Asymmetric Synthesis of 1,3-Dioxolanes by Organocatalytic Formal [3 + 2] Cycloaddition via Hemiacetal Intermediates

A novel asymmetric formal [3 + 2] cycloaddition reaction for the synthesis of 1,3-dioxolanes using cinchona-alkaloid-thiourea-based bifunctional organocatalysts is reported. The reaction proceeds via the formation of hemiacetal intermediates between γ-hydroxy-α,β-unsaturated ketones and aldehydes

Effects of a Flexible Alkyl Chain on a Ligand for CuAAC Reaction

Imidazole derivatives substituted by a normal alkyl group are shown to be efficient as a ligand for the copper(Ι)-catalyzed azide−alkyne cycloaddition (CuAAC) reaction. An alkyl chain on the imidazole ligands shows an efficient steric effect and benefits the reaction. Such functionalities of an alkyl chain allow a rapid CuAAC reaction of even a bulky alkyne, which has been difficult to perform under conventional conditions

Amphiphilic Organocatalyst for Schotten-Baumann-Type Tosylation of Alcohols under Organic Solvent Free Condition

A Tosylation of primary alcohol with tosyl chloride was performed effectively with an N-hexadecylimidazole catalyst in water containing K2CO3. aggregation of the catalyst carrying a hydrophobic methylene chain worked as a substitute for organic solvent

Asymmetric Catalytic Cycloetherification Mediated by Bifunctional Organocatalysts

Oxacyclic structures such as tetrahydrofuran (THF) rings are commonly found in many bioactive compounds, and this has led to several efforts toward their stereoselective syntheses. However, the process of catalytic asymmetric cycloetherification for their straightforward synthesis has remained a challenge. In this study, we demonstrate a novel asymmetric synthesis method for THF via the catalytic cycloetherification of ε-hydroxy-α,β-unsaturated ketones mediated by cinchona-alkaloid-thiourea-based bifunctional organocatalysts. This catalytic process represents a highly practical cycloetherification method that provides excellent enantioselectivities, even with low catalyst loadings at ambient temperature

Asymmetric Indoline Synthesis via Intramolecular Aza-Michael Addition Mediated by Bifunctional Organocatalysts

A novel method for the asymmetric synthesis of 2-substituted indolines, employing bifunctional amino(thio)urea catalysts, was developed. The reaction proceeded via an intramolecular aza-Michael addition mediated by activation through hydrogen bonding. The catalytic process was shown to be highly versatile and applicable to a wide range of substrates due to the flexible catalytic mechanism utilizing a noncovalent interaction

Facile Net Cycloaddition Approach to Optically Active 1,5‑Benzothiazepines

The 1,5-benzothiazepine moiety is well-known as a versatile pharmacophore, and its derivatives are expected to have antagonism against numerous diseases. Thus, it is desirable to develop a synthetic route that enables facile enantioselective preparation of a wide range of such derivatives. Although the cycloaddition approach could be considered a possible route to these compounds, to date, there has been no precedent of such a protocol. We therefore present the first example of a highly enantioselective net [4 + 3] cycloaddition to afford 1,5-benzothiazepines by utilizing α,β-unsaturated acylammonium intermediates generated by chiral isothiourea catalysts, which undergo two sequential chemoselective nucleophilic attacks by 2-aminothiophenols. This protocol provided cycloadducts in extremely high regioselectivity, with a good-to-excellent stereoselectivity being achieved regardless of the steric and electronic properties of the substrates. This method therefore offers promising synthetic routes for the construction of a library of optically active 1,5-benzothiazepines for assay evaluation

Procedure-Controlled Enantioselectivity Switch in Organocatalytic 2‑Oxazolidinone Synthesis

In a novel organocatalytic formal [3 + 2] cycloaddition to afford chiral 2-oxazolidinones, an enantioselectivity switch could be induced by changing the manner of addition of the reactants, even when the reaction components (cinchona-alkaloid-derived aminothiourea catalyst, substrates, and solvent) were the same

Facile Net Cycloaddition Approach to Optically Active 1,5‑Benzothiazepines

The 1,5-benzothiazepine moiety is well-known as a versatile pharmacophore, and its derivatives are expected to have antagonism against numerous diseases. Thus, it is desirable to develop a synthetic route that enables facile enantioselective preparation of a wide range of such derivatives. Although the cycloaddition approach could be considered a possible route to these compounds, to date, there has been no precedent of such a protocol. We therefore present the first example of a highly enantioselective net [4 + 3] cycloaddition to afford 1,5-benzothiazepines by utilizing α,β-unsaturated acylammonium intermediates generated by chiral isothiourea catalysts, which undergo two sequential chemoselective nucleophilic attacks by 2-aminothiophenols. This protocol provided cycloadducts in extremely high regioselectivity, with a good-to-excellent stereoselectivity being achieved regardless of the steric and electronic properties of the substrates. This method therefore offers promising synthetic routes for the construction of a library of optically active 1,5-benzothiazepines for assay evaluation

Pauson–Khand Reactions in a Photochemical Flow Microreactor

Pauson–Khand reactions were achieved at ambient temperature without any additive using a photochemical flow microreactor. The efficiency of the reaction was better than that in a conventional batch reactor, and the reaction could be operated continuously for 1 h