1333116-46-3Relevant academic research and scientific papers
Catalyst-controlled diastereoselection in the hydrogenation of heterocycloalkyl ketones
Akashi, Masaya,Arai, Noriyoshi,Inoue, Tsutomu,Ohkuma, Takeshi
, p. 1955 - 1960 (2011)
α-Substituted chiral ketones that have small steric and electronic differences around the reaction sites are difficult substrates to reduce with high diastereoselectivity. Metal hydride reduction of 2-(4-benzoylmorpholinyl) phenyl ketone and 3-(1-tert-butoxycarbonylpiperidinyl) phenyl ketone using sodium borohydride, zinc borohydride, and potassium tri-sec-butylborohydride as reducing agents affords the syn- and anti-alcohols in a lower than 80:20 ratio. Hydrogenation of these ketones with a catalyst system of RuCl 2(BIPHEP)(DMEN) and potassium tert-butoxide in 2-propanol results in the syn-alcohols with ≥ 99:1 selectivity [BIPHEP=2,2′- bis(diphenylphosphino)biphenyl, DMEN=N,N-dimethylethylenediamine]. The marked difference in the diastereoselectivity suggests that the stereoselection in this hydrogenation is primarily regulated by the structure of the catalyst's reaction field ("catalyst-controlled diastereoselection") but not the internal stereocontrol of the substrates. This chemistry is applied to the asymmetric hydrogenation through dynamic kinetic resolution with a RuCl 2[(S)-BINAP][(R)-DMAPEN]/potassium tert-butoxide catalyst [BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, DMAPEN=2-dimethylamino-1-phenylethylamine]. A series of aryl heterocycloalkyl ketones has been converted to the alcohols in excellent diastereo- and enantioselectivities. The modes of catalyst-controlled diastereoselection and enantioselection are interpreted by using transition-state molecular models. (S,S)-Reboxetine, a selective norepinephrine uptake inhibitor, was synthesized from one of product alcohols. Copyright
