl ethylamines from vinyl‐substituted N‐heterocycles and anilines is reported. A chiral phosphoric acid (CPA) catalyst promotes dearomatizing aza‐Michael addition to give a prochiral exocyclic aryl enamine, which undergoes asymmetric protonation upon rearomatization. The reaction accommodates a broad range of N‐heterocycles, nucleophiles, and substituents on the prochiral centre, generating the products in high enantioselectivity. DFT studies support a facile nucleophilic addition based on catalyst‐induced LUMO lowering, with site‐selective, rate‐limiting, intramolecular asymmetric proton transfer from the ion‐paired prochiral intermediate.     

Inside Cover: Ir‐Catalyzed Asymmetric Hydrogenation of α‐Alkylidene β‐Lactams and Cyclobutanones (Chin. J. Chem. 7/2018)

The inside cover picture shows Chiral β‐lactams and cyclobutanones are present in numerous natural and pharmaceutical products. A direct preparation of chiral four‐membered rings via metal‐catalyzed asymmetric hydrogenation has not been described yet. In this article, we report an Ir/BiphPHOX‐catalyzed asymmetric hydrogenation of α‐alkylidene β‐lactams and cyclobutanones for the direct preparation of β‐lactams and cyclobutanones bearing an α‐substituted stereocenter. Our tropos phosphine‐oxazoline biphenyl ligand is essential for the preparation of the desired products with high enantioselectivities. More details are discussed in the article by Zhang et al. on page 612–618.

     

Cover Picture: Highly Regioselective Sequential 1,1‐Dihydrosilylation of Terminal Aliphatic Alkynes with Primary Silanes (Chin. J. Chem. 5/2019)

The cover picture shows that sequential 1,1‐dihydrosilylation of terminal aliphatic alkynes with primary silanes enabled by one earth‐abundant cobalt catalyst has been developed. This protocol is operationally simple using readily available aliphatic alkynes, including simple acetylene and complex drug derivative, for efficient access to valuable gem‐bis(dihydrosilyl)alkanes in highly regioselective and atom‐economic manners. Corresponding asymmetric transformations are achieved with excellent enantioselectivities. More details are discussed in the article by Lu et al. on page 457–461.

     

Catalytic Enantioselective α‐Ketol Rearrangement

A highly enantioselective α‐ketol rearrangement has been developed. In the presence of a chiral Cu‐bisoxazoline complex, achiral β‐hydroxy‐α‐dicarbonyls were isomerized to chiral α‐hydroxy‐β‐dicarbonyls and their bicyclic derivatives in excellent yields and enantioselectivities. Enantioenriched 2‐acyl‐2‐hydroxy cyclohexan‐1‐ones, dihydroxyhexahydrobenzofuranones, and dihydroxyhexahydro‐cycloheptafuranones, with up to three stereocenters, were readily prepared from achiral starting materials in one operation. The reaction is applicable to the desymmetrization of meso substrates and kinetic resolution of racemic alcohols.     

Cover Picture: Transition‐Metal‐Free Defluorosilylation of Fluoroalkenes with Silylboronates* (Chin. J. Chem. 10/2019)

The cover picture shows a simple, inexpensive and robust method on defluorosilylation of diverse fluoroalkenes with silylboronates in the presence of alkoxy base to directly synthesize various silylated fluoroalkenes. Density functional theory calculations revealed that transient silyl anion complex undergoes S_N2’ or S_N^V substitution, which is responsible for this base‐mediated defluorosilylation reaction, thus obviating the need for copper salts. More details are discussed in the article by Shi et al. on page 1009–1014.

     

Inside Cover: Palladium‐Catalyzed Asymmetric Dihydroxylation of 1,3‐Dienes with Catechols (Chin. J. Chem. 3/2019)

The inside cover picture shows a palladium‐catalyzed asymmetric dihydroxylation of 1,3‐dienes with catechols utilizing chiral pyridinebis(oxazoline) ligand. The reaction is proposed to proceed via a cascade Wacker‐type hydroxypalladation/asymmetric allylation process. This methodology provides a direct and straightforward synthesis to prepare chiral 2‐substituted 1,4‐benzodioxane motifs in moderate to good yield and enantioselectivity from readily available starting materials. More details are discussed in the article by Gong et al. on page 226–232.