Ring Closure Reactions of Disubstituted 4-Penten-1-oxyl Radicals − Towards a Stereoselective Synthesis of allo-Muscarine

Abstract

Keywords: Radicals / Cyclizations / Pyridinethione / Tetrahydrofurans / Asymmetric synthesis / ThiazolethioneThe trisubstituted functionalized tetrahydrofurans 10, 11, 16, 18, and 19 were photochemically prepared from 2,3-syn-and 2,3-anti-configured N-(3-benzoyloxy-5-hexen-2-oxy)thiazole-2(3H)-thione anti-6, pyridinethiones 7, anti-8, and BrCCl 3 . The formation of tetrahydrofurans was achieved by an efficient and highly regioselective alkoxyl radical cyclization (5-exo-trig). The 2,3-anti substituted intermediates 9 and 12 cyclize stereoselectively whereas a 2,3-syn-configured O-

Synthesis of Functionalized 2-Alkylidenetetrahydrofurans by Cyclization of 1,3-Bis(trimethylsilyloxy)-1,3-butadienes with Epoxides

“…The reaction of bis‐silyl enol ether 1 a with threo ‐3‐bromo‐1,2‐butenoxide gave the diastereomerically pure 2‐alkylidenetetrahydrofuran 3 h with again good E diastereoselectivity and without epimerization at the carbon attached to the bromine atom. Tetrahydrofurans containing chloro or bromo substituents in the side chain have demonstrated considerable synthetic utility in functionalization reactions during natural product syntheses 20. In addition, halogenated tetrahydrofurans are interesting in their own right as they occur in biologically relevant marine natural products 21…”

On the 6-endoSelectivity in 4-Penten-1-oxyl Radical Cyclizations

“…Instrumentation and general remarks have been disclosed previously (see also Supporting Information) 7a…”

Chemoselective Oxygen-Centered Radical Cyclizations onto Silyl Enol Ethers

“…Advances in oxygen-centered radical cyclizations have enabled the formation of a wide range of tetrahydrofurans including several simple tetrahydrofuran-containing natural products. , Despite progress in the field, alkoxy-radical cyclizations are still not as highly utilized in natural product synthesis compared to carbon-centered cyclization analogues , as methods based on oxygen-centered radicals are not sufficiently developed for the synthesis of complex substrates. The synthetic utility of the cyclization product can be increased by trapping carbon radical 2 with functional groups such as halogen ,, or sulfur but it is difficult to access α-hydroxylated rings, a motif common in bioactive tetrahydrofuran- and tetrahydropyran-containing natural products . Furthermore, it is difficult to control the high reactivity of the oxygen-centered radicals as they readily undergo 1,5-hydrogen abstraction and β-fragmentation pathways (Scheme ).…”