Pauson–Khand reaction of fluorinated compounds

Abstract

The Pauson–Khand reaction (PKR) is one of the key methods for the construction of cyclopentenone derivatives, which can in turn undergo diverse chemical transformations to yield more complex biologically active molecules. Despite the increasing availability of fluorinated building blocks and methodologies to incorporate fluorine in compounds with biological interest, there have been few significant advances focused on the fluoro-Pauson–Khand reaction, both in the inter- and intramolecular versions. Furthermore, the use of vinyl fluorides as olefinic counterparts had been completely overlooked. In this review, we collect the advances both on the stoichiometric and catalytic intermolecular and intramolecular fluoro-Pauson–Khand reaction, with special attention to the PKR of enynes containing a fluoride moiety.

Computational Study on the Co-Mediated Intramolecular Pauson–Khand Reaction of Fluorinated and Chiral N-Tethered 1,7-Enynes

“…The PKR of enynes 1e and 1f was assayed experimentally, yielding bicyclic products 2e and 2f in 15 and 40% yields, respectively. 17 When evaluating the reactivity of dimethyl-substituted enyne 1g , the activation barrier for the alkene insertion ( TS1 ) was found to be significantly higher (25.3 kcal/mol), in agreement with previous reports, showing that trisubstituted alkenes are less reactive or, in some cases, unreactive substrates in the Pauson–Khand reaction. 36 , 37 A higher barrier for CO insertion ( 1g-TS2 ) was also observed due to the crowded environment around the alkene by the two methyl groups.…”

“…Both enynes 1a and 1c have been experimentally assayed in the Co-mediated intramolecular PKR, yielding the corresponding cyclopentenone derivatives with similar yields, 65 and 60% for enynes 1a and 1c , respectively. 12 , 17 The regioselectivity in TS1 involving the formation of a stereocenter was also investigated for enyne 1c and compared to the experimental results, which showed the formation of the final bicyclic products with excellent diastereoselectivities (dr > 20:1). 15 Theoretical results for 1c indicated an energy difference of 4.7 kcal/mol between both TSs, which is consistent with the experimental observation of only one diastereomer (dr > 20:1).…”

“… 16 In terms of synthesis, the Pauson–Khand reaction of fluorinated enynes creates the bicyclic molecular complexity in just one reaction. 17 …”

Study of the Pauson–Khand reaction in flow over alkynylphenyl vinyl ethers: towards the synthesis of tricyclic multisubstituted benzofurans

“…Despite the great number of substrates used to date, vinyl ethers continue to be challenging substrates for the PKr. 8 Only three reports, where these motifs were used as PK substrates have been reported. In 1981, Croudace and Schore attempted to use several vinyl ethers in an intramolecular PKr.…”

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

“…[9,10] or stereodiscriminating enantioselective ring-closing metathetic reactions [11][12][13]. Apart from metathesis, enynes are also interesting substrates for other catalytic reactions, e.g., for the Pauson-Khand reaction [14].…”