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

Modular Routes to 1,3-Dithian-2-ones and 1,2-Dithiolanes.

The reversible addition of aliphatic radicals to sulphur dioxide can be exploited to design a variety of tin-free chain reactions. This brief review summarises some of the possibilities, namely radical allylation, vinylation, alkynylation, and azidation of various substrates.

α-Scission of Sulfonyl Radicals: A Versatile Process for Organic Synthesis

Double bond isomerization of cycloalkenes is achieved via radical addition of p-chlorothiophenol, oxidation to sulfoxides, and thermal syn-elimination.

A Method for the Net Contra‐Thermodynamic Isomerization of Cyclic Trisubstituted Alkenes.

Xanthates have been readily converted into o-chlorophenyl thioethers using a one-step procedure conducted under radical conditions. In some selected cases, these aryl thioethers were successfully oxidized to the corresponding sulfoxides and sulfenic acid elimination afforded the corresponding vinylsilanes.

Radical, One-Step Approach to o-Chlorophenyl Thioethers from Xanthates. A Rapid Access to Vinylsilanes.

A variety of highly functionalized benzothiepinones, including libraries of complex aza-bridged derivatives, and highly functionalized 2,3-dihydrothieno[2,3-b]thiopyran-4-ones are prepared by combination of the radical and ionic reactions of xanthates.

Samir Z. Zard

Papers

Modular Routes to 1,3-Dithian-2-ones and 1,2-Dithiolanes.

α-Scission of Sulfonyl Radicals: A Versatile Process for Organic Synthesis

A Method for the Net Contra‐Thermodynamic Isomerization of Cyclic Trisubstituted Alkenes.

Radical, One-Step Approach to o-Chlorophenyl Thioethers from Xanthates. A Rapid Access to Vinylsilanes.

A Divergent Approach to Highly Substituted Benzothiepinones and to 2,3‐Dihydrothieno[2,3‐b]thiopyran‐4‐ones.