https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Cu-catalyzed azide-alkyne cycloaddition.

Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

Controlled/living radical polymerization: Features, developments, and perspectives

This paper presents a review of living radical polymerization achieved with thiocarbonylthio compounds [ZC(=S)SR] by a mechanism of reversible addition–fragmentation chain transfer (RAFT). Since we first introduced the technique in 1998, the number of papers and patents on the RAFT process has increased exponentially as the technique has proved to be one of the most versatile for the provision of polymers of well defined architecture. The factors influencing the effectiveness of RAFT agents and outcome of RAFT polymerization are detailed. With this insight, guidelines are presented on how to conduct RAFT and choose RAFT agents to achieve particular structures. A survey is provided of the current scope and applications of the RAFT process in the synthesis of well defined homo-, gradient, diblock, triblock, and star polymers, as well as more complex architectures including microgels and polymer brushes.

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Living radical polymerization by the RAFT process

The two regioisomeric β-ketoesters obtained by ring expansion of a cycloalkanone with ethyl diazoacetate and a Lewis acid give the same cycloalkyne upon exposure of the corresponding isoxazolinone to sodium nitrite / aqueous acetic acid and ferrous sulfate.

An Efficient Synthesis of Large Ring Acetylenes.

A short synthesis of (±)-γ-lycorane is described featuring a radical cascade whereby rings B and D are formed in one step.

An Expedient Synthesis of (.+-.)-γ-Lycorane.

Tributylphosphine–diphenyl disulphide is a self-drying reagent capable of reducing ketoximes and secondary aliphatic nitro compounds to the corresponding imines under strictly anhydrous conditions at room temperature. The imine may be hydrolysed to a ketone, acetylated to give an enamide, reduced to an amine, or captured by hydrogen cyanide to produce an α-amino nitrile. In the case of 1,4-nitro ketones or esters, intramolecular cyclisation leads to pyrroles or pyrrolin-2-ones. Aldoximes and primary nitro compounds are converted into nitriles by the reagent. Hydroxamic acids are reduced to the corresponding amides.

Reduction of Oximes and Aliphatic Nitro Compounds to Imines for Further in situ Reactions: A Novel Synthesis of Pyrroles and Pyrrolin-2-ones.

Heating carboxylic acids with O-benzyl-S-propargyl xanthate in refluxing toluene gives the corresponding benzyl esters in high yield; other acidic substances such as tetrazoles and pyridinols are benzylated selectively under the same conditions.

A Practical Synthesis of Benzyl Esters and Related Derivatives.

Heating γ-nitroketoncs bearing an electron-withdrawing group such as an ester geminal to the nitro group with formamidinesulfinic acid and triethylamine in isopropanol produces pyrroles in good yield.

Samir Z. Zard

Papers

An Efficient Synthesis of Large Ring Acetylenes.

An Expedient Synthesis of (.+-.)-γ-Lycorane.

Reduction of Oximes and Aliphatic Nitro Compounds to Imines for Further in situ Reactions: A Novel Synthesis of Pyrroles and Pyrrolin-2-ones.

A Practical Synthesis of Benzyl Esters and Related Derivatives.

A New and Practical Synthesis of Pyrroles.