Asymmetric Synthesis of Α-N,N-Dialkylamino Alcohols by Transfer Hydrogenation of N,N-Dialkylamino Ketones

Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 67 No. 6 pp. 717ñ721, 2010 ISSN 0001-6837 Polish Pharmaceutical Society

ASYMMETRIC SYNTHESIS OF α-N,N-DIALKYLAMINO ALCOHOLS BY TRANSFER HYDROGENATION OF N,N-DIALKYLAMINO KETONES

TOMASZ KOSMALSKI

Department of Organic Chemistry, Collegium Medicum, Nicolaus Copernicus University, M. Curie-Sk≥odowska 9, 85-067, Bydgoszcz, Poland

Keywords: β-amino alcohols, Noyori`s catalyst, asymmetric transfer hydrogenation (ATH)

β-Amino alcohols are important physiological- instrument. MS spectra were recorded on an AMD ly active compounds (1, 2a,b), also used as ligands 604 spectrometer. Optical rotations were measured (3, 4), and precursors of oxazaborolidines (5). on an Optical Activity PolAAr 3000 automatic Various methods for their asymmetric synthesis, polarimeter. GC analyses were performed on a such as the reduction of α-functionalized ketones Perkin-Elmer Auto System XL chromatograph, with hydrides (6, 7), catalytic hydrogenation of HPLC analyses were performed on a Shimadzu LC- amino ketones (8), reduction with borane/oxaza- 10 AT chromatograph. Melting points were deter- borolidines (9, 10), and other approaches (11ñ13) mined in open glass capillaries and are uncorrected. have been developed. However, the existing meth- Elemental analyses were performed by the ods are not ideal. For example, chiral β-chloro Microanalysis Laboratory, Institute of Organic hydrins, obtained by the reduction of α-chloro Chemistry, Polish Academy of Sciences, Warszawa. ketones, can be transformed into β-amino alcohols Silica gel 60, Merck 230ñ400 mesh was used for by treatment with secondary amines, however, mix- preparative column chromatography. Macherey- tures of isomers are sometimes formed (14). Nagel Polygram Sil G/UV254 0.2 nm plates were Asymmetric transfer hydrogenation (15, 16) used for analytical TLC. (ATH) of functionalized ketones is a new alternative RuCl[(R,R)-TsDPEN](η-p-cymene) was pre- η to the above mentioned methods (17). Recently, a pared from [RuCl2( -p-cymene)]2 and (1R,2R)-N-p- highly enantioselective ATH of α-imidazole-substi- tolylsulfonyl-1,2-diphenylethylenediamine tuted acetophenone was reported (18, 19). (TsDPEN) according to the literature (14, 20). Continuing my earlier work on ATH of α-dialkylamino ketones, this study extends the ATH with formic 2-(Dimethylamino)-1-phenylethanone (1) acid/triethylamine 5 : 2, catalyzed with RuCl[(R,R)- Prepared from 1-phenyl-2-bromoethanone and TsDPEN](p-cymene), to β-dimethylaminopropiophe- dimethylamine in benzene/diethyl ether, 12 h, room none and γ-dimethylaminobutyrophenone, representa- temperature, 60% yield, b.p. 76ñ78OC/0.5 mmHg. tives of β- and γ-dialkylamino ketones. [Lit. (17, 21) 130ñ132OC/20 mmHg]. 1H NMR (300 δ MHz, CDCl3, , ppm): 2.38 (s, 6 H, CH3), 3.76 (s, 2 EXPERIMENTAL H, CH2), 7.45 (tm, J = 7.2 Hz, 2 H, CH), 7.56 (tt, J = 7.2 Hz, J = 1.5 Hz, 1 H, CH), 7.99 (ddd, J = 7.2 Materials and methods Hz, J = 2.1 Hz, J = 1.5 Hz, 2 H, CH). 13C NMR (75

Experiments with air sensitive materials were MHz, CDCl3, d, ppm): 45.83 (2◊CH3), 65.61 1 13 carried under argon atmosphere. H and C NMR (CH2N), 128.09 (2◊CH), 128.53 (2◊CH), 133.16 spectra were recorded on a Varian Gemini 200 mult- (CH), 135.99 (C), 196.84 (CO). IR: 1677 cm-1, CO inuclear instrument and on a Bruker AMX 300 MHz (liquid film).

* Corresponding author: e-mail: [email protected]

717 718 TOMASZ KOSMALSKI

1-Phenyl-2-(piperidin-1-yl)ethanone (2) 3.5 h, room temperature, yield 64%, hydrochloride, Prepared from 1-phenyl-2-bromoethanone and m.p. 98ñ100OC [lit. m.p. 100OC (17, 23)]. 1H NMR O δ piperidine in benzene/diethyl ether, 9 h, 45 C, 79% (300 MHz, CDCl3, , ppm): 2.37 (s, 6 H, CH3), 3.72 O yield, b.p. 110ñ112 C/0.3 mmHg [lit. (17, 21) (s, 2 H, CH2), 3.92 (s, 3 H, OCH3), 3.93 (s, 3 H, O 1 δ 134ñ136 C/1 mm Hg]. H NMR (300 MHz, CDCl3, , OCH3), 6.86 (d, J = 8.2 Hz, 1 H, CH), 7.55 (d, J = ppm): 1.45 (quin., J = 5.4 Hz, 2 H, CH2), 1.64 (quin., 2.2 Hz, 1 H, CH), 7.66 (dd, J = 2.2 Hz, J = 8.2 Hz, 13 δ J = 5.4 Hz, 4 H, CH2), 2.53 (t, J = 5.4 Hz, 4 H, CH2), 1 H, CH). C NMR (75 MHz, CDCl3, , ppm): 3.77 (s, 2 H, CH2N), 7.44 (tm, J = 7.5 Hz, 2 H, CH), 45.72 (2◊NCH3), 55.97 (OCH3), 56.03 (OCH3), 7.56 (tt, J = 7.5 Hz, J = 1.5 Hz, 1 H, CH), 8.02 (dm, 65.30 (CH2), 110.09 (CH), 110.53 (CH), 122.80 13 δ J = 7.2 Hz, 2 H, CH). C NMR (75 MHz, CDCl3, , (CH), 129.38 (C), 149.10 (C), 153.44 (C), 195.40 ppm): 23.96 (CH2), 25.77 (2 ◊ CH2N), 54.83 (2◊CH2), (CO). 65.32 (CH2N), 128.14 (2◊CH), 128.44 (2◊CH), 133.05 (CH), 136.23 (C), 196.85 (CO). 3-(Dimethylamino)-1-phenylpropan-1-one (6) Prepared from 3-chloropropiophenone and 2-(Dimethylamino)-1-(2-naphthyl)ethanone (3) dimethylamine in diethyl ether with addition of Prepared from 1-(2-naphthyl)-2-bromoethan- sodium iodide, reflux 48 h, yield 72%, b.p. one and dimethylamine in diethyl ether, ñ10OC, 30 78ñ83OC/1 mmHg [lit. b.p. 94ñ97OC/7 mmHg (24)]. 1 δ min., room temperature 4 h, yield 86%, hydrochlo- H NMR (300 MHz, CDCl3, , ppm): 2.29 (s, 6 H, O O ride m.p. 215ñ217 C [lit. (17, 22) m.p. 216ñ217 C]. CH3), 2.76 (t, J = 7.2 Hz, 2 H, CH2), 3.60 (t, J = 7.2 1 δ H NMR (300 MHz, CDCl3, , ppm): 2.44 (s, 6 H, Hz, 2 H, NCH2), 7.46ñ7.57 (m, 3 H, CH), 7.97 (dm, 13 δ CH3), 3.91 (s, 2 H, NCH2), 7.54 (td, J = 7.5 Hz, J = J = 7.4 Hz, 2 H, CH). C NMR (75 MHz, CDCl3, , 1.5 Hz, 1 H, CH), 7.60 (td, J = 7.5 Hz, J = 1.5 Hz, ppm): 36.71 (CH2), 45.32 (CH3), 54.19 (NCH2), 1 H, CH), 7.82ñ7.92 (m, 2 H, CH), 7.96 (dm, J = 8.7 127.84 (2 ◊ CH), 128.40 (2◊CH), 132.84 (CH), Hz, 1 H, CH), 8.04 (dd, J = 8.7 Hz, J = 1.8 Hz, 1 H, 136.76 (C), 198.85 (CO). CH), 8.54 (d, J = 1.5 Hz, 1 H, CH). 13C NMR (75 δ MHz, CDCl3, , ppm): 45.73 (2◊CH3), 65.53 4-(Dimethylamino)-1-phenylbutan-1-one (7) (NCH2), 123.76 (CH), 126.62 (CH), 127.64 (CH), Prepared from 4-chlorobutyrophenone and 128.25 (CH), 128.35 (CH), 129.48 (CH), 129.62 dimethylamine in benzene with addition of sodium (CH), 132.34 (C), 133.22 (C), 135.52 (C), 196.66 iodide, reflux 48 h, yield 52%, b.p. 86ñ88OC/1 (CO). mmHg [lit. b.p. 122ñ125OC/0.5 mmHg (25)]. 1H δ NMR (300 MHz, CDCl3, , ppm): 1.91 (quin., J = 1-(Naphthalen-2-yl)-2-(piperidin-1-yl)ethanone (4) 7.2 Hz, 2 H, CH2), 2.24 (s, 6 H, CH3), 2.37 (t, J = Prepared from 1-(2-naphthyl)-2-bromoethan- 7.2 Hz, 2 H, CH2), 3.03 (t, J = 7.2 Hz, 2 H, NCH2), one and piperidine in diethyl ether with catalytic 7.45 (tdd, J = 7.2 Hz, J = 1.8 Hz, J = 1.5 Hz, 2 H, amount of sodium iodide (0.1 g), 4 h, room tempera- CH), 7.55 (tdd, J = 7.5 Hz, J = 1.8 Hz, J = 1.2 Hz, ture, yield 73%, m.p. 80ñ82OC [lit. (22) m.p. 84OC]. 1 H, CH), 7.98 (tdd, J = 7.5 Hz, J = 1.8 Hz, J = 1.5 1 δ 13 δ H NMR (300 MHz, CDCl3, , ppm): 1.46 (m, 2 H, Hz, 2 H, CH). C NMR (75 MHz, CDCl3, , ppm): CH2), 1.65 (m, 4 H, CH2), 2.56 (t, J = 7.2 Hz, 4 H, 22.08 (CH2), 36.16 (CH2), 45.34 (CH3), 58.91 NCH2), 3.88 (s, 2 H, CH2), 7.51 (d, J = 7.8 Hz, 1 H, (NCH2), 127.95 (2◊CH), 128.44 (2◊CH), 132.81 CH), 7.53 (td, J = 6.6 Hz, J = 1.2 Hz, 1 H, CH), 7.58 (CH), 136.98 (C), 200.05 (CO). (td, J = 6.6 Hz, J = 1.2 Hz, 1 H, CH), 7.65 (d, J = 8.7 Hz, 1 H, CH), 7.95 (d, J = 7.5 Hz, 1 H, CH), 8.05 (R)-(ñ)-2-(Dimethylamino)-1-(phenyl)ethanol (dd, J = 8.7 Hz, J = 1,8 Hz, 1 H, CH), 8.57 (s, 1 H, (1a): typical procedure 13 δ CH). C NMR (50 MHz, CDCl3, , ppm): 23.93 To a solution of 1 (1.63 g, 10 mmol) in ethyl η (CH2), 25.79 (2◊CH2), 54.87 (2◊NCH2), 65.53 acetate (5 mL), RuCl[(R,R)-TsDPEN]( -p-cymene) (NCH2) 123.94 (CH), 126.55 (CH), 127.63 (CH), (25 mg, 0.025 mmol, S/C 400:1), triethylamine (0.1 128.12 (CH), 128.27 (CH), 129.50 (CH), 129.73 mL), and an azeotropic mixture of formic acid-tri- (CH), 132.37 (C), 133.52 (C), 135.49 (C), 196.89 ethylamine 5 : 2 (2.5 mL) were added under argon at (CO). IR (heksachlorobutadiene): 1676 cm-1, CO. room temperature. The mixture was stirred for 5 days. The solvent was removed under reduced pres- 1-(3,4-Dimethoxyphenyl)-2-(dimethylamino) sure and 2 M sodium hydroxide (10 mL) was added ethanone (5) and the mixture was extracted with diethyl ether (2 Prepared from 1-(3,4-dimethoxyphenyl)-2- ◊ 40 mL) The combined extracts were washed with bromoethanone and dimethylamine in diethyl ether, water (10 mL), saturated with brine (5 mL) and Asymmetric synthesis of α-N,N-dialkylamino alcohols by transfer... 719 dried with anhydrous magnesium sulfate. The final (R)-(ñ)-1-(Naphthalen-2-yl)-2-(piperidin-1-yl)- product was isolated by distillation; 0.95 g, 58% ethanol (4a) yield, b.p. 66ñ68OC/1 mmHg. An analytical sample Yield 61 %, m.p. 106ñ107OC (purified on chro- was purified by preparative gas chromatography, matography column, from ethyl acetate-hexane 1 : 2, α α 20 [ ] ñ72.30 (c 1.536, MeOH), > 97% ee. Lit. (17, 26) v/v), [ ]D ñ63,8 (c 0,96, CHCl3), > 95% ee. The signals [α] +74,8 (c 0.95, MeOH, S enantiomer), 99 % ee. werenít separated in HPLC analyses on an OD-H and GC analysis on a chiral column Supelco β-DEX 325 OJ columns. Lit. (28) m.p. 110ñ112OC for the race- O α 20 30 m◊0.25 mm, isotherm 105 C, > 97%, tR 44.5 R, mate, [ ]D ñ66.4 (c 1.00, CHCl3), R enantiomer, 99% 1 1 δ 45.9 S. The racemate was also analyzed. H NMR ee. H NMR (300 MHz, CDCl3, , ppm): 1.50 (m, 2 H, δ (300 MHz, CDCl3, , ppm): 2.35 (s, 6 H, 2◊CH3), CH2), 1.55ñ1.72 (m, 4 H, CH2), 2.43 (m, 2 H, NCH2), 2.37 (dd, J = 12.2 Hz, J = 3.8 Hz, 1 H, NCH2), 2.49 2.48 (dd, J = 10.5 Hz, J = 12.6 Hz, 1 H, NCH2), 2,59 (dd, J = 12.2 Hz, J = 10.2 Hz, 1 H, NCH2), 3.95 (bs, (dd, J = 3.6 Hz, J = 12.6 Hz, 1 H, NCH2), 2.75 (m, 2 1 H, OH) 4.69 (dd, J = 10.2 Hz, J = 3.8 Hz, 1 H, H, NCH2), 4.90 (dd, J = 3.6 Hz, J = 10.5 Hz, 1 H, CH), OCH), 7.20ñ7.40 (m, 5 H, CH). 13C NMR (75 MHz, 7.44ñ7.50 (m, 3 H, CH), 7.81ñ7.86 (m, 4 H, CH). 13C δ δ CDCl3, , ppm): 45.21 (2◊CH3), 67.54 (NCH2), NMR (75 MHz, CDCl3, , ppm): 24.20 (CH2), 26.06 69.48 (CH), 125.75 (2◊CH), 127.27 (CH), 128.16 (2◊CH2), 54.49 (2◊NCH2), 66.77 (NCH2), 68.75 (2◊CH), 142.28 (C). (OCH), 123.99 (CH), 124.54 (CH), 125.59 (CH), 125.95 (CH), 127.63 (CH), 127.85 (CH), 127.97 (CH), (R)-(-)-1-Phenyl-2-(piperidin-1-yl)ethanol (2a) 132.95 (C), 133.34 (C), 139.93 (C). Yield 63%, m.p. 83ñ84OC (from n-hexane), α 29 [ ]D ñ80.50 (c 1.05, CHCl3). Lit. (17, 26) m.p. (R)-(ñ)-1-(3,4-Dimethoxyphenyl)-2-(dimethyl- O α 25 84ñ84.5 C. Lit. (27) (S)-isomer, [ ]D +81.4 (c 1.0, amino)ethanol (5a) O CHCl3). GC analysis on a chiral column Supelco Yield 55%, m.p. 63.0ñ63.5 C (from diethyl O α 24 Beta-DEX 325, 30 m, 0.25 mm, isotherm 140 C, ether/n-hexane, 1:1, v/v). [ ]D ñ43.75 (c 2.00, O α 25 99% ee, tR 63.0 R, 64.7 S, 99% ee. Racemate was EtOH). Lit. (17, 23) m.p. 66ñ67.5 C, [ ]D ñ42.6 (c 1 δ also analyzed. H NMR (200 MHz, CDCl3, , ppm): 2,00, EtOH). HPLC analysis on a chiral OD-H col- 1.50 (quintet, J = 5.6 Hz, 2H, CH2), 1,60ñ1.75 (m, umn n-hexane/isopropanol, 90:10, v/v + 0.5% O 4H, 2 CH2), 2.39 (dd, J = 12.6 Hz, J = 10.2 Hz), 1H, Et2NH, 0.6 mL/min, 15 C, 98% ee, tR 18.39 R, 28.70 1 δ CH2N), 2.30ñ2.50 (m, 2H, CH2), 2,50 (dd, J = 12.6, S. H NMR (300 MHz, C6D6, , ppm): 1.98 (s, 6H, J = 4.0 Hz, 1H, CHN), 2.60ñ2.80 (m, 2H, CH2), 3.95 CH3), 2.17 (dd, J = 12.0, J = 3.3 Hz, 1H, NCH2), (bs, 1H, OH), 4.72 (dd, J = 10.2, J = 4.0 Hz, 1H, 2.39 (dd, J = 12.3 Hz, J = 10.5 Hz, 1H, NCH2), 3.43 13 OCH), 7.20ñ7.40 (m, 5H, CH). C NMR (50 MHz, (s, 3H, CH3), 3.47 (s, 3H, CH3), 3.95 (s, 1H, OH), δ CDCl3, , ppm): 24.26 (CH2), 26.11 (2CH2), 54.45 4.71 (dd, J = 10.5 Hz, J = 3.3 Hz, 1H, OCH), 6.69 (CH2N), 66.90 (CH2N), 68.65 (OCH), 125.83 (d, J = 8.1 Hz, 1H, CH), 6.97 (dd, J = 8.1 Hz, J = (2◊CH), 127.32 (CH), 128.26 (2◊CH), 142.49 (C). 2.1 Hz, 1H, CH), 7.13 (d, J = 2.1 Hz, 1H, CH). 13C δ NMR (75 MHz, CDCl3, , ppm): 45.28 (2◊NCH3), (R)-(ñ)-2-(Dimethylamino)-1-(2-naphthyl)ethan- 55.82 (OCH3), 55.90 (OCH3), 67.55 (NCH2), 69.27 ol (3a) (OCH), 109.01 (CH), 110.98 (CH), 118.86 (CH), Yield 60 %, m.p. 64ñ66OC (from ethyl 134.86 (C), 148.34 (C), 149.02 (C). α 23 acetate), [ ]D ñ56.0 (c 1.11, MeOH). Lit. (17, 21) m.p. 53OC, racemate. HPLC analysis on a chiral (S)-(ñ)-4-(Dimethylamino)-1-(phenyl)butan-1-ol OD-H column, n-hexane/isopropanol, 98 : 2, v/v + (7a) O O α 21 0.5% Et2NH, 0.4 mL/min, 25 C, 98.0% ee, tR 15.5 Conversion 51%, b.p. 86ñ90 C/0.2 mmHg, [ ]D R, 17.4 S. Racemate was also analyzed. 1H NMR ñ14,1 (c 3.33, cyklopentane). GC analysis on a chiral δ β (200 MHz, CDCl3, , ppm): 2.41 (s, 6H, CH3), 2.47 column Supelco -DEX 325 30 m◊0.25 mm, O (dd, J = 12.2, J = 3.8 Hz, 1H, CH2N), 2,60 (dd, J = isotherm 140 C, 97.4% ee, tR 36.2 R, 38.4 S, The 12.2, J = 10.2 Hz, 1H, CH2N), 4.42 (bs, 1H, OH), racemate was also analyzed. 49% 4-(Dimethyl- 4,89 (dd, J = 10.2, J = 3,8 Hz, 1H, OCH), amino)-1-phenylbutan-1-one. Lit. (25) b.p. 120OC/0.4 α 20 7,44ñ7,52 (m, 3H, CH), 7.82ñ7.88 (m, 4H, CH). mmHg, [ ]D ñ28,6 (c 3.33, cyclopentane). 13 δ C NMR (50 MHz, CDCl3, , ppm): 45.25 (2◊CH3), 67.32 (CH2N), 69.53 (OCH), 123.97 RESULTS AND DISCUSSION (CH), 124.58 (CH), 125.64 (CH), 125.98 (CH), 127.63 (CH), 127.88 (CH), 128.00 (CH), 132.96 Aryl α-dialkylaminomethyl ketones 1-5 were (C), 133.32 (C), 139.63 (C). prepared from the corresponding methyl ketones by 720 TOMASZ KOSMALSKI

Table 1. Synthesis of dialkylamino ketones 1ñ7. Halo ketone N,N-Dialkylamino ketone Amine Solvent Time, nArX(equiv.) h No. Yield, % Ref.

1PhBrMe2NH (4) Et2O/benzene (2:1) 12 1 60 3

1 Ph Br Piperidine (2) Et2O/benzene (2:1) 9 2 79 3

1 2-Naphthyl Br Me2NH (4) Et2O43 86 3

1 2-Naphthyl Br Piperidine (2) Et2O34 73

1 3,4-(MeO)2C6H3 Br Me2NH (4) Et2O45 64 3

2PhClMe2NH (4) Benzene 48 6 72

3PhClMe2NH (6) Benzene 48 7 52

Table 2. Asymmetric transfer hydrogenation of ·-dialkylamino ketones 1-7 with formic acid-triethylamine, catalyzed by RuCl[(R,R)- TsDPEN](η-p-cymene) in ethyl acetate at room temperature (17). N,N-Dialkylamino ketone Time, N,N-Dialkylamino alcohol n Ar R days No. Yield, % ee, % Conf. Ref. 1PhMe51a 58 >97b R3

b 1 Ph (CH2)5 3 2a 63 99 R3 1 2-Naphthyl Me 6 3a 60 98c Re 3

d f 1 2-Naphthyl (CH2)5 5 4a 61 >95 R

c 1 3,4-(MeO)2C6H3 Me 7 5a 55 98 R3 2PhMe76a >95 S 3PhMe77a 51 >97 S aIsolated. bDetermined by GC on a chiral kolumn, Supelco ‚-DEX 325, 30 m◊0.25 mm. Racemates were also analyzed. cDetermined by HPLC on a chiral column, Daicel Chiralcel OD-H, 250◊4.6 mm, 5 ⎧m. Racemates were also analyzed. dAssigned by comparison of the sign of rotation with the literature data. eAssigned by X-ray analysis. fAssignment is based on the structural similarity to 3a

bromination, followed by treatment of the α-bromo and 64% yield. Amino alcohol 5a, (R)-(-)- ketones with secondary amines (17). Amino ketones macromerine, is a natural alkaloid of the cactus 6 and 7 were prepared by the reaction of 3-chloro- Coryphantha macromeris and exhibits a hallucino- propiophenone and 4-chlorobutyrophenone with genic activity (17, 23). dimethylamine (25) (Table 1).

Transfer hydrogenation of β-(dimethylamino) propiophenone (6) under the same conditions gave mainly propiophenone (71%) and chiral products: 3- dimethylamino-1-phenylpropanol 6a (> 95% ee) and (S)-1-phenylpropanol 6b (> 95%).

Transfer hydrogenation of the piperidino-sub- stituted ketones 2 and 4 is faster than the dimethylamino ketones 1 and 3 (Table 2). Selectivity of the reduction is high and the corresponding β-amino alcohols 1ñ4 are obtained with 95ñ99% ee. The A similar elimination of the dimethylamino methodology can also demonstrate, as an example, group is observed in the hydrogenation of 6 cat- an application of the ATH to the synthesis of natural alyzed by {[Rh(NBD)Cl]2, (R,R)-DIOP} (29). compounds ñ macromerine (17, 23) with 98% ee Apparently, phenyl vinyl ketone is formed, and Asymmetric synthesis of α-N,N-dialkylamino alcohols by transfer... 721 undergoes further incomplete reduction. A small 7. Cho B.T., Chun Y.S.: Tetrahedron Asymmetry amount 3-dimethylamino-1-phenylpropanol is also 3, 341 (1992). formed. 8. Klingler F.D.: Acc. Chem. Res. 40, 1367 In contrast, asymmetric transfer hydrogenation (2007). of γ-dimethylamino butyrophenone (7) gave 4- 9. Quallich G.J., Woodall T.M.: Tetrahedron Lett. dimethylamino-1-phenylbutanol 7a, > 97% ee with 34, 785 (1993). 51% conversion. 10. Zhang Y.-W., Shen Z.-X., Qin H.-B., Li Y.-H., Yu K.-B.: Chinese J. Chem. 19, 1130 (2001). 11. Miyano S., Lu D.L.L, Viti S.M., Sharpless B.K.: J. Org. Chem. 50, 4350, (1985). 12. Shibata T., Takahashi T., Konishi T., Soai K.: Angew. Chem. Int. Ed. Engl. 36, 2458 (1997). γ-Amino ketone 7 reacts slowly, and the con- 13. Yadav A. K., Manju M.: Indian J. Chem. 45B, version after 7 days was 51%, however, enantiose- 2770 (2006). lectivity of the reduction is high and (S)-4-dimethy- 14. Tanis S.P., Evans B.R., Nieman J.A., Parker lamino-1-phenylbutanol (7a) with 97% ee, was T.T., Taylor W.D., Haesley S.E., Herrington obtained. Slow reaction and incomplete conversion P.M. et al.: Tetrahedron Asymmetry 17, 2154 may indicate the lower catalytic activity in the pres- (2006). ence of 7. 15. Noyori R., Hashiguchi S.: Acc. Chem. Res. 30, The same configurations of the amino alcohols 97 (1997). 1añ5a indicate similar orientations of amino ketones 16. Noyori R., Yamakawa M., Hashiguchi S.: J. in the transition states. The (S) configuration of 7a Org. Chem. 66, 7931 (2001). reflects different priority of the groups in the con- 17. Kosmalski T., Wojtczak A., Zaidlewicz M.: figuration assignment of this compound as com- Tetrahedron Asymmetry 20, 1138 (2009). pared to 1añ5a. 18. Lennon I.C., Ramsden J.A.: Org. Process. Res. In conclusion, asymmetric transfer hydrogena- Dev. 9, 110 (2005). tion of α-dialkylamino ketones and γ-dialkylamino 19. Morris D.J., Hayes A.M., Wills M.: J. Org. ketones with formic acid/triethyamine, catalyzed Chem. 71, 7035 (2006). with RuCl[(R,R)-TsDPEN](p-cymene), provides a 20. Hashiguchi S., Fujii A., Takehara J., Ikariya T., convenient highly selective access to the correspon- Noyori R.: J. Am. Chem. Soc. 117, 7562 (1995). ding dialkylamino alcohols. 21. Chapman N.B., Triggle D.J.: J. Chem. Soc. 1385 (1963). REFERENCES 22. Immediata T., Day A.R.: J. Org. Chem. 5, 512 (1940). 1. Johnson R. L.: in Wilson and Gisvoldís Text- 23. Brown S.D., Hodgkins, J.E., Reinecke, M.G.: J. book of Organic Medicinal and Pharmaceutical Org. Chem. 37, 773 (1972). Chemistry; Block J.H., Beale J.M. Jr., Eds., 24. Snyder H.R., Brewster J.H.: J. Am. Chem. Soc. 11th edn., p. 524; Lippincott, Williams & Wil- 70, 4230 (1948). kins, Philadelphia 2004. 25. Yamaguchi S., Kabuto K.: Bull. Chem. Soc. 2. The Merck Index, M. J. O`Neil Ed., 14th edn., a) Jpn. 50, 3033 (1977). p. 636, b) nr 1047, Merck & Co., Whitehouse 26. Noyori R., Suga S., Kawai K., Okada S., Station , NJ 2006. Kitamura M.: J. Organomet. Chem. 382, 19 3. Palmer M., Walsgrove T., Wills M.: J. Org. (1990). Chem. 62, 5226 (1997). 27. Saravanan P., Bisai A., Baktharaman S., 4. Kenny J.A., Palmer M.J., Smith A.R.C., Chandrasakhar M., Singh V.K.: Tetrahedron Walsgrove T., Wills M.: Synlett 10, 1615 58, 4693 (2002). (1999). 28. Rossiter B.E. Miao G.: J. Org. Chem. 60, 8424 5. Corey E.J., Helal C.J.: Angew. Chem. Int. Ed. (1995). Engl. 37, 1986 (1998). 29. Tırˆs T., Kollàr L., Heil B.: J. Organomet. 6. Soai K., Niwa S., Kobayashi T.: J. Chem. Soc., Chem. 232, C17 (1982). Chem. Commun. 1987, 801.