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.

/pdf/living-radical-polymerization-by-the-raft-process-qf42rfce4m.pdf

Living radical polymerization by the RAFT process

The Invention of New Radical Chain Reactions. Part 10. High Yield Radical Addition Reactions of αβ-Unsaturated Nitroolefins.

The Art or the Soluble: Synthetic Problems from Industry as a Springboard for the Discovery of New Chemical Reactions

Xanthates are convenient precursors of a variety of radicals that can be captured in an inter-or intramolecular fashion. Overall, the process involves rupture of the sulfide C-S bond and addition of the elements of the xanthate to the olefinic trap. The xanthate in the product can be reductively removed in some cases simply by heating in isopropanol with stoichiometric amounts of dilauroyl peroxide. A new radical allylation reaction based on ally1 sulfones has also been devised where, in a manner similar to that with xanthates, a number of degenerate steps force the reaction in the desired direction. Over the past decade or so, the use of free radical processes in organic synthesis has witnessed an extraordinary development. Radical reactions offer in fact many of the properties desired by synthetic organic chemists in terms of mildness, variety, and potential for C-C bond formation as well as for functional group interchange. The main difficulty with radicals, one which has given them their bad reputation for decades, is that they interact with themselves (dimerisation, disproportionation) with extremely fast rates that axe practically diffusion controlled. It is therefore essential that the desired reaction sequence be made of very fast steps in order to keep the steady-state concentration of radical species very low and thus "tame" their wild behaviour by limiting radical-radical reactions. "He who rides a tiger is afraid to dismount" is a Chinese proverb; as long as the tiger is moving (fast), one is safe. Whence the title of this contribution. This notion is illustrated by the typical and now extremely popular chain process based on tributylstannane where the propagating steps are quite fast, as in scheme 1 below: E d R-X + Bu3Sn' + R' * dE B R

Riding the Tiger: Using Degeneracy to Tame Wild Radical Processes

1,2-Dicarbonyl compounds can be accessed by a radical addition-transfer of xanthates and used for the synthesis of pyrazines and quinoxalines, as well as in an unusual approach to benzimidazoles.

A Practical Route to Pyrazines and Quinoxalines, and an Unusual Synthesis of Benzimidazoles.

S-Succinimidomethyl- and S-phthalimidomethyl xanthates are added efficiently to various alkenes resulting in an overall aminomethylation process. In contrast, under similar conditions, S-pyrrolidon...

Samir Z. Zard

Papers

The Invention of New Radical Chain Reactions. Part 10. High Yield Radical Addition Reactions of αβ-Unsaturated Nitroolefins.

The Art or the Soluble: Synthetic Problems from Industry as a Springboard for the Discovery of New Chemical Reactions

Riding the Tiger: Using Degeneracy to Tame Wild Radical Processes

A Practical Route to Pyrazines and Quinoxalines, and an Unusual Synthesis of Benzimidazoles.

Radical Aminomethylation of Unactivated Alkenes.