90162-44-0

A one-pot continuous-flow method for hydrogen (deuterium) generation and subsequent hydrogenation (deuterogenation) was developed using a stainless-steel (SUS304)-mediated ball-milling approach. SUS304, especially zero-valent Cr and Ni as constituents of the SUS304, and mechanochemical processing played crucial roles in the development of the reactions.

The catalytic properties of a series of ruthenium complexes for H/D exchange between D2O and alcohols were studied. The catalytic activity of the ruthenium complexes and the regioselectivity of the H/D exchange reactions were found to be dependent on the auxiliary ligands. While ruthenium η6-cymene complexes such as [(η6-cymene)RuCl(NH2CH2CH2NTs)]Cl, (η6-cymene)RuCl2/NH2CH2CH2OH, and (η6-cymene)Ru{(S,S)-NHCHPhCHPhNTs} catalyzed regioselective deuteration of alcohols with D2O at the β-carbon positions only, octahedral ruthenium complexes such as RuCl2(2-NH2CH2Py)(PPh3)2 (2-NH2CH2Py = 2-aminomethylpyridine) and RuCl2(NH2CH2CH2NH2)(PPh3)2 catalyzed regioselective H/D exchange reactions of D2O with alcohols at both the α- and β-carbon positions of alcohols. The H/D exchange reactions proceed through reversible dehydrogenation of alcohols and hydrogenation of carbonyl compounds involving hydride species and H/D exchange among D2O and carbonyl and hydride species. The different regioselectivities of the H/D exchange reactions can be related to the relative ease of H/D exchange of ruthenium hydride intermediates with D2O. (Chemical Equation Presented).

Nickel(0) nanoparticles, generated from nickel(II) chloride, lithium powder and a catalytic amount of 4,4-di-tert-butylbiphenyl (DTBB) in THF at room temperature, have been found to promote the reduction of a variety of ketones and aldehydes by transfer hydrogenation using isopropanol as the hydrogen donor. The nickel nanoparticles were characterised and could be re-utilised with a good performance in the absence of a base. A mechanistic study demonstrates that the reaction proceeds through a dihydride-type mechanism.

The racemization of sec-alcohols catalyzed by pentaphenylcyclopentadienyl- ruthenium complex 3 a has been investigated. The mechanism involves ruthenium-alkoxide intermediates: reaction of tert-butoxide ruthenium complex 4 with a series of sec-alcohols with different electronic properties gave ruthenium complexes bearing a secondary alkoxide as a ligand. The characterization of these alkoxide complexes by NMR spectroscopy together with a study of the reaction using in situ IR spectroscopy is consistent with a mechanism in which the alkoxide substitution step and the β-hydride elimination step occur without CO dissociation. The alkoxide substitution reaction is proposed to begin with hydrogen bonding of the incoming alcohol to the active ruthenium-alkoxide intermediate. Subsequent alkoxide exchange can occur via two pathways: i) an associative pathway involving a η3-CpRu intermediate; or ii) a dissociative pathway within the solvent cage. Racemization at room temperature of a 1:1 mixture of (S)-1-phenylethanol and (5)-1-phenyl-[D4]-ethanol gave only rac-1-phenylethanol, and rac-1-phenyl-[D4]-ethanol, providing strong support for a mechanism in which the substrate stays coordinated to the metal center throughout the racemization, and does not leave the coordination sphere. Furthermore, racemization of a sec-alcohol bearing a ketone moiety within the same molecule does not result in any reduction of the original ketone, which rules out a mechanism where the intermediate ketone is trapped within the solvent cage. These results are consistent with a mechanism where η3-Ph5C5-ruthenium intermediates are involved. Competitive racemization on nondeuterated and α-deuterated α-phenylethanols was used to determine the kinetic isotope effect k H/kD for the ruthenium-catalyzed racemization. The kinetic isotope effect kH/kD for p-X-C6H 4CH(OH)CH3 was 1.08, 1.27 and 1.45 for X = OMe, H, and CF3, respectively.

Deuteriated 1-phenylethanols were prepared by reductive dehalogenation of the corresponding halogenoacetophenones with Raney Ni-Al and Cu-Al alloys in 5percent NaOD-D2O solution.It was found that the Ni-Al alloy introduced greater than expected numbers of deuterium atoms in the phenyl ring, but the expected deuteriated 1-phenylethanols were obtained in high yield and in high isotopic purity when Raney Cu-Al alloy was used.