Asymmetric Synthesis of Heterocyclic γ‐Amino‐Acid and Diamine Derivatives by Three‐Component Radical Cascade Reactions

An enantioselective three‐component radical reaction of quinolines or pyridines with enamides and α‐bromo carbonyl compounds by dual photoredox and chiral Brønsted acid catalysis is presented. A range of valuable chiral γ‐amino‐acid derivatives are accessible in high chemo‐, regio‐, and enantioselectivity from simple, readily available starting materials under mild reaction conditions. Using the same strategy, the asymmetric synthesis of 1,2‐diamine derivatives is also reported.     

Catalytic Enantioselective Protonation/Nucleophilic Addition of Diazoesters with Chiral Oxazaborolidinium Ion Activated Carboxylic Acids

A new chiral Brønsted acid derived from carboxylic acid and a chiral oxazaborolidinium ion (COBI), as an activator, is introduced. This acid was successfully applied as a catalyst for the highly enantioselective protonation/nucleophilic addition of diazoesters with carboxylic acids.     

Chiral Brønsted Acid‐Catalyzed Asymmetric Synthesis of N‐Aryl‐cis‐aziridine Carboxylate Esters

We report a multi‐component asymmetric Brønsted acid‐catalyzed aza‐Darzens reaction which is not limited to specific aromatic or heterocyclic aldehydes. Incorporating alkyl diazoacetates and, important for high ee's, ortho‐tert‐butoxyaniline our optimized reaction (i.e. solvent, temperature and catalyst study) affords excellent yields (61–98 %) and mostly >90 % optically active cis‐aziridines. (+)‐Chloramphenicol was generated in 4 steps from commercial starting materials. A tentative mechanism is outlined.     

Asymmetric Synthesis of Chiral 1,4‐Enynes through Organocatalytic Alkenylation of Propargyl Alcohols with Trialkenylboroxines

A highly enantioselective synthesis of 1,4‐enynes is described that proceeds through an organocatalytic reaction between propargyl alcohols and trialkenylboroxines. Our strategy relies on acid‐mediated generation of the carbocationic intermediate from propargyl alcohols followed by enantioselective alkenylation with trialkenylboroxines. A range of chiral 1,4‐enynes were obtained in moderate to good yields with high levels of enantioselectivity. Use of a highly acidic chiral N‐triflyl phosphoramide catalyst, which has two distant Lewis basic oxygen atoms, was found to be crucial for both high reactivity and selectivity in the present reaction.     

Controlling the α/γ‐Reactivity of Vinylogous Ketone Enolates in Organocatalytic Enantioselective Michael Reactions

The first regio‐, diastereo‐, and enantioselective direct Michael reaction of β,γ‐unsaturated ketones with nitroolefins is enabled by Brønsted base/hydrogen‐bonding bifunctional catalysis. A squaramide‐substituted tertiary amine catalyzes the reaction of a broad range of β,γ‐unsaturated ketones to proceed at the α‐site exclusively, giving rise to adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90–98 % ee range.