Rhodium-catalyzed [2+2+2] cycloaddition of various fluorine-containing alkynes—novel synthesis of multi-substituted fluoroalkylated aromatic compounds

Abstract

Treatment of various fluorinated internal alkynes with 10 mol% of RhCl(3).H(2)O and 30 mol% of i-Pr(2)NEt in toluene at the reflux temperature for 18 h gave the corresponding trimerization products as an isomeric mixture in high yields. Cycloaddition using 1.0 equiv. of fluorinated alkynes and 2.0 equiv. of non-fluorinated alkynes under the same reaction conditions as in the trimerization led to mono- and bis-fluoroalkylated benzene derivatives in high yields, together with small amounts of trimerization products. The reaction of fluorine-containing bispropargyl ether with non-fluorinated alkynes took place smoothly to afford the corresponding bicyclic molecules in good to high yields.

Practical Synthesis of α‐Trifluoromethylated Pyridines Based on Regioselective Cobalt‐Catalyzed [2+2+2] Cycloaddition using Trifluoromethylated Diynes with Nitriles

“…Methyl thiocyanate ( 1 m ) could also be applied successfully for this reaction (63%) under the modified reaction conditions using 100 mol% of Zn and 10 mol% of CoCl 2 (phen). It should be noted that various aliphatic nitriles which were not applicable in rhodium‐catalyzed system (Scheme 1, (b)), could also participate in the [2+2+2] cycloaddition well [9b] . When acetonitrile ( 1 n ) and isocapronitrile ( 1 o ) were used as a substrate, the corresponding trifluoromethylated pyridines 3 nA and 3 oA were obtained in 65% and 84% yield, respectively.…”

“…Our research group has reported that the [2+2+2] cycloaddition of the trifluoromethylated diyne with some nitriles in the presence of rhodium chloride and diisopropylethylamine leads to the construction of the corresponding multi‐substituted pyridine derivatives (Scheme 1, (b)) [9b] . However, a rare metal, rhodium, is extremely expensive, and this reaction requires the use of 10 mol% of the transition metal as well.…”

Recent Advances in Transition-Metal-Catalyzed [2+2+2]-Cyclo(co)trimerization Reactions

“…A recent example of a lack of regioselectivity is found in the synthesis of multisubstituted fluoroalkylated aromatic compounds reported by Ishihara and colleagues. 29 Nonetheless, the reported rhodium(I)-catalyzed reaction is an interesting example of broadening the substrate scope of transition-metal-catalyzed [2+2+2]-cyclotrimerization reactions.…”

Rhodium-Catalyzed [2+2+2] Cycloaddition of Alkynes for the Synthesis of Substituted Benzenes: Catalysts, Reaction Scope, and Synthetic Applications

“…21a,b Konno and co-workers reported that this rhodium(III) chloride plus amine system was also effective for the 1,2,4-selective [2+2+2] cycloaddition of trifluoromethyl-substituted arylacetylenes. 24…”

“…The same catalyst could be used for the synthesis of trifluoromethyl-substituted benzenes by way of [2+2+2] cycloaddition, as reported by Konno and co-workers (Schemes 43 and 44). 24 Although the reaction of terminal diynes and a trifluoromethyl-substituted alkyne proceeded in low yields (Scheme 43), the reaction of trifluoromethyl-substituted unsymmetrical diynes and alkynes proceeded in good yields with moderate regioselectivity (Scheme 44).…”