Conformational Control of Metallocene Backbone by Cyclopentadienyl Ring Substitution: A New Concept in Polyphosphane Ligands Evidenced by “Through-Space” Nuclear Spin−Spin Coupling. Application in Heteroaromatics Arylation by Direct C−H Activation

Abstract

The present study deals with the conformational control of the metallocene backbone within ferrocenyl polyphosphane ligands and their performance in the highly topical palladium-catalyzed heteroaromatics arylation by direct C-H activation. New substituted cyclopentadienyl rings were synthesized, which allowed the assembling of original tri-and diphosphanes. The bulky cyclopentadienyl lithium salts diphenylphosphino-3-(triphenyl)methylcyclopentadienyllithium (4) and 1,2-bis(diphenylphosphino)-4-(triphenyl)methylcyclopentadienyllithium (5) were prepared in excellent yield. The assembling of these new hindered cyclopentadienyl salts (Cp) with other Cp fragments was performed in order to prepare ferrocenyl ligands with controlled conformation. A comparison of conformations of 1,1′,2-tris(diphenylphosphino)-3′,4-di-tert-butylferrocene (3) and 1,1′,2-tris(diphenylphosphino)-3′-(triphenyl)methyl-4tert-butylferrocene (6) allowed us to determine, for the first time, the conditions of an efficient control of the orientation of the phosphino substituents on the ferrocene backbone in the absence of an ansabridge. The characterization of these metallo-ligands, by multinuclear NMR in solution and by X-ray diffraction in the solid state, focused on nonbonded J PP spin-spin couplings. These unusual couplings are especially useful for assessing the conformation of the ferrocene backbone in solution. The palladium complexes of the triphosphane ligand 6 and the diphosphane 1,1′-bis(diphenylphosphino)-3,3′-di(triphenyl)methylferrocene ( 7) were successfully used in the direct C-H activation of electron-rich heteroaromatics for coupling to demanding aryl bromides, whether electron rich and/or sterically congested. Products such as 2-butyl-5-(4-methoxyphenyl)furan (10), 2-butyl-5-o-tolylfuran (11), and thiophene analogues (12 and 13) were obtained in yields higher than 90%. The NMR examination of the reaction of [PdCl(η 3 -C 3 H 5 )] 2 with ligands 6 and 7 allowed us to determine the coordination chemistry of the precatalysts. The allylic palladium complexes 8 and 9 confirmed the unusual conformation present in 6. As a consequence, the selective and "genuinely" tridentate bonding of a triphosphane to one palladium center is reported. This seldom observed coordination mode is a direct consequence of the successful ferrocene backbone conformation control.

Highly Dispersed Palladium–Polypyrrole Nanocomposites: In‐Water Synthesis and Application for Catalytic Arylation of Heteroaromatics by Direct C–H Bond Activation

“…A fairly good conversion of 3‐bromotoluene was obtained after 20 h (entry 9, 60% conversion) with an excellent selectivity in 5‐arylated furan. These ligandless conditions did not promote the difficult oxidative addition of 2‐bromomesitylene to palladium;32 consequently no conversion of this reagent was observed . In order to get a better knowledge of our Pd@PPy catalytic system, several experiments and characterizations were conducted during catalysis and post‐catalysis, which are described in the following sections.…”

Highly Functionalized Ferrocenes

“…However, the analogous five‐functionalized triphosphines 23–25 – with a more constraint conformation – were found active in the use of demanding haloarenes such as aryl chlorides and congested aryl bromides. The ligands 23–25 associated with Pd have shown a very good activity for arylation of highly functionalized heteroaromatics with TONs up to 1 800 (Figure ) , , . Thus, ligand 25 was mainly used for bromoarene substrates, but by using triphosphine 23 , electron‐rich, electron‐poor and multifunctionalized furans, thiophenes, pyrroles or thiazoles were arylated by various chloroarenes at 0.1–0.5 mol‐% catalyst loadings.…”

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

“…[33] Hierso and co-workers had previously described that the C-5 arylation of furan 6 with aryl bromides could be achieved using allylic palladium complex 63 with a ferrocenyl ligand as the catalyst precursor (Scheme 26). [41] More recently, the direct C-5 arylation of 2-substituted furans, thiophenes and 1-methylpyrrole with aryl chlorides was performed using the robust and electron rich PCy 3 -carbene palladium complex 64. [42,43] As shown in Scheme 27, electron-rich aryl chlorides gave better yields than did electron-deficient aryl chlorides in complex 64-catalyzed arylations of furans 6 and 7b.…”

“…[42] On this subject it is worth noting that in a recent discussion of the parameters that govern the activation barriers of the C À H bond in heteroarenes, Gorelsky included furan in a class (Class II) for which heteroarene-catalyst electronic interaction energies define the most reactive C À H bonds and he reported that in arylation of furan Ca À H bonds are more reactive than Cb À H bonds in the CMD process due to more negative interaction energy at the Ca site. [45] We believe it is also useful to point out that, although intermolecular direct C-2 or C-5 arylation reaction of furans are strongly favoured, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]41,42,46] successful intermolecular Pd-catalyzed C-4 arylations of furan substrates have been described. Thus, in 2009, Zhu and co-workers found that 2,5-diaryl-3-fluorofurans 65 underwent C-4 arylation with a variety of aryl bromides in NMP at 110-120 8C in the presence of KOAc as the base and a catalytic amount of PdCl 2 A C H T U N G T R E N N U N G (PPh 3 ) 2 (Scheme 28).…”