Asymmetric syntheses. Part IX. Reduction of ketone oximes and theirO-substituted derivatives with the lithium aluminium hydride–3-O-benzyl-1,2-O-cyclohexylidene-α-D-glucofuranose complex to give optically active amines

摘要

1902 J.C.S. Perkin IAsymmetric Syntheses. Part IX. Reduction of Ketone Oximes and theirO-Substituted Derivatives with the Lithium Aluminium Hydride-3-0-Benzyl-I ,2-~-cyc~ohexy~idene-a-D-gfucofuranose Complex to give Optic-ally Active AminesBy Stephen R. Landor,'t Oluntunji 0. Sonola, and Austin R. Tatchell, Makerere University, Kampala, andThe asymmetric reduction of ketone oximes and their O-tetrahydropyranyl and O-methyl derivatives with thelithium aluminium hydride-3-O-benzyl-l.2-O-cyclohexylidene-ct-D-glucofuranose complex yields optically activeamines of up to 56 optical purity. The stereoselectivities obtained from reduction of the O-substituted oximeswere similar to those from the reduction of the free oximes. All the resulting amines have the S-configurationand this method may be used in determining the absolute configurations of amines.Asymmetric reductionwith the ethanol-modified glucofuranose complex gives optically active amines of the R-configuration.Thames Polytechnic, London SE18IN Parts 1-111 2-4 we reported the asymmetric re-duction of ketones by lithium aluminium hydride-mono-saccharide complexes to give optically active alcoholswith up to 70 stereoselectivity. We have nowextended these investigations to the reduction of theamines. Here the essential mechanistic step is similarto that in the case of the carbonyl group, which mustinvolve a kinetically controlled hydride transfer inwhich the sterically least hindered transition state pre-dominates. Thus the formation of optically activeamines depends on the fact that the free energies ofactivation corresponding to the approach of the hydridecomplex to either side of the carbon-nitrogen doublebond .must be different, leading to the formation of thetwo enantiomers (R and S) in unequal amounts; thegreater the steric differences and therefore the differ-ences in activation energies, the higher the stereo-selectivity obtained .Although the multiple bonds of the carbonyl andoxime groups are similar, the free oxime possesses anadditional hydroxy-group which reacts with the alu-reduction must proceed by an intermolecular hydridetransfer preferentially of HB from a second molecule ofisoelectronic imino-group and obtained optically active ---cH NH2--c ' c /HR2= HAL C1#12L06 , OMe, or minium hydride-monosaccharide reducing complex,hydrogen being evolved.Based on the evidence3P4 0 0reported previously it may be assumed that the hydrogenatom replaced in this reaction is predominantly Hg.However coplanarity of the Al, 0, N, and C atoms in thecomplex (I) thus formed renders intramolecular transferof HA to the oxime carbon atom sterically improbableand energetically unfavourable. Hence the asymmetrict Present address : Department of Chemistry, Exeter Univer-sity, Exeter EX4 4QD.Part VIII, S. R. Landor, B. J. Miller, J. P. Regan, and A. R.Tatchell, J.C.S. Perkin I , 1974, 557. * S. R. Landor, B. J. Miller, and A. R. Tatchell, J . Chem. SOC.(C), (a) 1966, 1822; ( b ) 1966, 2280; (c) 1967, 197.SCHEMEaluminium hydride-monosaccharide complex (11) to thecarbon atom of the oxime group in (I), and this wouldbe predicted to give optically active amines of theS-configuration (see Scheme).This was found to be the case.Ten examples,including both alkyl and aryl ketone oxirnes (Tables 1and 2), all gave optically active amines of the S-con-figuration. The three amines for which the configurationhad not been previously established have now beenassigned the S-configuration.The asymmetric reductions of oximes and theirO-methyl and O-tetrahydropyranyl derivatives all pro-ceeded with similar stereoselectivities (Table 3) aswould be expected if a common mechanism involving asecond molecule of reducing agent was operative. TheO-substituent on the oxime is evidently too remote to3 S.R. Landor, A. R. Tatchell, and R. H. Williams, un-published work.Y . M. Chan, S. I70. t Yields of amine ca.8 B.p. 160" a t 11 mmHg.60.I Rotations for methanolic solutions (c 12.6).b B.p. 100" at 35 mmHg. c B.p. 70" at 6 mmHg. d B.p. 138" a t 1 mmHg.TABLE 2Reduction of aliphatic ketone oximes with the glucofuranose complexKetone: Ethyl Methyl Isopropyl Butyl Isobutyl Methyl Hexyl Cyclohexylmethyl P'OPYl methyl methyl methyl t-butyl methyl methylketone ketone ketone ketone ketone ketnne ketone ketoneAmine : s-Butyl- 1-Methpl- 1,S-Dimethyl- l-Methyl- 1,3-Dimethyl- 1,2,2-Trimethyl- l-Methyl- l-Cyclohexylbutylamine *b propylamine * e pentylamine *d butylamine *e propylamine *I heptylamine *I ethylamine ** amine *a 0,' 0 ' LiAlH, I 0(moll aln 20 e.e. aD 20 4 .t ctlD 20 e.e.t a D e.e. 20 e.e. aD 20 e.e.t aD 20 e.e.0.012 +0*41 5.6 +0-27 +0*15 +0*18 4.2 +0.19 4.5 +0*18 +041 9.20.018 +0*60 6.73 +0-61 + 0.42 +0.64 12-5 +0*40 9.5 +0*67 +0-93 14.10.025 +0*66 8.96 +0*79 + 0.65 +0*90 21.00 +0*82 19.5 +0*95 +lea2 21.40.032 +1*1 14.60 f0.76 + 0.76 +0*96 21.80 +0-74 17.5 +0.91 +149 24.000.039 +0*58 7.84 +0*56 + 0.72 3.0.88 20.40 +043 12.5 +0.70 +1-43 21-600.046 +0*43 6.83 +0.48 + 0.48 1-0.82 19.00 +0.46 10.90 +0-66 +0*77 11-608 B.p.Yield of amine > 70.B.p. 63" at 76 cm Hg.t The specific rotation has not been reported previously.B.p. 92-94" a t 76 cm Hg. C B.p. 86" at 76 cm Hg. B.p. 320" at 76 cin Hg.Hg. I B.p. 102" a t 76 cm Hg. 0 B.p.70" at 26 mmHg. hB.p. 58" a t 12 mmHg..ID eo e.e.+0-60 18-8+0.90 27.2+1*56 48.8+1*82 66.2 + 1-59 50.2+1.44 46.8101" a t 76 cmTABLE 3Comparative results from the reduction of ketones, ketone oximes, and O-tetrahydropyranyl and O-methyl derivativesof the latterR1R2C=X x = o X = NOH X = NOThD * X = NOMe7 R1,MeE tMePhMeMeMeMeMeMeMeMeMe- R*PhPhPhCH,PhCH,EtPriPrBuButBut1 -GoH 7*76 e.e.33 (-)-(S) 238 (-)-(S) 24.8 (-)-(S) '3.0 ( + ) - ( S )6.1 (+)-(S)7.2 (+)-(S)8.6; 10.6' (+)-(S)18.3; 30 * (+)-(S)7.8; 3.0 (+)-(S)11.4 (+)-(S) '76 (+)-(S) ' tThp = tetrahydropyranyl. a D Z o- 3.1- 2.84 7.56- 3-05 - 7-56 + 1.1 + 0-79 + 0.76 + 0.95 + 0.82 + 0.95 + 1.59 + 1-82SSSSS sST$ +SstSS7 yo e.e.10.714.121.224.89.614.621.819.524.0056.2alD20 - 1-43 - 3.27- 3.12- 9.13+ 7.8+ 1-66 + 0.86+0.79 + 1.06 + 0.78 + 1.22 + 1.78 + 1.60yo e.c.3-5816.522.026.611.320-924.318.626.849.8aD2' - 6.1- 3.61 + 6.6- 3.32 - 10.1 + 1.33+ 0-96 + 0.77+ 1.43 + 1-41t Configurational assignment on the basis of the present work.yo e.e.12.818-018.027.213.818-0023.018.422.644.0differences in steric bulk between the alkyl substituents.For alkyl aryl systems, electronic as well as steric factorsdetermine the stereoselectivities, as shown by the factthat maximum stereoselectivity was shown by deoxy-benzoin oxime and not by methyl naphthyl ketone oxime,Maximum stereoselectivities were again obtained (cj.refs. 2 and 3) with ca.1 : 1 molar ratios of lithiumaluminium hydride to monosaccharide. A comparisonof the results from the reduction of oximes with thosepreviously obtained for ketones (Table 3) shows that thJ.C.S. Perkin Ia,20 -80.8"; l3 (S)-isobutylamine. aID20 + 7.4" 1A (1-methylbutylamine 1,2-dimethylpropylarnine, and 1,2, 2-tri-methylpropylamine, specific rotations not reported) ; (S)- 1-methylpentylamiue, aID2' +4-3" ; 99 l5 (S)-1,3-dimethyl-butylamine, aJD19 +4.2 : (MeOH) ; l6 (S)-l-methylheptyl-amine, aID2O 4- 6.63" ; l1 (S)- 1-cyclohexylethylamine, aID15and their O-Methyl6 andO-Tetrahydropyranyl Derivatives.6-(a) With the lithiumaluminium hydride-3-O- benzyl- 1,2-0-cyclo hexylidene-a+-glucofuranose coinplex.A solution of the glucofuranose 1(8.8 g , 0.025 mol) in dry ether (50 ml) was added t o a+ 3.2" Jh 17Reduction of KetofLe Oximesstereoselectivities for alkyl aryl ketone oximes werelower than for the corresponding ketones, but were onaverage higher for dialkyl ketone oximes than for dialkylketones (a notable exception is cyclohexyl methylketone).Asymmetric reductions of ketone oximes and theirO-substi tut ed derivatives with the et hanol-modifiedcomplex (111) gave amines of the R-configuration; thisobservation lends support to the proposed mechanisticscheme. Evidently the ethoxy-group replaces HB andreduction may only be effected by HA, leading to theTABLE 4Ethanol-modified reduction of ketone oximes and O-substituted derivatives with the glucofuranose complexPhMeC=NOH PhMeeNOThp PhMeGNOMe PhCH,(Me)CTNOH EtMeC=NOHPrimary amine Primary amine b Primary amine b Primary amine b Primary amine *-.a m a a D 20 e.e.0 s x a m a0.012 - 3.0 10.3 +1.17 3.3 +0.24 3.20.020 +3*0 10-3 +2*41 8.3 +2*67 9-2 +1*92 5.4 -0.36 4.90.026 +b*O 17-4 +3.32 11.5 +347 12.3 - 2.90 8.2 -0.95 13.80.032 +5-12 17.8 +3*68 12.7 +5.36 18.5 -4.84 13.6 - 0.61 8-30.039 + 2.5 8-46 +2.09 7.2 +4.29 14.8 -2.60 7.3 - 0.38 6.2EtOH -----7a All amines have the R-configuration.6 Yields of amine 50-60:;.R-amine as predicted. Yields of amine in this case areconsiderably lower (ca. 50) as would be expected,since transfer of the more sterically hindered HA wouldhave a higher activation energy (Table 4).The detailed mechanism of the reduction of ketoneoximes and their O-substituted derivatives by alkoxy-aluminium hydride complexes has recently been dis-cussed by US.^EXPERIMENTALT.1.c. of cabhydrate derivatives was performed onsilica gel with benzene-methanol (98 : 2) as solvent systemand a naphthoresorcinol-phosphoric acid spray for de-tection.The ether used in the reductions with lithiumaluminium hydride complexes was repeatedly dried oversodium. Solutions in chloroform were dried over calciumchloride and ethereal solutions over magnesium sulphate ;solvents were removed under reduced pressure at roomtemperature. The purity of the amines was established byg.1.c. on a 5 f t glass column of Carbowax 20M on ChromosorbW.Preparative g.1.c. was carried out with a 7 f t pre-parative column of Carbowax 20M. Rotations (f0-01")were determined for neat samples unless otherwise stated,with a Stanley photoelectric polarimeter and/or visually.Maximum specific rotations and absolute configurationsof the optically active amines have been reported asfollows : (S)-l-phenylethylamine, aID2O - 29' (MeOH) ; 7(S)-l-phenylpropylamine, aID2O - 19-85" ; 8 s 9 (S)-l-methyl-2-phenylethylamine, aID2O + 35.6" ; l0*l1 (S)-1,2-diphenyl-ethylamine, - 12.0" ; l2 (S)-1-(a-naphthyl)ethylamine,6 See S. R. Landor, 0. 0. Sonola, and A. R. Tatchell, J.C.S.Perkin I, 1974, 1294, for the preparation of ketone oximes andtheir O-methyl and O-tetrahydropyranyl derivatives.6 A.W. Ingersoll, Org. Synth., Coll. Vol. 11, 1943, p. b03.W. Leithe, B e y . , 1931, 64, 2827.8 M. E. Warren and H. E. Smith, J. Amer. Chem. SOL, 1965,F. M. Jaeger and J . A. van Dijk, Proc. Acad. Sci., Amster-l o V. M. Patapoo, V. M. Dmjanovich, and A. P. Terentiev,87, 1757.dam, 1941, 44, 2640.Zhur. obshchei Khim., 1965, 39(9), 1538.measured volume of a standardised ethereal solution oflithium aluminium hydride (ca. 18-20 g 1-l). Thc misturewas heated under reflux for 90 min, then the solution of theoxime or its O-substituted derivative (0.0125 mol) in dryether (20 ml) was added. Heating under reflux wascontinued for 2.5 11, then the mixture was cooled, thecomplex was decomposed with water (15 ml), and theprecipitated hydroxide was filtered off and washed withether (2 x 30 ml).The combined filtrate and washingswere extracted with dilute hydrochloric acid (3 x 20 ml)to separate all basic components. The aqueous acid layerwas strongly basified ( ~ M - N ~ O H ) and extracted with ether(3 x 50 ml), and the extract was washed with water(2 x 30 ml), dried (MgSO,), and evaporated to give an oilyproduct. The optically active primary amine was isolatedby fractional distillation under reduced pressure andcharacterised by i.r. and n.m.r. spectra; its purity waschecked by g.1.c.(b) With the ethanol-modi3ed complex. A solution of theglucofuranose (8.8 g, 0.025 mol) in dry ether (50 ml) wasadded to an ethereal solution of the hydride (1 g, 0.026 mol) .The mixture was heated under reflux for 90 min, afterwhich various amounts of ethanol in ether solution wereadded and heating under reflux was continued for 1 h. Asolution of the oxime or derivative (0.0125 mol) in dry ether(20 ml) was added. Heating under reflux was continuedfor 2.5 h. The mixture was then cooled and the excess ofreducing complex was decomposed with water ( 15 ml) .The products were separated as in (a).4/406 Received, 1st March, 1974111 W. Leithe, B e y . , 1932,65B, 660 (Chem. Abs., 1932,26, 3496).P. Pratesi, A. La Manna, and L. Fontanella, I2 Farmaco, ed.Sci., 1955, 10, 673; G. G. Lyle, J. Ovg. Chem., 1960, 26, 1779.13 H. Wolf, E. Bunnenberg, and C. Djerassi, Chem. Ber., 1964.97(2), 633; E. Samuelsson, Thesis, University of Lund, 1923(Chem. Abs., 1924, 18, 1833).l4 L. G. Thome, B e y . , 1903,36,682; A. Kjaerand S. E. Hannen,Acta Chem. Scand., 1967, 11, 898.15 P. A. Levene and M. Kuna, J. Biol. Chem., 1938,122,291.16 P. Karrer and P. Dinkel, Helv. Chim. Acta, 1953, 36, 122.1' N. Kornblum, W. D. Gurowitz, and D. E. Hardies, J . Amer.Chem. SOC., 1960, 83, 3099