CdS Quantum Dot Gels as a Direct Hydrogen Atom Transfer Photocatalyst for C-H Activation.

Here, we report CdS quantum dot (QD) gels, a three-dimensional network of interconnected CdS QDs, as a new type of direct hydrogen atom transfer (d-HAT) photocatalyst for C-H activation. We discovered that the photoexcited CdS QD gel could generate various neutral radicals, including α-amido, heterocyclic, acyl, and benzylic radicals, from their corresponding stable molecular substrates, including amides, thio/ethers, aldehydes, and benzylic compounds. Its C-H activation ability imparts a broad substrate and reaction scope. The mechanistic study reveals that this reactivity is intrinsic to CdS materials, and the neutral radical generation did not proceed via the conventional sequential electron transfer and proton transfer pathway. Instead, the C-H bonds are activated by the photoexcited CdS QD gel via a d-HAT mechanism. This d-HAT mechanism is supported by the linear correlation between the logarithm of the C-H bond activation rate constant and the C-H bond dissociation energy (BDE) with a Brønsted slope α = 0.5. Our findings expand the currently limited direct hydrogen atom transfer photocatalysis toolbox and provide new possibilities for photocatalytic C-H activation.

Overcoming the Potential Window-Limited Functional Group Compatibility by Alternating Current Electrolysis.

The functional group compatibility of an electrosynthetic method is typically limited by its potential reaction window. Here, we report that alternating current (AC) electrolysis can overcome such potential window-limited functional group compatibility. Using alkene heterodifunctionalization as a model system, we design and demonstrate a series of AC-driven reactions that add two functional groups sequentially and separately under the cathodic and anodic pulses, including chloro- and bromotrilfuoromethylation as well as chlorosulfonylation. We discovered that the oscillating redox environment during AC electrolysis allows the regeneration of the redox-active functional groups after their oxidation or reduction in the preceding step. As a result, even though redox labile functional groups such as pyrrole, quinone, and aryl thioether fall in the reaction potential window, they are tolerated under AC electrolysis conditions, leading to synthetically useful yields. The cyclic voltammetric study has confirmed that the product yield is limited by the extent of starting material regeneration during the redox cycling. Our findings open a new avenue for improving functional group compatibility in electrosynthesis and show the possibility of predicting the product yield under AC electrolysis from voltammogram features.

Selective C3-Allylation and Formal [3 + 2]-Annulation of Spiro-Aziridine Oxindoles: Synthesis of 5'-Substituted Spiro[pyrrolidine-3,3'-oxindoles] and Coerulescine.

Brønsted acid- and/or Lewis acid-catalyzed selective C3-allylation and formal [3 + 2]-annulation of spiro-aziridine oxindoles with allylsilanes have been demonstrated to deliver direct access to 3-allyl-3-aminomethyl oxindoles and 5-silyl methyl spiro[pyrrolidine-3,3'-oxindoles], respectively. The acid-catalyzed methods do not provide any stereoselectivity when chiral spiroaziridines are used. However, the reaction of nonracemic sprioaziridines with allyl-Grignard reagent under catalyst-free conditions afforded 3-allyl-3-aminomethyl oxindoles with good stereoselectivity (ee up to 80%). The allylation protocol is utilized for the short synthesis of coerulescine and various 5'-substituted spiro[pyrrolidine-3,3'-oxindoles].

Sequential one-pot synthesis of N-sulfonyl spiroaziridine oxindoles from spiroepoxy oxindoles.

The N-sulfonyl spiroaziridine oxindole is a recently developed versatile precursor in the synthesis of a wide range of 3,3-disubstituted spirooxindoles. It is usually prepared in three steps from isatin and needs costly and hardly available sulfinimides and hazardous peracid. A sequential and one-pot direct strategy for the synthesis of terminal N-sulfonyl spiroaziridine oxindoles has been developed under ambient conditions with excellent yields (up to 95%) from easily accessible spiroepoxy oxindoles by regioselective amination with aqueous ammonia and a subsequent ring enclosure reaction of the resulting 1,2-amino alcohol using easily available sulfonyl chloride and a base. Other salient features of the protocol include inexpensive substrate requirement and the ease of isolation of the desired product by performing single column chromatographic purification after two consecutive steps.

One-Pot Synthesis of Enantiopure Spiro[3,4-dihydrobenzo[b][1,4]oxazine-2,3'-oxindole] via Regio- and Stereoselective Tandem Ring Opening/Cyclization of Spiroaziridine Oxindoles with Bromophenols.

A highly efficient regio- and stereoselective spiroaziridine ring opening with 2-bromophenols and a subsequent tandem cyclization reaction was developed for the one-pot synthesis of enantiopure 3,4-dihydrospiro[benzo[b][1,4]oxazine-2,3'-oxindole] with excellent enantiopurity (ee up to >99%). It is further extended to asymmetric synthesis of NH-free 3,4-dihydrospiro[benzo[b][1,4]oxazine-2,3'-xindole] retaining the optical activity.

Organocatalytic Domino Reaction of Spiroaziridine Oxindoles and Malononitrile for the Enantiopure Synthesis of Spiro[dihydropyrrole-3,3'-oxindoles].

The first organocatalytic regio- and stereoselective domino reactions of spiroaziridine oxindoles and malononitrile have been developed using DBU as a catalyst without any metal/Lewis acid activation for the enantiopure synthesis of spiro[dihydropyrrole-3,3'-oxindoles] (ee up to >99%). The protocol is also equally effective for the phenyl aziridine with excellent regio- and stereoselectivity.

The one pot asymmetric synthesis of 3,3'-pyrrolidonyl spiroxindoles via a regio- and stereoselective domino reaction.

A highly efficient regio- and stereoselective domino aziridine ring opening and lactamization reaction between aziridines and 3-carboxy oxindole esters has been developed for the one pot asymmetric synthesis of 4-aryl-3,3'-spiropyrrolidonyl oxindoles with excellent selectivity (dr >99 : 1 and ee up to >99%). It was further extended to a sequential one pot protocol for the asymmetric synthesis of NH-free 3,3'-pyrrolidonyl spiroxindole, maintaining the same selectivity.

An asymmetric acetate-Mannich reaction of chiral isatin derived ketimines and its applications.

A highly efficient TMSOTf-mediated asymmetric acetate-Mannich reaction of isatin derived tert-butylsulfinyl ketimines and S-phenyl thioacetate was developed to afford the direct synthesis of indole-based ß3,3-amino acid thioester with excellent selectivity (dr > 98 : 2). Syntheses of (+)-AG-041R and 3-aminopyrroloindoline have been accomplished utilizing the developed method.

Revisiting Alternating Current Electrolysis for Organic Synthesis.

This review summarizes the recent advancements in alternating current (AC)-driven electroorganic synthesis since 2021 and discusses the reactivities AC electrolysis provides to achieve new and unique organic transformations.

Aqueous tert-Butyl Hydroperoxide Mediated Regioselective Ring-Opening Reactions of Spiro-aziridine-epoxy Oxindoles: Synthesis of 3-Peroxy-3-substituted Oxindoles and Their Acid-Mediated Rearrangement.

A highly efficient regioselective C3-peroxylation of spiro-aziridine and spiro-epoxy oxindoles has been developed with commercially available 70% aqueous tert-butyl hydroperoxide under solvent-free and metal/catalyst-free conditions. The protocol provides an easy access of 3-peroxyoxindoles, which undergo acid-mediated rearrangement to afford unprecedented 2-hydroxy-2-substituted-2H-benzo[b][1,4]oxazin-3(4H)-ones. The protocol is also equally effective for the ring opening of simple phenyl aziridine with excellent regio-selectivity.

Stereocontrolled Nucleophilic Fluorination at the Tertiary sp3-Carbon Center for Enantiopure Synthesis of 3-Fluorooxindoles.

The first asymmetric nucleophilic fluorination at the sp3-tertiary carbon center has been developed using inexpensive tetrabutylammonium fluoride (TBAF) without any metal/catalyst for the synthesis of 3-fluoro-3-substituted oxindoles with excellent enantioselectivity (ee up to >99%). Regio- and stereocontrolled ring opening of spiroaziridine with retention of configuration and other experiments revealed that the fluorination proceeded through an anchimeric assistance.