Ruthenium-Complex-Catalyzed N-(Cyclo)alkylation of Aromatic Amines with Diols. Selective Synthesis of N-(ω-Hydroxyalkyl)anilines of Type PhNH(CH₂)_nOH and of Some Bioactive Arylpiperazines

Abstract

A new class of well-defined neutral mono-, and dicationic ruthenium(II) complexes containing a neutral terdentate donor system [C 5 H 3 N(CH 2 E) 2-2,6] (E) PPh 2 (PNP) or NMe 2 (NN′N)) has been found effective as catalyst precursor in N-(cyclo)alkylation reactions of aromatic amines with diols Y(CH 2 CH 2 OH) 2 (Y) CH 2 , NR). With these catalysts, N-phenylpiperidine is synthesized from aniline and 1,5-pentanediol in 85% yield (at 180°C for 24 h in 1,4-dioxane). With neutral RuCl 2 (NN′N)-(PPh 3) as a catalyst precursor, aniline can be selectively N-monoalkylated with diols of the type HO(CH 2) n OH (n) 4-6, 10) to give N-(n-hydroxyalkyl)anilines in 40-75% yield. To our knowledge, this represents the first useful catalytic route to this type of compounds. The new catalysts can also be used in the synthesis of arylpiperazines. For example, N-phenyl-N′-methylpiperazine is obtained from aniline and MeN(CH 2 CH 2 OH) 2 in yields up to 34%. N-[m-(Trifluoromethyl)phenyl]-N′-methylpiperazine, TFMPMP, is successfully produced from m-(trifluoromethyl)aniline and MeN-(CH 2 CH 2 OH) 2 in 44% yield using monocationic [RuOTf(NN′N)(PPh 3)]OTf as the catalyst precursor. A mechanism for the N-(cyclo)alkylation reaction is proposed.

Neutral Tridentate PNP Ligands and Their Hybrid Analogues: Versatile Non‐Innocent Scaffolds for Homogeneous Catalysis

“…[61] This result can be related to the recent reactivity observed by Milstein and co-workers for analogous Ru complexes. [55] Gibson et al independently reported the formation of some Ru complexes with 12 tBu in 2004 (Scheme 13), [62] simultaneously with the first application of this catalyst system for the acceptorless dehydrogenation of alcohols by Milstein and co-workers.…”

Coordination of a Ru(II)-complex to a tetrafunctional P-ligand: a model for RuP carbosilane dendrimers

“…No peaks for any residual un-bounded dendritic phosphine groups were observed, suggesting high efficiency of metal loading on these organophosphine dendrimers. The spectrum of 7 resembled that of the corresponding PPh 3 complex [Ru(NN%N)PPh 3 Cl 2 ], which showed a signal at 37 ppm [4]. The coordination chemical shifts of 7 and 8 are 43.1 and 10.3 ppm, respectively.…”

“…In a previous study we found that mononuclear Ru(II) complexes, [Ru(NN%N)(PPh 3 )Cl 2 ] (1, NN%N = 2,6-bis[(dimethylamino)methyl]pyridine), are interesting catalysts for the cycloalkylation of aromatic amines with alcohols to give piperazines and piperidines [3].…”

“…Coordination of the Ru-complexes on the phosphine-functionalised CS-periphery and comprises a 2:1 reaction of the free phosphine ligand with the N 2 -bridged binuclear complex [{RuCl 2 (h 3 -NN%N)} 2 (m-N 2 )] (2) [4]. The inert PPh 3 Ru binding in 1 as well as its straightforward synthesis, prompted the present study which is directed to the synthesis of carbosilane (CS) dendrimers which carry a well-defined number of triarylphosphine or dicyclohexylphosphine ligands, and also the study of the binding of a RuCl 2 (NN%N)-unit to these phosphine ligands.…”

Neutrale dreizähnige PNP‐Liganden und deren Hybrid‐Analoga: vielseitige Liganden für die kooperative homogene Katalyse

“…[61] Dieses Resultat ähnelt den Ergebnissen von Milstein und Mitarbeitern für analoge Rutheniumkomplexe. [55] Gibson et al berichteten im Jahr 2004 davon unabhängig über die Bildung einiger Rutheniumkomplexe mit 12 tBu (Schema 13) [62] und deren erstmalige Anwendung bei der akzeptorfreien Dehydrierung von Alkoholen, was praktisch …”