Vinyl Fluorides: Competent Olefinic Counterparts in the Intramolecular Pauson–Khand Reaction

Abstract

Despite the great advances achieved in the Pauson–Khand reaction and the ever-increasing demand for fluorinated compounds, the use of vinyl fluorides as olefinic counterparts in the above-mentioned transformation had been completely overlooked. Herein, we describe, for the first time, the intramolecular Pauson–Khand reaction of enynes containing a vinyl fluoride moiety.

The Fluoro-Pauson–Khand Reaction in the Synthesis of Enantioenriched Nitrogenated Bicycles Bearing a Quaternary C–F Stereogenic Center

“…We recently reported the first Pauson-Khand reactions using enyne substrates containing a vinyl fluoride moiety as the olefin coupling partner, an effective way to construct molecular complexity and the coveted quaternary C-F group in one step, albeit in a racemic manner. 14 Owing to the complete diastereoselectivity observed in this process, we foresaw that enantiopure products bearing a stereodefined quaternary C-F unit within a similar monoterpenic skeleton could be obtained by using a suitable enantioenriched substrate. We were surprised to find that fluorinated examples of this class of structure had not yet been studied, the only example in the literature being a single racemic analogue based on the same 6H-cyclopenta[c]pyridin-6-one scaffold bearing a trifluoromethyl substituent, which was also synthesized using the Pauson-Khand reaction (Scheme 1b).…”

Asymmetric Synthesis of Fluorinated Monoterpenic Alkaloid Derivatives from Chiral Fluoroalkyl Aldimines via the Pauson‐Khand Reaction

“…[24] Unfortunately, after several attempts, the catalytic version of the Pauson-Khand could not be applied to the synthesis of this class of previously reported quaternary CÀ F containing bicycles, such as 5 n (Scheme 4). [6,23] The mechanism of the Pauson-Khand reaction catalyzed by Co 2 (CO) 8 was initially proposed by Magnus in 1985, [25] and the same mechanism has since been supported by theoretical studies. [26] In our case, 1,7-enyne 4 reacts with Co 2 (CO) 8 through a ligand exchange reaction to form the alkyne-coordinated Co 2 (CO) 6 complex I upon release of two molecules of CO (Scheme 5).…”

“…To this end, the allylation reaction of the homopropargyl sulfonamine 3 a was carried out with 2‐fluoroallyl mesylate 6 to afford enyne 4 n (Scheme ) . For the cyclisation of this enyne derivative, we followed the reaction conditions previously applied by our group in analogous fluoro‐Pauson‐Khand reactions, in which DMSO is used as the promoter instead of NMO . It is worth noting that this transformation involves the asymmetric construction of a carbon‐fluorine quaternary stereogenic centre, a goal that constitutes remarkable interest in organic synthesis .…”

“…It is worth noting that this transformation involves the asymmetric construction of a carbon‐fluorine quaternary stereogenic centre, a goal that constitutes remarkable interest in organic synthesis . Unfortunately, after several attempts, the catalytic version of the Pauson‐Khand could not be applied to the synthesis of this class of previously reported quaternary C−F containing bicycles, such as 5 n (Scheme ) …”

“…[22] For the cyclisation of this enyne derivative, we followed the reaction conditions previously applied by our group in analogous fluoro-Pauson-Khand reactions, in which DMSO is used as the promoter instead of NMO. [6,23] It is worth noting that this transformation involves the asymmetric construction of a carbon-fluorine quaternary stereogenic centre, a goal that constitutes remarkable interest in organic synthesis. [24] Unfortunately, after several attempts, the catalytic version of the Pauson-Khand could not be applied to the synthesis of this class of previously reported quaternary CÀ F containing bicycles, such as 5 n (Scheme 4).…”