“On Water’’ Promoted Ullmann-Type C–N Bond-Forming Reactions: Application to Carbazole Alkaloids by Selective N‑Arylation of Aminophenols

The Ullmann-type cross coupling of a variety of aromatic, aliphatic amines with aryl halides is reported using a CuI-based catalytic system in combination with an easily accessible prolinamide ligand in aqueous media. The method is mild and tolerant to air, moisture, and a wide range of functional groups, providing a novel way to access a variety of aminated products. Secondary amines like heteroaromatic amines and nucleobases have also been used, affording the corresponding coupling products in good to excellent yields. Moreover, this method has been employed for chemoselective C–N arylation of aminophenols and further utilized for the synthesis of carbazole natural products, avoiding the protection and deprotection steps

Thiazolidinedione–Isatin Conjugates via an Uncatalyzed Diastereoselective Aldol Reaction on Water

An uncatalyzed aldol reaction of N-substituted thiazolidinediones with isatin derivatives has been developed “on water” to afford a new class of pharmacologically important thiazolidinedione–isatin conjugates in excellent yields and diastereoselectivities. The isatin–thiazolidine conjugate undergoes a catalyst-free stereoselective transfer aldol reaction on water. Single-crystal X-ray studies reveal that the aldol products can self-assemble to form supramolecular DNA “zipper” like structures through intermolecular hydrogen bonds and aromatic π–π interactions

Asymmetric Synthesis of α‑Fluoro-β-Amino-oxindoles with Tetrasubstituted C–F Stereogenic Centers via Cooperative Cation-Binding Catalysis

Biologically relevant chiral 3,3-disubstituted oxindole products containing a β-fluoroamine unit are obtained in high yields and with excellent stereoselectivity (up to 99% ee, dr >20:1 for <i>syn</i>) through the organocatalytic direct Mannich reaction of 3-fluoro-oxindoles as fluoroenolate precursors and α-amidosulfones as the bench-stable precursors of sensitive imines by using a chiral oligoethylene glycol and KF as a cation-binding catalyst and base, respectively. This protocol can be easily scaled without compromising the asymmetric induction. Furthermore, this protocol was also successfully extended to generate tetrasubstituted C–Cl and C–Br stereogenic centers

Asymmetric Synthesis of α‑Fluoro-β-Amino-oxindoles with Tetrasubstituted C–F Stereogenic Centers via Cooperative Cation-Binding Catalysis

Biologically relevant chiral 3,3-disubstituted oxindole products containing a β-fluoroamine unit are obtained in high yields and with excellent stereoselectivity (up to 99% ee, dr >20:1 for <i>syn</i>) through the organocatalytic direct Mannich reaction of 3-fluoro-oxindoles as fluoroenolate precursors and α-amidosulfones as the bench-stable precursors of sensitive imines by using a chiral oligoethylene glycol and KF as a cation-binding catalyst and base, respectively. This protocol can be easily scaled without compromising the asymmetric induction. Furthermore, this protocol was also successfully extended to generate tetrasubstituted C–Cl and C–Br stereogenic centers

Organocatalytic Asymmetric Synthesis of Chiral Dioxazinanes and Dioxazepanes with <i>in Situ</i> Generated Nitrones via a Tandem Reaction Pathway Using a Cooperative Cation Binding Catalyst

Heterocyclic skeletons play major roles in pharmaceuticals and biological processes. Cycloaddition reactions are most suitable synthetic tools to efficiently construct chemically diverse sets of heterocycles with great structural complexity owing to the simultaneous or sequential formation of two or more bonds, often with a high degree of selectivity. Herein, we report an unprecedented formal cycloaddition of <i>N</i>-Boc-<i>N</i>-hydroxy amido sulfones as the nitrone precursors with terminal-hydroxy α,β-unsaturated carbonyls in the presence of Song’s chiral oligoethylene glycol as a cation-binding catalyst and KF as a base to afford a wide range of highly enantio- and diastereo-enriched six-membered dioxazinane and seven-membered dioxazepane heterocycles. In this process, nitrones as well as terminal-hydroxy α,β-unsaturated carbonyls serve as “amphiphilic” building units, and the reaction proceeds through a tandem pathway sequence of oxa-Mannich reaction/oxa-Michael reaction/tautomerization/protonation. The cation-binding catalysis in a densely confined chiral space <i>in situ</i> formed by the incorporation of potassium salt is the key to this successful catalysis. This strategy opens a new pathway for the asymmetric synthesis of diverse heterocyclic skeletons of great complexity

Spirocyclopentene Oxindoles through LiHMDS Based Allylation and Ring Closing Metathesis

Spirocyclopentene Oxindoles through LiHMDS Based Allylation and Ring Closing Metathesi

Fluoride Anions in Self-Assembled Chiral Cage for the Enantioselective Protonation of Silyl Enol Ethers

The potential of Song’s chiral oligoethylene glycols (oligoEGs) as catalysts was explored in the enantioselective protonation of trimethylsilyl enol ethers in combination with alkali metal fluoride (KF and CsF) and in the presence of a proton source. Highly enantioselective protonations of various silyl enol ethers of α-substituted tetralones were achieved, producing chiral α-substituted tetralones in full conversion and with up to 99% ee. The established protocol was successfully extended to the synthesis of biologically relevant chiral α-substituted chromanone and thiochromanone derivatives

Biomimetic Catalytic Retro-Aldol Reaction Using a Cation-Binding Catalyst: A Promising Route to Axially Chiral Biaryl Aldehydes

Here we describe a biomimetic catalytic retro-aldol reaction of racemic α-substituted β-hydroxy ketones utilizing a chiral oligoEG cation-binding catalyst as a type-II aldolase mimic. Our investigation of various aldol substrates has demonstrated that our biomimetic retro-aldol protocol enables rapid access to highly enantiomerically enriched aldols with a selectivity factor (s) of up to 70. Additionally, we have demonstrated the synthetic strategy’s feasibility for accessing diverse and valuable axially chiral aldehydes