Halogen Atoms as Reactive Centers for the Introduction of Functional Side Chains into (Arene)ruthenium(0) Complexes

Abstract

Substitution of the naphthalene ligand of [(COD)(η 6 -naphthalene)Ru] (2) (COD = 1,5-cyclooctadiene) by suitable haloarenes (halogen = F, Cl, Br, I) affords several new monoand dihaloarene(cyclooctadiene)ruthenium complexes. Depending on the number and position of the halogen and organyl substituents, the haloarenes form achiral or planarchiral π-ligands; [(η 6 -bromoarene)(COD)Ru] complexes are prone to rapid bromine/lithium exchange with nBuLi at low temperatures, while the chloro and fluoro derivatives undergo ortho-metalation under the same conditions. The lithiated species react readily with chiral or achiral electrophiles such as chlorodiorganophosphanes, carbonyl chlorides, aldehydes, lactones, ketones, and epoxides to yield subIntroduction (Arene)ruthenium(0) complexes are useful catalysts for hydrogenation, [2,3] isomerization, [4] and dimerization [5,6] reactions of alkenes. Their (arene)ruthenium() counterparts catalyze enantioselective hydrogen transfer to ketones [7,8] and imines [9] in the presence of enantiomerically pure chiral β-amino alcohols [7] or 1,2-diamines, [8,9] affording high yields and high ees at the same time. Thanks to the particular stability of the areneϪmetal bond, [10] (arene)ruthenium complexes may be converted from Ru 0 into Ru II without the loss of the arene ligand, simply by addition of hydrochloric acid.[2] Only the co-ligands that complete the coordination sphere are exchanged in parallel with the redox process. Of course, it would be very promising to perform the catalytic reactions of (arene)ruthenium complexes in both redox states with enantiopure species whose chirality was connected with the arene ligand. The preparation of [(η 6 -arene)-(COD)Ru] complexes is well known since the work of Bennett, Vitulli, and Pertici, [3,11,12] [13] The lithiated species can be treated with alkyl chloroformates to form ester-substituted [(η 6 -arene)(COD)Ru] compounds. Through the introduction of chiral alkyl chloroformates [alkyl ϭ (Ϫ)-menthyl], this directly affords enantiopure asymmetric complexes. To develop the high potential of this approach, we investigated the preparation and reactivity of (mono-and dihaloarene)ruthenium() complexes systematically. These allow the introduction of many electrophiles of choice. Examples are provided for chlorodiorganophosphanes, carbonyl chlorides, aldehydes, lactones, ketones, and epoxides. Novel (arene)ruthenium() complexes with donor functions such as PR 2 and OH in the side chain are of interest, as these functions should offer the potential to control the reactivity of the different types of (arene)ruthenium catalysts. Results and Discussion Preparation of [(COD)(η 6 -haloarene)Ru] ComplexesMono-or dihaloarenes (fluorobenzene, 1,3-difluorobenzene, 3-fluorotoluene, 3-chlorotoluene, 1,4-dichlorobenzene, 2-bromo-1,4-xylene, 1,3-dibromobenzene, 1-bromo-4-fluorobenzene, 1-bromo-4-iodobenzene, and 4,4Ј-difluoro-1,1Ј-biphenyl) replace the naphthalene ligand of [(COD)(η 6 -naphthalene)Ru] (2) in the presence of acetonitrile at room temperatur...

Tuning the Efficacy of Ruthenium(II)-Arene (RAPTA) Antitumor Compounds with Fluorinated Arene Ligands

“…Compound 1 is converted to the reactive ruthenium(0) species [Ru(η 6 -napthalene)(η 4 -cod)] using a modified but established procedure reported by the groups of Bennett and Vitulli . This compound readily undergoes facile exchange of the 10-electron naphthalene ligand with the appropriate fluoroarene, in the presence of a small amount of acetonitrile, to give [Ru(η 6 -fluoroarene)(η 4 -cod)] (fluoroarene = C 6 H 5 F 2a , C 6 H 5 CF 3 2b , 1,4-C 6 H 4 CH 3 F 2c , and 1,4-C 6 H 4 F 2 2d ) . In all cases, chromatographic separation was required using slightly basic alumina as the stationary phase and eluting with pentane.…”

“…In all cases, chromatographic separation was required using slightly basic alumina as the stationary phase and eluting with pentane. Compound 2a and meta analogues of 2c and 2d , i.e., [Ru(η 6 -1,3-C 6 H 4 CH 3 F)(η 4 -cod)] and [Ru(η 6 -1,3-C 6 H 4 F 2 )(η 4 -cod)], are known compounds . While the mono- and difluoro complexes were successfully prepared by the described method, 1,3,5-trifluorobenzene proved to be too weakly coordinating to displace the naphthalene ligand, with attempts involving low-pressure hydrogenation of [Ru(η 4 -cot)(η 4 -cod)] (cot = cyclooctatetraene) also proving unsuccessful …”

“…Compounds 2a − 2d were prepared using the method described by Bodes et al The complex [Ru(η 6 -C 10 H 8 )(η 4 -C 8 H 12 )] (1.083 g, 3.2 mM) and the appropriate arene (20 mL, Acros, degassed and dried over 4 Å molecular sieves) were stirred in THF (10 mL, dried and degassed) and MeCN (0.833 g, extra dry quality from Acros) for 7−12 days. The brown solution became slightly lighter in color over time.…”

The crystal structure of 1-bromo-4-iodo-benzene, C6H4BrI

“…The structure of the latter has been determined previously [17]; however, the chosen technique of powder diffraction precluded the availability of 3D coordinates. Furthermore, structural information about the title compound as a ligand in a ruthenium coordination compound [18] as well as a co-crystallizate with a derivative of pyridine [19] is available. The title structure shows the presence of a parasubstituted derivative of benzene featuring a bromo as well as an iodo substituent.…”

New arene ruthenium complexes with planar chirality

“…Areneruthenium complexes with planar chirality have been studied first by Bennett and co-workers [2]. They are of great interest because of their potential as chiral catalysts for asymmetric synthesis [3][4][5].…”