Squaramide-Catalyzed Asymmetric Mannich Reactions of Azlactones with Isatin-Derived Ketimines: Access to α,ß-Diamino Acid Derivatives Bearing Vicinal Quaternary Stereocenters.

A highly stereoselective Mannich reaction of α-amino acid derived azlactones with isatin-derived ketimines enabled by a chiral bifunctional squaramide organocatalyst is reported, affording α,ß-diamino acid derivatives bearing vicinal quaternary stereocenters in moderate to good yields (40-95%), moderate to excellent diastereoselectivities (3:1 → 20:1), and good to excellent enantioselectivities (66-97%). This reaction can be readily performed on gram scale, and the Mannich adduct could be easily converted to the corresponding α,ß-diamino ester via simple operations.

Asymmetric Synthesis of Spirocyclic Oxindole δ-Lactams via NHC-Catalyzed Formal [2+4] Annulation of Aliphatic Aldehydes with Oxindole-Derived α,ß-Unsaturated Ketimines.

An N-heterocyclic carbene (NHC)-catalyzed formal [2+4] annulation reaction of aliphatic aldehydes with oxindole-derived α,ß-unsaturated ketimines under oxidative conditions is reported, affording spirocyclic oxindole δ-lactams with good yields, moderate diastereoselectivies, and good to excellent enantioselectivies. This reaction can be readily carried out on a gram scale, and the products could be further transformed to other synthetically useful compounds.

Cu(ii)-mediated direct intramolecular cyclopropanation of distal olefinic acetate: access to cyclopropane-fused γ-lactones.

Cyclopropane-fused ring scaffolds represent one of the most appealing structural motifs in organic chemistry due to their wide presence in bioactive molecules and versatility in organic synthesis. These skeletons are typically prepared from olefinic diazo compounds via transition-metal catalysed intramolecular carbenoid insertion, which suffers from prefunctionalization of starting materials and limited substrate scope. Herein, we disclose a practical copper-mediated direct intramolecular cyclopropanation of distal olefinic acetate to synthesize cyclopropane-fused γ-lactones and lactams. This cascade reaction is postulated to proceed through a hydrogen atom transfer event induced radical cyclization and copper-mediated cyclopropanation sequence. The protocol features high atom- and step-economy, excellent diastereoselectivity, broad tolerance of functional groups, and operational simplicity.

Visible-Light-Induced Alkylarylation of Unactivated Alkenes via Radical Addition/Truce-Smiles Rearrangement Cascade.

We disclosed a visible-light-induced alkylarylation reaction of unactivated alkenes via a metal-free radical addition/aryl translocation cascade sequence. Distal olefinic sulfonate was designed as a unique molecular scaffold allowing for a domino process to synthesize valuable alkylarylated alcohols in good yields with excellent diastereoselectivity, featuring mild reaction conditions, broad substrate scope, and excellent functional group tolerance. The mechanism investigation suggests that a visible-light-induced radical chain process dominates the cascade transformation.

Silver(I)-Mediated Cascade Reaction of 2-(1-Alkynyl)-2-alken-1-ones with 2-Naphthols.

An efficient cascade reaction of 2-(1-alkynyl)-2-alken-1-ones with 2-naphthols promoted by silver trifluoroacetate is disclosed, providing an expeditious access to 1,2-dihydronaphtho[2,1-b]furans with moderate to good yields. This domino process involves highly regio- and diastereoselective sequential cyclization/nucleophilic addition/oxidative ring opening/oxa-Michael addition reactions to construct three new chemical bonds and one new five-membered ring. A gram-scale experiment and the preliminary results to develop an asymmetric variant are also presented to show the practicality and potential of the current reaction.

Stereoselective [8 + 2] Cycloaddition Reaction of Azaheptafulvenes with α-Chloro Aldehydes via N-Heterocyclic Carbene Catalysis.

A highly efficient [8 + 2] cycloaddition reaction of azaheptafulvenes with α-chloro aliphatic aldehydes enabled by N-heterocyclic carbene catalysis is presented, delivering cis-cycloheptatriene-fused γ-lactams with good yields, moderate to good diastereoselectivies, and excellent enantioselectivies. This higher order cycloaddition reaction can be readily expanded to the gram scale, and the products could be further transformed to other useful compounds via simple operations.