Umpolungsreaktionen mit dem Malonyl‐Radikal

Abstract

Das Malonyl-Radikal 3 la& sich aus Chlor-oder Brommalonester mit Tributylzinnhydrid in einer Radikalkettenreaktion erzeugen. Dieses Radikal reagiert mit Enolethem 6 zu den Additionsprodukten 7 oder den Substitutionsprodukten 10. Bei der Bildung von 7 werden die Adduktradikale 12 dwch Zinnhydrid, bei der Bildung von 10 durch den Brommalonester abgefangen. Anschliehnde HBr-Abspaltung liefert die Substitutionsprodukte 10. Konkurrenzkinetische Messungen rnit den substituierten Styrolen 14 zeigen, daD das MalonylRadikal 3 elektrophile Eigenschaften besitzt. So reagiert es mit dem Enamin 14f 23mal rascher als rnit dem estersubstituierten Alken 14b (Tab. 1). Reaction with Umpolung of the Malonyl RadicalThe malonyl radical 3 can be generated from chloro-or bromomalonate in a radical chain reaction. This radical reacts with enol ethers 6 to addition products 7 or substitution products 10. During the formation of 7 the adduct radicals 12 are trapped by tin hydride whereas the formation of 10 occurs via bromine abstraction from bromomalonate. Succeeding HBr elimination gives the substitution products 10. Kinetic experiments with substituted styrenes show that malonyl radical 3 is an electrophile. It reacts 23 times faster with enamine 14f than with the ester-substituted alkene 14b ( Table 1). Seit einigen Jahren findet die Radikalchemie zum Aufbau des CC-Bindungsgeriistes vonZielmolekulen durch intramolekulare und intermolekulare Additionsreaktionen breite Anwendung '). Diese Synthesen zeichnen sich durch ihre milden Reaktionsbedingungen, ihre kurzen Reaktionszeiten und ihre hohen Chemoselektivitaten aus. Ein weiteres Merkmal liegt darin, daB iiber radikalische CC-Bindungsbildungen Produkte leicht zuganglich gemacht werden kiinnen, die aus der Sicht der Ionenchemie die Produkte der Reaktivit5tsumpolung2) sind. So ist in Carbonylverbindungen das Carbonylkohlenstoffatom ein Akzeptoratom, das bevorzugt rnit Nucleophilen reagiert, wahrend das CH-acide P-Kohlenstoffatom als Anion und damit als Donoratom in Synthesen fungiert.

A Giese reaction for electron-rich alkenes

“…Various diand trisubstituted enol esters were tested using different electrophilic radical precursors. The method worked efficiently with terminal (3-12) as well as non-terminal enol esters (13)(14)(15) and can be also extended to the phosphonate ester (16). A broad range of 2-iodoesters such as simple iodoacetates (3-7, 11-16), 2-iodopropionates (8), the iodolactone (9) and the difluoroiodoacetae (10) were all found to react cleanly under these reaction conditions.…”

“…[3][4][5][6][7] As for the hydroalkylation process, most of the reported methods described the addition of nucleophilic radicals to electron-poor olefins (the classical Giese reaction), [8][9][10][11][12] the reversed process, i.e., addition of electrophilic radical to electron-rich olefins, remains scarce. The addition of diethyl chloromalonate to vinyl ethers and silyl enol ethers using tributyltin hydride as the hydrogen source was reported by Giese et al (Scheme 1, A), 13 followed a few years later by Renaud et al who reported the hydroalkylation of enamines with sulfinylated and sulfonylated carbon-centered radicals in the presence of tributyltin hydride. [14][15][16] Examples of two-step procedures involving a xanthate group transfer reaction followed by a reduction step have been reported by Zard.…”

“…Similar reactions have been reported by Giese in his seminal work. 13 Scheme 5. Reaction of phenyl iodoacetate with butyl vinyl ether.…”

A Giese Reaction for Electron-Rich Alkenes

“…[3][4][5][6][7] As for the hydroalkylation process, most of the reported methods described the addition of nucleophilic radicals to electron-poor olefins (the classical Giese reaction), [8][9][10][11][12] the reversed process, i.e., addition of electrophilic radical to electronrich olefins, remains scarce. The addition of diethyl chloromalonate to vinyl ethers and silyl enol ethers using tributyltin hydride as the hydrogen source was reported by Giese et al (Scheme 1, A), [13] followed a few years later by Renaud et al who reported the hydroalkylation of enamines with sulfinylated and sulfonylated carbon-centered radicals in the presence of tributyltin hydride. [14][15][16] Examples of two-step procedures involving a xanthate group transfer reaction followed by a reduction step have been reported by Zard.…”

Synthetic applications of radical C-C bond forming reactions

“…give the highest yields, whereas with electrophilic radicals like 9, enol ethers are used most successfully [7]. R3C.…”