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An efficient and straightforward method has been developed for the synthesis of β-benzyl-substituted five-membered heterocyclic carbaldehydes via transient directing group-enabled direct γ-C(sp3)−H...

Propargyl α-aryl-α-diazoacetate a new class of reagent is developed for the effective C H bond functionalization of 1,3-diketones at room temperature. The combination of scandium triflate and propargyl α-aryl-α-diazoacetate proved to be efficient catalyst-reagent system for the controlled C H bond functionalization to afford 1,3-dicarbonyl alkylation. The protocol uses inexpensive Sc(OTf)3 (5 mol%) and the reaction did not require the use of expensive catalysts or ligands and worked efficiently at room temperature. The practicality of the protocol has been demonstrated by the gram scale synthesis.

A dual cooperative organocatalytic approach for the synthesis of α, β-unsaturated ketones is described. This one pot transformation is realized via a domino Knoevenagel-Michael-retro Michael reaction sequence. Various aliphatic ketones reacted smoothly with aromatic as well as aliphatic aldehydes in presence catalytic amount of Meldrum’s acid and bifunctional amine. The highlights of this protocol are the easy availability of catalysts, high selectivity, and functional group tolerance. The reaction proved to highly E-selective with no side products emanating from self-condensation, unlike the base-mediated reactions.

The operationally simple, robust and straightforward organocatalytic protocol is developed for the synthesis of E-selective α,β-unsaturated ketones. The method utilizes simple and easily accessible starting materials such as Meldrum’s acid, carboxylic acid, aldehyde and simple bifunctional amine catalyst. The tandem organocatalytic process utilizes acyl/aroyl Meldrum’s acid as an enol surrogate for the effective Doebner-Knoevenagel type condensation reactions. A wide variety of aldehydes, carboxylic acids and base sensitive functional groups are well tolerated under the mild reaction conditions.

A highly diastereoselective organocatalytic synthesis of cyclopentenyl bis-spirooxindoles and cyclopropyl spirooxindoles has been achieved via [3 + 2] and [2 + 1] annulations. The tertiary amine catalysts have been effectively employed to tune the cycloaddition of isatin-derived MBH carbonates and 3-methyleneoxindoles for the outcome of two different spirooxindole frameworks with vicinal quaternary spiro centers and three contiguous stereocenters. The reactions worked under mild and practical conditions to afford the spirooxindoles in good to excellent yields with very high diastereoselectvity.

FeCl3·6H2O/triethylsilane composite catalyst system is successfully developed for the selective conjugate reduction of carbon-carbon double bond of Michael acceptor-alkylidene-β-keto esters and alkylidene-1,3-diketones under mild reaction conditions to afford the corresponding saturated β-keto esters and 1,3-diketones. The process involves the iron-catalyzed hydrosilylation, followed by in situ hydrolysis of silyl enol ether. The optimal reaction conditions include 20 mol% of FeCl3·6H2O and triethylsilane in dichloromethane at room temperature. A broad range of substrates undergoes the reduction in 1, 4-selective manner to afford the corresponding saturated compounds in excellent yields.

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. This mild protocol provides an easy access to enantiopure carboxylic acids, esters and amides and the method is scalable on a gram quantity. DFT calculations were carried out on the proposed reaction mechanism and they were in close agreement with the experimental results.

One-pot expedient and direct carbamolyation of heterocyclics is described. The transformation is realized via direct dehydrogenative aminocarbonylation of heterocyclic compounds under transition-metal-free conditions. This method is regioselective and the protocol is proved to be scalable on a gram scale. Further, the therapeutically useful antitubercular agent pyrazinecarboxamide is successfully synthesized by employing this protocol

An efficient diastereoselective synthesis of substituted piperidines is accomplished by using catalytic amount of FeCl3·6H2O via intramolecular aza-Michael addition of carbamate on alkylidene β-keto (L)-menthyl esters in a very short time.

An expedient and straightforward protocol is developed for the synthesis of highly enantiopure synthesis of γ-butyrolactones. For the first time, one pot enantioselective organocatalytic multicomponent reaction (OMCR) is explored to construct functionalized butyrolactones without the use of pre-functionalized substrates and expensive transition metals. The protocol is proved to be reproducible on a gram scale. Density functional theory (DFT) calculations strongly support the mechanism and were in close agreement with the observed high stereoselectivity.

One-pot transition-metal-free synthesis of aromatic aldehydes and ketones via oxidative decarboxylation of arylacetic acids in water is developed. Protocol relies on the direct decarboxylation of sp3-hybridized carbon in water without any over oxidation into carboxylic acids with minimal waste. Reaction mechanism is investigated and application of this protocol is demonstrated on a gram scale .

Facile and convenient synthesis of α,β-unsaturated esters and thioesters from alkylidene derivatives of Meldrum’s Acid is described. This method uses catalytic amount of FeCl3·6H2O (0.001–0.005 equiv) with alcohols/thiols (1 equiv) in dry CH3NO2 followed by catalytic amount of piperidine. A variety of α,β-unsaturated esters and thioesters have been synthesized with high E-stereoselectivity in good to excellent yields. The application of this methodology is demonstrated by gram scale synthesis of octinoxate, a sunscreen agent, and other p-methoxycinnamate esters.

An expedient direct and regioselective thiocyanation of phenols, anilines and heterocycles is described. Transformation is realized via the direct C H functionalization under transition metal free conditions at ambient temperature in excellent yields. Method proved to be monoselective and variety of functional groups tolerated the reaction conditions. The practicality of the protocol is demonstrated in gram scale synthesis of a precursor of PPAR δ agonist in excellent yield.

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. The generality of the synthesis is exemplified by the use of a wide variety of aldehydes including enolizable aliphatic aldehydes, while substrates are stable under reaction conditions.

Visible light mediated facile and selective dithiane deprotection under metal free conditions is developed. Eosin Y (1 mol%) proved to be an effective catalyst for the dithiane deprotection under the ambient photoredox conditions. The standard household compact fluorescent light source (CFL bulb) proved to be effective under open-air conditions in aqueous acetonitrile at room temperature. The protocol that exhibits a broad substrate scope and functional group tolerance has been shown to expand to a range of transformations for the electron-rich and -deficient thioacetals and thioketals. The synthetic utility of this protocol has also been demonstrated by gram-scale application.

We report the X-ray crystal structure of Au36-xAgx(SPh-tBu)24 alloy nanomolecules, optical properties, and the substitutional disorder refinement protocol to obtain a reliable structural model. Single crystal X-ray crystallography (SC-XRD) revealed a composition of Au33.17Ag2.83(SPh-tBu)24 with 2 Ag doped on the 28-atom face centered cubic core surface and 0.83 Ag distributed over metal atoms on dimeric staple motifs. Electrospray ionization mass spectrometry revealed a composition of Au32.5Ag3.5(SPh-tBu)24 complementing the SC-XRD data. Optical properties were investigated by steady-state and transient absorption spectroscopies and computational studies, showing faster excited-state decay for Ag-doped clusters due to enhanced electronic coupling. A previously published SC-XRD based Au36-xAgx(SPh-tBu)24 structure used positional disorder refinement and concluded that the structure is "solely motif-doped". But the structure has unusually large and small thermal ellipsoids indicating potential problems with the atom assignment. Here, we have modeled our SC-XRD data using both positional disorder and substitutional disorder. Subtitutional disorder modeling gave better R1 and other refinement indicators, and similarly sized thermal ellipsoids. The resulting substitutional disorder model structure has Ag atoms not as "solely motif-doped" but is found both in the staple motifs and in the core. The substitutional disorder refinement for alloy nanomolecules must be performed at each metal site with independent free variables to determine the partial occupancy of hetero atoms. The positional disorder refinement should be performed for atoms or groups disordered over different positions typically found in disordered tBu group ligands.

Understanding the evolution of the structure and properties in metals from molecule-like to bulk-like has been a long sought fundamental question in science, since Faraday's 1857 work. We report the discovery of a Janus nanomolecule, Au191(SPh-tBu)66 having both molecular and metallic characteristics, explored crystallographically and optically and modeled theoretically. Au191 has an anisotropic, singly twinned structure with an Au155 core protected by a ligand shell made of 24 monomeric [-S-Au-S-] and 6 dimeric [-S-Au-S-Au-S-] staples. The Au155 core is composed of an 89-atom inner core and 66 surface atoms, arranged as [Au3@Au23@Au63]@Au66 concentric shells of atoms. The inner core has a monotwinned/stacking-faulted face-centered-cubic (fcc) structure. Structural evolution in metal nanoparticles has been known to progress from multiply twinned, icosahedral, structures in smaller molecular sizes to untwinned bulk-like fcc monocrystalline nanostructures in larger nanoparticles. The monotwinned inner core structure of the ligand capped Au191 nanomolecule provides the critical missing link, and bridges the size-evolution gap between the molecular multiple-twinning regime and the bulk-metal-like particles with untwinned fcc structure. The Janus nature of the nanoparticle is demonstrated by its optical and electronic properties, with metal-like electron-phonon relaxation and molecule-like long-lived excited states. First-principles theoretical explorations of the electronic structure uncovered electronic stabilization through the opening of a shell-closing gap at the top of the occupied manifold of the delocalized electronic superatom spectrum of the inner core. The electronic stabilization together with the inner core geometric stability and the optimally stapled ligand-capping anchor and secure the stability of the entire nanomolecule.