Ruthenium(II)-Catalyzed Alkenylation of Ferrocenyl Ketones via C–H Bond Activation

Abstract

The alkenylation with alkyl acrylates of ferrocenyl alkyl ketones is performed with the [RuCl 2 (pcymene)] 2 /AgSbF 6 catalytic system and leads, via ferrocene C−H bond activation, to moderate yields of the 1,2-disubstituted ferrocene derivatives in the presence of Cu-(OAc) 2 ·H 2 O under aerobic conditions at 80−110°C. The alkenylation of ferrocenyl phenyl ketone, in contrast, takes place at room temperature to afford quantitative yields of the phenyl monoalkenylated product, demonstrating the strong influence of the ferrocenyl group on arene C−H bond functionalization. Small amounts of 2-alkenylferrocenyl 2′-phenyl ketones can also be obtained. F unctional ferrocene derivatives constitute a family of chemicals offering useful properties in several areas. They are the basis of practical ligands, 1 including planar chirality ligands for efficient enantioselective catalysis. 2 They have found applications in material science as metallocene-containing polymers 3 and as materials for optical applications. 4 Most of the synthetic methods functionalizing ferrocene involve either a Friedel−Crafts type electrophilic substitution or a stoichiometric C−H bond metalation followed by coupling with an electrophile. 5 It thus remains a challenge to develop new, general catalytic methods to derivatize the stable ferrocene derivatives.The direct catalytic sp 2 C−H bond activation/functionalization of arenes and heterocycles has considerably improved synthetic methods via selective C−C bond cross-couplings. 6 In contrast, simple ferrocene derivatives have shown resistance to their catalytic C−H bond functionalization, likely due to the electron richness of this metallocene and its inertness to C−H bond deprotonation via a concerted metalation−deprotonation process. 7 However, several examples of stoichiometric C−H bond activation of ferrocene derivatives leading to cyclometalated complexes have been reported. 8 Only a few reports have already demonstrated the possibility of catalytic ferrocene C−H bond functionalization leading to arylated and alkenylated products. Ferrocene itself was first alkenylated by Moritani and Fujiwara 9 with Pd(OAc) 2 catalyst in dioxane/AcOH solvent in modest yields. A cross-coupling reaction between two C−H bonds of ferrocenyloxazoline and of an arene has been performed using a stoichiometric amount of Pd(OAc) 2 , but in the additional presence of Cu(OAc) 2 the cross-coupling became catalytic and led to a good yield of the diarylated ferrocene. 10 Recently the direct alkenylation of ferrocene with acrylates has been observed with Pd(OAc) 2 catalyst in acetic acid, leading only to moderate yields in monoalkenylated ferrocenes. 11 In contrast, in the presence of a directing dimethylaminomethyl group, ferrocene C−H bonds were recently functionalized with Pd(II) catalyst on reaction with diarylacetylenes to give highly arylated naphthalenes, 12 and effective borylation of ferrocene C−H bonds has been performed with iridium catalyst. 13 Recently it was shown that stable and inexpensive ruthenium(II) cat...

Recent Advances in C–H Bond Functionalization with Ruthenium-Based Catalysts

“…The reaction proceeds in a highly regio-and stereoselective manner, resulting in the ortho-alkenylated product with acetophenone, but a mixture of mono-and dialkenylated products were observed for benzophenone. Subsequently, Singh and Dixneuf demonstrated the alkenylation of a ferrocenyl ketone using [RuCl 2 (p-cymene)] 2 /AgSbF 6 in the presence of Cu(OAc) 2 •H 2 O [125]. The reaction leads to the ortho-alkenylation of ferrocene C-H bond when ferrocenyl methyl ketone reacted with acrylate, obtaining a modest yield of the alkenylated product.…”

Selective Syntheses of Planar-Chiral Ferrocenes

“…378 Functionalized ferrocenes have been obtained by treatment with alkynes, 379 alkenes, 380 arenes, 381 arylboronic acids, 382 carbon monoxide, 383 and phosphides. 384 Gu, You, and co-workers, for example, converted ferrocene 53 into planar-chiral 1,2-disubstituted 268 in up to 99% ee by means of a palladium-catalyzed direct arylation with arylboronic acids (Scheme 80).…”

Recent advances in transition metal-catalyzed C–H bond functionalization of ferrocene derivatives

“…18 This dehydrogenative coupling is limited 40 to the use of alkyl substituted ketones (R 1 = alkyl group). Even though the reported yields are in all the cases modest (14-26%), this process represents the unique ruthenium-catalyzed C-H bond functionalization of ferrocene derivatives reported to date.…”