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

This review article describes briefly some of the radical processes developed in the authors’ laboratory as they pertain to the concise assembly of complex molecular scaffolds. The emphasis is placed on the use of nitrogen-centred radicals, on the degenerate addition–transfer of xanthates, especially on its potential for intermolecular carbon–carbon bond formation, and on the generation and capture of radicals through electron transfer processes.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-9-61.pdf

Some aspects of radical chemistry in the assembly of complex molecular architectures

ConspectusRadical allylations represent effective routes to various alkenes, but to date they have relied chiefly on organostannane derivatives and still suffer from significant limitations with respect to the substitution pattern of the starting allylating agent. Indeed, while substituents at the β-position relative to the radical leaving group are well-tolerated, introduction of α-substituents induces a major complication due to the rapid and usually irreversible isomerization of the starting allylating agents. Although a number of research groups have made substantial efforts to develop heavy-metal-free radical allylations, methods compatible with α-substitution of the allylating agent are still scarce. Furthermore, quite a few systems are limited by the relative inaccessibility of the substrates. This Account summarizes our sustained efforts regarding the development of allylic alcohols into “ideal” radical allylating agents and presents published as well as some unpublished results. The systems we ha...

Allylic Alcohols: Ideal Radical Allylating Agents?

A convergent, modular access to complex amines

Nitroalkenes or vicinal acetoxy nitro derivatives undergo a clean reaction with sodium azide in hot dimethyl sulfoxide to give the corresponding 1,2,3-triazoles in good yield. © Georg Thieme Verlag Stuttgart.

Samir Z. Zard

Papers

Some aspects of radical chemistry in the assembly of complex molecular architectures

Allylic Alcohols: Ideal Radical Allylating Agents?

A convergent, modular access to complex amines

The Synthesis of 1,2,3-Triazoles from Nitroalkenes - Revisited

An unusual route to deoxysugars by hydrogen atom transfer from cyclohexane. possible manifestation of polar effects in a radical process