Radical Cyclization Reactions

Abstract

Radical cyclization reactions are among the most powerful and versatile methods for the construction of mono‐ and polycyclic systems. The advantages these reactions offer to the synthetic organic chemist include high functional group tolerance and mild reaction conditions combined with high levels of regio‐ and stereochemistry. Furthermore, the recent progress in radical chemistry has led to the development of a broad range of very useful practical methods to conduct radical cyclization reactions. In general, radical cyclization reactions comprise three basic steps: selective radical generation, radical cyclization, and conversion of the cyclized radical to the product. For the generation of the initial radical a broad variety of suitable precursors can be employed, such as halides, thio‐ and selenoethers, alcohols, aldehydes and hydrocarbons. The cyclization step usually involves the intramolecular addition of a radical to a multiple bond. Most often carbon–carbon multiple bonds are employed; however, there are also examples known for the addition to carbon–oxygen and carbon–nitrogen bonds. Depending on the method employed, the cyclized radical is converted to the desired product by trapping with a radical scavenger, by a fragmentation reaction, or by an electron transfer reaction. The section Mechanism, Regio‐ and Stereochemistry provides an introduction to the key features of radical cyclization with a special emphasis on the factors controlling the regio‐ and stereochemistry. The section Scope and Limitations covers the different methods used to conduct radical cyclization. The basic principles of radical chemistry and general practical considerations when conducting radical cyclizations are not discussed in detail. Several excellent review articles and books dealing with these topics are available.

Stannyl Radical Addition-Cyclization of Oxime Ethers Connected with Olefins

“…The layers were separated, and the aqueous phase was extracted with AcOEt. The combined organic phase was dried over Na 2 N-(tert-Butoxycarbonyl)-N-(2-propenyl)aminoethanal O-Benzyloxime (1) To a solution of 3 (4.83 g, 23.7 mmol) in acetone (100 ml) was added a solution of Na 2 CO 3 (4.27 g, 40.3 mmol) in H 2 O (15 ml) under a nitrogen atmosphere at room temperature. After di-tert-butyl dicarbonate (7.39 g, 35.5 mmol) was added dropwise at 0°C, the reaction mixture was stirred at room temperature for 20 h. After the reaction mixture was filtered through a pad of Celite, the filtrate was concentrated at reduced pressure.…”

“…The layers were separated, and the aqueous phase was extracted with AcOEt. The combined organic phase was dried over Na 2 N-(2-Hydroxyethyl)aminoethanal O-Benzyloxime (13) To 2-aminoethanol (10 ml, 166 mmol) was added chloroacetaldehyde O-benzyloxime (2) (10.0 g, 54.5 mmol) under a nitrogen atmosphere at 0°C. After being stirred at room temperature for 12 h, the reaction mixture was added to saturated aqueous NaHCO 3 and CH 2 Cl 2 .…”

“…[2][3][4][5] Although a number of extensive investigations into radical reactions were reported in recent years, the majority of them employ methods utilizing typical radical precursors such as halides, selenides, and xanthates. [2][3][4][5] One drawback in traditional procedures using such radical precursors is loss of the inherent functional groups. 6,7) Our laboratory is interested in developing the effective and convenient methods for the synthesis of highly functionalized cyclic compounds.…”

Solid-Phase Tandem Radical Addition-Cyclization Reaction: Triethylborane-Induced Reaction of Oxime Ethers Anchored to Polymer Support

“…16,17) Free radical-mediated cyclization has been developed as a powerful method for preparing various types of cyclic compounds via carbon-carbon bond-forming processes. [18][19][20][21][22][23][24][25][26][27][28][29] Our laboratory is interested in developing the effective and convenient methods for the synthesis of highly functionalized cyclic compounds. For this purpose, we have studied the radical reaction using oxime ether group as a radical acceptor.…”

Synthesis of Phenanthridinone Derivatives by Direct Arylation. Characterization of the Absorption and Emission Spectra for Representative Examples

“…60 Uma reação tipo Goldberg catalisada por um sal de cobre utilizando derivados de ácido 2-clorobifenil-2'-carboxílico com anilinas forneceu 1a (72%) e 1r (96%). 77 Métodos radicalares incluem: o uso de t-BuOK (Figura 2, C) fornecendo 1q (bromo substrato, 61-70%, iodo substrato, 63%), 38 deidrogenação de N-fenil bifenil-2-carboxamida (Figura 2, D) utilizando persulfato de potássio para obter 1r (97%), 78 ou por geração fotolítica de um íon N-acilnitrênio gerando 1r (65%), 79 ou por foto-deidro-halogenação (Figura 2, C) fornecendo 1r (25%). C podemos confirmar as principais modificações nos grupos, como por exemplo a ausência da ligação C-I (~90 ppm), que pode indicar a ciclização ou somente a redução da ligação C-I.…”