Carbonylation Reactions of Alkyl Iodides through the Interplay of Carbon Radicals and Pd Catalysts

Abstract

Numerous methods for transition metal catalyzed carbonylation reactions have been established. Examples that start from aryl, vinyl, allyl, and benzyl halides to give the corresponding carboxylic acid derivatives have all been well documented. In contrast, the corresponding alkyl halides often encounter difficulty. This is inherent to the relatively slow oxidative addition step onto the metal center and subsequent β-hydride elimination which causes isomerization of the alkyl metal species. Radical carbonylation reactions can override such problems of reactivity; however, carbonylation coupled to iodine atom transfer (atom transfer carbonylation), though useful, often suffers from a slow iodine atom transfer step that affects the outcome of the reaction. We found that atom transfer carbonylation of primary, secondary, and tertiary alkyl iodides was efficiently accelerated by the addition of a palladium catalyst under light irradiation. Stereochemical studies support a mechanistic pathway based on the synergic interplay of radical and Pd-catalyzed reaction steps which ultimately lead to an acylpalladium species. The radical/Pd-combined reaction system has a wide range of applications, including the synthesis of carboxylic acid esters, lactones, amides, lactams, and unsymmetrical ketones such as alkyl alkynyl and alkyl aryl ketones. The design of unique multicomponent carbonylation reactions involving vicinal C-functionalization of alkenes, double and triple carbonylation reactions, in tandem with radical cyclization reactions, has also been achieved. Thus, the radical/Pd-combined strategy provides a solution to a longstanding problem of reactivity involving the carbonylation of alkyl halides. This novel methodology expands the breadth and utility of carbonylation chemistry over either the original radical carbonylation reactions or metal-catalyzed carbonylation reactions.

Cu‐Catalyzed Hydroxymethylation of Unactivated Alkyl Iodides with CO To Provide One‐Carbon‐Extended Alcohols

“…[4] Ac omplementary strategy to these hydroxymethylation reactions of alkenes and other p-systems would be hydroxymethylation of electrophiles such as alkyl and aryl halides. [9] Ak ey advance in this regard is the work of Alexanian and co-workers on Co-and Mn-catalyzed C(sp 3 )À Xc arbonylative CÀCc oupling reactions,w hich occur at milder conditions. [8] Carbonylation reactions of C(sp 3 )ÀXe lectrophiles are significantly less common.…”

“…Thecorresponding alcohols 5 and 7, derived from radical ring closing and opening, respectively, were obtained in 68 %and 40 %yield. [9,18] Subsequently,n ucleophilic substitution takes place between B and ac oncomitantly formed copper hydride to yield aldehyde C.T of urnish the final silyl-protected alcohol E, aldehyde C undergoes reduction by established copper hydride catalysis via alkoxide intermediate D. [19] Based on this hypothetical mechanism, b-hydride elimination is avoided because of al ack of any metal-alkyl intermediates. Collectively,t hese observations are indicative of alkyl radical intermediates during catalysis.…”

A Palladium/Light System Combined with Hanztsch Ester: Radical Vinylation of Alkyl Iodides with Vinyl Bromides

“…Increasing the amount of 2b resulted in an increase in the yield of 3b (Table 1, entries 3a nd 4). Increasing the concentrationa lso resultedi na ni mprovedy ield of 3b (Table 1, entries [4][5][6]. In all reactions, the E-isomer was obtained selectively.…”

“…[1,2] We have been engaged in developingaseries of cascade reactions of alkyl iodides, CO, and alkenes using aP d/light combined system. [3][4][5] Recently we reportedt hat using aP d/light combined system, Giese-type reactions of alkyl iodides with electron deficient alkenes proceed in the presence of Hanztsch ester as the hydrogen source. [6] The first step of the Pd/light system is SET between Pd 0 and R-I to form the RC and Pd I -I pair and we thought that the Pd/ light system would thus be usefula lso for radicalv inylation employing vinyl bromides.…”

Katalyse mit durch sichtbares Licht angeregten Palladiumkomplexen

“…[2] Unlängst wurde berichtet, dass die Anregung mittels sichtbaren Lichts in Abwesenheit exogener Photosensibilisatoren [3][4][5] dazu führt, dass gebildete,p hotoangeregte Pd-Komplexe Einelektronentransfer-Prozesse (SETs;s ingleelectron transfers) durchlaufen, die zur Bildung hybrider Pd/ Radikal-Spezies [6] über einen Pd 0 /Pd I -Reaktionspfad führen (Schema 1, angeregter Zustand). [8] 2. Zusätzlich sind die photoangeregten Pd-Komplexe in der Lage,b ekannte Pd-katalysierte Umsetzungen, wie Heck-und Negishi-Kreuzkupplungen von Arylhalogeniden, drastisch zu beschleunigen.…”