Copper/Iron‐Cocatalyzed Cascade Perfluoroalkylation/Cyclization of 1,6‐Enynes with Iodoperfluoroalkanes

Abstract

A copper/iron‐cocatalyzed fluoroalkylative cyclization of 1,6‐enynes with readily available iodoperfluoroalkanes reagents for the synthesis of the corresponding fluoroalkylated pyrrolidines and benzofuran derivatives is reported. This novel protocol provides a mild method for the construction of Csp3‐CF2 and exocyclic double bonds in one step with high regio‐ and stereo‐selectivities.

Palladium‐Catalyzed Perfluoroalkylative Carbonylation of Unactivated Alkenes: Access to β‐Perfluoroalkyl Esters

“…With the optimal reaction conditions established, the scope of phenol substrates for this multi-component carbonylation was explored (Scheme 1). Satisfactorily,scaling up the model reaction to 0.2 mmol and 1.0 mmol smoothly provided the required product 4 in 87 %and 83 %, respectively.Phenols with different functional groups,i ncluding methoxy,p henyl, acetyl, and even carbamoyl at the ortho-position were tolerated well, affording the corresponding products 5-8 in moderate to good yields.B oth electron-donating and electron-withdrawing substituents on the meta-o rpara-position of phenols were all transformed into the desired products 9-20 in 61-84 %yields with excellent chemoselectivity.Notably, this multi-component carbonylation exhibited excellent functional group compatibility,resulted in products bearing acetyl (7, 10,a nd 13), carbamoyl ( 8), cyano (14), ester (15), bromo ( 16), aldehyde (17), hydroxyl (18), and amide (19)i ng ood yields.P oly-substituted phenols with more steric hindrance can also be utilized to give the targeted products 21-24,albeit in slightly decreased yields.Naphthols (25-27)and 2-hydroxycarbazole (28)were also worked well here.Asweexpected, diphenol and 4-aminophenol can be transformed into the corresponding double carbonylated compounds (29, 30, 32, and 33)successfully.Notably,mono-carbonylated product 31 can also be selectively obtained by controlling the loading of 1,1'-bi-2-naphthol. Finally,r eplacing phenol with different alcohols can gave the corresponding b-perfluoroalkyl esters 34-36 as well.…”

Iron-catalyzed domino coupling reactions of π-systems

“…In 2018, the Xia laboratory reported a Cu/Fe-cocatalyzed cascade perfluoroalkylation/cyclization of 1,6-enynes 183 / 185 for the synthesis of fluoroalkylated pyrrolidines and benzofurans 184 / 186 ( Scheme 41 ) [ 152 ]. When either catalyst was used on its own, the reaction had little to no success, demonstrating the necessity for tandem catalysis.…”

Palladium‐Catalyzed Cycloisomerization of 1,6‐Enynes Using Alkyl Iodides as Hydride Source: a Combined Experimental and Computational Study

“…[3b] A variety of reaction conditions, including different solvents and bases, were investigated to show the significance in this cyclization reaction, and only combination of toluene and K 2 CO 3 can result in a better yield. Other solvents such as dioxane, chlorobenzene, and trifluorotoluene did not provide significant amounts of the target product (entries [6][7][8]. Among a series of bases, only N,N-diisopropyl-ethylamine, KOAc, and K 3 PO 4 can provide the desired products, and no reaction occurred without base (entries 9-15).…”

“…In 2018, a Pd-catalyzed cycloisomerization of 1,6-diynes to afford silylated 2-azafluorenes using ammonium halide salts as the hydride source was reported by Lautens. [7c] Inspired by these advances and based on our previous works in 1,6-enynes, [8] we hypothesized that a new cycloisomerization of 1,6-enynes could be accomplished by using alkyl iodides as initial hydride sources under the palladium-catalyzed conditions. In our opinion, the alkyl iodides can transform into palladium (II) hydride [5,9] via SN 2 -type oxidative addition and βhydride elimination, and then the in situ formed palladium(II) hydride went through region-selective migratory insertion and intramolecular cyclization of 1,6-enynes containing terminal alkenes to give hetero-cyclic compounds.…”