Utilization of α‐Oxygenated Radicals in Synthesis

Abstract

@-Oxygenated radical intermediates play an important role in modern synthetic chemistry and the stereochemistry of radical reactions is an area of considerable interest. These intermediates are important in a number of stereoselective transformations, including the radical-mediated syntheses of C-glycosides, 2-deoxy-P-glycosides, spironucleosides, and axial (2-tetrahydropyrany1)lithium and 1-glycosyllithium reagents. Substituted 2-tetrahydropyranyl radicals exhibit anisotropic interactions between the radical center and the adjacent oxygen atom which dictate the stereochemical outcome of these radical reactions. In general, xoxygenated radicals are rapidly equilibrating intermediates, but recent advances have shown that non-equilibrium radical reactions are now possible as a result of the inherent conformational memory present in the radical intermediate. This chapter will focus on the conformations of a-oxygenated (anomeric) radicals in cyclic ethers, the stereoselectivities associated with their reactions, and the applications of these important synthetic intermediates. Conformation and Stereoelectronic Effects of Cyclic a-Oxygenated RadicalsStereoelectronic effects dominate in the reactivities of simple 2-tetrahydropyranyl radicals [I]. In these ring systems, anomeric radicals are best characterized as an equilibrating mixture of pseudoaxial and pseudoequatorial radicals, which tend to be slightly pyramidalized because of the presence of the a-oxygen atom. Moreover, 2-tetrahydropyranyl radicals prefer to be axial in order to maximize overlap with the lone pair of the ring ether oxygen; ab initio calculations predict the axial radical to be >2 kcal/mol more stable than the equatorial radical [2]. In terms of molecular orbital theory, the stabilization between the axial oxygen lone pair and the singly occupied molecular p-orbital (SOMO) of an axial carbon- Radicals in Organic Synthesis Edited by Philippe Renaud andMukund P. Sibi

Tin-Free Radical Addition of Acyloxymethyl to Imines

“…The major problem of this strategy was, however, the requirement of a large amount (usually 20−250 equiv) of the corresponding ether or alcohol as a radical source. The generation of this class of radical via C−heteroatom bond cleavage using a tin compound has been utilized in sugar chemistry as well as in a number of total syntheses . Although α-oxygenated C-centered radicals were efficiently generated from the radical sources in these examples, the use of organotinhydrides is a critical drawback, especially from an ecological point of view, because of difficulty in complete removal and toxicity of tin compounds .…”

β-Fragmentation of Primary Alkoxyl Radicals versus Hydrogen Abstraction: Synthesis of Polyols and α,ω-Differently Substituted Cyclic Ethers from Carbohydrates

“…To provide stabilization to the C-radical (II), some functional groups R 3 such as aromatic rings, carbonyl groups, and heteroatoms could be used. When the C-radical is stabilized by heteroatoms, it can evolve under oxidative conditions to a carbenium ion (III), thus making the fragmentation process irreversible. We reasoned that by carrying out the scission of primary alkoxyl radicals in carbohydrate chains (Figure , eq 1), the resultant radical would be stabilized by the adjacent oxygen functions and under oxidative conditions would evolve to an oxycarbenium ion, which could be trapped by nucleophiles.…”