Direct Zinc(II)‐Catalyzed Enantioconvergent Additions of Terminal Alkynes to α‐Keto Esters

The addition of terminal alkynes to racemic β‐stereogenic α‐keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by a non‐toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition.     

Delineating the Mechanism of Ionic Liquids in the Synthesis of Quinazoline‐2,4(1H,3H)‐dione from 2‐Aminobenzonitrile and CO2

Ionic liquids (ILs) are versatile solvents and catalysts for the synthesis of quinazoline‐2,4‐dione from 2‐aminobenzonitrile and CO₂. However, the role of the IL in this reaction is poorly understood. Consequently, we investigated this reaction and showed that the IL cation does not play a significant role in the activation of the substrates, and instead plays a secondary role in controlling the physical properties of the IL. A linear relationship between the pK _a of the IL anion (conjugate acid) and the reaction rate was identified with maximum catalyst efficiency observed at a pK _a of >14.7 in DMSO. The base‐catalyzed reaction is limited by the acidity of the quinazoline‐2,4‐dione product, which is deprotonated by more basic catalysts, leading to the formation of the quinazolide anion (conjugate acid pK _a 14.7). Neutralization of the original catalyst and formation of the quinazolide anion catalyst leads to the observed reaction limit.     

Transition Metal‐Free Reduction of Activated Alkenes Using a Living Microorganism

Microorganisms can be programmed to perform chemical synthesis via metabolic engineering. However, despite an increasing interest in the use of de novo metabolic pathways and designer whole‐cells for small molecule synthesis, the inherent synthetic capabilities of native microorganisms remain underexplored. Herein, we report the use of unmodified E. coli BL21(DE3) cells for the reduction of keto‐acrylic compounds and apply this whole‐cell biotransformation to the synthesis of aminolevulinic acid from a lignin‐derived feedstock. The reduction reaction is rapid, chemo‐, and enantioselective, occurs under mild conditions (37 °C, aqueous media), and requires no toxic transition metals or external reductants. This study demonstrates the remarkable promiscuity of central metabolism in bacterial cells and how these processes can be leveraged for synthetic chemistry without the need for genetic manipulation.