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Herein we report on the umpolung of Morita-Baylis-Hillman type intermediates and application to the α-functionalization of enone C-H bonds. This reaction gives direct access to α-chloro-enones, 1,2-diketones and α-tosyloxy-enones. The latter are important intermediates for cross-coupling reaction and, to the best of our knowledge, cannot be made in a single step from enones in any other way. The proposed mechanism is supported by spectroscopic studies. The key initial step involves conjugate attack of an amine (DABCO or pyridine), likely assisted by hypervalent iodine acting as a Lewis acid leading to formation of an electrophilic β-ammonium-enolonium species. Nucleophilic attack by acetate, tosylate, or chloride anion is followed by base induced elimination of the ammonium species to give the noted products. Hydrolysis of α-acetoxy-enones lead to formation of 1,2-diketones. The α-tosyl-enones participate in Negishi coupling reactions under standard conditions.

Due to their closely matched reactivity, the coupling of two dissimilar ketone enolates to form a 1,4-diketone remains a challenge in organic synthesis. We herein report that umpolung of a ketone trimethylsilyl enol ether (1 equiv) to form a discrete enolonium species, followed by addition of as little as 1.2–1.4 equivalents of a second trimethylsilyl enol ether, provides an attractive solution to this problem. A wide array of enolates may be used to form the 1,4-diketone products in 38 to 74% yield. Due to the use of two TMS enol ethers as precursors, an optimization of the cross-coupling should include investigating the order of addition.

Enolonium species, resulting from the umpolung of ketone enolates by Koser's hypervalent iodine reagents activated by boron trifluoride, react with a variety of nitrogen heterocycles to form α-aminated ketones. The reactions are mild and complete in 4-5 h. Additionally, α-azidation of the enolonium species takes place using trimethylsilyl azide as a convenient source of azide nucleophile.

Herein it is shown, for the first time, that enolonium species are powerful electrophiles capable of reacting with aromatic compounds in an intermolecular manner to afford α-arylated ketones. The reaction is compatible with a variety of functional groups, is of wide scope with respect to aromatic compounds and ketone, and even works for polymerization-prone substrates such as substituted pyrroles, thiophenes, and furans. Only 1.6 to 5 equiv of the commodity aromatic substrates is needed.

α-Functionalization of ketones via umpolung of enolates by hypervalent iodine reagents is an important concept in synthetic organic chemistry. Recently, we have developed a two-step strategy for ketone enolate umpolung that has enabled the development of methods for chlorination, azidation, and amination using azoles. In addition, we have developed C-C bond-forming arylation and allylation reactions. At the heart of these methods is the preparation of the intermediate and highly reactive enolonium species prior to addition of a reactive nucleophile. This strategy is thus reminiscent of the preparation and use of metal enolates in classical synthetic chemistry. This strategy allows the use of nucleophiles that would otherwise be incompatible with the strongly oxidizing hypervalent iodine reagents. In this paper we present a detailed protocol for chlorination, azidation, N-heteroarylation, arylation, and allylation. The products include motifs prevalent in medicinally active products. This article will greatly assist others in using these methods.

An efficient eliminative deoxygenation reaction is reported for the conversion of aliphatic and aromatic epoxides to olefins. Polyphosphoric acid (PPA) is used in 30 mol % as a promoter to afford the products in excellent yield (85–96%) at 50 °C under neat condition. Our method has advantages such as inexpensive reagents, high yield, stereoselective product in short reaction time under eco-friendly reaction conditions.

A highly efficient and green protocol is reported for the reductive deoxygenation of organic epoxides to olefins using tin(II) chloride/sodium iodide as a novel reagent. The reaction gives an excellent yield (85–96%) in ethanol under reflux within 2–10 minutes, without affecting other functional groups. The advantages of our method are the use of inexpensive reagents, the eco-friendly and green reaction conditions, and the short reaction times and high yields.

SeO2 in water provided an efficient and one-pot deprotection of acetyl, tetrahydropyranyl and methoxymethyl ethers in alcohols and phenols and sequel oxidation of methyl/methylene carbons of alpha carbonyl carbon to dicarbonyl functional groups at 80 °C in 30–60 min. Using a substrate, SeO2 in a 1 : 3 ratio, the reaction gave excellent yields (85–95%) for acetyl and tetrahydropyranyl deprotections and a moderate yield (35–40%) for methoxymethyl deprotection without affecting other functional groups.

SnCl4 or TiCl4 catalysts provided a rapid and efficient detetrahydropyranylation and demethoxymethylation of phenolic ethers and a sequential one-pot intramolecular Friedel–Crafts alkylation of chalcone epoxides under mild reaction conditions. The reaction took 2–3 min to give the phenols and 1-indanones in an excellent yield (90–98%) at 0 °C without affecting other functional groups. With these catalysts, our protocol gave regioselective products as trans-3-aryl-2-hydroxy-1-indanones in an excellent yield (76–98%) and an enantiomeric excess of up to 99.9% under the same conditions.

We described the synthesis of flavone–estradiol adducts and indanophen based tamoxifen analogs using a novel SnCl4–Zn reagent via a McMurry cross-coupling reaction and their anti-proliferative evaluation against human cervical cancer cell lines (HeLa) and human breast cancer cell lines (MCF-7 and MDA-MB-231). A library of 32 tamoxifen analogs was synthesized using indanone and propiophenone derivatives and evaluated for anti-proliferative activities. Among them, compounds 3ac, 3ad, 3ae and 3ao exhibited better anti-proliferative potencies (IC50 2.13–3.81 μM) than the drug doxorubicin (IC50 < 28 μM). The flavones–estradiol adducts 6ab and 6ad exhibited good anti-proliferative activity (IC50 2.85 ± 0.17 μM and 2.42 ± 0.23 μM; 3.64 ± 0.28 μM and 2.93 ± 0.14 μM) against breast cancer cells (MCF-7 and MDA-MB-231) respectively and IC50 2.17 ± 0.18 μM and 2.56 ± 0.32 μM against cervical cancer cells (HeLa) respectively than the standard drug. However, compounds 6ac, 6ae, 6af and 6ag showed moderate activity (IC50 < 10 μM). The structure–activity relationship analysis revealed that the optimal combination of side chains at the para-position of propiophenone and fluoro substituent on the indanone moiety enhanced the anti-proliferative activities of tamoxifen analogs.

Sn(IV)Cl 4 catalyst provided a rapid and efficient deprotection method for the phenolic THP and MOM ethers and sequel intramolecular Friedel–Crafts alkylation reaction of THP and MOM protected chalcone epoxides under mild conditions. The reaction took 2–3 min to give the products in excellent yield (90–98%) at 0 °C without affecting the other functional groups.

An efficient eliminative deoxygenation reaction is reported for the conversion of aliphatic and aromatic epoxides to olefins. Polyphosphoric acid (PPA) is used in 30 mol % as a promoter to afford the products in excellent yield (85–96%) at 50 °C under neat condition. Our method has advantages such as inexpensive reagents, high yield, stereoselective product in short reaction time under eco-friendly reaction conditions.

SnCl4 or TiCl4 catalysts provided a rapid and efficient detetrahydropyranylation and demethoxymethylation of phenolic ethers and a sequential one-pot intramolecular Friedel–Crafts alkylation of chalcone epoxides under mild reaction conditions. The reaction took 2–3 min to give the phenols and 1-indanones in an excellent yield (90–98%) at 0 °C without affecting other functional groups. With these catalysts, our protocol gave regioselective products as trans-3-aryl-2-hydroxy-1-indanones in an excellent yield (76–98%) and an enantiomeric excess of up to 99.9% under the same conditions.

A novel, efficient, and economical tin-reagent for the reductive cross-coupling reaction of carbonyl compounds under McMurry coupling with aliphatic and aromatic ketones, aldehydes, chalcone epoxides, and indanones is developed.

Sn(IV)Cl 4 catalyst provided a rapid and efficient deprotection method for the phenolic THP and MOM ethers and sequel intramolecular Friedel–Crafts alkylation reaction of THP and MOM protected chalcone epoxides under mild conditions. The reaction took 2–3 min to give the products in excellent yield (90–98%) at 0 °C without affecting the other functional groups.