Highly stereoselective synthesis of 1,3-aminoalcohols via Mannich reactions

Article abstract of DOI:10.1016/S0957-4166(99)00342-0

Diastereoselective synthesis of β-amino ketones by a one-pot Mannich reaction and their subsequent reduction afforded sterically congested enantiomerically pure 1,3-aminoalcohols in high diastereoselectivity: dr up to >98:<2 over two steps. The absolute configurations of the newly created stereogenic centers were assigned by NMR spectroscopy and chemical correlation.

Full text of DOI:10.1016/S0957-4166(99)00342-0

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3409–3416
Highly stereoselective synthesis of 1,3-aminoalcohols via
Mannich reactions
Michael Kossenjans and Jürgen Martens ∗
Fachbereich Chemie der Universität Oldenburg, Carl-von-Ossietzky-Strasse 9–11, D-26129 Oldenburg, Germany
Received 26 July 1999; accepted 9 August 1999
Abstract
Diastereoselective synthesis of β-amino ketones by a one-pot Mannich reaction and their subsequent reduction
afforded sterically congested enantiomerically pure 1,3-aminoalcoholsin high diastereoselectivity: dr up to >98:<2
over two steps. The absolute configurations of the newly created stereogenic centers were assigned by NMR
spectroscopy and chemical correlation. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
Considering the widespread interest in stereoselective organic chemistry towards the end of this
century, the synthesis of optically active aminoalcohols still remains an attractive and challenging
target.1–3 Since these compounds have found enormous applications as chiral ligands in metal-mediated
organic reactions, there has been a continual interest aimed at their structure modification. In particular,
1,2-aminoalcohols have received much attention, not least because they are generally readily accessible
in enantiomerically pure form in a few steps from natural precursors, e.g. α-amino acids, carbohydrates,
camphor, etc. With regard to 1,3- and 1,4-aminoalcohols as chiral auxiliaries, especially as ligands in
enantioselective catalysis, publications focused on the design and application of these compounds are
rather rare and only a few results are known.4–6 This prompted us to prepare new sterically congested 1,3-
aminoalcohols by highly diastereoselective reduction of β-amino ketones prepared before by Mannich
reactions.7
In the context of our studies on the utilization of industrial waste materials we used the enantio-
merically pure 2-azabicyclo[3.3.0]octane 2c as the starting material for the synthesis of the new chiral
auxiliaries.8
The chiral heterocyclic amine 2c could be prepared by the cyclohexen-2-one catalyzed thermal
decarboxylation of 2b,9 a derivative of the non-recyclable enantiomerically pure benzyl 2-
∗
Corresponding author. E-mail: martens@uni-oldenburg.de
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00342-0

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M. Kossenjans, J. Martens / Tetrahedron: Asymmetry 10 (1999) 3409–3416
azabicyclo[3.3.0]octane-3-carboxylate 2a, which was obtained as a waste material in the process
of synthesizing the angiotensin converting enzyme inhibitor Ramipril 1 by Hoechst AG (Scheme 1).10
Scheme 1.
2. Results and discussion
The general synthesis of β-amino ketones 5a–c by reaction of optically active amine 2c with benzal-
dehyde and several enamines 4a–f is shown in Scheme 2. In a one-pot procedure the secondary amine 2c
was first silylated by Me3SiI (generated in situ from Me3SiCl, NaI and NEt3), followed by the addition
of benzaldehyde to afford the corresponding iminium salt 3, which was finally used without further
purification for the aminoalkylation of enamines 4a–f.11
Scheme 2.
Enamine 4a (Table 1) was aminoalkylated according to this general procedure providing β-amino
1
ketone 5a after acidic work-up. Based on the H NMR data, on the integrals of a doublet originating
from the single benzylic proton H10, a diastereomeric ratio of dr (83:17) was determined.
With the intention of improving the stereochemical outcome of this reaction, enantiomerically pure
enamines 4b–d were used for the synthesis of ketone 5a. As can be seen from Table 1, the bicyclic
pyrrolidine analog 4d was aminoalkylated with higher diastereoselectivity compared to 4a [entries 1 and
4 (matched situation)] whereas the optical antipode 4c as well as SMP-enamine 4b afforded 5a only in
moderate diastereomeric ratios [entries 2 and 3 (mismatched situation)]. However, as indicated by the
coupling constant value between H10 and H2, two anti-configured diastereomeric β-amino ketones were
0
0
formed in all four cases (JH1 H2=11.6 Hz for major diastereomer, JH1 H2=9.4 Hz for minor diastereomer).
Using α-tetralone and propiophenone based optically inactive enamines 4e–f, the corresponding
β-amino ketones 5b and 5c were each produced as a single and anti-configured diastereomer (5b:
0
J
H3H2=11.2 Hz, 5c: JH1 H2=9.4 Hz, entries 5 and 6).
Although it is known that β-amino ketones are generally sensitive towards heating or any purification
method,12 we were able to isolate the major diastereomers of 5a–c by column chromatography on silica
gel and store these Mannich bases in the refrigerator for several weeks without loss of chemical or
enantiomeric purity.
The reduction of diastereomerically pure β-amino ketones 5a–c by LiAlH4 at −70°C afforded the
corresponding 1,3-aminoalcohols 6a–c in excellent chemical yields between 91 and 94% (Scheme 3).

M. Kossenjans, J. Martens / Tetrahedron: Asymmetry 10 (1999) 3409–3416
3411
Table 1
Diastereoselective synthesis of β-amino ketones 5 via Mannich reaction
Concerning the stereoselectivity, the formation of only one diastereomer was observed for aminoalcohol
6a as well as for 6b (dr >98:<2). In contrast, the reduction of 5c provided two stereoisomers, namely
(1R)-6c and (1S)-6c in a ratio of dr (62:38). By using DIBAH instead of LiAlH4 at −70°C, 1,3-
aminoalcohol (1R)-6c was obtained completely diastereoselectively.
Based on the value of vicinal coupling constants between H1 and H2 as well as H10 and H2,
respectively, H3 and H2 the relative configurations of compounds 6b–c were assigned, but determination
of the absolute stereochemistry was not possible by NMR spectroscopy. Concerning aminoalcohol
6a, neither the complete relative nor the absolute configuration could be established by this method.
Therefore, we decided to pursue the chemical correlation by converting aminoalcohols 6a–c to the well-

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M. Kossenjans, J. Martens / Tetrahedron: Asymmetry 10 (1999) 3409–3416
Scheme 3.
known optically active α-substituted cyclohexanol, respectively, propanone and indanone derivatives 7,
8a and 8b (Scheme 4).
Scheme 4.
In the case of aminoalcohol 6a, the benzylic carbon–nitrogen bond was cleaved by treatment with
HCO2NH4/Pd–C resulting in the formation of the enantiomer of the known (1S,2S)-configured α-
benzylcyclohexanol 7,13 which now allowed the absolute stereochemistry at position C10 to be assigned
based on the coupling constant between the benzylic proton H10 and H2 of 6a (Scheme 4).
Aminoalcohols 6b and (1R)-6c [or (1S)-6d] were then subjected to the same procedure (Scheme 4)
as described for 6a, but the corresponding propanol and indanol derivatives were subsequently oxidized
to the known chiral ketones 8a and 8b. Due to the agreement of the obtained analytical data for 8a,b
with those described for these compounds in the literature,14,15 the absolute configuration of 8a was
assigned as R and of 8b as S. Consequently, based on these results the stereochemical assignment
for aminoalcohols 6b,c and amino ketones 5b,c, respectively, was carried out in the same manner as
described above.

M. Kossenjans, J. Martens / Tetrahedron: Asymmetry 10 (1999) 3409–3416
3413
In summary, we have shown that 1,3-aminoalcohols 6 may be obtained in high stereoselectivity by
Mannich reactions and successive reductions of the amino ketones 5. Nevertheless, the application of 1,3-
aminoalcohols 6a–c as chiral auxiliaries in the enantioselective addition of diethylzinc to benzaldehyde
is under investigation at present.
3. Experimental
All reactions were carried out in oven dried glassware, under argon atmosphere using anhydrous
solvents. Optical rotations were measured on a Perkin–Elmer polarimeter 241 MC. IR spectra were
1
recorded on a Philips PU 9706 spectrophotometer. H- and 13C-NMR spectra were recorded on a Bruker
AM 300 (300 MHz) spectrometer using TMS as internal standard. Mass spectra were measured with
a Finnigan-MAT 212 (data system SS 300; CI, isobutane). Elemental analyses (CHN) were performed
by using a Carlo Erba Stumentalione (MOD 1104) analyzer. The enamines 4 were either purchased, or
synthesized according to literature procedures: 4a (Aldrich), 4b–f.16
3.1. General procedure for the synthesis of β-amino ketones 5a–d (GP 1)
To a solution of 1.65 g (11 mmol) anhydrous NaI in 11 mL dry acetonitrile were added 0.56 g (5
mmol) amine 2c, 0.51 g (5 mmol) NEt3 and 1.19 g (11 mmol) Me3SiCl. After stirring for 1 h, 0.53 g
(5 mmol) freshly distilled benzaldehyde was added and stirring was continued for a further 1 h 30 min.
Subsequently, 5 mmol of enamine 4 were added and the reaction mixture was stirred for 2 h at ambient
temperature. The mixture was acidified with 20 mL 6N HCl and stirred for 30 min, then basified with
aqueous NaOH (20%) and extracted with Et2O (3×10 mL). The combined organic layers were dried
(MgSO4) and concentrated in vacuo. The major diastereomer was isolated by column chromatography
on silica gel 60.
3.1.1. (10S,100R,2R,500R)-2-[Phenyl-(10-(200-azabicyclo[3.3.0]octane-200 -yl)methyl]cyclohexanone 5a
Synthesis according to GP 1; diastereomeric ratio: see Table 1. Eluent: n-hexane:NEt3 (7:3), Rf-value:
0.74, yield: 1.08 g (73%). [α]20 −45.1 (c=1.11, CH2Cl2). IR (NaCl): ν=1700 cm−1 (CO). H NMR
1
D
(CDCl3): δ=1.24–2.37 (2m, 17H, 2×H3, 2×H4, 2×H5, 2×H6, 2×H400, H500, 2×H600, 2×H700, 2×H800);
2.69 (m, 2H, 2×H200); 3.03 (m, 1H, H100); 3.12 (m, H, H2); 4.31 (d, J=11.69 Hz, 1H, CHN); 7.16–7.42
(2m, 5H, aromatic-H). 13C NMR (CDCl3, 75.47 MHz): δ=20.62, 23.97, 28.01, 29.31, 31.21, 31.52,
33.14, 38.99 (C3, C4, C5, C6, C400, C600, C700, C800); 40.91 (C500); 45.92 (C2); 53.02 (C200); 62.35,
64.21 (C10, C100); 127.31, 127.88, 129.59 (aromatic-C); 134.09 (q.-aromatic-C); 212.93 (CO). MS (CI,
isobutane): m/z (%)=298 (95) [MH+]; 200 (100) [M+−C6H9O]. C20H27NO (297.4): calcd C 80.76, H
9.15, N 4.71; found C 80.39, H 9.02, N 4.50.
3.1.2. (10R,2R,3S,50R)-3-(-20-Azabicyclo[3.3.0]octane-20 -yl)-2-methylpropanone 5b
Synthesis according to GP 1. Diastereomeric ratio: dr >95:5. Eluent: n-hexane:ethyl acetate (8:2),
addition of 2% NEt3. Rf-value: 0.68, yield: 1.16 g (70%). [α]20 −81.0 (c=0.75, CH2Cl2). IR (KBr):
D
1
ν=1740 cm−1 (CO). H NMR (CDCl3): δ=0.98 (d, J=6.58 Hz, 3H, CH3); 1.11–1.58 (m, 7H, H40,
2×H60, 2×H70, 2×H80); 1.74–1.92 (m, 2H, H40, H50); 2.04 (m, 1H, H20); 2.67–2.76 (2m, 2H, H20,
H10); 4.15 (d, J=11.21 Hz, 1H, CHN); 4.30 (m, 1H, H2); 7.25–7.57, 8.01 (2m, 10H, aromatic-H). 13C
NMR (CDCl3): δ=15.50 (CH3); 24.04, 30.65, 31.24, 33.24 (C40, C60, C70, C80); 40.83, 41.96 (C2, C50);
46.81 (C20); 64.58, 67.69 (C10, C3); 127.10, 127.57, 127.79, 127.94, 128.32, 129.73, 132.11 (aromatic-

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M. Kossenjans, J. Martens / Tetrahedron: Asymmetry 10 (1999) 3409–3416
C); 134.47, 138.89 (aromatic-C); 205.20 (CO). MS (CI, isobutane): m/z (%)=334 (64) [MH+]; 200 (100)
[M+−C9H9O]. C23H27NO (333.47): calcd C 82.84, H 8.16, N 4.20; found C 82.64, H 8.11, N 4.17.
3.1.3. (10R,100R,2S,500R)-2-[Phenyl-(10-(200-azabicyclo[3.3.0]octane-200 -yl)methyl]1,2,3,4-tetrahydro-
1-naphthalinone 5c
Synthesis according to GP 1. Diastereomeric ratio: dr >95:5. Eluent: n-hexane:NEt3 (8:2). Rf-value:
0.71, yield: 1.34 g (78%). [α]20 −5.6 (c=0.85, CH2Cl2). IR (KBr): ν=1710 cm−1 (CO). H NMR
1
D
(CDCl3): δ=1.18–1.84 (m, 9H, 2×H400, H500, 2×H600, 2×H700, 2×H800); 2.03 (m, 1H, H3); 2.25 (m, 2H,
H3, H4); 2.82 (m, 2H, H4, H200); 3.05 (m, 2H, H100, H200); 3.42 (m, 1H, H2); 4.25 (d, J=9.43 Hz, 1H,
CHN); 7.21–7.47, 7.97 (2m, 9H, aromatic-H). 13C NMR (CDCl3): δ=24.06, 25.71, 31.68, 33.09 (C3, C4,
C400, C600, C700, C800); 41.44 (C500); 48.14, 49.76 (C2, C200); 62.67, 65.04 (C10, C100); 126.37, 127.13,
127.39, 127.77, 128.54, 129.58, 132.62 (aromatic-C); 133.61, 135.74, 142.44 (aromatic-C); 199.61 (CO).
MS (CI, isobutane): m/z (%)=346 (66) [MH+]; 200 (100) [MH+−C10H9O]. C24H27NO (345.48): calcd C
83.44, H 7.88, N 4.05; found C 82.98, H 7.90, N 3.99.
3.2. General procedure for the synthesis of 1,3-aminoalcohols 6a–c by reduction of amino ketones 5a–c
(GP 2)
A solution of 3 mmol of the respective β-amino ketone 5 in 10 mL anhydrous THF was cooled down
to −70°C. LiAlH4 (0.15 g, 4 mmol) was cautiously added in three portions and the reaction mixture
was stirred for 1 h 30 min at this temperature. Excess reducing reagent was destroyed by adding 2 mL
of aqueous KOH (10%). The resulting white precipitate was filtered off and washed twice with a small
amount of ethyl acetate. The combined organic layers were dried (MgSO4) and the solvent was removed
under reduced pressure. The obtained residue was finally purified by column chromatography on silica
gel 60.
3.2.1. (1R,10S,100R,2R,500R)-2-[Phenyl-(10-(200-azabicyclo[3.3.0]octane-200 -yl)methyl]cyclohexanol 6a
Synthesis according to GP 2. Diastereomeric ratio: dr >98:<2. Eluent: n-hexane:ethyl acetate (6:4). Rf-
value: 0.36, yield: 0.82 g (92%). Mp: 97°C. [α]20 −24.9 (c=1.0, CH2Cl2). IR (KBr): ν=3000–3500, 1450
D
1
cm−1. H NMR (CDCl3): δ=1.10–2.07 (m, 17H, 2×H3, 2×H4, 2×H5, 2×H6, 2×H400, H500, 2×H600,
2×H700, 2×H800); 2.18 (m, 1H, H300); 2.64, 2.82, 3.10 (3m, 3H, H100, H300, H2); 3.94 (m, 1H, H1);
4.22 (d, J=11.77 Hz; 1H, CHN); 6.79 (bs, 1H, OH); 7.13, 7.27–7.40 (2m, 5H, aromatic-H). 13C NMR
(CDCl3): δ=20.76, 24.35, 24.52, 27.67, 30.99, 31.25, 31.93, 33.03 (C3, C4, C5, C6, C400, C600, C70,
C800); 37.89 (C2); 40.83 (C500); 46.78 (C200); 62.35, 64.43 (CHN, C100); 72.63 (C1); 127.20, 127.75,
130.14 (aromatic-C); 133.27 (aromatic-C). MS (CI, isobutane): m/z (%)=300 (100) [MH+]. C20H29NO
(299.4): calcd C 80.22, H 9.76, N 4.68; found C 80.49, H 9.61, N 4.60.
3.2.2. (1R,10R,2R,3S,50R)-3-(-20-Azabicyclo[3.3.0]octane-20 -yl)-2-methylpropanol 6b
Synthesis according to GP 2. Diastereomeric ratio: dr >98:<2. Eluent: n-hexane:ethyl acetate (8:2),
addition of 1% NEt3. Rf-value: 0.36, yield: 94 g (94%) colorless oil. [α]20 −47.6 (c=0.63, CH2Cl2). IR
D
(KBr): ν=3500–3100, 1520, 1410 cm−1. 1H NMR (CDCl3): δ=0.33 (d, J=6.68 Hz, 3H, CH3); 1.29–1.94
(m, 7H, H40, 2×H60, 2×H70, 2×H80); 2.95 (m, 2H, H40, H50); 2.27 (m, 1H, H20); 2.48 (m, 1H, H2);
2.99 (m, 1H, H10); 3.24 (m, H2); 3.91 (d, J=11.04 Hz, 1H, CHN); 4.58 (d, J=9.17 Hz, 1H, CHOH);
7.28–7.45 (m, 10H, aromatic-H); 9.02 (bs, 1H, OH). 13C NMR (CDCl3): δ=15.82 (CH3); 24.32, 30.94,
31.48, 33.07 (C40, C60, C70, C80); 38.61 (C2); 40.95 (C50); 47.18 (C20); 64.72, 70.61 (CHN, C10); 82.88
(C1); 125.92, 127.31, 127.39, 127.83, 128.08, 12.32 (aromatic-C); 133.81, 144.14 (aromatic-C). MS (CI,

M. Kossenjans, J. Martens / Tetrahedron: Asymmetry 10 (1999) 3409–3416
3415
isobutane): m/z (%)=336 (100) [MH+]. C23H29NO (335.49): calcd C 82.34, H 8.71, N 4.18; found C
82.01, H 8.68, N 4.20.
3.2.3. (1R,10R,100R,2S,500R)-2-[Phenyl-(10-(200-azabicyclo[3.3.0]octane-200 -yl)methyl]1,2,3,4-tetra-
hydro-1-naphthalinol (major diastereomer) (1R)-6c
Synthesis according to GP 2. Diastereomeric ratio: dr (1R)-6c:(1S)-6c (62:38). Eluent: n-hexane:ethyl
acetate (8:2). Rf-value: 0.10, yield: 0.57 g (55%) slightly yellow oil. [α]20 +8.4 (c=0.5, CH2Cl2). IR
D
1
(NaCl): ν=3400–3200, 1520 cm−1. H NMR (CDCl3): δ=0.87–2.06 (m, 12H, 2×H3, 2×H4, 2×H400,
2×H600, 2×H700, 2×H800); 2.17 (m, 1H, H500); 2.55 (m, 1H, H200); 2.74 (m, 1H, H200); 2.94 (m, 1H,
H100); 3.16 (m, 1H, H2); 3.95 (d, J=11.72 Hz, 1H, CHN); 5.04 (d, J=4.3 Hz, 1H, H1); 7.07–7.41,
7.82 (2m, 9H, aromatic-H). 13C NMR (CDCl3): δ=23.94, 24.26, 25.27, 30.64, 31.14, 33.04, 36.45 (C3,
C4, C5, C6, 2×cyclo-CH2); 40.67 (C3a); 46.79 (C2); 62.56, 64.52 (C6a, CHN); 72.23 (COH); 125.92,
126.45, 127.43, 127.78, 127.89, 130.14 (aromatic-C); 133.24, 135.49, 140.35 (aromatic-C). MS (CI,
isobutane): m/z (%)=348 (100) [MH+]; 200 (28) [M+−C10H12O]. C24H29NO (347.5): calcd C 82.95, H
8.41, N 4.03; found C 83.06, H 8.43, N 3.99.
3.2.4. (1S,10R,100R,2S,500R)-2-[Phenyl-(10-(200-azabicyclo[3.3.0]octane-200 -yl)methyl]1,2,3,4-tetra-
hydro-1-naphthalinol (minor diastereomer) (1S)-6c
Synthesis according to GP 2. Diastereomeric ratio: dr (1R)-6c:(1S)-6c (62:38). Eluent: n-hexane:ethyl
acetate (8:2). Rf-value: 0.27, yield: 0.33 g (32%) colorless crystals. Mp: 88°C. [α]20 −78.1 (c=0.5,
D
CH2Cl2). IR (KBr): ν=3400–3200, 1490 cm−1. 1H NMR (CDCl3): δ=1.21–2.05 (m, 11H, 2×H3, 2×H4,
H400, 2×H600, 2×H700, 2×H800); 2.23–2.45 (m, 2H, H400, H500); 2.66–2.87 (m, 2H, 2×H200); 2.98–3.12
(m, 2H, H100, H2); 3.89 (d, J=11.13 Hz, 1H, CHN); 4.90 (d, J=9.19 Hz, H1); 7.04–7.48, 7.72 (2m, 9H,
aromatic-H); 7.98 (bs, 1H, OH). 13C NMR (CDCl3): δ=24.52, 25.29, 29.02, 31.01, 31.79, 33.10 (C3, C4,
C400, C600, C700, C800); 40.94 (C500); 47.27 (C200); 64.83, 70.05 (C10, C100); 75.96 (C1); 126.10, 126.22,
126.52, 127.44, 127.89, 127.98 (aromatic-C), 133.52, 135.57, 139.77 (aromatic-C). MS (CI, isobutane):
m/z (%)=348 (100) [MH+]; 200 (75) [M+−C10H12O]. C24H29NO (347.5): calcd C 82.95, H 8.41, N 4.03;
found C 82.71, H 8.36, N 4.10.
3.3. Hydrogenolysis of aminoalcohols 5a–c
A solution of 1 mmol of the respective aminoalcohol 5, 16 mmol NH4HCO2·5H2O and 0.5 g Pd–C in
20 mL EtOH was stirred at 40°C for 4 h. After filtration, the heterogeneous catalyst was washed twice
with methanol and the combined solvents were evaporated under reduced pressure. The resulting residue
was purified by micro column chromatography on silica gel.
3.4. (1R,2R)-2-Phenylmethyl-cyclohexanol 7
Eluent: n-hexane:diethyl ether (8:2). Rf-value: 0.49, yield: 0.15 g (80%). [α]20 −24.8 (c=1.0, CHCl3);
D
lit.13 [α]20 +28.2 (c=1.0, CHCl3) for (1S,2S)-7. op: 88%. Mp: 67–68°C; lit.13 mp: 67–69°C. The spectral
D
data are in accord with those described in the literature.13
3.5. Synthesis of ketones 8a,b according to the procedure of Dess and Martin17
A solution of the corresponding secondary alcohol (0.75 mmol) in 3 mL CH2Cl2 was added with
stirring to a suspension of 0.86 mmol Dess–Martin periodinane in 3 mL dry CH2Cl2. Two drops of

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M. Kossenjans, J. Martens / Tetrahedron: Asymmetry 10 (1999) 3409–3416
CF3CO2H were added and the reaction mixture was stirred for 30 min. The homogeneous reaction
mixture was diluted with 20 mL Et2O and 20 mL 1 N NaOH and stirred for a further 20 min. The
separated organic layer was washed twice with water, dried over MgSO4 and concentrated in vacuo.
Final purification was performed by micro column chromatography (silica gel 69) to afford the optical
active products.
3.6. (2R)-1,3-Diphenyl-2-methyl-propan-1-one 8a
Eluent: n-hexane:ethyl acetate (8:2). Rf-value: 0.60, yield: 0.15 g (66% referred to 6b). [α]20 −70.2
D
(c=0.84, CHCl3); lit.14 [α]20 −71.7 (c=0.84, CHCl3). The spectral data are in accord with those in the
D
literature.14
3.7. (2S)-2-Phenylmethyl-1,2-tetrahydro-2H-naphthalin-1-one 8b
Eluent: n-hexane:ethyl acetate (8:2). Rf-value: 0.68, yield: 0.13 g (55% referred to 6c). [α]20 −16.7
D
(c=1.80, MeOH); lit.15 [α]20 +17.8 (c=1.89, MeOH) for (1R)-8b (92% ee). The spectral data are in
D
accord with those in the literature.15
Acknowledgements
We express our thanks to HMR Deutschland GmbH for the generous provision of chemicals and the
Heinz Neumüller Stiftung as well as the Fond der Chemischen Industrie for financial support. We thank
Professor Fuganti for a sample of enantiopure (1S,2S)-6.
References
1. Blaser, H.-U. Chem. Rev. 1992, 92, 935–952.
2. Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833–856.
3. Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835–875.
4. Oppolzer, W.; Radinow, R. N. Tetrahedron Lett. 1988, 29, 5645–5648.
5. Cho, B. T.; Kim, N. Synth. Commun. 1995, 25, 167–175.
6. Eilers, J.; Wilken, J.; Martens, J. Tetrahedron: Asymmetry 1996, 7, 2343–2357.
7. For a recent review see: Arend, M.; Westermann, B.; Risch, N. Angew. Chem. 1998, 110, 1096–1122; Angew. Chem., Int.
Ed. Engl. 1998, 37, 1044–1070.
8. Part 13 of our investigations concerning the utilization of industrial waste materials. For part 12 see: Wilken, J.; Gröger,
H.; Kossenjans, M.; Martens, J. Tetrahedron: Asymmetry 1997, 8, 2761–2771.
9. Wallbaum, S.; Mehler, T.; Martens, J. Synth. Commun. 1994, 24, 1381–1387.
10. (a) Teetz, V.; Geiger, R.; Henning, R.; Urbach, H. Arzneim.-Forsch. 1984, 34 (II), 1399–1401; (b) Teetz, V.; Geiger, R.;
Gaul, H. Tetrahedron Lett. 1984, 25, 4479–4482; (c) Henning, R.; Lerch, U.; Urbach, H. Synthesis 1989, 265–268.
11. Arend, M.; Risch, N. Synlett 1997, 974–976.
12. Seebach, D.; Betschart, C.; Schiess, M. Helv. Chim. Acta 1984, 67, 1593–1597.
13. Fogliato, G.; Fronza, G.; Fuganti, C.; Lanati, S.; Rallo, R.; Rigoni, R.; Servi, S. Tetrahedron 1995, 51, 10231–10240.
14. Oppolzer, W.; Darcel, C.; Rochet, P.; Rosset, S.; De Brabander, J. Helv. Chim. Acta 1997, 80, 1319–1337.
15. Murakata, M.; Nakajima, M.; Koga, K. J. Chem. Soc., Chem. Commun. 1990, 1657–1658.
16. Stork, G.; Brizzolara, A.; Landesman, H.; Szmuszkovicz, J.; Terrell, R. J. Am. Chem. Soc. 1963, 85, 207–222.
17. Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155–4156.