Directed Diastereoselective Cyclopropanation and Epoxidation of Alkenyl Cyclopropyl Carbinol Derivatives.

We report the directed diastereoselective Simmons-Smith cyclopropanation and vanadium-catalyzed epoxidation reactions of alkenyl cyclopropyl carbinol derivatives. The reaction furnished densely substituted stereodefined bicyclopropanes and cyclopropyl oxiranes as a single diastereomer in each case. The remarkable selectivity is obtained thanks to the rigidity of the cyclopropyl core, allowing diastereoselective reactions on the alkenyl moiety. This emphasizes the uniqueness of the cyclopropyl ring as a central platform in stereoselective synthesis.

Preparation of Distant Quaternary Carbon Stereocenters by Double Selective Ring-Opening of 1,1-Biscyclopropyl Methanol Derivatives.

The diastereoselective double carbometalation reaction of cyclopropenes provides, in a single-pot operation, two ω-ene-[1,1]-bicyclopropyl ester derivatives. One regioisomer then undergoes a Pd-catalyzed addition of aryl iodide to provide skipped dienes possessing several distant stereocenters including two congested quaternary carbon centers with excellent diastereoselectivity.

Iodine-Catalyzed Chemoselective C-N Bond-Forming Reactions Using Benzylic or Cinnamyl Alcohols with Heterocyclic Thiols and Thiones.

A chemoselective formation of C-N bond catalyzed by iodine has been developed using heterocyclic thiols and thiones. The reaction occurs at the nitrogen center over the sulfur, leading to the amination against the traditional sulfenylation. A wide variety of allylic and benzylic alcohols serve as coupling partners. This method showed a good tolerance toward 1 H-tetrazole-5-thiol, 5-methyl-1,3,4-thiadiazole-2-thiol, benzo[ d]thiazole-2(3 H)-thione, and benzo[ d]oxazole-2(3 H)-thione derivatives.

Regioselective Sulfenylation of α'-CH3 or α'-CH2 Groups of α,ß-Unsaturated Ketones with Heterocyclic Thiols.

A rare regioselective sulfenylation of α'-CH3 or α'-CH2 bonds adjacent to α,ß-unsaturated ketones using dimethyl sulfoxide as an oxidant and a substoichiometric amount of aq HI as an additive is described. This methodology employs a strong acid such as aq HI or iodine and exhibits a high regioselectivity without undergoing conjugate addition, which is difficult to achieve under the cross dehydrogenative coupling method.

Iodine-Catalyzed Chemoselective Hydroamination Reaction Using 5-Mercaptotetrazoles Derivatives.

Metal-free chemoselective hydroamination of styrene derivatives has been achieved with high chemoselectivity over sulfenylation of 1H-tetrazole-5-thiol using a catalytic amount of iodine. The scope of this methodology has been extended for the hydroamination of α-substituted styrene derivatives. This reaction involves a single-step C-N-bond formation under atom economical process. This eco-friendly method uses readily available and inexpensive iodine in a catalytic amount.

Iodine-catalyzed sulfenylation of pyrazolones using dimethyl sulfoxide as an oxidant.

An iodine catalyzed sulfenylation of pyrazolones with a diverse range of heterocyclic thiols, heterocyclic thiones and disulfides has been described using dimethyl sulfoxide as an oxidant, which is an inexpensive, readily available and green oxidant. The present methodology exhibits a wide range of substrate scope and targeted products were obtained in good to excellent yields under metal-free conditions in a short duration. This methodology provides a simple process for the formation of C-S bonds through the thioetherification of pyrazolones.

Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: Sulfenylation of Enaminones Using Dimethyl Sulfoxide as an Oxidant.

Synthesis of polyfunctionalized aminothioalkenes has been demonstrated using iodine as a catalyst (30 mol %) and dimethyl sulfoxide as an oxidant under metal-free reaction conditions. This methodology allows a facile sulfenylation of enaminones with a broad range of heterocyclic thiols and thiones using cross dehydrogenative coupling methods. In addition, this strategy is highly practical as it employs inexpensive and readily available iodine and DMSO with a short reaction time. The current methodology is one of the simplest methods and provides a straightforward approach to sulfenylation of enaminones via the cross dehydrogenative coupling method.

Iodine Promoted Regioselective α-Sulfenylation of Carbonyl Compounds using Dimethyl Sulfoxide as an Oxidant.

A metal-free regioselective sulfenylation of the α-CH3 group of ketones has been achieved in the presence of the α-CH2 or α-CH group using the cross dehydrogenative (CDC) strategy. Aldehydes also exhibit good selectivity forming the corresponding α-sulfenylated products. This efficient sulfenylation of ketones or aldehydes with thiones or heterocyclic thiols utilizes dimethyl sulfoxide (DMSO) as an oxidant in the presence of iodine. This eco-friendly method uses readily available and inexpensive I2 and DMSO. The application of this methodology has been demonstrated by synthesizing precursors for Julia- Kocienski olefination intermediates.

Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: A Regioselective Sulfenylation of Imidazoheterocycles Using Dimethyl Sulfoxide as an Oxidant.

A regioselective formation of C-S bonds has been achieved using a cross dehydrogenative coupling (CDC) protocol using iodine as a catalyst and dimethyl sulfoxide as an oxidant under green chemistry conditions. This strategy employs the reaction of easily available heterocyclic thiols or thiones with imidazoheterocycles. This protocol provides an efficient, mild, and inexpensive method for sulfenylation of imidazoheterocycles with a diverse range of heterocyclic thiols and heterocyclic thiones.

A chemoselective α-aminoxylation of aryl ketones: a cross dehydrogenative coupling reaction catalysed by Bu4NI.

Tetrabutyl ammonium iodide (TBAI) catalyzed α-aminoxylation of ketones using aq. TBHP as an oxidant has been accomplished. We have shown that the CDC (cross dehydrogenative coupling) reactions of ketones with N-hydroxyimidates such as N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI), N-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt) lead to the corresponding oxygenated products in good to moderate yields. The application of this method has been demonstrated by transforming a few coupled products into synthetically useful intermediates and products.

Iodine promoted α-hydroxylation of ketones.

A novel method for α-hydroxylation of ketones using substoichiometric amount of iodine under metal-free conditions is described. This method has been successfully employed in synthesizing a variety of heterocyclic compounds, which are useful precursors. α-Hydroxylation of diketones and triketones are illustrated. This strategy provides a novel, efficient, mild and inexpensive method for α-hydroxylation of aryl ketones using a sub-stoichiometric amount of molecular iodine.

A transition metal-free Minisci reaction: acylation of isoquinolines, quinolines, and quinoxaline.

Transition metal-free acylation of isoquinoline, quinoline, and quinoxaline derivatives has been developed employing a cross dehydrogenative coupling (CDC) reaction with aldehydes using substoichiometric amount of TBAB (tetrabutylammonium bromide, 30 mol %) and K2S2O8 as an oxidant. This intermolecular acylation of electron-deficient heteroarenes provides an easy access and a novel acylation method of heterocyclic compounds. The application of this CDC strategy for acylation strategy has been illustrated in synthesizing isoquinoline-derived natural products.