Francesco Fringuelli

Recent Advances in Lewis Acid Catalyzed Diels−Alder Reactions in Aqueous Media

Recently the aqueous medium has attracted the interest of organic chemists, and many, sometimes surprising, discoveries have been made. Among the organic reactions investigated in aqueous medium, the Diels−Alder cycloaddition has been the most widely studied because of its great importance in the synthetic and theoretical fields. The Diels−Alder reaction is greatly enhanced by Lewis acid catalysis, and this review illustrates recent significant results in this field when the reaction is performed in aqueous medium.

Condensation reactions in water of active methylene compounds with arylaldehydes. One-pot synthesis of flavonols

Abstract The condensation reactions of acetophenone, cyclohexanone, isophorone, phenylacetonitrile, p-nitrophenylacetonitrile, (phenylsulfonyl)acetonitrile and indene with benzaldehyde were studied in water in heterogeneous phase in the presence and absence of anionic and cationic surfactants such as SLS, CTACl, (CTA)2SO4 and CTAOH. All the reactions occur with excellent yields. The cationic surfactants favour the reaction and the comparison with the corresponding tetrabutylammonium salts show that the micellar catalysis is effective mainly towards the dehydration reaction following that of condensation. Anionic surfactant SLS is inactive. 2′-hydroxychalcones were prepared in aqueous medium in good-excellent yields and the one-pot synthesis of 7- and 3′,4′-substituted flavonols was achieved.

Recent developments on the chemistry of aliphatic nitro compounds under aqueous medium

Aliphatic nitro derivatives represent an important class of useful molecules in organic synthesis. The versatility of these compounds is largely due to their easy availability and transformation into a variety of diverse functionalities. Moreover, aliphatic nitro compounds are very important building blocks (both as nucleophiles or as electrophiles) for the generation of new carbon–carbon bonds, mainly via nitroaldol-Henry reactions, Michael reactions and Diels–Alder cycloadditions. Usually, organic solvents are believed to be necessary for achieving the best efficiency in the reactions of aliphatic nitro compounds and, only recently, it has been shown that these reactions are also very efficient using water as reaction medium. Such progress in the chemistry of aliphatic nitro compounds is particularly attractive to industry since the replacement of toxic solvents still remains a crucial (and expensive) challenge. Thus, this report is focused on the chemistry of aliphatic nitro derivatives performed in aqueous media.

Thiolysis of 1,2-epoxides by thiophenol catalyzed under solvent-free conditions

Thiolysis of alkyl- and aryl-1,2-epoxides was investigated under solvent-free conditions in the presence of Lewis and Bronsted acid and base catalysts (InCl3, p-TsOH, n-Bu3P, K2CO3). Five mol% of catalyst was sufficient and the best results were obtained by using InCl3 and K2CO3. β-Hydroxy sulfide was isolated in excellent yields.

A green route to β-amino alcohols via the uncatalyzed aminolysis of 1,2-epoxides by alkyl- and arylamines

Under mildly basic and pH-controlled aqueous conditions the aminolysis of 1,2-epoxides 1a–g by alkyl- and arylamines 2a–k is generally highly regioselective giving the corresponding β-amino alcohols in satisfactory to excellent yields.

Epoxidation of α,β-unsaturated ketones in water. An environmentally benign protocol

An easy, cheap procedure is proposed for the epoxidation of α,β-unsaturated ketones in water as the sole reaction medium and using bases such as NaOH and CTAOH as promoting agents and hydrogen peroxide as oxidant. By using solely water, the reaction medium can be recycled which is important for reducing wastes. An example of an α-functionalization of α,β-unsaturated ketones by a one-pot procedure in water is reported.

Water, a clean, inexpensive, and re-usable reaction medium. One-pot synthesis of (E)-2-aryl-1-cyano-1-nitroethenes

The Knoevenagel addition of aryl aldehydes 1 with nitroacetonitrile 2 in water followed by dehydration of β-nitroalcohols 3, allows (E)-2-aryl-1-cyano-1-nitroethenes 4 to be prepared by a one-pot procedure without using organic solvents. The reuse of the aqueous medium makes this process inexpensive and highly environmentally friendly. The protocol was used to synthesize the benzo[b]pyrane [4,3-d][1,2]oxazine-2-oxide skeleton by a domino Knoevenagel–Diels–Alder process.

Epoxidation reaction with m-chloroperoxybenzoic acid in water

Abstract Epoxidation reaction of liquid alkenes with m-chloroperoxybenzoic acid in water at room temperature gives oxiranes in high yield.

An E-factor minimized protocol for the preparation of methyl β-hydroxy esters

We report the optimization of the preparation of methyl β-hydroxy esters (3a–l) in 75–93% yield by a solvent-free aldol reaction of aldehydes (1a–l) with KSA (2) followed by a de-silylation step. Amberlite IRA900F and Dowex 50Wx8 H were found to be the most efficient solid catalysts for the aldol addition and de-silylation steps, respectively. In order to minimize the use of organic solvent and automate the recovery of the catalysts and reaction products, we have developed an automated cyclic continuous-flow reactor operating under solvent-free or highly concentrated conditions. This system, applied to the reactions of 1a–c with 2, avoids the mechanical degradation of the catalysts and allowed reduction of the E-factor of the process to a very low value that ranges from 1.41 to 2.09.

Thiolysis of Alkyl‐ and Aryl‐1,2‐epoxides in Water Catalyzed by InCl3

The pH dependence of thiolysis of 1,2-epoxides with thiophenol in water and the influence of a Lewis acid catalyst is investigated. InCl3 showed a very high efficiency in catalyzing this process at pH 4.0. The regioselectivity of the nucleophilic attack is markedly influenced going from pH 9.0 to pH 4.0. A one-pot procedure running solely in water to prepare trans-2-(phenylsulphinyl)cyclohexan-1-ol is reported starting from epoxycyclohexane, via thiolysis reaction and oxidation with t-butyl hydroperoxide.