General Asymmetric Hydrogenation of α-Branched Aromatic Ketones Catalyzed by TolBINAP/DMAPEN−Ruthenium(II) Complex

Arai, Noriyoshi; Ooka, Hirohito; Azuma, Keita; Yabuuchi, T.; Kurono, Nobuhito; Inoue, and Tsutomu; Ohkuma, Takeshi

doi:10.1021/ol070125+

Cited by 62 publications

(19 citation statements)

References 22 publications

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“…Ru complex (S,R)-11 (1.9 mg, 2 mmol), [14] ketone 1c (11.57 g, 40 mmol), and 2-propanol (38.8 mL) were placed in a 200-mL SUS autoclave with a stirring propeller. A solution of t-C 4 H 9 OK in 2-propanol (1 M, 1.2 mL, 1.2 mmol) was added to the autoclave, and the contents in the autoclave were degassed.…”

Section: Methodsmentioning

confidence: 99%

“…[13,14] When (AE)-1a (4.45 g, 15 mmol) was hydrogenated with (S,R)-11 (S/C = 5000) in t-C 4 H 9 OK containing 2-propanol under 50 atm of H 2 for 20 h, the syn-alcohol (1R,2S)-2a (2a/3a = > 99:1) was obtained in 99% ee quantitatively (entry 1). Both the diastereoface and enantioface selections of 1a were successfully performed by the (S,R)-11/t-C 4 H 9 OK catalyst with a rapid stereomutation at the a chiral center of 1a.…”

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Catalyst‐Controlled Diastereoselection in the Hydrogenation of Heterocycloalkyl Ketones

et al. 2011

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a-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 A C H T U N G T R E N N U N G (BIPHEP)A C H T U N G T R E N N U N G (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 catalysts 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 aA 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 transitionstate molecular models. (S,S)-Reboxetine, a selective norepinephrine uptake inhibitor, was synthesized from one of product alcohols.Keywords: diastereoselectivity; enantioselectivity; hydrogenation; ketones; reboxetine; ruthenium Diastereoselective reduction of a-substituted chiral ketones to the 1,2-syn-or 1,2-anti-alcohols is a fundamental and indispensable reaction in modern organic synthesis.[1] Metal hydride reducing agents have made notable contributions to advance this important class of chemistry. The stereoselective outcome has been explained by using transition-state molecular models, such as the Felkin-Anh model and the chelation-controlled model (Figure 1). [1][2][3] In both cases the metal hydride reagent is recognized as just a hydride, and it reacts within the region of the substrate molecules. Therefore, the intramolecular stereoinduction principally depends on the substrate structure (substrate control), but not the shape of the metal hydrides (reagent control).[4] High diastereoselectivity in this reaction is achieved only when the substrates have a-substituents (L, M, S, and X) with marked differences in size and/or electronic properties. Thus, we thought that a new conceptual approach is required to develop a general method for the diastereoselective reduction of a-substituted ketones.We selected heterocycloalkyl ketones 1a and 1c as substrates to examine the diastereoselective ability of reducing agents [Eq. (1)]. The small electronic and Figure 1. Typical transition-state models in the diastereoselective hydride reduction of a-substituted chiral ketones. L, M, and S = large-, medium-, and small-sized substituents, respectivel...

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Section: Methodsmentioning

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Catalyst‐Controlled Diastereoselection in the Hydrogenation of Heterocycloalkyl Ketones

et al. 2011

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“…When this catalyst system was applied to asymmetric hydrogenation of racemic 2-(benzoylmethylamino)propiophenone, the (1R,2R)-amido alcohol (syn: anti = >99:1) in 98% ee was obtained through base-assisted dynamic kinetic resolution (Scheme 17). 23 The reaction of 2-(pivaloylamino)propiophenone proceeded in the same way. The excellent syn selectivity is explained by the Felkin-Anh model with a bulky metal hydride.24 The (S)-To1BINAP/(R)-DMAPEN-Ru(II) catalyzed hydrogenation of racemic benzoin methyl ether preferentially gave the 1R,2S alcohol (syn:anti = 3:97) in 98% ee.…”

Section: Catalysts For Construction Of Various Chiral Environmentsmentioning

confidence: 99%

Tailor-made Catalysts for Asymmetric Hydrogenation of Ketones

Ohkuma

2007

J. Syn. Org. Chem., Jpn.

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“…Since then, the asymmetric hydrogenation of the conformationally anchored racemic α-substituted cycloalkanones has received intensive attention; excellent enantioselectivities and diastereoselectivities have been achieved [13][14][15][16][17][18][19]. High enantioselectivities and diastereoselectivities have also been obtained in the asymmetric hydrogenation of racemic α-substituted arylketones with RuCl 2 -diphosphine/diamine catalysts [20,21]. However, the asymmetric hydrogenation of conformationally flexible racemic α-substituted acyclic dialkyl ketones is far from success.…”

Section: Introductionmentioning

confidence: 99%

Chiral ruthenium-SDPs/diamine complexes-catalyzed enantioselective hydrogenation of α-alkyl arylacetones via dynamic kinetic resolution

et al. 2009

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The asymmetric hydrogenation of the conformationally flexible racemic α-substituted acyclic dialkyl ketones via dynamic kinetic resolution (DKR) has been developed by using Ru-SDPs/diamine catalysts. Chiral alcohols were produced in high yields with good to excellent enantioselectivities (85%-97% ee) and diastereoselectivities (up to 97:3). This hydrogenation reaction provided a new approach to the synthesis of the key intermediate of J-104118.

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General Asymmetric Hydrogenation of α-Branched Aromatic Ketones Catalyzed by TolBINAP/DMAPEN−Ruthenium(II) Complex

Cited by 62 publications

References 22 publications

Catalyst‐Controlled Diastereoselection in the Hydrogenation of Heterocycloalkyl Ketones

Catalyst‐Controlled Diastereoselection in the Hydrogenation of Heterocycloalkyl Ketones

Tailor-made Catalysts for Asymmetric Hydrogenation of Ketones

Chiral ruthenium-SDPs/diamine complexes-catalyzed enantioselective hydrogenation of α-alkyl arylacetones via dynamic kinetic resolution

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