An improved preparation of epoxides from carbonyl compounds by using diiodomethane/methyllithium: Synthetic applications

Article abstract of DOI:10.1016/S0040-4020(01)00890-0

Synthesis of epoxides starting from different carbonyl compounds is easily carried out by using a diiodomethane and methyllithium at 0°C and a short reaction time. Starting from α-aminoaldehydes the reaction affords amino epoxides, with high diastereoselectivity. The products were transformed into 1,3-diaminoalkan-2-ols by treatment with different amines.

Full text of DOI:10.1016/S0040-4020(01)00890-0

TETRAHEDRON
Pergamon
Tetrahedron 57 12001) 8983±8987
An improved preparation of epoxides from carbonyl compounds
by using diiodomethane/methyllithium: synthetic applications
p
Jose M. Concellon, Humildad Cuervo and Ramon Fernandez-Fano
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Departamento de Quõmica Organica e Inorganica, Facultad de Quõmica, Universidad de Oviedo, Julian Claverõa 8, 33071Oviedo, Spain
Received 2 July 2001; revised 13 August 2001; accepted 4 September 2001
AbstractÐSynthesis of epoxides startingfrom different carbonyl compounds is easily carried out by usinga diiodomethane and methyl-
lithium at 08C and a short reaction time. Startingfrom a-aminoaldehydes the reaction affords amino epoxides, with high diastereoselectivity.
The products were transformed into 1,3-diaminoalkan-2-ols by treatment with different amines. q 2001 Elsevier Science Ltd. All rights
reserved.
1. Introduction
compounds by usinghalomethyllithium at 0 8C has not
been reported in the literature to date.
Transformation of carbonyl compounds into epoxides is a
reaction of considerable importance, because of the fact that
the epoxide obtained can be manipulated further in a variety
of synthetically useful reactions. In this sense, an oxirane
ringcan be opened by a variety of nucleophiles, affording
1,2-difunctionalized systems which can undergo rearrange-
ment reactions, such as chain elongation or ring expansion
processes.1
On the other hand, 1,3-diamines are used as catalyst and
chiral auxiliaries in asymmetric synthesis11 and these
compounds 1especially chiral ones) are also of great interest
in medicinal chemistry, e.g. in cancer12 or AIDS research
1protease inhibitors).13 However, although the number of
reports on the preparation of 1,3-diamines14 has grown
over the last few years, this class of compounds is not
receivingthe attention which has been devoted to its 1,2-
analogues.15
The classical reagents to transform carbonyl compounds
into epoxides are sulfur ylides.2 Other epoxidation reagents
are the a-heterosubstituted organometallic reagents,3
including a-halogenated organometallic compounds
1principally, chloromethyllithium, generated by lithiation
of chloroiodomethane at 2788C).4 In this sense, we have
reported the synthesis of chiral amino epoxides with high
diastereoselectivity, by treatment of a-amino aldehydes
with halomethyllithium generated in situ at 2788C.5
However, the use of a-halogenated organolithium
Here we wish to report a general, easy and simple trans-
formation of aldehydes and ketones into epoxides using
iodomethyllithium generated in situ 1from diiodomethane
and methyllithium) at 08C and the transformation of the
prepared amino epoxides 1from a-aminoaldehydes) into
the corresponding1,3-diaminoalkan-2-ols 4, by treatment
with different amines.
È
compounds 1Kobrich reagents) is limited by their thermal
instability.6 For this reason, a number of methods to carry
2. Results and discussion
È
out the addition of Kobrich reagents to carbonyl compounds
The reaction of different aldehydes or ketones 1 with iodo-
methyllithium 1generated in situ from diiodomethane and
methyllithium) at 08C led to the expected iodinated alkoxide
2, which undergoes spontaneous epoxidation yielding, after
the usual work-up, the correspondingoxirane 3 1Scheme 1).
While reactions with aldehydes were carried out usinga
molar ratio 1/CH2I2/MeLiˆ1:1.5:2, in the case of ketones
a higher molar ratio was necessary 11/CH2I2/MeLiˆ1:2:3)
due to their lower reactivity in comparison to aldehydes.
at higher temperature have been described. Thus, addition of
this anions with sonication at 2158C,7 the use of phase
transfer catalysis at room temperature,8 ¯uoride catalysis
from TMS-containingprecursor at 0 8C,9 or replacement of
the lithium counterion 1normally present) with a variety of
transition metals 1chie¯y, titanium, hafnium and copper) at
08C10 have been reported. However, to the best of our
knowledge, synthesis of epoxides from carbonyl
Keywords: epoxides; diastereoselection; iodomethyllithium; carbonyl
compounds.
Correspondingauthor. Tel.: 134-8-510-3457; fax: 134-98-510-3446;
e-mail: jmcg@sauron.quimica.uniovi.es
Analysis of Table 1 reveals that the reaction is general:
oxiranes derived from lineal, branched and cyclic aliphatic,
and aromatic aldehydes and linear, cyclic aliphatic and
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020101)00890-0

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J. M. Concellon et al. / Tetrahedron 57 +2001) 8983±8987
8984
Scheme 1. Transformation of carbonyl compounds into epoxides 3.
Table 1. Epoxidation reaction of carbonyl compounds
de®ciency syndrome 1AIDS).18 This hydroxyethylamine
moiety can be obtained by treatment of amino epoxides
with different amines. For this reason and to prove the
synthetic usefulness of the amino epoxides obtained, we
have prepared 1,3-diaminoalkan-2-ols from 3f and 3g.
Entry
Product
R1
R2
Yield 1%)a
1
2
3
4
5
6
7
8
3a
3b
3b
3b
3c
3d
3e
3f
3g
3h
3i
3j
3j
Cyclohexyl
Ph
Ph
Ph
pClPh
C7H15
H
72
70b
83
H
H
H
H
H
80c
Treatment of a solution of erythro amino epoxides 3f and 3g
in acetonitrile with different amines in the presence of
lithium perchlorate19 led to the corresponding1,3-di-
aminoalkan-2-ols 4 1Scheme 2) in high yield 1Table 2).
The reaction was completely regioselective with the attack
of the nucleophile on the less substituted oxirane carbon.
91
83
Citronellal
Alaninal
Phenylalaninal
95
93d
91e
9
10
11
12
13
14
15
C5H11
Me
45 172)
35 180)
89b
79
79
70
±1CH2)7±
Ph
Ph
Ph
Bn
Me
Me
Et
3k
3l
Me
a
Yield based on the startingcarbonyl compound 1; all epoxides were fully
characterized by spectroscopy methods 1IR, NMR and MS).
Reaction temperature 2788C.
b
c
d
The reaction was carried out without nitrogen atmosphere.
deˆ90% 1determined by 300 MHz 1H NMR analysis of the crude
product.
Scheme 2. Synthesis of 1,3-diaminoalkan-2-ols 4.
Table 2. Synthesis of 1,3-diaminoalkan-2-ols 4
e
deˆ94% 1determined by 300 MHz 1H NMR analysis of the crude
product.
Entry
Product
R1
NHR2R3
Yield 1%)a
aromatic ketones have been obtained. In addition, under
these reaction conditions, the epoxides 3 obtained from
aldehydes, were obtained in high yield, similar to that
obtained at 2788C 1Table 1, entries 2 and 12), and the iso-
lation of pure epoxides 3 only required the removal of the
solvents 1purity .95%). The yield of 3, obtained from
ketones, was lower and the epoxide appeared contaminated
by small amounts of the correspondingmethyl alcohol
1addition of methyllithium to the ketone); consequently,
puri®cation by column chromatography was necessary.
1
2
3
4ab
4bc
4cc
Me
Bn
Bn
BnNH2
Et2NH
BnNH2
97.5
78
80
a
Yield of 4 based on the startingaminoepoxide 3f and 3g.
Reaction time 48 h.
Reaction time 16 h.
b
c
3. Conclusion
We have described a simple and general transformation of
carbonyl compounds into epoxides at 08C, which take place
in high yield and with high diastereoselectivity. We believe
that the methodology described represents an important
improvement in the transformation of carbonyl compounds
into epoxides by usingiodomethyllithium. We have also
described an easy transformation of the amino epoxides,
obtained by means of the described methodology, into
1,3-diaminoalkan-2-ols.
It is noteworthy that the epoxidation reaction at 08C take
place with high diastereoselectivity. Starting from N,N-
dibenzylalaninal or phenylalaninal, the corresponding
erythro amino epoxides have been obtained with high dia-
stereoselective excess 190 and 94%, respectively) this being
similar to that obtained at 2788C 1deˆ98 and 92%).3 The
diastereoisomeric excess was determined by using300 MHz
1H NMR and the stereochemistry of amino epoxides was
established unambiguously by comparison with the same
compounds obtained at 2788C.5 The observed stereo-
chemistry can be explained by assuminga nonchelation
control model in the iodomethylation reaction of carbonyl
compounds, due to the steric constraints imparted by the
bulky N,N-dibenzyl protectinggroup.
4. Experimental
4.1. General
The protease inhibitors, such as VX-478 1Vertex-Glaxo
Wellcome)16 and SC-52151 1Searle-Monsanto),17 involving
the hydroxyethylamine moiety are very promisingthera-
peutic agents for the treatment of acquired immuno-
Reactions requiringan inert atmosphere were conducted
under dry nitrogen, and the glassware was oven dried
11208C). THF and ether were distilled from sodium/benzo-
phenone ketyl immediately prior to use. All reagents were

Â
J. M. Concellon et al. / Tetrahedron 57 +2001) 8983±8987
8985
purchased from Aldrich or Merck and were used without
further puri®cation. Silica gel for ¯ash chromatography was
purchased from Scharlau or Merck 1200±450 mesh), and
compounds were visualized on analytical thin layer chro-
matograms 1TLC) by UV light 1254 nm). Optical rotations
were measured in chloroform 1H NMR spectra were
recorded at 200, 300 or 400 MHz. 13C NMR spectra and
DEPT experiments were determined at 50 or 75 MHz.
Chemical shifts are given in ppm relative to tetramethyl-
silane 1TMS), which is used as an internal standard, and
couplingconstants 1 J) are reported in Hz. The diastereo-
Jˆ4.61 Hz); 13C NMR 1CDCl3, 50 MHz) d 52.1 1CH),
46.8 1CH2), 32.3 1CH2), 31.6 1CH2), 29.2 1CH2), 29.0
1CH2), 25.8 1CH2), 22.4 1CH2), 13.8 1CH3); MS 1EI) m/z
1%): 142 1M1, 8), 127 140), 57 1100); IR 1NaCl) 2927,
2856, 1265.
4.2.5. 2-(2,6-Dimethylhept-5-enyl)oxirane (3e). Rfˆ0.25
1
1hexane/AcOEt 10/1); H NMR 1CDCl3, 200 MHz) d 5.06
11H, t, Jˆ7.08 Hz), 2.92±2.89 11H, m), 2.76±2.70 11H, m),
2.44±2.38 11H, m), 1.98±1.95 12H, m), 1.65 16H, s), 1.48±
1.34 15H, m), 0.98 and 0.96 13H, 2d, Jˆ3.08 Hz); 13C NMR
1CDCl3, 50 MHz) d 131.1 1C), 124.3 1CH), 47.3 1CH), 46.8
1CH2), 39.6 1CH2), 37.1 1CH2), 36.7 1CH2), 30.9 1CH), 30.4
1CH), 25.5 1CH3), 25.2 1CH2), 19.7 1CH3), 19.3 1CH3), 17.4;
IR 1NaCl) 3050, 2960.
1
meric excesses were obtained using H NMR analysis and
GC±MS of crude products. Only the most important IR
absorptions 1in cm21) and the molecular ions and/or base
peaks in MS are given.
4.2.6. (1S)-[10(S)-(Dibenzylamino)ethyl]oxirane (3f).
4.2. General procedure for the preparation of epoxides 3
from carbonyl compounds
25
[a]D ˆ19.38 1c 0.65, CHCl3); Rfˆ0.51 1hexane/AcOEt
1
10/1); H NMR 1CDCl3, 300 MHz) d 7.45±7.22 110H, m),
3.87 12H, d, Jˆ14.00 Hz), 3.64 12H, d, Jˆ14.00 Hz), 3.15±
3.10 11H, m), 2.92±2.77 11H, m), 2.72 11H, dd, Jˆ4.11 and
4.87 Hz), 2.44 11H, dd, Jˆ2.90 and 4.80 Hz), 1.07 13H, d,
Jˆ7.00 Hz); 13C NMR 1CDCl3, 75 MHz) d 140.1 1C), 128.2
1CH), 128.1 1CH), 126.6 1CH), 55.2 1CH), 53.9 1CH2), 53.4
1CH), 44.5 1CH2), 8.5 1CH3); MS 1EI) m/z 1%): 267 1M1, 2),
224 18), 91 1100); IR 1NaCl) 3066; Anal. calcd for
C18H21NO: C, 80.86, H, 7.92, N, 5.24. Found: C, 80.60,
H, 7.98, N, 5.26.
To a solution of the correspondingaldehyde 1 12.5 mmol)
and diiodomethane 10.3 ml, 3.75 mmol) in THF 110 ml) was
added dropwise methyllithium 13.4 ml of 1.5 M solution in
diethyl ether, 5 mmol) over 5 min and under nitrogen to a
08C. After stirringat 0 8C for 30 min, the mixture was stirred
for one additional hour at room temperature. The resulting
mixture was treated with ice and extracted with dichloro-
methane 13£5 ml). The combined organic layers were dried
1NaSO4), ®ltered and the solvents were removed to provide
the correspondingcrude epoxides 3. Column ¯ash chroma-
tography over silica gel 175/1 n-hexane/triethyl amine)
provided pure epoxides 3.
4.2.7. (1S)-[10(S)-(Dibenzylamino)-2-phenylethyl]oxirane
25
(3g). [a]D ˆ16.58 1c 0.82, CHCl3); Rfˆ0.36 1hexane/
1
AcOEt 15/1); H NMR 1CDCl3, 300 MHz) d 7.39±7.16
115H, m), 3.95 12H, d, Jˆ13.70 Hz), 3.80 12H, d,
Jˆ13.70 Hz), 3.25±3.20 11H, m), 3.12±3.05 11H, m),
2.95±2.87 12H, m), 2.85 11H, dd, Jˆ4.11 and 5.10 Hz),
2.56 11H, dd, Jˆ2.80 and 5.12 Hz); 13C NMR 1CDCl3,
75 MHz) d 139.3 1C), 139.2 1C), 129.4 1CH), 128.3 1CH),
128.2 1CH), 128.0 1CH), 126.7 1CH), 126.0 1CH), 60.2
1CH), 54.1 1CH2), 51.9 1CH), 46.1 1CH2), 33.6 1CH2); MS
1EI) m/z 1%): 344 1M111, ,1), 343 1M1, ,1), 91 1100); IR
1NaCl) 3051; Anal. calcd for C24H25NO: C, 83.93, H, 7.34,
N, 4.08. Found: C, 83.71, H, 7.40, N, 4.07.
4.2.1. 2-Cyclohexyloxirane (3a). Rfˆ0.61 1hexane/AcOEt
5/1); 1H NMR 1CDCl3, 200 MHz) d 2.63 12H, t,
Jˆ3.08 Hz), 2.45±2.41 11H, m), 1.85±1.40 15H, m),
1.20±0.94 16H, m); 13C NMR 1CDCl3, 50 MHz) d 56.6
1CH), 45.9 1CH2), 40.2 1CH), 29.6 1CH2), 28.7 1CH2),
26.2 1CH2), 25.6 1CH2), 25.4 1CH2); MS 1EI) m/z 1%): 126
1M1, ,1), 96 170), 55 1100); IR 1NaCl) 2924, 2852, 1260.
4.2.2. 2-Phenyloxirane (3b). Rfˆ0.54 1hexane/AcOEt 5/1);
1H NMR 1CDCl3, 200 MHz) d 7.50±7.30 15H, m), 3.92
11H, dd, Jˆ2.56 and 4.10 Hz), 3.19 11H, dd, Jˆ4.10 and
5.39 Hz), 2.84 11H, dd, Jˆ2.56 and 5.39 Hz); 13C NMR
1CDCl3, 50 MHz) d 137.3 1C), 128.1 1CH), 127.7 1CH),
125.1 1CH), 52.0 1CH), 50.7 1CH2); MS 1EI) m/z 1%): 121
1M111, 13), 120 1M1, 84), 89 1100), 77 153); IR 1NaCl)
3042, 2963, 2914, 1260.
4.2.8. 2-Methyl-2-pentyloxirane (3h). Rfˆ0.26 1hexane/
1
AcOEt 10/1); H NMR 1CDCl3, 200 MHz) d 2.52 11H, d,
Jˆ5.0 Hz), 2.48 11H, d, Jˆ5.0 Hz) 1.48±1.10 18H, m), 1.22
13H, s), 0.81 13H, t, Jˆ6.41 Hz); 13C NMR 1CDCl3,
50 MHz) d 56.8 1C), 53.6 1CH2), 36.5 1CH2), 31.6 1CH2),
24.7 1CH2), 22.4 1CH2), 20.6 1CH3), 13.7 1CH3); MS 1EI)
m/z 1%): 128 1M1, 4), 123 142), 41 1100); IR 1NaCl) 2930,
2857, 1260.
4.2.3. 2-(4-Chlorophenyl)oxirane (3c). Rfˆ0.35 1hexane/
1
AcOEt 10/1); H NMR 1CDCl3, 200 MHz) d 7.27±7.10
14H, m), 3.74 11H, dd, Jˆ2.56 and 4.11 Hz), 3.05 11H, dd,
Jˆ4.11 and 5.52 Hz), 2.67 11H, dd, Jˆ2.56 and 5.52 Hz);
13C NMR 1CDCl3, 50 MHz) d 135.7 1C), 133.2 1C), 128.1
1CH), 126.4 1CH), 51.2 1CH), 50.6 1CH2); MS 1EI) m/z 1%):
154 1M1, 50), 119 192), 89 1100); IR 1NaCl) 3051, 2990,
2918; Anal. calcd for C9H7ClO: C, 62.15; H, 4.56. Found C,
61.90; H, 4.60.
4.2.9. 1-Oxa-spiro[2.7]decane (3i). Rfˆ0.24 1hexane/
1
AcOEt 10/1); H NMR 1CDCl3, 200 MHz) d 2.61 12H, s),
1.50±1.11 114H, m); 13C NMR 1CDCl3, 50 MHz) d 59.6
1C), 55.3 1CH2), 34.2 1CH2), 26.1 1CH2), 25.0 1CH2), 23.9
1CH2); MS 1EI) m/z1%): 140 1M1, 10); IR 1NaCl) 2925,
2867, 1262.
4.2.10. 2-Methyl-2-phenyloxirane (3j). Rfˆ0.22 1hexane/
4.2.4. 2-Heptyloxirane (3d). Rfˆ0.4 1hexane/AcOEt 10/1);
1H NMR 1CDCl3, 200 MHz) d 2.82±2.80 11H, dd Jˆ2.56
and 3.85), 2.62 11H, dd, Jˆ3.85 and 5.13 Hz), 2.35 11H, dd,
Jˆ2.56 and 5.13 Hz), 1.41±1.33 112H, m) 0.78 13H, t,
1
AcOEt 10/1); H NMR 1CDCl3, 200 MHz) d 7.42±7.34
15H, m), 2.99 11H, d, Jˆ5.39), 2.82 11H, d, Jˆ5.39 Hz),
1.76 13H, s); 13C NMR 1CDCl3, 50 MHz) d 140.8 1C),

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J. M. Concellon et al. / Tetrahedron 57 +2001) 8983±8987
8986
127.9 1CH), 127.1 1CH), 124.9 1CH), 56.6 1CH2), 56.3 1C),
21.4 1CH3); IR 1NaCl) 3050, 3048, 2972, 2924, 1266; Anal.
calcd for C9H10O: C, 80.56, H, 7.51. Found: C, 80.34, H,
7.62.
54.3 1CH2), 46.71CH2), 32.5 1CH2), 11.9 1CH3); MS 1EI) m/z
1%): 401 1M1, ,1), 91 1100); IR 1NaCl) 3420. Anal. calcd
for C28H36N2O: C, 80.73, H, 8.71, N, 6.72. Found: C, 80.21,
H, 8.56, N, 6.73.
4.2.11. 2-Ethyl-2-phenyloxirane (3k). Rfˆ0.5 1hexane/
4.3.3. (2R,3S)-3-Dibenzylamino-1-benzylamino-4-phenyl-
1
AcOEt 10/1); H NMR 1CDCl3, 300 MHz) d 7.39±7.28
25
butan-2-ol (4c). [a]D 1 ˆ210.78 1c 1.00, CHCl3); Rf.ˆ0.33
15H, m), 2.98 11H, d, Jˆ5.39 Hz), 2.74 11H, d,
Jˆ5.39 Hz), 1.83 12H, q, Jˆ7.44 Hz), 0.97 13H, t,
Jˆ7.44 Hz); 13C NMR 1CDCl3, 75 MHz) d 139.8 1C),
128.1 1CH), 127.9 1CH), 127.2 1CH), 125.8 1CH), 60.8
1C), 55.2 1CH2), 28.1 1CH2), 8.9 1CH3); MS 1EI) m/z 1%):
148 1M1, 22), 119 158), 84 1100); IR 1NaCl) 3053, 3051,
2980, 2940, 1260; Anal. calcd for C10H12O: C, 81.04, H,
8.16. Found: C, 80.84, H, 8.22.
1AcOEt/hexane 2/1); H NMR 1CDCl3, 200 MHz) d 7.36±
7.15 1m, 20H), 4.01±3.84 1m, 1H), 3.77 1s, 2H), 3.68 1d, 2H,
Jˆ6.4 Hz), 3.10±2.81 1m, 5H), 2.62±2.52 1m, 2H); 13C
NMR 1CDCl3, 50 MHz) d 142.9 1C), 141,3 1C), 139.7
1C), 129.4 1CH), 128.3 1CH), 127.9 1CH), 127.1 1CH),
126.9 1CH), 125.6 1CH), 69.3 1CH), 61.9 1CH), 54.4
1CH2), 53.2 1CH2), 52.1 1CH2), 32.5 1CH2); IR 1NaCl)
3356, 3061, 3026, 2926, 1494, 1453: Anal. calcd for
C31H54N2O: C, 82.63, H, 7.61, N, 6.22. Found: C, 82.45,
H, 7.49, N, 6.21.
4.2.12. 2-Benzyl-2-methyloxirane (3l). Rfˆ0.45 1hexane/
1
AcOEt 10/1); H NMR 1CDCl3, 200 MHz) d 7.32±7.26
15H, m), 2.89 11H, d, Jˆ4.87 Hz), 2.69 11H, d,
Jˆ4.87 Hz), 1.52±1.30 12H, m), 1.38 13H, s); 13C NMR
1CDCl3, 50 MHz) d 137.0 1C), 129.3 1CH), 128.1 1CH),
126.3 1CH), 57.0 1C), 53.1 1CH2), 42.8 1CH2), 20.6 1CH3);
MS 1EI) m/z 1%): 148 1M1, ,1), 106 165), 91 177), 59 1100);
IR 1NaCl) 3040, 2988, 1264; Anal. calcd for C10H12O: C,
81.04, H, 8.16. Found: C, 80.80, H, 8.10.
Acknowledgements
Â
We thank Ministerio de Educacion y Cultura 1PB97-1278)
for ®nancial support.
References
4.3. General procedure for the preparation of 1,3-
diaminoalkan-2-ols 4 from amino epoxides 3
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To a room temperature solution of the corresponding
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ringat room temperature for 16 or 48 h 1see Table 1), the
resultingmixture was treated with H 2O 12 ml) and extracted
with dichloromethane 13£5 ml). The combined organic
layers were dried 1NaSO4), ®ltered and the solvents were
removed to provide, the correspondingcrude 1,3-diamino-
alkan-2-ols 4. The excess of amine was distilled at reduced
pressure providingpure 1,3-diaminoalkan-2-ols 4 1purity
.95%).
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Chem. 1982, 106, 55±78.
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ol (4a). [a]D ˆ111.68 1c 0.76, CHCl3); 1H NMR 1CDCl3,
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200 MHz) d 7.28±7.41 115H, m), 3.71±3.93 11H, m), 3.75
12H, d, Jˆ13.1 Hz), 3.41 12H, d, Jˆ13.1 Hz) 3.36±2.97
12H, m), 2.68±2.61 12H, m), 2.58±2.42 11H, m), 1.24
13H, d, Jˆ6.5 Hz); 13C NMR 1CDCl3, 50 MHz) d 139.6
1C), 128.0 1C), 127.9 1CH), 127.8 1CH), 127.7 1CH),
126.6 1CH), 126.5 1CH), 126.4 1CH), 70.8 1CH), 55.4
1CH), 53.6 1CH2), 53.2 1CH2), 51.8 1CH2), 8.0 1CH3);
Anal. calcd for C25H50N2O: C, 80.17, H, 8.07, N, 7.48.
Found: C, 79.88, H, 7.40, N, 4.27.
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4.3.2. (2R,3S)-3-Dibenzylamino-1-diethylamino-4-phenyl-
25
butan-2-ol (4b). [a]D ˆ113.68 1c 0.51, CHCl3); Rfˆ0.45
1
1AcOEt); H NMR 1CDCl3, 200 MHz) d 7.24±7.40 115H,
m), 4.01±4.10 11H, m), 3.85 12H, d, Jˆ14.3 Hz), 3.75 12H,
d, Jˆ14.3 Hz) 3.02±3.22 12H, m), 2.88±2.95 11H, m),
2.44±2.79 15H, m), 2.18 11H, dd, Jˆ10.8, 12.4 Hz), 1.07
16H, t, Jˆ7.3 Hz);13C NMR 1CDCl3, 50 MHz) d 141.4 1C),
140.0 1C), 129.6 1CH), 128.8 1CH), 128.6 1CH), 127.9 1CH),
126.5 1CH), 125.5 1CH), 65.6 1CH), 62.3 1CH), 57.7 1CH2),
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