Synthesis of 10-membered and larger rings via free radical methods

Unconventional Macrocyclizations in Natural Product Synthesis

“…The generation of radical species allows swift carbon–carbon bond formation in contexts that are often orthogonal to, and not as susceptible to the negative effects of steric hindrance as, classical polar reactivity. It is therefore only logical that radical processes have been heavily employed in the formation of large rings . Examples of the wide range of radical-based named reactions utilized for macrocyclization in natural product synthesis shall be presented in this section.…”

“…It is therefore only logical that radical processes have been heavily employed in the formation of large rings. 135 Examples of the wide range of radical-based named reactions utilized for macrocyclization in natural product synthesis shall be presented in this section. 7.1.…”

Photochemical Methods for Peptide Macrocyclisation

“…However, in line with a wider renaissance of the fields of photo‐ and radical chemistry, recent developments have brought this area to the fore. Photochemical strategies are highly attractive for macrocyclisation: reactive open‐shell or photoexcited‐state species are known to readily participate in macrocyclisation through mechanisms that are fundamentally different to their two‐electron ground‐state counterparts, offering ample scope for novel cyclisation manifolds that overcome some of the limitations of two‐electron and transition‐metal‐catalysed methods [49, 50] . Given that most peptides are largely transparent to light of wavelengths >320 nm (and those without aromatic amino acids or disulfide bonds, >250 nm), [51] photochemical methods allow targeted excitation of chromophores in a reaction mixture, affording the potential for both mild and highly selective processes to take place, which are compatible with complex biological systems [52–54] .…”

Synthesis of 23-, 25-, 27-, and 29-Membered (Z)-Selective Unsaturated and Saturated Macrocyclic Lactones from 16- and 17-Membered Macrocyclic Lactones and Bromoalcohols by Wittig Reaction, Yamaguchi Macrolactonization, and Photoinduced Decarboxylative Radical Macrolactonization

“…These lactones are found in a variety of natural products such as exaltolide 1 (16-membered macrocyclic lactone) and cyclohexadecanolide 2 (17-membered macrocyclic lactone), which are used in perfumes, and synthetic pharmaceuticals such as erythromycin and clarithromycin, which have strong antibacterial and antitumor activities (Scheme a) . Therefore, a number of efficient synthetic routes to macrocyclic lactones have been developed based on transition-metal-catalyzed ring-closing metathesis, Horner–Wadsworth–Emmons reaction, Yamaguchi macrolactonization, Shiina macrolactonization, and intramolecular radical cyclization using azobisisobutyronitrile and Bu 3 SnH . We recently reported a radical cyclization of carboxylic acids bearing electron-deficient alkenes via photoinduced decarboxylation under mild photoredox catalyst conditions for the formation of macrocyclic lactones in high yields (Scheme b) .…”