Universal Reagent for Mild and Stereospecific Nucleophilic Substitution of Alcohols with Amines.

A user-friendly reagent for mild and general activation of alcohols towards bimolecular nucleophilic substitution (S2) leveraging diverse nucleophiles, including primary and secondary amines is reported herein. The new ion-paired reagent discovery was based upon the putative zwitterionic betaine intermediate of the Mitsunobu reaction and enabled the one-step conversion of enantioenriched alcohols to valuable chiral C-X bonds (where X=N, C, S, O or halide). The described activating reagent has also been applied to a one-step methylation reaction using methanol and to an intermolecular amination/intramolecular cyclization sequence that generates heterocycles, such as tetrahydroisoquinolines.

On-Demand Continuous Flow Synthesis of Pentafluorosulfanyl Chloride (SFCl) Using a Custom-Made Stirring Packed-Bed Reactor.

The pentafluorosulfanyl (SF-) group has been the subject of a surge of interest in the past decade, but there is still little practicality associated with its synthesis and installation. Herein is reported the first continuous flow synthesis of pentafluorosulfanyl chloride (SFCl), the most common reagent for the synthesis of SF-substituted compounds. The synthesis is based on inexpensive and easy-to-handle reagents: sulfur powder (S), trichloroisocyanuric acid (TCCA) and potassium fluoride (KF).

1,3-Dipolar Cycloaddition of SF-Alkynes with Nonstabilized Diazo: Synthesis of Highly Substituted SF-3-Pyrazoles.

This work presents the 1,3-dipolar cycloaddition of SF-alkynes with nonstabilized diazo compounds under mild conditions, producing highly substituted SF-3-pyrazoles. Eighteen examples are given, with yields of up to 91%. The two regioisomers were obtained in ratios ranging from 27:73 to 73:27.

Asymmetric Synthesis of (-)-Cannabidiol (CBD), (-)-Δ-Tetrahydrocannabinol (Δ-THC) and Their Analogs Using an Enantioselective Organocatalyzed Diels-Alder Reaction.

Herein we describe an asymmetric synthesis of the pharmacologically relevant natural (-)--CBD and psychoactive (-)--Δ-THC, as well as their synthetic diastereomers. The key step is an enantioselective Diels-Alder reaction catalyzed by a prolinol-based catalyst, which provides the cyclohexene carbaldehyde intermediate in good yield and high enantiomeric excess. Optimization of the substituted resorcinol protecting groups to avoid harsh and low-yield deprotection of the acid sensitive resorcinol moiety is also described.

Synthesis of 2-substituted bicyclo[1.1.0]butanes zincocyclopropanation using bromoform as the carbenoid precursor.

Through a revisited Simmons-Smith type zincocyclopropanation using bromoform as the carbenoid source, the synthesis of 2-, 2,2- and 2,4-substituted bicyclo[1.1.0]butanes is reported.

Organocatalyzed Visible Light-Mediated -Borosilylcyclopropanation.

The borosilylcyclopropanation of styrene derivatives using a (diiodo(trimethylsilyl)methyl)boronic ester carbene precursor is reported herein. The key reagent was synthesized in a 4-step sequence using inexpensive and commercially available starting materials. This method enabled the preparation of novel 1,1,2-tri- and 1,1,2,2-tetrasubstituted borosilylcyclopropanes up to excellent yields and diastereoselectivity.

Access to hexahydroazepinone heterocycles palladium-catalysed C(sp)-H alkenylation/ring-opening of cyclopropanes.

In this communication, we describe the synthesis of novel hexahydroazepinone derivatives starting from two simple building blocks in presence of a readily available palladium catalyst. The reaction proceeds through a selective C(sp)-H alkenylation/ring-opening process to obtain the seven-membered ring products in good to excellent yields on a wide variety of substrates under batch, microwave, and continuous flow conditions.