One obstacle for practical glycosylations is the high cost of promoters and low-temperature equipment. This problem has been at least partially solved by using MeSCH2Cl/KI as a low-cost promoter system. MeSCH2Cl has an estimated cost of <$1/mol compared with $1741/mol for AgOTf and $633/mol for TMSOTf. This new promoter system is capable of activating various leaving groups including anomeric Cl, F, trichloroacetimidate, and acyloxy groups. Stable and easy-to-prepare anomeric benzoloxy carbohydrate donors were investigated in the glycosylations of carbohydrates, aliphatic alcohols, amino acids, steroids, and nucleoside acceptors. Most of these glycosylations were operationally simple with fast reaction rates and moderate yields of 35–79%. In addition, direct glycosylations of nucleosides using less than 2 equiv of anomeric benzoloxy donors and high stereoselective mannosylation have been achieved. From an economic point of view, this glycosylation method should be highly applicable to industrial processes.Topics: Biochemistry; Carbohydrates; Reaction kinetics; Reaction kinetics;

AbstractCyanuric chloride activated dimethyl sulfoxide (DMSO) was found to catalyze the hydration of glycals and the hydrolysis of enol ethers, esters, oximes, O-methyl oximes, and hydrazones. Overall, 68 examples of these 6 types of substrates were efficiently transformed into 2-deoxysugars, phenols, and carbonyl compounds. Methyl methylene sulfonium chloride (a bulky weak Lewis acid) is presumed to be the active catalytic species. This assumption is strongly supported by the fact that the same reactions catalyzed by chloromethyl methyl sulfide/KI gave similar results to those catalyzed by the cyanuric chloride activated DMSO. We further employed the chloromethyl methyl sulfide/KI precatalyst to carbohydrate benzylidenations, decanal acetalizations, and the stereoselective transformations of 2-deoxy-2-iodo-α-d-mannopyranosyl acetate into 2,3-unsaturated O-glycosides. Key features of this precatalyst include that it is water tolerant, cost-effective, and easily removed during workup.

The use of large amounts of volatile organic solvents in industrial chemical processes contributes to widespread environmental pollution. To help solve this problem, water and a phase transfer catalyst were used to replace organic solvents in the transformations of bromoacetophenones into chloroacetophenones and aroyl epoxides into aroyl chlorohydrins. The reactions were promoted by sulfonyl chlorides and gave quantitative or close to quantitative yields. Notably, chromatographic purification, which is laborious and consumes large amounts of organic solvents, was not needed. These two processes have opened a green and cost-effective channel to prepare the chemical intermediates chloroacetophenones and aroyl chlorohydrins. The reaction mechanisms are discussed based on control experiments.

Subquantitative synthetic esterification reactions have been transformed into quantitative aqueous reactions. The esterification reactions involve carboxylic acids, alkyl halides or mesylate with granular polytetrafluoroethylene (PTFE), lithium carbonate, tetrabutyl ammonium bromide and were mediated solely by water. Various alkyl donors were employed including α-halo ketones, α-halo esters, α-halo amide, allyl bromide, benzyl chloride, alkyl iodides and alkyl mesylate. The scope of the carboxylic acids ranged from aromatic to aliphatic and from water-soluble to water-insoluble. Among the 58 reaction examples, 54 esterifications were quantitative and the other four had yields above 94%. Six of the reactions were scaled up to more than 10 g. In 30 examples and all the enlarged scale examples, no organic solvents were used at all and the products were collected simply by filtration. The yields for esterification reactions with secondary halides were quantitative compared to previous reported yields of only 65–89%. The promotion effect of the granular PTFE in combination with the modified mechanical stirrer is demonstrated based on a set of comparison experiments. Finally, the mechanism for these quantitative esterifications mediated by water is discussed in comparison with those mediated by organic solvents.Keywords: Aqueous reaction; Esterification; Granular PTFE; Green synthesis; Quantitative reaction;

Four types of skeletally diverse compounds have been synthesized from protected aldosyl hemiacetals and methyl ketones using cheap catalysts in water in one pot. Among the four skeletons, two of them are not accessible by current methods. The reactions are operationally simple, high yielding and scalable, which opens a practical channel for utilizing carbohydrates to produce chemical and pharmaceutical intermediates and products.

Highly substituted 1,5-diketones have been synthesized in water via the reactions between aryl methyl ketones and aldehydes and the subsequent dimerizations. The reaction was catalyzed by aqueous KOH. The advantages of these aqueous reactions over organic-solvent mediated reactions are better yields, better diastereoselectivities, faster reaction rates, simpler workups, and being more energy efficient. The reaction can be scaled up to 13.9 gram scale and the aqueous KOH can be reused for five cycles. A possible mechanism is proposed to explain the high diastereoselectivities.

A new method of synthesizing β-glycosyl esters stereospecifically has been developed by treating O-benzyl-protected glycosyl chlorides with Cs2CO3, tetrabutylammomium bromide (TBAB), a carboxylic acid, water, and granular polytetrafluoroethylene (PTFE) at 80 °C under mechanical agitation. d-Glucosyl, d-xylosyl, and d-galactosyl chlorides and 20 carboxylic acids were used to demonstrate the scope of the reaction. Control experiments showed that the water and granular PTFE had indispensable roles. Water-soluble TBAB has been found to be as efficient as N-methyl-N,N,N-trioctyloctan-1-ammonium chloride (Aliquat 336) in the reactions. After scaling up to 5–12 g, all of the products were obtained quantitatively via simple filtration and no organic solvents or chromatography was needed for the entire process.

The direct chlorination and bromination of (E)-enamines and (Z)-enamides to the corresponding (Z)-configurated α-chloroenamines, α-bromoenamines, and α-chloroenamides have been realized using NiCl2·6H2O or tetrabutyl ammonium bromide as a halide source and (1,1-diacetoxyiodo)benzene as an oxidant. The high stereoselective reactions which produce products with only (Z)-configurations can be attributed to the structure of the intermediates, the conformations of which are controlled by the electrostatic attractions between the positively charged nitrogen atoms and the oxygen atoms of the carbonyl group. This type of electrostatic effect has never been reported in olefin halogenations. For this reason, the three-membered bromonium ion is only a minor intermediate in the enamine bromination pathway. These methods open pathways to prepare α-chloroenamines and α-chloroenamides, which are not accessible via the currently used methods.

A selective synthesis of methyl d-glucopyranoside or furanoside has been developed using 2,4,6-trichloro-1,3,5-triazine (TCT)-activated DMSO and d-glucose in methanol. At higher concentrations of DMSO, only pyranoside was formed and at lower concentrations of DMSO, only furanoside was formed. This method was also successfully applied to other sugars. In terms of reaction rates, selectivities, and yields, this method is better than most of the currently used methods.

The reductions of high melting-point imines and nitroarenes to amines in aqueous media using Zn powder, granular PTFE (polytetrafluoroethylene), catalytic Aliquat 336 and NH4Cl or 5% NaOH at room temperature have been achieved. A major advantage of this procedure is that the cost of the catalyst is only 1/7200 of that of a previously reported nitroaromatic aqueous reduction catalyst. Altogether 13 imines and 11 nitroarenes were reduced to the corresponding amines with excellent yields. The effects of the amount of granular PTFE, and solubilities and melting points of the substrates, and melting points of the products on the reaction rates are discussed. For the first time, the relationship between the aqueous reaction rates and melting points of the products was investigated, which leads to a conclusion that lower melting-point products form faster than higher melting-point ones in the aqueous reductions. The Aliquat 336, granular PTFE and water are all recyclable.

Darzens reactions between halocarbonyls and aldehydes have been carried out in water in the presence of a Li+-containing base, a phase-transfer catalyst, and granular polytetrafluoroethylene under mechanical stirring. Reactions using both aromatic and aliphatic aldehydes produced epoxides stereoselectively in good to excellent yields. This is the first time that aliphatic aldehydes with α-H have been used in aqueous Darzens reactions. The Darzens reactions were much faster in water than in organic solvents. This aqueous rate enhancement occurred for Darzens reactions between enantiopure steroidal haloketones and aldehydes, yielding enantiopure spiroepoxides with a high level of kinetically controlled diastereoselectivity. Chromatography was avoided in the purifications of the steroidal spiroepoxides. This is an example of preparing enantiopure epoxyketones via aqueous Darzens reaction using chiral α-haloketone substrates.

The reactions of ketones and aldehydes in the presence of Li+ and in the presence or absence of PTC mediated by water were performed to produce aldol products. Several advantages of the aqueous reactions over organic solvent-mediated ones have been demonstrated including higher yields, shorter reaction times, simpler purifications, and better functional group tolerance. Some reactions that do not take place in organic solvents have been realized in water. The successes are attributed to the neighboring heteroatom effect. In the aqueous aldol condensations, Li2CO3 was an efficient catalyst, and therefore base-liable groups such as epoxides, esters, and silyl groups could survive. For heteroaromatic ethanones, the aqueous aldol reactions were accomplished without PTC to give β-hydroxyketones in good yields. The water-mediated condensations of aldosyl hemiacetals with aromatic ketones led to a new carbohydrate-derived skeleton in quantitative yields. To some extent, this research has expanded the applicablities of aldol condensations and reactions.

Dihydroxylated steroids have been prepared quantitatively by stirring a mixture of a very sparingly soluble high-melting-point (VSSHMP) steroidal epoxide, polytetrafluoroethylene (PTFE) sand, and aqueous H2SO4; no organic solvents or phase transfer catalysts were used. The sand and aqueous H2SO4 are highly recyclable. The promoting effects of the sand for these “on water” reactions have been demonstrated for the first time. This is a green, waste-free, mild, and operationally simple procedure. Various functional groups such as ketones, esters, ethers, ketals, epoxides on D-rings, and α,β-unsaturated ketones all survived these reaction conditions. This methodology is useful for using less organic solvents, reducing the cost of the products and protecting the environment.

Dihydroxylated Δ5-steroids are key intermediates in preparing steroids bearing a 5α-hydroxy-6-oxo moiety, which are plant growth hormones. Quantitative and stereospecific dihydroxylations of Δ5-steroids have been realized, using H2O2 catalyzed by KI and H2SO4 at 80 °C in aqueous dioxane. The workup consisted only of concentrating the solvents and filtering the products; no chromatography was needed. The reaction conditions tolerate various functional groups on the Δ5-steroids. A mechanism for this reaction is proposed and the reason that the reaction is quantitative and stereospecific is explained.

A practical solution to the problem of performing aqueous reactions for very sparingly soluble high-melting-point (VSSHMP) organic substrates has been developed, which entails mechanically stirring a mixture of the substrate, the corresponding reagent(s), water, catalytic Aliquat 336 and sand. When the melting points of the substrates which include steroids, ketones, aldehydes, aromatics and alkaloids are around 200 °C, the reactions can be performed at 20 °C. The substrate solubility can be as low as 1 × 10−10 mol L−1.

The current syntheses of imines from benzylamines are often performed in organic solvents or under harsh reaction conditions. Clean oxidation of primary benzylamines to imines has been successfully achieved using H2O2 in water at room temperature catalyzed by V2O5. Among the 10 imine products, 5 of them precipitated from the reaction and led pure products after simple filtration. No organic solvents are needed in the whole process. The yields are good to quantitative. This represents an efficient and green procedure of the synthesis of imines. A similar green oxidation of benzylamines to aromatic aldehydes is also reported. A benzylic anion-involved mechanism is proposed based on the experiments.

The current syntheses of imines from benzylamines are often performed in organic solvents or under harsh reaction conditions. Clean oxidation of primary benzylamines to imines has been successfully achieved using H2O2 in water at room temperature catalyzed by V2O5. Among the 10 imine products, 5 of them precipitated from the reaction and led pure products after simple filtration. No organic solvents are needed in the whole process. The yields are good to quantitative. This represents an efficient and green procedure of the synthesis of imines. A similar green oxidation of benzylamines to aromatic aldehydes is also reported. A benzylic anion-involved mechanism is proposed based on the experiments.