Radical Rearrangements of Esters

Abstract

Long considered inert toward radicals, esters are now known to have a rich and interesting spectrum of free-radical chemistry. The purpose of this chapter is to highlight this reactivity and its applications, real and potential, in synthetic organic chemistry. Application and mechanism are intimately linked and it is therefore necessary to begin by placing the very broad spectrum of reactivity within as comprehensive a mechanistic framework as possible, which should provide a solid basis for further rational development of the area. The subject was comprehensively reviewed in 1997 [ I] and the reader is referred to that article for a detailed discussion of the early development of the field as well as for a complete listing of kinetic parameters available at the time. In the meantime, however, there have been major developments, particularly with regard to mechanism, and a brief recapitulation is needed in order that they may be fully appreciated. Kinetic parameters that have appeared since 1997 are to be found in articles by Crich and Newcomb [2-41; illustrative rate constants are given, whenever available, in the Schemes below. MechanismThe mechanism of the p-( phosphatoxy)alkyl and /I-(acy1oxy)alkyl rearrangements and their less well known but closely related cousins, the /?-(su1fatoxy)alkyl and pnitroxyalkyl rearrangements, has long presented a conundrum to workers in the field [ 11. Instances of reactions proceeding via pure 2,3-shifts [ I ] and pure 1,2-shifts [5] are known as are apparent mixed mechanisms, leading to the suggestion [ 11 that 5-center-5-electron and 3-center-3-electron concerted pathways both exist, with the precise selection for a particular example being a function of substituent effects and solvent. However, the possibility that all rearrangements occurred via a rapid radical ionic fragmentation, to give an alkene radical cation and a carboxylate or phosphate counter ion followed by rapid recombination, advocated by Sprecher [6], Radicals in Organic Synthesis Edited

Thiyl Radicals in Organic Synthesis

“…In deoxygenation reactions of 1,2- O -benzylidene acetals, the process is complicated by the competitive 1,2-migration of the benzoate group (Surzur–Tanner rearrangement) in the resulting 2-benzoyloxyalkyl (Scheme , eq a) . As a result, the overall regioselectivity does not depend only upon the selectivity of the fragmentation process.…”

Radical Clock Probes to Determine Carbohydrate Radical Stabilities

“…The generation of carbohydrate radicals is well established in organic chemistry and has been applied for many synthetic transformations . For example, the rearrangement of ester groups to anomeric radicals 1a affords easy and the most simple access to 2-deoxy sugars 2b via radical 1b . However, this process is only feasible if the concentration of the hydrogen atom donor is very low; otherwise, 1-deoxy sugars 2a are formed directly without rearrangement (Scheme ).…”

“…The mechanism of such rearrangements has been intensively investigated. Thus, concerted [3,2] or [1,2] migrations, five-membered ring intermediates, and contact ion pairs have been discussed . Additionally, theoretical investigations have been performed at various levels .…”

The Stereoselective Total Synthesis of the Elusive Cephalosporolide F

“…A detailed rationale of the stereoelectronic model of the radical cation intermediates reveals that the progress of the phosphate cleavage of the β-phosphatoxy radical E goes beyond to contact ion pair ( CIP ); otherwise, the intramolecular attack of hydroxyl group would allow the formation of the ceph E. Accordingly, under nonthermodynamic conditions (low temperature and absence of base), the destabilization of Pauli repulsions at CIP becomes determinant for the formation of radical cation F , which is trapped by the hydroxyl group, enabling thus the stereoselective formation of the spiroketal center of (+)-cephalosporolide F (Scheme ).…”