A Mechanochemical, Catalyst-Free Cascade Synthesis of 1,3-Diols and 1,4-Iodoalcohols Using Styrenes and Hypervalent Iodine Reagents.

A mechanochemical and solvent/catalyst-free functionalization of olefins with hypervalent iodine reagents has been developed, enabling the synthesis of 1,3-dioxygenated compounds. Under similar reaction conditions with the addition of molecular iodine, 1,4-iodoalcohols can be synthesized. These valuable products are non-trivial to achieve via standard solution-phase methods. Mechanistic study reveals that the hypervalent iodine reagent might dimerize at solid state with the help of mechanical force. The active monomeric form of hypervalent iodine reagent might trigger the 1,3- and 1,4-difunctionalization reactions in an intermolecular cascade manner.

Hypervalent Chalcogenonium⋠⋠⋠π Bonding Catalysis.

A proof-of-concept study of hypervalent chalcogenonium⋅⋅⋅π bonding catalysis was performed. A new catalytic strategy using 1,2-oxaselenolium salts as chalcogen bond donors and alkenes as chalcogen bond acceptors is described. The feasibility of this concept is demonstrated by the use of trisubstituted selenonium salts in the metal-free catalytic hydrofunctionalization and polymerization of alkenes via unconventional seleniranium ion-like intermediates. The results indicate that counter anions have a significant effect on the catalysis based on hypervalent chalcogenonium⋅⋅⋅π bonding interactions.

A Catalyst-Controlled Enantiodivergent Bromolactonization.

A catalyst-controlled enantiodivergent bromolactonization of olefinic acids has been developed. Quinine-derived amino-amides bearing the same chiral core but different achiral aryl substituents were used as the catalysts. Switching the methoxy substituent in the aryl amide system from meta- to ortho-position results in a complete switch in asymmetric induction to afford the desired lactone in good enantioselectivity and yield. Mechanistic studies, including chemical experiments and density functional theory calculations, reveal that the differences in steric and electronic effects of the catalyst substituent alter the reaction mechanism.

Silver Salt-Mediated Allylation Reactions Using Allyl Bromides.

A facile, efficient, and chemoselective synthesis of allylic amides has been developed. Allyl bromides were used as the precursors activated by silver triflate. A Ritter-type reaction readily proceeded to give various allyl amides under mild conditions. The reaction protocol was also applicable to different nucleophilic partners to give a wide range of allyl-substituted products in the absence of a base.

Zwitterion-Catalyzed Isomerization of Maleic to Fumaric Acid Diesters.

Fumaric acid diesters are important building blocks for organic synthesis. A class of zwitterionic organocatalysts based on an amide anion/iminium cation charge pair were found to be effective in catalyzing the isomerization of maleic acid diesters to give fumaric acid diesters. Comparison of the performance of different zwitterionic organocatalysts toward the reaction revealed that nonclassical hydrogen bonding was involved in the stabilization of the Michael adduct intermediate.

Lipophilic Indole-Catalyzed Intermolecular Bromoesterification of Olefins in Nonpolar Media.

An environmentally benign and highly versatile catalytic protocol has been successfully applied in the intermolecular bromoesterification between various olefins and carboxylic acids. The use of a highly lipophilic indole catalyst and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as the bromine source allows the reaction to proceed in heptane via a solid-liquid phase transfer mechanism, affording the corresponding bromoester products in good-to-excellent yields.

Halogen Bond Catalyzed Bromocarbocyclization.

A halogen bond catalyzed bromo-carbocyclization of N-cinnamyl sulfonamides and O-cinnamyl phenyl ethers has been developed. N-methyl 4-iodopyridinium triflate is used as the halogen-bonding organocatalyst and the reaction is highly chemoselective. This report represents the first proof-of-concept for halogen-bonding organocatalyst-promoted electrophilic halogenation. Mechanistic study suggests the autocatalytic nature of this reaction.

Lewis Base-Promoted Ring-Opening 1,3-Dioxygenation of Unactivated Cyclopropanes Using a Hypervalent Iodine Reagent.

A facile and effective system has been developed for the regio- and chemoselective ring-opening/electrophilic functionalization of cyclopropanes through C-C bond activation by [bis(trifluoroacetoxy)iodo]benzene with the aid of the Lewis basic promoter p-toluenesulfonamide. The p-toluenesulfonamide-promoted system works well for a wide range of cyclopropanes, resulting in the formation of 1,3-diol products in good yields and regioselectivity.

Applications of Selenonium Cations as Lewis Acids in Organocatalytic Reactions.

The use of trisubstituted selenonium salts as organic Lewis acids in electrophilic halogenation and aldol-type reactions has been developed. The substrate scope is broad. The reaction conditions are mild and compatible with various functionalities. This study opens a new avenue for the development of nonmetallic Lewis acid catalysis.

Lewis Base Catalyzed Stereo- and Regioselective Bromocyclization.

Oxygen- and nitrogen-containing heterocyclic compounds are widely recognized as key components in many natural products and biologically relevant molecules, but often the problem comes down to methodologies in synthesizing them. Halocyclization of olefinic substrates is a promising strategy in the construction of O- and N-heterocyclic compounds, which further signifies the development of their asymmetric variants. Over the past years, our group has been devoted to this particular area of asymmetric electrophilic halocyclization with chalcogen-containing molecules as catalysts. In this account, the main focus is on the development of our novel chiral catalysts and applications derived from the reaction products.

Ring strain-dictated divergent fluorinating Prins cyclization or semipinacol rearrangement.

We have developed ring-strain dictated divergent diastereoselective fluorinating Prins cyclization reactions or semipinacol rearrangement reactions to access tetrahydropyrans containing a fluorohydrin or a carbonyl moiety at quaternary carbon centers under mild conditions, respectively.

An unexpected Bromolactamization of Olefinic Amides Using a Three-Component Co-catalyst System.

Reaction between (N,N-dimethylamino)pyridine and isocyanate unexpectedly produced a three-component mixture. By using this mixture as an unprecedented three-component catalyst system, a facile and selective bromolactamization of olefinic amides has been developed. The protocol confers enhanced selectivity of N- over O-cyclization, leading to the formation of a structurally diverse range of lactams including both small and medium ring sizes.

A convenient method for the synthesis of α-carboxylate ester bromolactones via bromolactonization of alkenoic diesters.

We developed a simple and efficient method to construct a variety of α-ester bromolactones in good to excellent yields with high diastereoselectivies. The protocol uses readily prepared malonate ester derivatives as substrates, water as an additive and inexpensive N-bromosuccinimide as the halogen source; no catalyst or toxic additive is required. The resulting substituted bromolactones are the fundamental units of many useful molecules.

Trifluoroacetic acid catalyzed highly regioselective bromocyclization of styrene-type carboxylic acid.

A trifluoroacetic acid catalyzed highly 6-endo regioselective bromocyclization of styrene-type carboxylic acid has been developed. The resulting 3,4-dihydroisocoumarines are valuable building blocks in organic synthesis.

Highly ortho-Selective Chlorination of Anilines Using a Secondary Ammonium Salt Organocatalyst.

An organocatalytic, highly facile, efficient, and regioselective ortho-chlorination of anilines is described. A secondary ammonium chloride salt has been employed as the catalyst and the reaction can be conducted at room temperature without protection from air and moisture. In addition, the reaction is readily scalable and the catalyst can be recycled and reused. This catalytic protocol has been applied to the efficient synthesis of a highly potent c-Met kinase inhibitor. Mechanistic studies revealed that unique structural features of the secondary ammonium chloride salt are important for both the catalysis and regioselectivity of the electrophilic ortho-chlorination.

An unexpected 2,3-dihydrofuran derivative ring opening initiated by electrophilic bromination: scope and mechanistic study.

An unexpected 2,3-dihydrofuran ring opening process at the C(4)-C(5) bond has been developed. N-Bromosuccinimide and DABCO were used as the electrophilic halogen source and the catalyst, respectively. Mechanistic study indicates that moisture in the solvent might contribute to the reaction. The resulting brominated product could be further oxidized to yield a synthetically valuable 1,2-diketo building block.

Catalyst-free and metal-free electrophilic bromoamidation of unactivated olefins using the N-bromosuccinimide/sulfonamide protocol.

An efficient, catalyst-free, and metal-free bromoamidation of unactivated olefins has been developed. 4-(Trifluoromethyl)benzenesulfonamide and N-bromosuccinimide were used as the nitrogen and halogen sources, respectively. The methodology is applicable to both cyclic and aliphatic olefins.

Carbamate-catalyzed enantioselective bromolactamization.

A highly facile, efficient, and enantioselective bromolactamization of olefinic amides was effected by a carbamate catalyst and ethanol additive. The amide substrates underwent N-cyclization predominantly to give a diverse range of enantioenriched bromolactam products containing up to two stereogenic centers.

Catalytic asymmetric bromoetherification and desymmetrization of olefinic 1,3-diols with C2-symmetric sulfides.

An enantioselective and highly diastereoselective bromoetherification and desymmetrization of olefinic 1,3-diols has been developed using a C2-symmetric cyclic sulfide catalyst. This methodology has been successfully applied to the synthesis of the key intermediate of an orally active antifungal drug posaconazole (Noxafil).

Synthesis of reboxetine intermediate and carnitine acetyltransferase inhibitor via NBS-induced electrophilic multicomponent reaction.

N-Bromosuccinimide-induced electrophilic multicomponent reaction has been applied to the synthesis of Reboxetine intermediate, a highly potent selective norepinephrine reuptake inhibitor. By simply changing the olefinic partner, the synthesis of a carnitine acetyltransferase inhibitor, which contains a 2,6,6-trisubstituted morpholine system, can be accomplished.