Oxonium/Sulfonium Ylide Rearrangements to Access Chromenes and Thiochromenes: Concerted or Stepwise Pathway?

Dirhodium(II)-catalyzed regio-divergent intramolecular rearrangement of oxonium and sulfonium ylides, generated from diazo arylidene succinimides (DAS), has been achieved at room temperature. Allyloxy-substituted DAS derivatives were strategically designed and synthesized to explore their reactivity under metal catalysis. The transformation is proposed to proceed via oxonium ylide intermediate, followed by [1,2]- and [1,4]-shifts, leading to the chromene framework.

Aryl Thiocyanate as an Organic 'CN' Source: Access to Thiocyano-Thioesters from Cyclic Thioacetals.

A facile, transition metal-free method has been developed for the synthesis of thiocyano-thioesters. It employs cyclic thioacetals and aryl thiocyanate as an organic 'CN' source, facilitated by organophotocatalyst under the visible light irradiation. Additionally, the diaryl disulfide by-products have been efficiently repurposed as a recyclable and reusable substrates for the sustainable synthesis of aryl thiocyanates, supporting the circular chemical economy.

Palladium Catalyzed C3-(sp)-H Alkenylation of Pyrroles via a Benzothiazole Directing Group: A Direct Access to Organic Thermally Activated Delayed Fluorescence Materials.

A Pd (II)-catalyzed direct C3-(sp)-H alkenylation of heteroarenes using benzothiazole as a directing group was successfully achieved. A wide range of 2--alkylpyrroles undergo an oxidative coupling with a variety of acrylates to furnish highly regio- and chemoselective E-alkenylation products at the C3 position. An important intermediate complex has been isolated and characterized so as to have an insight into the mechanism.

Visible-Light-Induced Copper-Catalyzed Radical Reactions of Diazo Arylidene Succinimides to Access the Pyromellitic Diimide (PMDI) Core.

The synthesis of pyromellitic diimides (PMDIs) through visible-light-promoted copper-catalyzed reaction of diazo arylidene succinimides has been accomplished without the use of external oxidants. This transformation involves a carbon radical from diazo arylidene succinimides with a copper catalyst or photocatalyst via the proton-coupled electron transfer (PCET) process. This approach successfully challenges a long-standing paradigm in the synthesis of PMDIs.

The Reactivity of Acceptor-Acceptor Diazo Pyrazolones with Allyl Thioethers under Visible Light: Access to Homoallyl Sulfides, Spiropyrazolones - Pesticide Analogues and Photoflow Synthesis.

The novel reactivity of a less selective and more reactive acceptor-acceptor kind of diazo pyrazolone (DIPOL) has been explored under visible light for the first time. We have successfully demonstrated the reaction of DIPOL and different allyl thioethers under blue light to construct a wide variety of products including a pesticidal analogue exclusively in excellent chemoselectivity in good to excellent yields. Moreover, possible side products emanating from ketene were not observed.

Visible Light-Induced Organophotoredox-Catalyzed β-Hydroxytrifluoromethylation of Unactivated Alkenes.

Herein, we report a mild transition metal-free organophotoredox-catalyzed approach for β-hydroxytrifluoromethylation of unactivated alkenes using CFSONa and acridinium salt. The protocol is compatible with various mono-, di-, and trisubstituted aliphatic unactivated alkenes containing numerous functional groups and natural product derivatives. Further, the postsynthetic modifications of the synthesized trifluoromethylated products have been demonstrated through cross-coupling and functional group interconversion reactions.

Photosensitizer-Free Photoinduced Ground-State Triplet Carbene-Assisted Persistent Aryloxy Radical Generation via Hydrogen Atom Transfer.

The traditional intermolecular O-H insertion strategy is typically associated with the reactivity exhibited by the singlet spin state, or it can alter the spin state from triplet to singlet by hydrogen bonding. Herein, we report diazoarylidene succinimide that generates a persistent ground-state triplet carbene under visible light (Blue LED, 456 nm) without a photosensitizer. This triplet carbene undergoes an intramolecular O-H insertion via hydrogen atom transfer, forming a persistent aryloxy radical without altering its spin state and leading to biologically relevant 2-chromenes.

Umpolung Reactivity of Diazo Arylidene Succinimides: Distal C-H Functionalization of α-Thiocarbonyls from the Reactive Carbenoid Center.

Herein, for the first time we have explored the umpolung reactivity of the vinylogous carbon center of diazo arylidene succinimide (DAS) through rhodium catalysis to achieve [2,3]-Stevens rearrangement of α-thioether esters. The protocol has successfully demonstrated the distal C-H bond functionalization of the α-thioether esters. Alongside, the carbenoid reactivity of DAS has also been achieved with Doyle-Kirmse reaction of allyl/propargyl phenyl sulfides.

A visible light-driven direct synthesis of industrially relevant glutaric acid diesters from aldehydes.

A straightforward and practical method has been developed to access α-substituted glutaric diesters from acrylates and aldehydes using visible light, with Eosin Y facilitating hydrogen atom transfer (HAT) and subsequent Giese-type addition. Also, sunlight has been successfully used as an alternative sustainable light source. The method has also been explored to access substituted 4,5-dihydro-2H-pyridazinones, which have potential biological and industrial applications.

Direct Access to Strained Fused Dihalo-Aziridino Quinoxalinones via C3-Alkylation Followed by Tandem Cyclization.

Quinoxalinones are a privileged class of compounds, and their structural framework is found in many bioactive compounds, natural compounds, and pharmaceuticals. Quinoxalinone is a promising scaffold for different types of functionalization, and the slight modification of the quinoxalinone skeleton is known to offer a wide range of compounds for drug discovery. Owing to the importance of the quinoxalinone scaffold, we have developed a base-mediated protocol for the C3-alkylation of quinoxalinone followed by tandem cyclization to access novel types of strenuous and fused dihalo-aziridino-quinoxalinone heterocycles via the construction of C-C and C-N bonds.

Base Dependent Rearrangement of Dithiane and Dithiolane under Visible-light Photoredox catalysis.

The rearrangement of dithiolanes and dithianes to access disulfide-linked-dithioesters under visible-light photoredox catalysis via controlled C-S bond cleavage has been disclosed. Unlike, the usual deprotection of dithioacetals to corresponding aldehydes under the oxidative conditions, we observed unique regioselective oxidative reactivity of five and six membered cyclic dithioacetals to form disulfide-linked-dithioesters by exchanging DMAP and imidazole bases. The generality of the protocol has been demonstrated by exploring a wide range of substrates.

Highly Site-Selective Direct C-H Bond Functionalization of Unactivated Arenes with Propargyl α-Aryl-α-diazoacetates via Scandium Catalysis.

Highly chemo- and regio-selective C-H bond functionalization of unactivated arenes with propargyl α-aryl-α-diazoacetates has been developed using scandium catalysis. A variety of unactivated, mildly deactivated, and electronically activated arenes have been functionalized using this protocol. The synergistic combination of scandium triflate as a catalyst and propargyl α-aryl-α-diazoacetate as a reagent played a pivotal role in the effective C-H bond functionalization of arenes without the assistance of any directing group or ligand.

Direct synthesis of 1,3-dithiolanes from terminal alkynes visible light photoredox catalysis.

A visible light-mediated, metal-free, regioselective dihydrothionation of terminal aromatic as well as heteroaromatic alkynes has been achieved using Eosin Y as a photoredox catalyst at room temperature. The protocol gives direct access to different 1,3-dithiolanes under neutral and mild reaction conditions without the use of any base or additives. The electron-donating, electron-withdrawing and electron-deactivating groups tolerated the photocatalytic reaction conditions.

An easy and practical approach to access multifunctional cylcopentadiene- and cyclopentene-spirooxindoles [3 + 2] annulation.

A highly regioselective [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates of isatin with aurone/thioaurone is developed. Spiroheterocycles such as spirooxindole cyclopentadiene and spirooxindole fused hydroxy cyclopentene derivatives are constructed in one pot by exploring the reactivity of Lewis bases. Combined experimental and density functional theory (DFT) calculations offered an insight into the reaction mechanism.

Access to Hetero-Benzyl Scaffolds via Transient-Ligand-Enabled Direct γ-C(sp)-H Arylation of 3-Methylheteroarene-2-Carbaldehydes.

An efficient and straightforward method has been developed for the synthesis of β-benzyl-substituted 5-membered heterocyclic carbaldehydes via transient directing-group-enabled direct γ-C(sp)-H arylation of 3-methylheteroarene-2-carbaldehydes. A wide range of 3-methylheteroarene carbaldehydes undergo coupling with a variety of aryl iodides, including less reactive iodo pyridine derivatives to provide a library of highly selective functionalized products in good to excellent yields. Some of these products have been successfully utilized in synthesizing useful synthetic intermediates.

Access to highly enantioselective and diastereoselective spirooxindole dihydrofuran fused pyrazolones.

A tertiary amine catalyzed highly diastereoselective and enantioselective [3 + 2] annulation between Morita-Baylis-Hillman (MBH) carbonates derived from isatin and pyrazolone 4,5-diones has been developed. A series of structurally diverse and multifunctional spirooxindole dihydrofuran fused pyrazolone derivatives with two adjacent quaternary spirocenters has been achieved in excellent yields with good to excellent enantioselectivity. Further synthetic utility of this protocol has been successfully demonstrated by employing the bromo derivative of spirooxindole dihydrofuran fused pyrazolone to Suzuki coupling.

Multicomponent synthesis of pyroglutamic acid derivatives via Knoevenagel-Michael-hydrolysis-lactamization-decarboxylation (KMHL-D) sequence.

A novel and practical method for the synthesis of 3-substituted pyroglutamic acid derivatives is described. One pot multicomponent reaction of Meldrum's acid, aldehyde and Schiff's base followed an unprecedented chemoselective Knoevenagel-Michael-hydrolysis-lactamization domino sequence to afford 4-carboxy 3-substituted pyroglutamic acid derivatives under mild conditions. A carboxy intermediate formed appears to accelerate its own formation.

An Adverse Effect of Higher Catalyst Loading and Longer Reaction Time on Enantioselectivity in an Organocatalytic Multicomponent Reaction.

An enantioselective organocatalytic multicomponent reaction of aldehydes, ketones, and Meldrum's acid has been developed. A cinchona-based primary amine (1 mol %) catalyses the multicomponent reaction via the formation of the Knoevenagel product and a chiral enamine to form enantiopure δ-keto Meldrum's acids in a tandem catalytic pathway. An adverse effect of higher catalyst loading and longer reaction time on enantioselectivity was studied.

Chemoselective N-deacetylation under mild conditions.

A mild and efficient chemoselective N-deacetylation using the Schwartz reagent at room temperature in rapid time is described. The mild and neutral conditions enable orthogonal N-deacetylation in the presence of some of the common protecting groups (viz. Boc, Fmoc, Cbz, Ts).

A practical and convenient protocol for the synthesis of (E)-α,β-unsaturated acids.

α,β-Unsaturated acids are very useful and versatile reagents in organic synthesis. A novel, practical, and convenient catalytic protocol comprising FeCl3·6H2O (0.5 mol %) and H2O (1 equiv) in CH3NO2 is described for the rapid synthesis of α,β-unsaturated acids with high E-stereoselectivity under both microwave and conventional heating conditions with high TON and TOF values.

Stereoselective approach to cis-2,3-disubstituted piperidines via reduction of N-acyliminium ion intermediate: enantioselective synthesis of (+)-(2S,3S)-CP-99,994.

A very simple and efficient stereoselective approach to cis-2,3-disubstituted piperidines via the reduction of N-acyliminium ion intermediates is described. Application of this methodology is exemplified by the enantioselective total synthesis of (+)-(2S,3S)-CP-99,994.

Enantiopure synthesis of side chain-modified α-amino acids and 5-cis-alkylprolines.

A short, concise synthesis of enantiopure, side chain-modified α-amino acids such as 4-oxo-L-norvaline, 6-oxo-L-homonorleucine, and 5-cis-alkyl prolines is described. Knoevenagel condensation of l-aminocarboxylate-derived β-ketoesters with aldehydes followed by reductive decarboxylation results in unnatural α-amino acids in good yield. A fluorescent amino acid is synthesized using a similar protocol.

Synthesis of 2-amido, 2-amino, and 2-azido derivatives of the nitrogen analogue of the naturally occurring glycosidase inhibitor salacinol and their inhibitory activities against O-GlcNAcase and NagZ enzymes.

Seven 2-substituted derivatives of the nitrogen analogue of salacinol, a naturally occurring glycosidase inhibitor, were synthesized for structure-activity studies with hexosaminidase enzymes. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the 2-azido-1,4-dideoxy-1,4-imino-D-arabinitol at the least hindered carbon atom of 2,4-O-benzylidene-L-erythritol-1,3-cyclic sulfate. Hydrogenation of the azido zwitterionic compound in methanol resulted in the reduction of the azide and subsequent methylation of the resulting amine in one pot.

Synthesis of phosphate derivatives related to the glycosidase inhibitor salacinol.

The syntheses of polyhydroxylated imino- and anhydro thio-alditol compounds related to the naturally occurring glycosidase inhibitor, salacinol, containing a phosphate group in the side chain are described. The compounds lack hydroxyl groups on the acyclic side chain and are prototypes of the exact salacinol analogue. The synthetic strategy relies on the Mitsunobu reaction of N- and S-hydroxyalkyl derivatives of 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino-D-arabinitol and 1,4-anhydro-2,3,5-tri-O-benzyl-1-thio-D-arabinitol with dibenzyl phosphate to yield the corresponding protected heteroalditol phosphates.