Ruthenium-catalyzed anti-Markovnikov hydroamination of vinylarenes.
A ruthenium-catalyzed intermolecular, anti-Markovnikov hydroamination of vinylarenes with secondary aliphatic and benzylic amines is reported. The combination of Ru(cod)(2-methylallyl)2, 1,5-bis(diphenylphosphino)pentane, and triflic acid was the most effective catalyst of those tested. Control reactions conducted without ligand or acid did not form the amine. The reaction of morpholine, piperidine, 4-phenylpiperazine, 4-BOC-piperazine, 4-piperidone ethylene ketal, and tetrahydroisoquinoline with styrene in the presence of 5 mol % of this catalyst formed the corresponding beta-phenethylamine products in 64-96% yield, with 99% regioselectivity, and without enamine side products. Acyclic amines such as n-hexylmethylamine and N-benzylmethylamine reacted with styrene in 63 and 50% yields, respectively. Alkyl-, methoxy-, and trifluoromethyl-substituted styrenes reacted with morpholine in the presence of this catalyst or a related one containing 1,1'-bis(diisopropylphosphino)ferrocene as ligand to give the products in 51-91%. Further, the hydroamination of alpha-methyl styrene was observed for the first time with a homogeneous transition metal catalyst. Preliminary mechanistic studies showed that the reaction occurred by direct, irreversible, anti-Markovnikov hydroamination and that the mechanism of the ruthenium-catalyzed hydroamination is likely to be distinct from that of the recently reported rhodium-catalyzed reaction.
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, USA.
Masaru
M
Utsunomiya
John F
JF
Hartwig
D000586:Amination; D000588:Amines / Q000138:chemical synthesis*; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D009025:Morpholines / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D020058:Styrene / Q000737:chemistry; D014753:Vinyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D000588:Amines; D001593:Benzyl Compounds; D009025:Morpholines; D009942:Organometallic Compounds; D014753:Vinyl Compounds; D020058:Styrene; D012428:Ruthenium; C037574:morpholine