Catalytic Carbonyl-Olefin Metathesis of Aliphatic Ketones: Iron(III) Homo-Dimers as Lewis Acidic Superelectrophiles

Abstract

Catalytic carbonyl-olefin metathesis reactions have recently been developed as a powerful tool for carbon-carbon bond formation. However, currently available synthetic protocols rely exclusively on aryl ketone substrates while the corresponding aliphatic analogs remain elusive. We herein report the development of Lewis acid-catalyzed carbonyl-olefin ring-closing metathesis reactions for aliphatic ketones. Mechanistic investigations are consistent with a distinct mode of activation relying on the in situ formation of a homobimetallic singly bridged iron(III)-dimer as the postulated active catalytic species. These "superelectrophiles" function as more powerful Lewis acid catalysts that form upon association of individual iron(III)-monomers. While this mode of Lewis acid activation has previously been postulated to exist, it has not yet been applied in a catalytic setting. The insights presented are expected to enable further advancement in Lewis acid catalysis by building upon the activation principle of "superelectrophiles" and to broaden the current scope of catalytic carbonyl-olefin metathesis reactions.

Interrupted Carbonyl‐Alkyne Metathesis

“…We have recently shown that Lewis acidic superelectrophiles can function as potent catalysts for the activation of less reactive substrates in carbonyl-olefin metathesis reactions. [15] Specifically, suitable silver salts can abstract halides X from neutral metal complexes MX n resulting in the formation of superelectrophilic heterobimetallic ion pairs. [16] Based on these results, we next evaluated various Lewis acid superelectrophiles, obtained via chloride abstraction from neutral Lewis acids, for their ability to catalyze the formation of 8.…”

Synthesis of Medium-Sized Carbocycles by Gallium-Catalyzed Tandem Carbonyl-Olefin Metathesis/Transfer Hydrogenation

“…8,9 In contrast with the diene RCM, it is achieved from readily available ene-arylketones, or more recently using aliphatic ketones, 10 using simple Lewis acids. Iron(III) complexes have been especially utilized for that purpose, mostly by Schindler et al 9,10 Due to our interest in the development of galliumcatalyzed transformations, 11 and our recent work on the gallium-catalyzed transfer hydrogenation of alkenes using 1,4-cyclohexadiene as hydrogen donor, 12,13 we decided to investigate a tandem process combining a carbonyl-olefin metathesis and a transfer hydrogenation to form cycloalkanes (Scheme 1B). We kept in mind that the judicious installation of substituents (R 1 and R 2 ) could allow the formation of two contiguous stereocenters and possibly address the issue of the formation of 1,2-cis-disubtituted cyclopentanes.…”

“…Using a catalytic amount of an equimolar mixture of GaCl3/GaBr3 (entry 6) increased proportion of 3a, suggesting the formation of a heterobimetallic superelectrophile known to have a higher Lewis acidity than the homobimetallic (GaCl3)2 superelectrophilic dimer. 10 The intervention of superelectrophilic species in this chemistry will be further discussed below and in the Supporting Information (IR and DFT studies). When using a catalytic mixture of GaCl3 and AgSbF6, the desired product 3a was observed as major component of the mixture but significant decomposition lowered the isolated yield to 27% (entry 7).…”

“…When using a catalytic mixture of GaCl3 and AgSbF6, the desired product 3a was observed as major component of the mixture but significant decomposition lowered the isolated yield to 27% (entry 7). Among the other Lewis acids tested (entries [8][9][10][11][12][13], BF3•OEt2 proved to be the only catalyst offering a reactivity apparently similar to A, yet the isolated yield was lower (entry 11). Importantly, while B(C6F5)3 has been demonstrated to be a good transfer hydrogenation catalyst, 18 it failed at promoting the carbonyl-olefin metathesis step (entry 9).…”

“…The mechanism of the tandem process can be hypothesized as follows (Scheme 4). With FeCl3 as catalyst, the formation of the metathesis product E was shown to be a non-cationic process through just B and the [2+2] cycloadduct C. 10 The formation of C and its scission were described as concerted. Two catalytic cycles can be envisaged for the reduction of E into K. According to our previous proposal in the case of gallium catalysis, 12 it could be the result of a hydride transfer from 1,4-CHD to carbocation F, followed by protodegallation of G. Alternatively, as suggested in the case of boron catalysis, 18e 1,4-CHD could react with the catalyst to form species I.…”