Stereoselective synthesis of 2-(α-hydroxyalkyl)benzimidazoles

Article abstract of DOI:10.1016/S0957-4166(98)00202-X

Lithiated oxazolo[3,4-a]benzimidazole 4 reacted with various alkyl halides to give oxazolo[3,4-a]benzimidazoles 5a-d in good yields as single diastereoisomers. (R)-Benzimidazol-2-yl carbinols 6a-d were obtained upon hydrolysis under acidic conditions of 1

Full text of DOI:10.1016/S0957-4166(98)00202-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 2245–2251
Stereoselective synthesis of 2-(α-hydroxyalkyl)benzimidazoles
Alan R. Katritzky,∗ Diana C. Aslan and Daniela C. Oniciu
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA
Received 24 February 1998; accepted 7 May 1998
Abstract
Lithiated oxazolo[3,4-a]benzimidazole 4 reacted with various alkyl halides to give oxazolo[3,4-
a]benzimidazoles 5a–d in good yields as single diastereoisomers. (R)-Benzimidazol-2-yl carbinols 6a–d
were obtained upon hydrolysis under acidic conditions of 1H,3H-oxazolo[3,4-a]benzimidazole derivatives.
© 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
2-(α-Hydroxybenzyl)benzimidazoles and related 2-(α-hydroxyalkyl)benzimidazoles are compounds
with high biological potential, as shown by the numerous reports on their various physiological actions:
respiratory, analeptic, analgesic, spasmolytic, antiinflammatory and antihypertensive.1a–d QSAR studies
and biological tests demonstrated that, of the two optical isomers of 2-(α-hydroxybenzyl)benzimidazole
derivatives, the (R)-enantiomer is more active and selective than the (S)-enantiomer.2 Previous syn-
thetic approaches to 2-(α-hydroxybenzyl)benzimidazoles have involved lithiation of an N-protected
benzimidazole, followed by the electrophilic attack of a carbonyl compound3a–c or direct reaction of
a benzimidazole with a ketone,1d these approaches provide the products as racemic mixtures.
We now report the synthesis of enantiomerically pure 2-(α-hydroxyalkyl)benzimidazoles 6b–d util-
izing 1H,3H-oxazolo[3,4-a]benzimidazoles 5b–d as key intermediates, themselves derived from chiral
(R or S)-2-(α-hydroxyethyl)benzimidazole 3 obtained from o-phenylenediamine 1 and the appropriate
enantiomer of lactic acid (R or S)-2.
∗
Corresponding author. E-mail: Katritzky@chem.ufl.edu
0957-4166/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00202-X

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2. Results and discussion
2.1. Synthesis of (1R,3R)-3-alkyl-3-methyl-1-phenyl-3H-[1,3]oxazolo[3,4-a]benzimidazoles and 2-(α-
hydroxyalkyl)benzimidazoles
We previously obtained excellent diastereoselectivity in the synthesis of 5-ethyl-5-methyl-1H,3H-
oxazolo[3,4-a]benzimidazole 5a by the route shown in Scheme 1.4 Condensation of 3 (obtained from
o-phenylenediamine 1 with (S)-lactic acid 2) with benzaldehyde dimethyl acetal in refluxing perfluoro-
carbon fluid using catalytic p-toluenesulfonic acid, following our previous work,4 yielded 50% of
compound 4 as a single diastereoisomer.
Scheme 1.
As before,4 lithiation of compound 4 with s-butyllithium in the presence of N,N,N0,N0-
tetramethylethylenediamine (TMEDA), followed by quenching with ethyl bromide gave compound 5a
as a single diastereoisomer and novel compounds 5b–d were obtained similarly in yields of 78–80%.
Thus this lithiation at the 5-C of the oxazole ring proceeded by the attack of the electrophile with
retention of configuration (Scheme 1). NOEDIF measurements together with earlier X-ray findings for
compounds 4 and 5a4 prove that the newly formed chiral center has a (R)-configuration, as is further
discussed below.
1
The analysis of the H-NMR and GC–MS spectra of the crude reaction mixtures of products 5a–d
showed that the isomers of 5a–d with an inverted configuration at C-5 were formed in less than 5%,
and substitution in position 2 does not occur. However, the regioselectivity of the method does not prove
a higher thermodynamic acidity of the proton attached to 5-C, as steric effects may be involved. The
stereoselectivity is strongly influenced by the molarity of the reaction mixture: when the concentration is
higher than 8×10−3 M, the ratio between the two diastereomers increases up to 1:1 for a concentration
of 2×10−2 M.
1
The structures assigned to compounds 5a–d were confirmed by H- and 13C-NMR. All compounds
present signals characteristic for the 5-methyl group: a singlet in the 1H-NMR spectra at about 1.80–1.90
ppm, and a signal at 25–26 ppm in the 13C-NMR spectra, the latter was unequivocally assigned to

A. R. Katritzky et al. / Tetrahedron: Asymmetry 9 (1998) 2245–2251
2247
Fig. 1. Results of NOE experiments for compounds 5b and 5d
1
a methyl group by ‘attached proton test’ experiments. The H-NMR spectra of compounds 5a–d all
feature the characteristic benzimidazole coupling pattern: d–t–t–d with 8.10–8.40 Hz coupling constants
(ortho coupling), corresponding to four adjacent aromatic protons (exceptionally for compound 5c the
aromatic signals of the benzyl group overlap those of benzimidazole). In the 13C-NMR spectra, the six
benzimidazole ring signals are also well defined, at about 160, 149, 135, 123, 122, 120 and 110 ppm.
The chemical shifts of the hydrogen (5.70–6.70 ppm, singlet) and carbon (88 ppm) in the 2-position of
the oxazole ring are deshielded, due to the presence of vicinal heteroatoms.
The results of NOEDIF experiments for compounds 5b and 5d are depicted in Fig. 1. In compound
5b, irradiating the 2-H induced positive NOE’s at the signals characteristic for the 5-butyl group.
Interestingly, there is a higher positive NOE on the β-CH2 of the n-butyl group than on the α-CH2,
which may suggest that the molecule adopts a specific conformation in solution. Irradiating the signal
characteristic for the phenyl group caused a positive NOE to be observed at the 5-CH3 hydrogen atoms.
In compound 5d, irradiation of the allylic methylene produced a positive NOE at the hydrogen in position
2. In agreement with this, irradiation of the 5-CH3 protons produced a positive NOE on the phenyl ring
protons.
Compounds 5a–d were hydrolyzed under mild acidic conditions (Et2O, 5% HCl) to give enan-
tiomerically pure 2-(α-hydroxyalkyl)-benzimidazoles 6a–d. The enantiomeric purity was determined
by measuring the rotation angles of the polarized light: αD values for compounds 5a–d range between
66 and 94, while for compounds 6a–d are found between 16.3 and 89.1.
1H,3H-Oxazolo[3,4-a]benzimidazole derivatives 5b–d were converted to the benzimidazolium iodides
7b–d, which were reduced, in the presence of sodium borohydride, to compounds 8b–d (Scheme 2). Sur-
prisingly, the hydrolysis of compounds 8b–d under mild acidic conditions as described by Mukaiyama
for the cleavage of similar imidazole derivatives5a,b did not afford the expected α-hydroxy aldehydes,
but decomposition products, perhaps due to the extended conjugation of the unshared pair of electrons of
the nitrogen atom in position 3 with the fused benzene ring.
Scheme 2.

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3. Conclusions
In the present work the yield of compound 5a was significantly improved compared to that previ-
ously reported.4 1H,3H-Oxazolo[3,4-a]benzimidazoles 5a–d were converted into 2-(α-hydroxyalkyl)-
benzimidazoles 6a–d in excellent yields, thus providing an efficient approach to stereoselective synthesis
of 2-(α-hydroxyalkyl)benzimidazoles as pure (R)-enantiomers.
4. Experimental
4.1. General procedure for the synthesis of compounds 5a–d
A solution of 5-methyl-2-phenyl-oxazolo[3,4-a]benzimidazole 4 (1 equiv.) in THF at −78°C under an
argon atmosphere was treated with s-BuLi (1.1 equiv., 1.3 M in cyclohexane) and TMEDA (1 equiv.),
with stirring. The resulting suspension was kept at −78°C for 2 h, when the appropriate electrophile
(alkyl halide) (1 equiv.) was added. The reaction mixture was stirred at −78°C for 2 h, and then at room
temperature overnight. The reaction was quenched with saturated NH4Cl, extracted with diethyl ether,
and the organic layer dried (Na2SO4). The solvent was removed under vacuum to give the product as a
yellow oil. The crude product was purified by column chromatography on silica gel using a 1:2 mixture
of hexane:diethyl ether as eluent.
4.1.1. (1R,3R)-3-Ethyl-3-methyl-1-phenyl-3H-[1,3]oxazolo[3,4-a]benzimidazole (5a)4
Yield 85%, m.p. 122–123°C (lit.4 122–124°C); [α]D=103.0.
4.1.2. (1R,3R)-3-Butyl-3-methyl-1-phenyl-3H-[1,3]oxazolo[3,4-a]benzimidazole (5b)
Yield 80%, m.p. 120–121°C; [α]D=78.4 at 25°C (c=0.01 g/ml, chloroform); δH (CDCl3): 7.78 (d,
J=8.1 Hz, 1H), 7.42 (s, 5H), 7.23 (t, J=7.2 Hz, 1H), 7.08 (t, J=7.5 Hz, 1H), 6.85 (d, J=7.9 Hz, 1H), 6.70
(s, 1H), 2.07–2.02 (m, 2H), 1.83 (s, 3H), 1.59–1.57 (m, 1H), 1.37–1.22 (m, 3H), 0.88 (t, J=6.0 Hz, 3H);
δC (CDCl3): 161.5, 149.2, 136.1, 130.3, 130.0, 129.0, 127.1, 122.4, 122.4, 120.1, 110.0, 88.4, 82.2, 39.9,
26.0, 25.9, 22.7, 13.8. Anal. calcd for C20H22N2O: C, 78.40; H, 7.24; N, 9.14. Found: C, 78.08; H, 7.36;
N, 9.16.
4.1.3. (1R,3R)-3-Benzyl-3-methyl-1-phenyl-3H-[1,3]oxazolo[3,4-a]benzimidazole (5c)
Yield 78%, oil; [α]D=94.1 at 25°C (c=0.01 g/ml, chloroform); δH (CDCl3): 7.78 (d, J=8.4 Hz, 1H),
7.39–6.98 (m, 12H), 6.64 (d, J=8.1 Hz, 1H), 5.74 (s, 1H), 3.44 (d, J=13.8 Hz, 1H), 3.25 (d, J=13.8
Hz, 1H), 1.91 (s, 3H); δC (CDCl3): 160.5, 149.1, 135.6, 135.4, 130.2, 130.1, 129.8, 128.8, 127.9,
127.6, 127.0, 126.8, 122.2, 120.0, 109.7, 88.4, 82.3, 46.1, 26.3. HRMS (POS FAB NBA) m/e calcd
for C23H20N2O+H+: 341.1653. Found: 341.1659 (M+1).
4.1.4. (1R,3R)-3-Allyl-3-methyl-1-phenyl-3H-[1,3]oxazolo[3,4-a]benzimidazole (5d)
Yield 79%, oil; [α]D=66.7 at 25°C (c=0.01 g/ml, chloroform); δH (CDCl3): 7.76 (d, J=8.4 Hz, 1H),
7.42 (m, 5H), 7.22 (t, J=7.4 Hz, 1H), 7.07 (t, J=7.4 Hz, 1H), 6.84 (d, J=8.0 Hz, 1H), 6.69 (s, 1H),
5.87–5.75 (m, 1H), 5.20 (d, J=17.0 Hz, 1H), 5.11 (d, J=10.2 Hz, 1H), 2.81–2.72 (m, 2H), 1.83 (s, 3H);
δC (CDCl3): 161.0, 149.3, 135.9, 131.8, 130.4, 130.1, 129.0, 127.1, 122.5, 122.4, 120.2, 119.9, 110.0,
88.5, 81.6, 44.2, 25.7. Anal. calcd for C19H18N2O: H, 6.25; N, 9.65. Found: H, 6.50; N, 9.88.

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4.2. General procedure for the synthesis of 2-(α-hydroxyalkyl)benzimidazoles 6a–d
A solution of compound 5 (4 mmol) in ether was treated with an excess of 5% HCl and the reaction
mixture stirred for 2 days at room temperature. The mixture was extracted with chloroform (2×100 ml),
the aqueous layer was neutralized with 5% NaHCO3 aqueous solution and extracted with chloroform
(2×50 ml). This second organic layer was dried (Na2SO4) and evaporated under vacuum to give a white
solid.
4.2.1. (2R)-2-(1H-Benzimidazo-2-yl)-1-butan-2-ol (6a)
Yield 78%, m.p. 170–172°C; [α]D=16.3 at 25°C (c=0.01 g/ml, methanol) δH (DMSO-d6): 7.49–7.47
(m, 2H), 7.12–7.09 (m, 2H), 5.44 (s, 1H), 3.37 (br s, 1H), 1.88–1.83 (m, 2H), 1.54 (s, 3H), 0.76 (t, J=7.2
Hz, 3H); δC (DMSO-d6): 160.5, 125.6, 123.0, 121.1, 121.0, 120.9, 112.8, 71.6, 35.2, 27.8, 8.3. Anal.
calcd for C11H14N2O: N, 14.72. Found: N, 14.82. HRMS (POS FAB NBA) m/e calcd for C11H14N2O
190.1106. Found: 190.1106 (M).
4.2.2. (2R)-2-(1H-Benzimidazo-2-yl)-1-hexan-2-ol (6b)
Yield 80%, m.p. 158–160°C; [α]D=22.8 at 25°C (c=0.01 g/ml, methanol); δH (DMSO-d6): 12.07 (br
s, 1H), 7.48 (s, 2H), 7.12–7.09 (m, 2H), 5.45 (s, 1H), 1.91–1.74 (m, 2H), 1.56 (s, 3H), 1.40–1.00 (m,
4H), 0.80 (t, J=6.9 Hz, 3H); δC (DMSO-d6): 160.6, 120.8, 114.0, 112.9, 71.2, 42.3, 28.1, 25.6, 22.3, 13.8
(the benzimidazole signals are not always observable). Anal. calcd for C13H18N2O: C, 71.53; H, 8.31;
N, 12.83. Found: C, 71.34; H, 8.49; N, 12.92.
4.2.3. (2R)-2-(1H-Benzimidazo-2-yl)-1-phenylpropan-2-ol (6c)
Yield 71%, m.p. 207–208°C; [α]D=80.4 at 25°C (c=0.01 g/ml, methanol); δH (DMSO-d6): 12.07 (br
s, 1H), 7.57 (s, 1H), 7.42 (s, 1H), 7.14–7.05 (m, 7H), 5.71 (s, 1H), 3.19 (q, J=13.2 Hz, 2H), 1.54 (s, 3H);
δC (DMSO-d6): 160.5, 143.2, 137.4, 134.1, 130.4, 127.6, 126.1, 121.5, 120.9, 118.4, 111.4, 71.9, 48.1,
27.9. Anal. calcd for C16H16N2O: N, 11.10. Found: N, 11.03. HRMS (POS FAB NBA) m/e calcd for
C16H16N2O 252.1262. Found: 252.1259 (M).
4.2.4. (2R)-2-(1H-Benzimidazo-2-yl)-4-penten-2-ol (6d)
Yield 60%, m.p. 165–167°C; [α]D=89.1 at 25°C (c=0.01 g/ml, methanol); δH (DMSO-d6): 12.13 (br
s, 1H), 7.56–7.53 (m, 1H), 7.44–7.41 (m, 1H), 7.15–7.07 (m, 2H), 5.82–5.71 (m, 1H), 5.63 (s, 1H),
5.03–4.96 (m, 2H). 2.62 (d, J=6.9 Hz, 2H), 1.55 (s, 3H); δC (DMSO-d6): 160.3, 143.1, 134.2, 134.2,
121.4, 120.8, 118.4, 117.6, 111.3, 71.1, 46.8, 27.6. Anal. calcd for C12H14N2O: C, 71.26; H, 6.98; N,
13.85. Found: C, 70.89; H, 7.00; N, 13.90.
4.3. General procedure for the synthesis of compounds 7b–d
A solution of (1R,3R)-3-alkyl-3-methyl-1-phenyl-3H-[1,3]oxazolo[3,4-a]benzimidazole 5b–d (1
equiv.) was stirred into an excess of MeI (10 equiv.), until no more starting material was observed (by
GC). The excess MeI was evaporated under vacuum to give a yellow oil.
4.3.1. (1R,3R)-3-Butyl-3,4-dimethyl-1-phenyl-3H-[1,3]oxazolo[3,4-a]benzimidazol-4-ium iodide (7b)
Yield 93%, oil; [α]D=12.0 at 25°C (c=0.01 g/ml, chloroform), mixture of diastereomers A:B=1:1.5;
δH (CDCl3): 8.00–7.93 (m, 2H, A+B), 7.75–7.37 (m, 16H, A+B), 7.09 (d, J=8.4 Hz, 1H, A), 7.01 (d,
J=8.4 Hz, 1H, B), 4.32 (s, 6H, A+B), 2.45–2.02 (m, 10H, A+B), 1.70–1.61 (m, 2H, A+B), 1.48–1.23 (m,

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A. R. Katritzky et al. / Tetrahedron: Asymmetry 9 (1998) 2245–2251
6H, A+B), 0.95–0.90 (m, 6H, A+B); δC (CDCl3): 156.2 (A), 156.0 (B), 137.4 (B), 137.3 (A), 131.8 (A),
131.8 (B), 131.4 (A), 131.4 (B), 129.3 (A), 129.1 (B), 129.1 (A), 128.6 (B), 127.8 (B), 127.8 (A), 127.1
(B), 127.0 (A), 126.3 (A), 125.8 (B), 114.2 (B), 114.1 (A), 113.1 (A), 113.0 (B), 91.3 (B), 90.7 (A), 84.5
(B), 84.4 (A), 37.8 (B), 37.3(A), 33.8 (B), 33.2 (A), 25.9 (A), 25.5 (B), 24.1 (A), 24.1 (A), 22.1 (B), 22.0
(A), 13.6 (B), 13.5 (A) (the benzimidazole signals are not always observable). HRMS (POS FAB NBA)
m/e calcd for C21H25N2O+ 321.1967. Found: 321.1967 (M−I−).
4.3.2. (1R,3R)-3-Benzyl-3,4-dimethyl-1-phenyl-3H-benzo[4,5]imidazo[1,2-c][1,3]oxazol-4-ium iodide
(7c)
Yield 96%, oil; [α]D=27.8 at 25°C (c=0.01 g/ml, chloroform), mixture of diastereomers A:B=1:2; δH
(CDCl3): 8.11 (d, J=7.8 Hz, 1H, A), 7.87 (d, J=8.7 Hz, 1H, A), 7.84 (d, J=8.7 Hz, 1H, B), 7.63 (d, J=6.9
Hz, 1H, B), 7.59–7.00 (m, 12H, A+B), 6.91 (d, J=8.4 Hz, 1H, B), 6.84 (d, J=8.3 Hz, 1H, A), 4.38 (s,
3H, A), 4.00 (s, 3H, B), 3.69 (s, 2H, B), 3.61 (s, 2H, A), 2.17 (s, 3H, B), 2.14 (s, 3H, A); δC (CDCl3):
155.7 (A), 155.2 (B), 137.3 (A), 137.2 (B), 133.3 (A), 133.1 (B), 131.6 (B), 131.5 (A), 131.5 (B), 131.3
(A), 130.2 (A), 130.2 (B), 129.2 (B), 128.9 (A), 128.8 (B), 128.6 (A), 128.0 (A), 128.0 (B), 127.9 (A),
127.9 (B), 127.5 (A), 127.4 (A), 127.2 (B), 127.1 (B), 126.3 (A), 125.8 (B), 116.1 (A), 114.1 (B), 113.1
(A), 112.9 (B), 91.4 (B), 91.1 (A), 85.1 (2C, A+B), 44.5 (B), 44.2 (A), 34.7 (A), 34.0 (B), 24.8 (A),
24.1 (B). Anal. calcd for C24H23N2OI: N, 5.81. Found: N, 5.42. HRMS (POS FAB NBA) m/e calcd. for
C24H23N2O+ 355.1810. Found: 355.1810 (M−I−).
4.3.3. (1R,3R)-3-Allyl-3,4-dimethyl-1-phenyl-3H-benzo[4,5]imidazo[1,2-c][1,3]oxazol-4-ium iodide
(7d)
Yield 96%, oil; [α]D=7.1 at 25°C (c=0.01 g/ml, chloroform), mixture of diastereoisomers A:B=3:1;
δH (CDCl3): 7.90 (d, 1H, J=8.4 Hz, A), 7.89 (d, 1H, J=11.0 Hz, B), 7.74 (d, 1H, J=6.17 Hz, A), 7.68
(d, 1H, J=6.87 Hz, B), 7.62–7.35 (m, 7H, A+B), 7.06 (d, J=8.4 Hz, 1H, A), 7.00 (d, J=8.4 Hz, 1H, B),
6.00–5.89 (m, 1H, A+B), 5.45–5.38 (m, 1H, A+B), 5.31–5.25 (m, 1H, A+B), 4.31 (s, 3H, A), 4.27 (s,
3H, B), 3.25–3.06 (m, 2H, A+B), 2.14 (s, 3H, A), 2.12 (s, 3H, B); δC (CDCl3): 155.4 (A), 155.4 (B),
137.4 (A+B), 131.7 (A), 131.4 (A+B), 131.2 (B), 129.9 (B), 129.5 (A), 129.3 (B), 129.2 (A), 128.7 (B),
127.9 (2C, A+B), 127.1 (A), 127.1 (B), 125.9 (A), 122.4(A), 121.4 (B), 114.1 (A), 114.0 (B), 113.1 (B),
113.0 (A), 91.4 (A), 90.8 (B), 84.6 (B), 84.4 (A), 42.7 (A), 42.0 (B), 34.5 (A), 34.2 (B), 24.2 (B), 24.1
(A). HRMS (POS FAB NBA) m/e calcd for C20H21N2O+ 305.1653. Found: 305.1653 (M−I−).
4.4. General procedure for the synthesis of compounds 8b–d
A solution of (1R,3R)-3-alkyl-3-methyl-1-phenyl-3H-[1,3]oxazolo[3,4-a]benzimidazole 5b–d (1
equiv.) was stirred in an excess of MeI (10 equiv.), until no more starting material was observed (by
GC). The excess MeI was evaporated under vacuum and the resulting yellow oil was dissolved in 20
ml of MeOH at 0°C. To the stirred solution NaBH4 (10 equiv.) was added portionwise, and the reaction
mixture was refluxed for 18 h. The solvent was evaporated under vacuum, and the residue dissolved
in methylene chloride (50 ml). The organic layer was washed with water (2×30 ml), dried (Na2SO4),
and the solvent evaporated. Purification by flash chromatography (silica gel/hexane:ether=1:2) gave the
product as a yellow oil.
4.4.1. (1R,3R)-3-Butyl-3,4-dimethyl-1-phenyl-3a,4-dihydro-3H-[1,3]oxazolo[3,4-a]benzimidazole (8b)
Yield 84%, oil; [α]D=6.02 at 25°C (c=0.01 g/ml, chloroform), mixture of diastereoisomers A:B=1:1,
δH (CDCl3): 7.55 (d, J=6.9 Hz, 2H, A+B), 7.40–7.30 (m, 3H, A+B), 6.78 (t, J=6.0 Hz, 1H, A), 6.75

A. R. Katritzky et al. / Tetrahedron: Asymmetry 9 (1998) 2245–2251
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(t, J=6.0 Hz, 1H, B), 6.52 (t, J=6.0 Hz, 1H, A), 6.50 (t, J=6.0 Hz, 1H, B), 6.39–6.29 (m, 2H), 5.55 (s,
1H, A), 5.49 (s, 1H, B), 4.91 (s, 1H, A), 4.86 (s, 1H, B), 2.83 (s, 3H, A+B), 2.76–1.17 (m, 9H, A+B),
0.95–0.84 (m, 3H, A+B); δC (CDCl3): 145.7 (B), 145.7 (A), 140.8 (B), 140.6 (A), 128.7 (A), 128.6 (B),
128.4 (A), 128.3 (B), 127.1 (A), 127.0 (B), 122.3 (B), 122.0 (A), 118.2 (A), 118.0 (B), 110.9 (B), 110.2
(A), 105.7 (A), 105.2 (B), 95.1 (A), 94.8 (B), 94.7 (A), 93.0 (B), 85.0 (A), 84.4 (B), 39.7 (1C, A+B),
34.8 (A), 34.5 (B), 31.5 (A), 31.2 (B), 25.9 (A), 25.0 (B), 23.3 (A), 23.2 (B), 18.1 (1C, A+B), 14.0 (A),
13.9 (B). Anal. calcd for C21H26N2O: N, 8.69. Found: N, 8.55.
4.4.2. (1R,3R)-3-Benzyl-3,4-dimethyl-1-phenyl-3a,4-dihydro-3H-[1,3]oxazolo[3,4-a]benzimidazole
(8c)
Yield 88%, oil, mixture of diastereomers A:B=5:1; [α]D=118.5 at 25°C (c=0.01 g/ml, chloroform);
δH (CDCl3): 7.87 (d, J=6.9 Hz, 1H, A), 7.64–7.15 (m, 9H, A), 7.64–7.15 (m, 10H, B), 6.80 (t, J=6.0 Hz,
1H, A), 6.78 (t, J=6.0 Hz, 1H, B), 6.57 (t, J=6.0 Hz, 1H, A), 6.54 (t, J=6.0 Hz, 1H, B), 6.42 (t, J=8.7 Hz,
2H, A+B), 5.83 (s, 1H, A), 5.56 (s, 1H, B), 5.04 (s, 1H, A), 5.00 (s, 1H, B), 3.00 (d, J=14.4 Hz, 1H, B),
2.94, (d, J=19.2 Hz, 1H, A), 2.94 (s, 3H, A+B), 2.61 (d, J=19.2 Hz, 1H, A), 2.55 (d, J=14.4 Hz, 1H, B),
1.27 (s, 3H, A+B); δC (CDCl3): 145.6 (2C, A+B), 140.7 (1C, A+B), 140.5 (1C, A+B), 137.1 (A), 139.4
(B), 130.8 (B), 130.5 (A), 128.9 (B), 128.8 (A), 128.5 (A), 128.4 (B), 128.1 (B), 127.9 (A), 127.3 (B),
127.0 (A), 126.7 (B), 126.2 (A), 122.4 (B), 122.2 (A), 118.4 (A), 118.2 (B), 110.8 (B), 110.3 (A), 105.7
(A), 105.7 (B), 95.1 (B), 95.0 (A), 94.9 (A), 91.6 (B), 84.9 (B), 84.3 (A), 46.0 (B), 37.4 (A), 35.1 (A),
31.6 (B), 23.3 (A), 22.6 (B). Anal. calcd for C24H24N2O: N, 7.86. Found: N, 5.42.
4.4.3. (1R,3R)-3-Allyl-3,4-dimethyl-1-phenyl-3a,4-dihydro-3H-[1,3]oxazolo[3,4-a]benzimidazole (8d)
Yield 85%, oil; [α]D=23.6 at 25°C (c=0.01 g/ml, chloroform), mixture of diastereomers A:B=2:1; δH
(CDCl3): 7.54 (d, J=7.8 Hz, 2H, A+B), 7.39–7.23 (m, 3H, A+B), 6.79–6.73 (m, 1H, A+B), 6.53 (d, J=7.5
Hz, 1H, A), 6.50 (d, J=7.5 Hz, 1H, B), 6.38–6.32 (m, 2H, A+B), 5.95–5.83 (m, 1H, A+B), 5.85 (s, 1H,
A), 5.57 (s, 1H, B), 5.16–5.01 (m, 2H, A+B), 4.92 (s, 1H, A), 4.90 (s, 1H, B), 2.82 (s, 3H, A), 2.79 (s,
3H, B), 2.46–2.37 (m, 2H, A), 2.11–2.04 (m, 2H, B), 1.36 (s, 3H, A), 1.17 (s, 3H, B); δC (CDCl3): 145.4
(1C, A+B), 140.5 (1C, A+B), 133.2 (B), 133.0 (A), 128.7 (A), 128.6 (B), 128.4 (A), 128.3 (B), 128.2
(B), 127.9 (A), 127.1 (B), 126.9 (A), 122.4 (B), 122.1 (A), 118.5 (B), 118.2 (A), 118.2 (A), 117.8 (B),
110.9 (B), 110.1 (A), 105.8 (B), 105.4 (A), 95.0 (A), 94.9 (B), 94.1 (A), 92.0 (B), 84.2 (B), 83.7 (A),
44.3 (A), 36.5 (B), 34.8 (B), 34.7 (A), 23.2 (A), 18.5 (B). Anal. calcd for C20H22N2O: N, 9.14. Found:
N, 8.73.
References
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