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 total synthesis of (±)-cinnamolide 9 and (±)-methylenolactocin 15 is accomplished using as the key step a radical cyclisation involving alkoxycarbonyl radicals derived from S-alkoxycarbonyl xanthates.

Total Synthesis of (.+-.)-Cinnamolide and (.+-.)-Methylenolactocin - An Approach to Butenolides Using S-Alkoxycarbonyl Xanthates.

Unprotected vinyl carbinols react with the radicals generated from xanthanes involving a rare cleavage of a C—C bond in a non-strained open chain structure.

From a Remarkable Manifestation of Polar Effects in a Radical Fragmentation to the Convergent Synthesis of Highly Functionalized Ketones.

Xanthates and related thiocarbonylthio derivatives have proved to be exceedingly useful substrates for both inter- and intra- molecular radical additions. The intermolecular addition to unactivated alkenes, in particular, provides tremendous opportunities for synthesis: various functional groups can be brought together under mild, neutral conditions. Since the adduct is also a xanthate, iteration allows the formation of block polymers through a controlled radical polymerisation (the RAFT/MADIX technology). Also of some importance is the access to highly substituted aromatic and heteroaromatic derivatives.

Some Aspects of the Radical Chemistry of Xanthates

A route to 3-arylpiperidines and 3-arylpyrrolidines involving radical 1,4- and 1,2-aryl migrations has been explored For the piperidines, the first route requires a xanthate addition to an N-allylarylsulfonamide, followed by acetylation and treatment with lauroyl peroxide to give the corresponding 1,4-aryl transfer product This compound can be converted into the desired piperidine derivative following acidic hydrolysis For the second approach to piperidines, addition of an α-keto xanthate to olefins of type 14 causes 1,2-aryl migration leading to an α,β-unsaturated ester, which can be converted into a piperidine by the action of ammonia or a primary amine and sodium cyanoborohydride Substituted 3-arylpyrrolidines can be obtained by simply starting with an α-amido substituted xanthate

Synthesis of Substituted 3‐Arylpiperidines and 3‐Arylpyrrolidines by Radical 1,4 and 1,2‐Aryl Migrations.

SYNTHESIS 2008, No. 18, pp 2996–3008xx.xx.2008 Advanced online publication: 24.07.2008 DOI: 10.1055/s-2008-1067198; Art ID: M01708SS © Georg Thieme Verlag Stuttgart · New York Abstract: 2-, 3-, or 4-Pyridylmethyl radicals can be made to add to nonactivated alkenes to give a variety of otherwise inaccessible pyridine derivatives. Bicyclic structures can be obtained by combining the radical addition with ionic ring-closure steps.

Samir Z. Zard

Papers

Total Synthesis of (.+-.)-Cinnamolide and (.+-.)-Methylenolactocin - An Approach to Butenolides Using S-Alkoxycarbonyl Xanthates.

From a Remarkable Manifestation of Polar Effects in a Radical Fragmentation to the Convergent Synthesis of Highly Functionalized Ketones.

Some Aspects of the Radical Chemistry of Xanthates

Synthesis of Substituted 3‐Arylpiperidines and 3‐Arylpyrrolidines by Radical 1,4 and 1,2‐Aryl Migrations.

Generation and Intermolecular Additions of Pyridylmethyl Radicals.