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Arduengo et al., isolated the first ‘bottleable’ carbene, the first N-heterocyclic carbene (NHC) 1,3-di(adamantyl)imidazol-2-ylidene resulted to an explosion of experimental and theoretical studies of novel NHCs being synthesized and analyzed have huge practical significance. These compounds emerged as successful ligands for coordinating transition metals, the complexes with NHC show diverse applications in the field of catalysis and organic transformation, NHC as ligand to main group elements and their properties and applications. Here this chapter provides the concise overview of N-heterocycle carbene as an organocatalyst that provides different organic transformation on to a carbonyl group. The majority of the NHC catalyzed reactions are employed in the phenomenon of reversing the electrophilic character of carbonyl carbon to nucleophilic carbon (umpolung activity) on coordination suggests benzoin, Stetter and hydroacylation reactions. Also, non-umpolung activity of bis-electrophile α,β-unsaturated acylazoliums reaction with suitable bis-nucleophiles in the organic synthesis have been studied.

Present work describes the T3P® mediated one pot four component reaction between 2-aminoacetamide, methylene-active carbonyl compounds, S8 and isothiocyantes in synthesizing 1-(3-cyanothiophen-2-yl)-3-phenylureas. The strategy developed here comprises Gewald reaction followed by the T3P intervened unique intra-molecular rearrangement. The novel and eco-friendly route achieved here is operationally facile and offers versatile 1-(3-cyanothiophen-2-yl)-3-phenylureas, which are expected to show good biological activities.

Novel and convenient methodology for the construction of N-substituted amide derivatives have been developed from nitriles and alcohols using propylphosphonic anhydride (T3P®). This methodology is an alternate approach to the synthesis of amides via Ritter reaction, which is one of the classical methods for the synthesis of N-substituted amides from nitriles and alcohols. In this approach, first T3P® activates the alcohol which is then attacked by nitrile to form N-substituted amides. This methodology can also apply for the synthesis of benzhydryl ether. This developed protocol is one of the novel applications of T3P®.

The synthesis of (2S,3S,4S)-N-benzyl-3-hydroxy 4-methyl proline and its stereoisomer (2R,3R,4S)-N-benzyl-3-hydroxy 4-methyl proline has been achieved starting with the conjugate addition of methyl methacrolate and benzylamine. The other key reactions performed in our strategy include enzymatic separation of an α-methyl β-amino alcohol, Sharpless asymmetric dihydroxylation of an α,β-unsaturated δ-amino ester, and intramolecular cyclization of a sulfonate to a pyrrolidine ring system. Two stereoisomers were synthesized from the common α,β-unsaturated δ-amino ester intermediate. This protocol is simple, straightforward, efficient, highly stereoselective, and economically viable.

A new approach for the synthesis of novel bis(imidazol-1-yl)vinyl-1,2,4-oxadiazoles has been developed. This method operates in a single step giving the products in good to excellent yields. Antiproliferative efficiency of the synthesized compounds was tested against HCT116 (colon cancer) and A549 (lung cancer) cell lines. Among them, compounds 3m (IC50, 9.7 μM) and 3h (IC50, 20.3 μM) were found to be the best antiproliferative agents.

Iodine-mediated synthesis of 3-sulfenylimidazo[1,5-a]pyridines via C–H functionalization has been achieved using dithioesters, 2-methylaminopyridines and sulfonyl hydrazides. A library of 3-sulfanylimidazopyridines and imidazopyridines with broad functionalities are synthesized under metal-free reaction conditions.

T3P–DMSO mediated desulfurative cyclization of in situ generated thioamides serves as an efficient and versatile method for the synthesis of imidazo[1,5-a]pyridines and [1,2,4]-triazolo[4,3-a]pyridines with good to excellent yields. Substrates such as 2-methylaminoquinoline and pyrazin-2-yl-methanamine also undergo the corresponding reactions at room temperature. This efficient protocol has several advantages such as mild conditions, short reaction time, operational simplicity and high yields.

An efficient ligand- and catalyst-free intramolecular S-arylation leading to the direct synthesis of indalothiochromen-4-ones from simple dithioesters under mild conditions has been developed. This method is particularly noteworthy given its experimental simplicity, high generality, and good functional group toleration.

Synthesis of polycyclic amines was achieved by benzoic acid catalysed reaction of 1-aryl THIQs and 1-aryl trypolines with o-allyl salicylaldehydes through the in situ generated azomethine ylide intermediates that undergo intramolecular [3+2]-cycloadditions with four new stereogenic centers in excellent diastereoselectivities under simple and mild conditions.

Efficient synthesis of benzo[b]thiophenes from o-halophenyl acetonitrile has been achieved. This novel one-pot procedure involves CuI and pivalic acid catalyzed C–S bond formation using dithioesters followed by a heterocyclization reaction. This efficient protocol has the advantages of one-pot synthesis, short reaction time, good yields (62–78%) and operational simplicity.

Iodine-mediated synthesis of 3-sulfenylimidazo[1,5-a]pyridines via C–H functionalization has been achieved using dithioesters, 2-methylaminopyridines and sulfonyl hydrazides. A library of 3-sulfanylimidazopyridines and imidazopyridines with broad functionalities are synthesized under metal-free reaction conditions.

A new approach for the synthesis of novel bis(imidazol-1-yl)vinyl-1,2,4-oxadiazoles has been developed. This method operates in a single step giving the products in good to excellent yields. Antiproliferative efficiency of the synthesized compounds was tested against HCT116 (colon cancer) and A549 (lung cancer) cell lines. Among them, compounds 3m (IC50, 9.7 μM) and 3h (IC50, 20.3 μM) were found to be the best antiproliferative agents.

The kinetics of oxidation of α-amino acids (AAs) by chloramine-T (CAT) using β-cyclodextrin (BCD) as catalyst was studied in aqueous sodium hydroxide medium at 313 K. The kinetics of reactions was fractional-order with respect to [amino acids] and [β-cyclodextrin]. First-order with respect to [chloramine-T] and inverse fractional-order with respect to [OH − ] have been found. Effect of ionic strength, added salt and reaction product (PTS) had no effect on reaction rate. The dependence of the reaction rate on temperature was studied and activation parameters were computed from Arrhenius–Eyring plots. The reaction mechanism and the derived rate law are consistent with the observed experimental results.

Trifluoroethanol is an efficient and recyclable medium in promoting one-pot, three-component condensation reactions of β-ketoesters, aldehydes, and urea (or thiourea) to afford the corresponding dihydropyrimidones in good yields. This protocol does not require the use of an acid or base catalyst.

Synthesis of polycyclic amines was achieved by benzoic acid catalysed reaction of 1-aryl THIQs and 1-aryl trypolines with o-allyl salicylaldehydes through the in situ generated azomethine ylide intermediates that undergo intramolecular [3+2]-cycloadditions with four new stereogenic centers in excellent diastereoselectivities under simple and mild conditions.

The reaction is proposed to proceed via initial reaction of the activated methylene group with the dithioester to give an intermediary thioketone which undergoes intramolecular Cu-catalyzed cyclization to yield the title compounds.

Trifluoroethanol acts as solvent and reaction mediator at the same time, hence no further activator is required.