Iodine-Mediated Synthesis of 2-(Methylthio)-4H-chromen-4-ones and Study of Their Halogenation Reactions.

An efficient iodine-mediated method is developed for the synthesis of functionalized 2-(methylthio)-4H-chromen-4-ones by intramolecular cyclization of easily accessible 1-(2-benzyloxy-aryl)-3,3-bis-methylsulfanyl-propenones. The synthesized chromen-4-ones turn out to be a key precursor for various kinds of chemical reactions. Mechanistically, we observed that iodine-mediated intramolecular cyclization of ketene dithioacetal proceeded through a radical pathway. 3-Halo-2-(methylthio)-4H-chromen-4-ones were achieved via various two- or one-pot halogenation approaches.

Step-wise and one-pot synthesis of highly substituted conjugated trienes from 2-oxobenzo[h]chromenes/2H-pyran-2-ones.

A mild and efficient route for the synthesis of conjugated trienes via nitroethane-mediated ring contraction of 2-oxobenzo[h]chromenes/2H-pyran-2-ones followed by decarboxylative rearrangement of the obtained spirobutenolides and butenolides is described. The (E)-isomer of trienes was obtained by step-wise and one-pot approaches from 2-oxobenzo[h]chromenes. Butenolides 4a-l as new substrates have been developed for the construction of trienes. The mixture of the (E)- and (Z)-isomers of spirobutenolides undergoes decarboxylative rearrangement in the presence of sodium ethoxide as a base to yield the (E)-isomer of trienes, while the (E)-isomer of butenolides reacts to give a mixture of (2E,4E)- and (2E,4Z)-isomers of trienes in an almost steady ratio of 45 : 55 or 1 : 1.2. The structure and geometry of the obtained butenolides and trienes were confirmed by single-crystal X-ray analysis.

Base mediated synthesis of functionalized 2-(alkynyl)arylnitriles and their molecular docking study with aromatase receptor.

A simple, efficient, and transition metal-free approach to synthesize functionalized 2-(alkynyl)benzonitriles has been developed using suitably functionalized 2H-pyran-2-ones and 4-phenyl/trimethylsilanyl-but-3-yn-2-ones as precursors. The reaction proceeds in the presence of a base at room temperature to yield internal as well as terminal alkynes. The structure of the synthesized compound was confirmed by single-crystal X-ray analysis. The molecular docking study was performed to evaluate the binding mode of action of newly synthesized alkyne derivatives with known human breast cancer target receptor aromatase (PDB ID: 3EQM).

Transition metal-free synthesis of sterically hindered allylarenes from 5-hexene-2-one.

A simple, efficient and transition metal-free strategy was established for the synthesis of highly functionalized, sterically hindered allylarenes (6, 7 & 8) by base-mediated ring transformation of 2-oxo-6-aryl-4-(methylthio/sec-amino)-2H-pyran-3-carbonitriles (3/4) with 5-hexene-2-one (5). This provides a method for the synthesis of allylarenes functionalized with different electron donating and withdrawing groups in one pot. The structures of isolated products 6c and 7a were ascertained by spectroscopic and single crystal X-ray diffraction analyses. In addition, we have performed a molecular docking study to predict the biological activity of the synthesized molecules for binding to estrogen receptor alpha (ERα) and estrogen receptor beta (ERß).

A [5 + 1] annulation strategy for the synthesis of multifunctional biaryls and p-teraryls from 1,6-Michael acceptor ketene dithioacetals.

A new type of ketene dithioacetal, 2-(3,3-bis-methylsulfanyl-1-arylallylidene)malononitriles containing 1,4 and 1,6-Michael acceptors, were synthesized to study their reactivity for the synthesis of a new molecular entity. We report a [5 + 1] annulation strategy for the construction of multifunctional biaryls and p-teraryls by the selection of a suitable nucleophilic source. The reaction of p-nitrotoluene with 2-(3,3-bis-methylsulfanyl-1-aryl-allylidene)malononitriles under basic conditions produces p-teraryls in good yields, while the use of nitroethane as the nucleophile source provides functionalized biaryls through cyclization, followed by denitration. This reaction requires mild conditions and exhibits good functional group tolerance.

Synthesis of alkynes from non-alkyne sources.

Alkynes are a very important class of compounds and used as precursors for the assembly of a variety of carbocycles and heterocycles. Alkynes are classified into two classes: terminal alkynes and internal alkynes. Terminal alkynes were used as one of the precursors for the synthesis of internal alkynes. Besides, various elimination reactions were conducted to obtain alkynes. Various applications of alkynes are known but no compiled review is reported so far regarding their synthesis. Therefore, we have compiled the literature available for the synthesis of various functionalized alkynes from non-alkyne sources in this review. We have not discussed the synthesis of internal alkynes from terminal alkynes. Based on the available literature, the synthesis of alkynes can be classified into three major types of reactions: (a) synthesis of alkynes through α,ß-elimination, (b) synthesis of alkynes through carbene rearrangement and (c) synthesis of alkynes via miscellaneous approaches. In this review, we have focused on the different methods available for these transformations including their scope, limitations and recent developments. We have also discussed the mechanism involved during the reaction.

Synthesis of Highly Functionalized Spirobutenolides via a Nitroalkane-Mediated Ring Contraction of 2-Oxobenzo[ h]chromenes through Denitration.

A facile synthesis of highly functionalized spirobutenolides was carried out by a nitroalkane carbanion-induced ring opening and relactonization via a denitration reaction of 2-oxo-5,6-dihydro-2 H-benzo[ h]chromene-3-carbonitriles and 2-oxo-2,5-dihydrothiochromeno[4,3- b]pyran-3-carbonitriles. However, when nitroethane was used as a nucleophile source in lieu of nitromethane, a mixture of ( E)- and ( Z)-isomers of the corresponding spirobutenolides was obtained in a different ratio. The structure and geometry of the product were confirmed by single-crystal X-ray diffraction. The isolated ( E)- and ( Z)-butenolides with the treatment with sodium ethoxide in DMF at room temperature provided highly substituted trienes via an allylic ring opening followed by decarboxylation.

Chemoselective synthesis of m-teraryls through ring transformation of 2H-pyran-2-ones by 2-(1-arylethylidene)-malononitriles.

We have developed a simple, efficient and chemoselective approach for the synthesis of m-teraryls by the reaction of 6-aryl-2-oxo-4-(sec.amino)-2H-pyran-3-carbonitriles and 2-(1-arylethylidene)malononitriles under basic conditions. We used 6-aryl-2-oxo-4-methylsulfanyl-2H-pyran-3-carbonitriles as precursors and successfully afforded 5'-methylsulfanyl-[1,1';3',1'']teraryl-4'-carbonitriles. We tried to understand the difference in the reactivity of structurally symmetrical molecules, such as allyl cyanide, 2-cyanomethylbenzonitrile and 2-(1-arylethylidene)malononitrile. The structure of 4''-methyl-5'-(piperidin-1-yl)-[1,1':3',1''-terphenyl]-4'-carbonitrile was confirmed by single crystal X-ray diffraction analysis.

Base controlled diverse reactivity of allyl cyanide for synthesis of multi-substituted benzenes.

A base controlled regioselective 1,6-cyanoallylation of suitably functionalized 2H-pyran-2-ones has been demonstrated for the synthesis of various multi-substituted benzenes through a tandem process. We observed that lithium hydroxide provides a major product from α-attack and a minor product from γ-attack of allyl cyanide, while the use of sodium hydride as a base exclusively provides the product by γ-attack of allyl cyanide. We have also performed NMR experiments to understand the mechanistic pathway. The structure of the compound was confirmed by single crystal X-ray analysis.