摘要:

1978 371 Asymmetric Induction in the Borohydride Reduction of Carbonyl Com-pounds by Means of Chiral Phase-transfer Catalysts. Part 2.l By Stefan0 Coionna and Roberto Fornasier, Centro C.N.R. e lstituto di Chimica lndustriale dell'Universita, Via C. Golgi 19, 20133 Milano, Italy Reaction of carbonyl compounds with sodium borohydride in a two-phase system, in the presence of chiral ammonium salts containing a secondary hydroxy-group affords the corresponding carbinols with 0-32% enantio-meric excess. The optical yields are higher when the hydroxy group is p to the ' onium ' function and the catalyst is conformationally more rigid. INthe last few years growing attention has been devoted to asymmetric synthesis under phase-transfer conditions in the presence of optically active ' onium' salts as catalysts.1$2 In particular, carbonyl compounds having a chiral atom a to the carbonyl group and/or sterically hindered undergo borohydride reduction in the presence of N-alkyl-N-methylephedrinium bromide (1) to afford t PhCHX eCHMe-hMe2 Br-I PhCH (OH) CH .CH2.NMez I X' C12H25 R (1) X= OH (3) R = C,2HZ5, X=Br (2) X = H (C) R = CHzPh X = CI (7) optically active carbinols.1 The highest optical yield (13.7%) was obtained for phenyl t-butyl ketone.The presence of a hydroxy-group in the catalyst was essential to achieve asymmetric induction. A readily available chiral reagent affording con-sistently high stereoselectivity would represent a valuable synthetic tool for optically active carbinols.t The excellent behaviour of benzylquininium chloride (7) as phase-transfer catalyst is in accord with the 25% enantiomeric excess obtained by Wynberg in epoxidation reacti~ns.~f*g For this reason we have now investigated the behaviour of the series of 'onium ' salts (1)-(7) in the borohydride reduction of carbonyl compounds under phase-transfer conditions, in order to ascertain the influence of struc-tural variations within the catalyst on asymmetric in-duction. The ammonium salts chosen not only differ in the position and in the number of hydroxy-groups, but also in the degree of conformational freedom. Alkyl phenyl ketones (8)-( 11) were reduced with sodium borohydride at 0 "C in the two-phase system benzene-water in the presence of catalytic amounts (0.05 mol.equiv.) of (1)-(7). The results are listed in Tables 1 and 2. TABLE1 Reduction of phenyl t-butyl ketone with sodium boro-hydride a in benzene-water in the presence of the catalysts (1)-(7) at 0 "C Reaction Catalyst time Yield (%) [a]~~~E.e. yo Configuration (1) 1 77 $4.20 13.7 (+)-(R) (2) 1 75 0 (3) 2 86 $0.34 1.1 (+)-(R) (4) 4 80 f0.34 1.1 (+1-v)20 77 0 (5)(5) 120 = 93 +1.15 3.8 (+)-(R) (6) 7 25 0 (7) 2 95 +9.75 32.0 (+ )-(R) (7) 2-f 100 +7.70 25.2 (+)-(R) 0.6 mol per mol of substrate. 0.05 Mol per mol of sub-strate. Based on material isolated. d Enantiomeric excess; maximum value for [a]~*~+30.6 (c 3.64 in Me,CO); W. Winstein, B. K. Morse, J.Amer. Chem. SOC.,1952, 74, 1133. In absence of water. -f At 25 "C. Among the catalysts tested, benzylquinium chloride (7) is generally the best optically active phase-transfer cata1yst.t Indeed in the reduction of phenyl t-butyl ketone (ll),catalyst (7) afforded (+)-(R)-(15) in an optical purity of 32%. To our knowledge, this is the highest enantiomeric excess found in asymmetric syntheses using chiral ammonium salts as catalysts under phase-transfer conditions. Part I, J. Balcells, S. Colonna and R. Fornasier, Synthesis, 1976, 266. (a) S. Colonna and R. Fornasier, Synthesis, 1975, 531 ; (b) T. Hijama, T. Mishima, H. Sawada and H. Nozaki, J. Amer. Chem. Soc., 1975, 97, 1626; (c) T. Hijama, H. Sawada, M. Tsukanaka, and H. Nozaki, Tetrahedron Letters, 1975, 3012; (d) J.C. Fiaud, ibid., 1975, 3495; (e) T. Hijama, T. Mishima, H. Sawada, and H. Nozaki, J. Amer. Chem. SOC.,1976, 98, 641 ; (f)R. Helder, J. C. Hummelen, R. W. P. M. Laane, J. C. Wiering, and H. Wynberg,Tetrahedron Letters, 1976, 1831; (g) H. Wynberg, Chimia, 1976, 30, 445; (h)J. P. Mass6 and E. R. Parayre, J.C.S. Chem. Comm.. 1976, 438. With the ' onium ' salts (3) and (4), whose reactivity was similar to that of the ephedrinium salt (1),(+)-(R)-(phenyl-t-butylcarbinol) (15) was obtained in 1.1% enantiomeric excess. Wpen N-(2-hydroxyethyl) -N-methylamphetaminium chloride (5)was used, the reduction was much slower and the isolated alcohol was racemic. This is because (5) is very soluble in the aqueous phase, with a partition co- efficient in benzene-water of ca.1 : 99. Furthermore, when the reaction was repeated with (5) under solid- liquid phase-transfer conditions, phenyl-t-butylcarbinol (15) was obtained in 3.8% enantiomeric excess. This J.C.S. Perkin I and (+)-(I?) for R = Pri and But. The stereo-chemical course of the borohydride reduction of alkyl phenyl ketones in the benzene-water system is con-sistent with that previously found in alkyl-metal asymmetric reduction. Such results can be rationalised if account is taken of the increased steric effects of the bulkier isopropyl and t-butyl groups over that of a phenyl substituent . In a previous paper we reported1 that reduction of acetophenone (8) at 25 "C with sodium borohydride catalysed by the ephedrinium salt (1) (0.05mol.equiv.) in a benzene-water system afforded the corresponding TABLE2 Reduction of the ketones (8)-( 10) with sodium borohydride a in benzene-water in presence of the catalysts (1) and (7) R Catalyst Reaction time (h) Temp./"C Yield ("/o) Me (1)Me (7)Me (7)Me (7)Et (1)Et (7)Et (7)Pri (1)Pri (1)Pr' (7)Pr* (7) (I 0.6 Mol. equiv. a 0.05 Mol. equiv. 1 0 97 6 0 75 1 25 96 0.5 45 95 2 0 87 6 0 85 1 25 85 16 0 100 6 25 100 3 0 55 2 25 60 Based on material isolated. r.1~~~ E.e. yo Configuration0 -1.90 4.5 d (-14s)-2.62 6.2 ( -14s) -2.55 6.1 (-14s)0 -1.16 3.3 (--)-(W -2.00 5.7 (-)-(S)4-1.70 3.6 (+)-(R)+1.50 3.1 ( +)-(R)+2.43 5.1 ( +1-(R)+1.60 3.35 (+)-(R) Maximum value for [a]nzo -42.0" (c 3.7 in MeOH) '.+34.8 (c 8 in Et,O) ; P. A. Levene and L. A. Mikeska, J. Biol. Chem. 1926,70, 355. f Maximum value Maximum value for [a]~~~for [a]~~~+47.7 (c 6.8 in Et,O); see ref in e. probably implies that in the benzene-water system only the uncatalysed reduction takes place. The quinium salt (7) in contrast to the ephedrinium salt (1) also gave asymmetric induction in the reduction of acetophenone (8)and propiophenone (9). The results as a whole (Table 2) seem to indicate that two factors are important in order to achieve asym- metric induction in the borohydride reduction of carbonyl compounds under phase-transfer conditions : (i) the catalyst must be conformationally rigid, as is the quininium salt (7); (ii) the hydroxy-group must be in the p position to the ' onium ' function, possibly in order to interact with the carbonyl group and to favour one of the diastereomeric transition states which lead to carbinol (15); asymmetric induction is much lower with a y-hydroxy-group. The degree of asymmetric induction is similar for the carbinols (12)-(14) and substantially lower with respect to phenyl-t-butylcarbinol (15) (see Table 1).For acetophenone (8) and propiophenone (9) the enantio- meric purity of the alcohols obtained increased with the temperature. This behaviour which is difficult to account for, parallels that found in the asymmetric reduction of acetophenone by lithium aluminium hydride-quinine reagents in tet rahydrofuran.In the case of catalyst (7) the absolute configurations of the alcohols (12)-(15) were (-)-(S) for R = Me, Et, J. D., Morrison and H. S. Mosher, 'Asymmetric Organic Reactions ,Prentice-Hall, New Jersey, 1971, p. 210. optically inactive alcohol (12). In contrast, Mass6 2h re-ported that the same reaction carried out at 20 "C in a water-1 ,2-dichloroethane system in the presence of the salt (1) (0.01 mol. equiv.), afforded (+)-(R)-phenyl-methylcarbinol (12), 0.35% optically pure. It was also claimed that the optical purity of the carbinol (12) increased with the amount of (1) used, to give a 39% enantiomeric excess with a 0.4 mol. equiv. of (1). We have now repeated the latter experiment and obtained (-)-(S)-phenylmethylcarbinol (1) enantiomerically en-riched by 4.7%.When the borohydride reduction of acetophenone (8) was performed at 20 "C in the presence of 0.05 and 0.4 mol. equiv. of benzylquinium chloride (7) the resulting (S)-methylphenylcarbinol had values of of -3.42 and -2.50' respectively which corresponded to enantio- meric purities of 8.1 and 5.9%. Furthermore, reduction in the same reaction conditions of phenyl t-butyl ketone (11) in the presence of 0.05 and 0.4 mol. equiv. of catalyst (7) gave (+)-(R)-(lq having enantiomeric purities of 19.2 and 18.3% respectively These results (i) throw doubts on the high values of enantiomeric purity for methylphenylcarbinol (12) claimed by Mass4 2h; (ii) indicate that only with the ephedrinium salt (1)does asymmetric synthesis increase with the concentration of the catalyst; and (iii) vari- ation of the concentration of catalysts (1) and (7) in the G.P. Giacomelli, R. Menicagli, and L. Lardicci, J. Amev. Chem. Soc., 1975, 97, 4.009. range 0.054.4mol. equiv. may affect the nature of the reaction medium and thus influence the asymmetric induction. EXPERIMENTAL Light petroleum had b.p. 40-60 "C. lH N.m.r. spectra were recorded on a Varian A-60 spectrometer and optical rotations were measured on a 141 Perkin-Elmer polarimeter. Optically Active Calalysts.-( -)-( lR,2S)-N-Dodecyl-N-methylephedrinium bromide (l), (-)-(R)-N-dodecyl-NN- dimethvlamphetaminium bromide (2), ( +) -N-dodecyl-NN-dimethyl- (3-h ydroxy- 3-phenylpropyl) ammonium bromide 373 addition of ethylene chlorohydrin (12 mmol) to a solution of (-)-(R)-NN-dimethylamphetamine (10 mmol), [oL]~,~ -13.5" (G 10 in H,O, hydrochloride salt),2a in dimethyl- formamide (5 ml) and heating of the mixture under reflux for 4 days.The reaction mixture was cooled and diluted with hexane to precipitate (5),which was filtered off (92% yield), m.p. 124-125 "C (hydroscopic), [aIDz5-5.12" (c 3 in EtOH) (Found: C, 64.1; H, 9.0; N, 5.6. C,,H,,ClNO requires C, 64.2; H, 9.05; N, 5.75'70). Reduction of Ketones.-Carbonyl compound ( 10 mmol), sodium borohydride (6 mmol), benzene (6 ml), water (10 ml), and the catalyst were mixed in a flask and stirred dimethylammonium chloride (4) were prepared as previously de~cribed.'.~ ( -) -N-( 2-Hydroxyethyl)-N-methylephedrinium chloride (5).This compound was prepared by dropwise addition of ethylene chlorohydrin (1 1 mmol) to a solution of N-methyl- ephedrine (10 mmol) in ethanol (10 ml). The reaction mixture was refluxed for 5 days after which the solvent was evaporated under reduced pressure to give (4) (70y0),m.p. 158-160 "C (from MeCN-Pr'OH), [,IDz5 -34" (c 0.24 in EtOH) (Found: C, 60.0; H, 8.5; N, 5.35. C,,H2,C1N0, requires C, 60.1; H, 8.5; N, 5.4%). ( -)-Benzylquininium chloride (7). This compound was prepared by adding benzyl chloride (10 mmol) to a solution of quinine (10 mmol) in benzene (10 ml) and ethanol (2 ml). After 26 h at room temperature the solvent was evaporated off and the residue washed with pentane to give (7) (79% yield) as a monohydrate, m.p.169-172 "C (decomp.), [tiIDz5 -212.5" (c 0.5 in EtOH) (lit.,s m.p. 183-188 "C as anhydrous salt), [alDz2-230.5" (c 1.479 in H,O), C1- content 97% by Volhard method. ( -) -N-(2- Hydroxyethyl) -NN-dirnethy Zarnplzetaminium chloride (6). This compound was prepared by dropwise S. Colonna, R. Fornasier, and U. Pfeiffer, J.C.S. Perkin I, 1978, 8. 6 W. A. Jacobs and M. Heidelberger, J. Amer. Chem. SOC., 1919,41,2090. at 0, 25, or 45 "C for a suitable time (see Tables 1 and 2). (3), and ( +)-N-benzyl-(3-hydroxy-3-phenylpropyl)-NN-The reaction was followed by g.1.c. or t.1.c. The organic layer was separated, the aqueous phase extracted with methylene chloride, and the combined organic fraction dried (Na,SO,).After evaporation of the solvent the residue was chromatographed on silica with ether-light petroleum (2 : 8) as eluant. Yields, optical rotations, and enantiomeric excesses are reported in Tables 1 and 2. Reduction of acetophenone was also carried out in 1,2- dichloroethane as described in the literature.2h After work up (-)-(S)-1-phenylethanol (12) was obtained in 97% yield; [aIDz5-2.0 (c 3.7 in MeOH) which corresponds to an optical purity of 4.7%.' Reduction of acetophenone (8) under the same reaction conditions in the presence of 0.05 and 0.4 mol. equiv. of catalyst (7) gave, in 40 and 94% yield, the (-)-(S)-carbinol (12), [a],zo -3.42" and [aID2O-2.50" (c 3 in MeOH), 8.1 and 5.9% enantio- merically pure, respectively. Reduction of phenyl t-butyl ketone (11) in (CH,Cl), under the conditions already described, in the presence of 0.05 and 0.4 mol. equiv. of (7) afforded in 95 and lOOyo yield, the (+)-(R)-carbinol (15), [aID2O15.88 and + 5.60" (c3.6 in Me,CO), 19.2 and 18.3% enantiomerically pure, respectively. [7/1201 Received, 7th July, 19771 G. Barbieri, V. Davoli, I. Moretti,F.Montanari, and G.Torre, J. Chem. Soc. (C),1969, 731.

ISSN:1472-7781    

DOI:10.1039/P19780000371

出版商:RSC    

年代:1978

数据来源: RSC