Lithium Malonate Enolates as Precursors for Radical Reactions − Convenient Induction of Radical Cyclizations with either Radical or Cationic Termination

Abstract

Lithium malonate enolates 4 or 13 are oxidized to the corresponding radicals by ferrocenium hexafluorophosphate (1) or CuCl2 (2). Trapping by TEMPO (5) to produce 6, dimerization to 7, or radical 5‐exo cyclizations are possible subsequent reaction steps following radical generation. The structure of the radical cyclization acceptor determines the outcome of the overall reaction sequence. Tertiary benzylic, alkyl, and α‐alkoxy radicals are oxidized by 1. The carbenium ions are stabilized by nucleophilic trapping or deprotonation to give compounds 14 and 18. Secondary alkyl and vinyl radicals are not oxidized and, in the absence of trapping reagents, form radical‐derived products. Radical 5‐exo cyclization of 13 induced by CuCl2 (2) was also efficient. At least for alkyl radicals, however, ligand transfer is the exclusive stabilization pathway, giving access to chloroalkylcyclopentane derivatives 21. Radical scavenging studies revealed that malonyl radical trapping is slow, so that 5‐exo cyclizations occurred. The cyclized radicals couple with TEMPO (5) to afford oxygenated cyclopentane derivatives 31, depending on the rate of radical SET oxidation. The reaction behavior of compounds 14, 22, 23, and 31 was investigated. Mechanistic issues are discussed and implications for synthetic planning are given.

Highly Functionalized Cyclopentane Derivatives by Tandem Michael Addition/Radical Cyclization/Oxygenation Reactions

“…Although coupling products similar to 31 were observed before by coupling of malonyl radicals with an excess of 5 ,22 coupling products 31 were never detected in the tandem processes. This can be rationalized, on one hand, by the operation of the Thorpe–Ingold effect to accelerate the cyclization and, on the other hand, by the concentration of 5 being kept low through portionwise addition of a mixture of 4 and 5 .…”

A New Reaction Motif: “Homo-SN2′-Like” Direct Nucleophilic Addition to Neutral η3-Allylmolybdenum Complexes. Total Synthesis of the Antimalarial (+)-Isofebrifugine

“…In earlier work, Pearson used different non-basic annulative demetalation reagents such as I 2 8 or NOBF 4 9 for related transformations, but exposing our substrates to these reagents (as well as prolonged standing in CDCl 3 ) yielded only the undesired elimination product (i.e., 16 , Scheme 2) through ionization of the carbon nucleophile10 and subsequent proton loss. Mechanistically, we suggest that the reactions of Table 2 proceed through 1-electron oxidation of the stabilized enolate to a radical11 that then reacts with the adjacent η 3 -allylmolybdenum moiety.…”

Nitroxide: Anwendungen in der Synthese und in der Polymerchemie

“…Um aus dem Metallenolat das entsprechende Enoylradikal zu erzeugen, wird in der Regel ein externes Oxidationsmittel benötigt. [120] Das Oxoammoniumsalz von TEMPO hingegen ist ein wesentlich stärkeres Oxidationsmittel (siehe Abschnitt 2) und ergibt mit Metallenolaten direkt die Alkoxyamine. So reagieren die Na-und Li-Enolate von b-Ketoestern oder Malonaten mit TEMPO + BF 4 À bei 0 8C zu den Alkoxyaminen 30 (47-89 % Ausbeute, Schema 16).…”