Satoshi Minakata

Organic Reactions on Silica in Water

In nature, many biological processes occur in aqueous environments, and these fascinating in vivo reactions should prompt organic chemists to explore the potential of water as a medium for organic reactions. In addition to scientific interest in aqueous reaction media, social pressure to find environmentally benign alternatives to current organic chemical processes has made these reactions attractive from an ecological point of view. The use of aqueous media in organic reactions offers significant environmental advantages and has attracted a great deal of interest because water is a desirable solvent for the following reasons: low cost, safety, and environmental concerns. Groundbreaking studies of organic reactions in aqueous environments demonstrated that Diels-Alder reactions and Claisen rearrangement of hydrophobic reactants are accelerated in aqueous solutions. In addition to these discoveries, aqueous environments result in reactivity and selectivity that are unique from reactions in organic solvents. As a result, many versatile and efficient organic reactions have been developed. Although many organic reactions are facilitated in aqueous media, some reactions proceed very slowly because the solubility of most organic molecules in pure water is limited. Because solubility is a prerequisite for reactivity, a variety of strategies expanding the scope of water-based organic syntheses have been investigated. Most commonly, organic cosolvents, such as the lower alcohols, acetone, DMF, and acetonitrile, are used to increase the solubility of hydrophobic solutes in water. Some alternative means of achieving aqueous solubility are the use of phase-transfer catalysts and surfactants. In addition to these processes, substrate modifications, such as the addition of a positive or negative charge to an ionizable substrate or the grafting of hydrophilic groups onto insoluble reactants, have been investigated. However, these approaches change the chemical behavior of the substrates and tend to complicate the reactions. Recent studies indicate that water is a promising medium for heterogenized homogeneous catalysis. Although the efficiency of heterogeneous catalysis is generally inferior to that of homogeneous systems, the advantage of immobilized catalysts include their easy recovery from reaction mixtures and their reusability. Catalysts heterogenized through covalent and non-covalent attachment to either inorganic or organic materials, such as silica, layered clays, and polymers, have been successfully employed in aqueous media. The chemical stability of the inorganic supports is important, especially under oxidizing conditions; the mechanical and thermal stability of inorganic supports is often excellent as well. This review will focus on the use of silica as an inorganic support for organic reactions in water. The hydroxy group on the silica surface readily reacts with alkoxyor chlorosubstituted silyl compounds, leading to functionalized silica supports. This manipulation allows not only for the introduction of catalysts to the surface of the support but also for the control of surface hydrophobicity. The proteiform and unique character of silica surfaces have been utilized for organic reactions in aqueous media. This review is organized into three main parts, each devoted to one form of silica that has unique effects on organic reactions in water: heterogenized catalysts on silica (immobilization by covalent binding or adsorption of catalysts on silica), hydrophobic and fluorous reverse-phase silica, and unmodified silica. The first section is subdivided into three heterogenized catalyst systems, as follows: water phase only, water-organic biphasic systems, and water-ionic liquid systems.

Iodine-catalyzed aziridination of alkenes using Chloramine-T as a nitrogen source

Abstract Iodine was found to be an efficient catalyst for the aziridination of alkenes utilizing Chloramine-T (N-chloro-N-sodio-p-toluenesulfonamide) as a nitrogen source. For example, when two equivalents of styrene were added to Chloramine-T in the presence of a catalytic amount of iodine in a 1 : 1 solvent mixture of acetonitrile and neutral buffer, the corresponding aziridine 1 was obtained in 91% yield. The reaction could be applied to other acyclic and cyclic alkenes such as 1-octene and cyclohexene. The aziridination of p-substituted styrene derivatives 2–5 with Chloramine-T showed that electron-rich alkenes reacted faster than electron-poor ones. Several Chloramine-T analogs were also examined and were found to give the corresponding aziridines 8–10 in only moderate yields.

Utilization of N-X bonds in the synthesis of N-heterocycles.

Nitrogen-containing heterocycles--such as aziridines, pyrrolidines, piperidines, and oxazolines--frequently show up as substructures in natural products. In addition, some of these species show potent biological activities. Therefore, researchers would like to develop practical and convenient methods for constructing these heterocycles. Among the available methods, the transfer of N(1) units to organic molecules, especially olefins, is a versatile method for the synthesis of N-heterocycles. This Account reviews some of our recent work on the synthesis of N-heterocycles using the N-X bond. A nitrogen-halogen bond bearing an electron-withdrawing group on the nitrogen can be converted to a halonium ion. In the presence of C-C double bonds, these species produce three-membered cyclic halonium intermediates, which can be strong electrophiles and can produce stereocontrolled products. N-Halosuccinimides are representative sources of halonium ions, and the nitrogen of succinimide is rarely used in organic synthesis. If the nitrogen could act as a nucleophile, after releasing halonium ions to C-C double bonds, we expect great advances would be possible in the stereoselective functionalization of olefins. We chose N-chloro-N-sodio-p-toluenesulfonamide (chloramine-T, CT), an inexpensive and commercially available reagent, as our desired reactant. In the presence of a catalytic amount of CuCl or I(2) and AgNO(3), we achieved the direct aziridination of olefins with CT. The reaction catalyzed by I(2) could be carried out in water or silica-water as a green process. The reaction of iodoolefins with CT gave pyrrolidine derivatives under extremely mild conditions with complete stereoselectivity. We also extended the utility of the N-chloro-N-metallo reagent, which is often unstable and difficult to work with. Although CT does not react with electron-deficient olefins without a metal catalyst or an additive, we found that N-chloro-N-sodiocarbamates react with electron-deficient olefins in the presence of a phase transfer catalyst to give the corresponding aziridines. We also used this method to synthesize asymmetric aziridines using quaternary cinchona alkaloid catalysts. We also developed a facile synthetic method for preparing N-heterocycles that involves the in situ generation of an N-X bond using tert-butyl hypochlorite or tert-butyl hypoiodite (tert-BuOI). Treatment of alkenylamides containing an active hydrogen on the nitrogen with tert-BuOI led to the production of various N-heterocycles via intramolecular cyclization. Iodination of readily available sulfonamides or carboxamides with tert-BuOI generated reactive N-iodinated amides, which smoothly reacted with olefins to give aziridines or oxazolines. The reaction of fullerene, C(60), with CT also led to aziridination: the resulting aziridinofullerene underwent a unique rearrangement to an azafulleroid. Chlorination of readily available amide derivatives with tert-BuOCl, followed by a reaction with C(60) in the presence of an organic base, afforded aziridinofullerenes with various substituents on the nitrogen. The results in this Account contribute to the development of convenient methods for constructing simple and useful heterocycles.

Nitrogen atom transfer to alkenes utilizing Chloramine-T as a nitrogen source

Abstract Aziridination of alkenes proceeds successfully using Chloramine-T (N-chloro-N-sodio-p-toluenesulfonamide). When anhydrous Chloramine-T was added to an acetonitrile solution of alkenes in the presence of various CuCl catalysts and MS-5A, the corresponding aziridines were obtained in moderate to good yields.

Generation of Nitrile Oxides from Oximes Using t-BuOI and Their Cycloaddition

tert-Butyl hypoiodite (t-BuOI) was found to be a powerful reagent for the cycloaddition of oximes and alkenes/alkynes, leading to the formation of a variety of isoxazolines or isoxazoles under mild conditions.

Novel Asymmetric and Stereospecific Aziridination of Alkenes with a Chiral Nitridomanganese Complex

The addition of pyridine N-oxide is necessary to obtain high enantioselectivities in the asymmetric aziridination of styrene derivatives through transfer of a nitrogen atom from chiral, toluenesulfonic anhydride activated nitridomanganese complex 1 [Eq. (a)]. Remarkably, high stereospecificity was observed in all the aziridinations of trans- and cis-1,2-disubstituted alkenes. R1 =H, Me, nPr, iPr; R2 =H, Me; Ts=p-toluenesulfonyl.

Dibenzo[a,j]phenazine‐Cored Donor–Acceptor–Donor Compounds as Green‐to‐Red/NIR Thermally Activated Delayed Fluorescence Organic Light Emitters

A new family of thermally activated delayed fluorescence (TADF) emitters based on U-shaped D-A-D architecture with a novel accepting unit has been developed. All investigated compounds have small singlet-triplet energy splitting (ΔEST ) ranging from 0.02 to 0.20 eV and showed efficient TADF properties. The lowest triplet state of the acceptor unit plays the key role in the TADF mechanism. OLEDs fabricated with these TADF emitters achieved excellent efficiencies up to 16 % external quantum efficiency (EQE).

Pd/NHC-catalyzed enantiospecific and regioselective Suzuki-Miyaura arylation of 2-arylaziridines: synthesis of enantioenriched 2-arylphenethylamine derivatives.

A palladium-catalyzed stereospecific and regioselective cross-coupling of enantiopure 2-arylaziridines with arylboronic acids under mild conditions to construct a tertiary stereogenic center has been developed. N-heterocyclic carbene (NHC) ligands efficiently promote the coupling, suppressing β-hydride elimination. The enantiospecific cross-coupling allowed us for preparation of a series of biologically important 2-arylphenethylamine derivatives in an enantiopure form.

2-Halogenoimidazolium Salt Catalyzed Aza-Diels–Alder Reaction through Halogen-Bond Formation

2-Halogenoimidazolium salts are found to catalyze aza-Diels-Alder reaction of aldimines with Danishefsky diene in an efficient manner. Comparative studies and titration experiments support the formation of halogen bonding between imines and catalysts.

INITIATION OF TIN-MEDIATED RADICAL REACTIONS BY DIETHYLZINC-AIR

Abstract Diethylzinc-air system can serve as an initiator of tin hydride mediated radical reactions of organic halides.