Stereoselective reduction of enaminones to syn γ-aminoalcohols

Article abstract of DOI:10.1016/S0040-4039(02)01545-9

One-pot reduction of enaminones to syn γ-aminoalcohols can be efficiently performed by lithium borohydride in the presence of cerium chloride as Lewis acid. Selectivities are very good with respect to classical reduction method of these products.

Full text of DOI:10.1016/S0040-4039(02)01545-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7441–7444
Stereoselective reduction of enaminones to syn g-aminoalcohols
Giuseppe Bartoli,a Giovanna Cupone,b Renato Dalpozzo,b Antonio De Nino,b,* Loredana Maiuolo,b
Antonio Procopiob and Antonio Tagarellib
aDipartimento di Chimica Organica ‘A. Mangini’, Universita` di Bologna, viale Risorgimento 4, I-40136 Bologna, Italy
bDipartimento di Chimica, Universita` della Calabria, ponte Bucci cubo 15/c, I-87030 Arcavacata di Rende, Italy
Received 17 May 2002; accepted 25 July 2002
Abstract—One-pot reduction of enaminones to syn g-aminoalcohols can be efficiently performed by lithium borohydride in the
presence of cerium chloride as Lewis acid. Selectivities are very good with respect to classical reduction method of these products.
© 2002 Elsevier Science Ltd. All rights reserved.
The structural unit of g-aminoalcohol is present with a
stereodefined geometry in many compounds having
interesting pharmacological and biological properties.1
In addition, aminols are often useful building blocks in
the synthesis of many natural products.2
In the first phase of this work, we tested TiCl4 mediated
reduction. The reduction of 1,3-amidoketones is, in
fact, reported to occur with high diastereoselectivity in
the presence of LiAlH4 and TiCl4 as chelating agent.8 A
useful method to obtain 1,3-aminols from enaminones
was not found. Reduction of 3-(N-methylamino)-1-
phenylbut-2-en-3-one (1b) was carried out with various
agents and the reaction was monitored by GC/MS.
BH3/Py gives good diastereomeric ratios, but products
cannot be separated from pyridine. BH3/THF and BH3/
Et2NH give compounds whose mass spectra can be
rationalised as boron complexes with 1,3-aminols which
are very difficult to decompose; BH3/Me2S gives low
diastereoisomeric ratios (ranging from 1/1 to 3/2) and
often low yielding owing to the presence of many such
as monoreduced and dehydrated by-products; LiBH4
gives only by-products.
The reduction of b-enaminoketones is certainly a very
useful tool in the hand of the organic chemists to build
1,3-aminoalcohols, because many available functionali-
sation opportunities exist.
Some years ago, we studied both the regioselective
synthesis of enaminones3 and their dianion reactivity.4
On that occasion, reduction of the enaminone unit was
set up by sodium in isopropanol,5 since catalytic hydro-
genation of these compounds takes place with
difficulty,6 and, in our hands, reduction with metal
hydrides alone or together with Lewis acids afforded no
appreciable results.5a However, high diastereoselectivity
was not generally reached.
Therefore, we focused our attention to the alternative
CeCl3 mediated reduction, but it was also unsuccessful
with many reducing agents: DIBAH and Red-Al are
non-reactive; BH3/THF, Superhydride and L-Selectride
give only by-products; NaBH4 had already been unsuc-
cessfully tested.5a Only LiBH4 was able to efficiently
reduce enaminones in the presence of CeCl3 as promot-
ing Lewis acid at −20°C (Table 1).9
More recently, we well explored the reduction of car-
bonyl bidentate compounds with borane complexes or
LiBH4 in the presence of TiCl4 and CeCl3 and sug-
gested the rules to predict the stereochemistry of
reduction.7
We have re-investigated reduction of enaminones with
hydrides under these new conditions and results are
reported in this paper.
The reaction usually proceeds with high yields, the low
recovered yields of 3-(N-isopropylamino)-2-pentanol
(2l, entry 12) being very likely due to inefficient extrac-
tion from water, because no by-products were detected
even in traces by GC/MS on the crude reaction before
quenching.10
* Corresponding author. Tel.: +39-0984-49-2043; fax: +39-0984-49-
2055; e-mail: denino@unical.it
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01545-9

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G. Bartoli et al. / Tetrahedron Letters 43 (2002) 7441–7444
Table 1. Reduction of enaminones 1a–m in the presence of CeCl3/LiBH4 system at −20°C
Entry
Cmpd
R1
R2
R3
R4
Time (h)
Yield (%)
syn/anti
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
Ph
Ph
Ph
Ph
Ph
Ph
Me
Ph
Ph
Ph
Ph
Me
i-Bu
Me
Me
Me
Me
Me
Me
Me
Me
i-Bu
i-Pr
i-Bu
Me
Me
H
H
H
H
H
H
H
H
Me
Et
i-Pr
t-Bu
Ph
16
2.5
5
8
144
8
76
90
66
76
96
0a
67/33
93/7
88/12
85/15
78/22
–
50/50
84/16
91/9
85/15
86/14
84/16
93/7
Ph
5
19b
96
96
89
87
32
80
(CH2)5
Me
Me
i-Pr
i-Pr
i-Pr
16
72
144
270
58
295
9
H
H
H
H
H
10
11
12
13
2j
2k
2l
2m
a N,4-Diphenylbut-3-en-2-amine was only recovered.
b N-Phenylpent-3-en-2-amine was also recovered in about 30% yield.
LiBH4/
CeCl3
Compared with reported enaminone reductive methods
it appears much more useful. In fact, reduction with
NaBH4 alone did not exceed 3/2 diastereoselective
ratios and its application is very restricted.11 Palmieri’s
reduction with sodium and isopropanol has good selec-
tivity only with cyclic compounds.5 Grenhill’s catalytic
hydrogenation gives good 15/1 selectivity but takes
place with difficulty.6 Finally, Barluenga’s reduction of
4-amino-1-azadienes is a three-step procedure, if high
stereoselectivity must be obtained.8
Cl2Ce
H
Ph
N
O
1f,g
R1
Ph
Ph
N
HN
eq. A
R1
R1
CeCl3
LiBH4/
CeCl3
R4 R3
N
O
1a-e,h-m
2a-e,h-m
eq. B
R2
R1
The most remarkable finding is a strong dependence of
the reaction from the nitrogen substituent. A phenyl
group linked to the nitrogen atom favours a dehydra-
tion reaction leading to significative or exclusive forma-
tion of substituted allylamines (entries 6 and 7). We
previously found that the site of organocerium addition
depends from nitrogen substituents.12 An aryl group
lowers ability of nitrogen atom to co-ordinate cerium,
enhancing therefore co-ordination to oxygen atom and
consequently 1,2-addition to carbonyl function. On the
other hand, an alkyl nitrogen substituent favours
cerium co-ordination to nitrogen atom allowing 1,4-
addition to unsaturated carbonyl moiety. In a fashion
of such a mechanism also in the present reaction N-
phenylallylamine arises from N-phenyl substituted
enaminones via carbonyl reduction, elimination, and
imine reduction steps (Scheme 1, Eq. (A)). On the other
hand, 1,3-aminols come from N-alkyl substituted
enaminones via 1,4-reduction, followed by carbonyl
reduction (Scheme 1, Eq. (B)). Actually, b-(N-alkyl-
amino)ketone can be detected in the first times of the
reaction by monitoring the reaction progress by GC/
MS.13
Scheme 1.
(entries 2, 9–11) reaction times prolong significantly,
allowing for a growing difficulty of the incoming
hydride to approach the reaction centre. Between the
nitrogen substituents the alkyl one should occupy a
position able to discriminate among different transition
states, as demonstrated by the high increase in selectiv-
ity which occurs passing from no substituents to the
methyl group (entries 1 and 2), while R3 substituents
seems to have no influence (entries 4 and 8). However,
every increase in crowding the nitrogen atom or the g
position decreases selectivities, accounting for transition
states strongly influenced by steric interactions between
these substituents. On the other hand, bulkier a% sub-
stituents increase selectivity (entries 4, 12, and 13).
Compound identification was made by comparison of
vicinal coupling constants. It is well-established that
both syn and anti isomers should be featured as chair-
shaped molecules, owing to the strong intramolecular
hydrogen bond between the amino and the hydroxy
functions15 In the most stable conformation, the anti
isomer would have Ha and Hb in a diaxial relationship,
giving rise to a larger coupling constant than the syn
isomer, which will have Ha and Hb in a axial–equatorial
relationship in both conformations. On these bases, all
authors are always in agreement to attribute the larger
coupling constant to the anti isomer.5,8,15,16
Rationalisation of the actual transition state which is
travelled in the second reductive step is highly specula-
tive.14 Some features can be deduced, however, from
results reported in Table 1. The transition state should
have a geometry which accounts for a strong depen-
dence of reaction times from steric hindrance. Increas-
ing bulkiness both on the nitrogen atom (entries 1–5)
and in the a% (entries 4, 12, and 13) or in g-positions

G. Bartoli et al. / Tetrahedron Letters 43 (2002) 7441–7444
7443
In conclusion, the present results offer an interesting
synthetic procedure to obtain syn 1,3-aminoalcohols,
particularly easy to perform, from easy available and
functionalisable starting materials. Diastereoselectivities
reported are generally high compared with reported in
related reactions. From this paper the optimum condi-
tions to obtain high diastereoselectivity in reduction of
enaminones can be deduced, i.e. the presence of a little
nitrogen substituent is necessary.
Chem. 1999, 64, 1986–1992; (d) Bartoli, G.; Bellucci, M.
C.; Bosco, M.; Dalpozzo, R.; Marcantoni, E.; Sambri, L.
Org. Lett. 2000, 2, 45–47; (e) Ballini, R.; Bosica, G.;
Marcantoni, E.; Vita, P.; Bartoli, G. J. Org. Chem. 2000,
65, 5854–5857; (f) Bartoli, G.; Bosco, M.; Dalpozzo, R.;
Marcantoni, E.; Massaccesi, M.; Rinaldi, S.; Sambri, L.
Tetrahedron Lett. 2001, 42, 8811–8815.
8. Barluenga, J.; Aguilar, E.; Olano, B.; Fustero, S. Synlett
1990, 463–465.
9. General procedure: A solution of b-enaminoketone 1a–l (5
mmol) in dry THF (10 mL) was added dropwise to a cold
(−78°C) suspension of CeCl3 (5 mmol) in dry THF (15
mL). The mixture was stirred for 1 h at this temperature
and LiBH4 (22.5 mmol, 2 M solution in THF) was then
added. The mixture was allowed to stir for an appropri-
ate time (Table 1), before adding dropwise 10% aqueous
HCl and then NaOH pellets were added up to basic pH.
The crude product was extracted with AcOEt, then dried
over Na2SO4 and concentrated under reduced pressure.
Flash column chromatography (eluent CHCl3/MeOH,
95:5) gave diastereoisomeric mixture of syn and anti
g-aminoalcohols as pale yellow syrups.
References
1. (a) Shibahara, S.; Kondo, S.; Maeda, K.; Umezawa, H.;
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Davies, S. G.; Ichihara, O. Tetrahedron Lett. 1999, 40,
9313–9316.
10. Spectroscopic data of unknown compounds follow: 3-
Amino-1-phenyl-1-butanol, 2a: lH 1.14 (d, 2H, J=6.37,
CH
J=10.46, 14.19 CH
14.19 CHHCHOH), 2.81–3.20 (m, 4H, OH
4.88 (dd, 0.67H, J=2.01, 10.46 CHOH), 5.30 (dd, 0.33H,
J=4.02, 7.04 CH6 OH), 7.03–7.50 (m, 5H, Ar). m/z (%):
6
3CH), 1.15 (d, 1H, J=6.37, CH3
HCHOH), 1.73 (dt, 1H, J=3.02,
, CHNH2),
6 CH), 1.48 (dt, 1H,
6
6
6
6
6
6
3. (a) Bartoli, G.; Cimarelli, C.; Palmieri, G.; Bosco, M.;
Dalpozzo, R. Synthesis 1990, 895–898; (b) Bartoli, G.;
Cimarelli, C.; Dalpozzo, R.; Palmieri, G. Tetrahedron
1995, 51, 8613–8622.
165 (M+ 1), 148 (12.5), 104 (25), 77 (25), 44 (100). Anal.
calcd for C10H15NO: C, 72.69; H, 9.15; N, 8.48. Found:
C, 72.60; H, 9.15; N, 8.50%. 3-N-(Methylamino)-1-phenyl-
4. (a) Bartoli, G.; Bosco, M.; Dalpozzo, R.; Cimarelli, C.;
Palmieri, G. Synlett 1991, 29–230; (b) Bartoli, G.; Bosco,
M.; Dalpozzo, R.; Cimarelli, C.; Guerra, M.; Palmieri, G.
J. Chem. Soc., Perkin Trans. 2 1992, 649–655; (c) Bartoli,
G.; Bosco, M.; Dalpozzo, R.; Cimarelli, C.; Palmieri, G.
J. Chem. Soc., Perkin Trans. 1 1992, 2095–2100; (d)
Bartoli, G.; Bosco, M.; Dalpozzo, R.; Guercio, G.;
Cimarelli, C.; Palmieri, G.; Demunno, G. J. Org. Chem.
1992, 57, 6020–6025; (e) Bartoli, G.; Bosco, M.;
Cimarelli, C.; Dalpozzo, R.; Demunno, G.; Palmieri, G.
Tetrahedron: Asymmetry 1993, 4, 1651–1665; (f) Bartoli,
G.; Bosco, M.; Dalpozzo, R.; De Nino, A.; Palmieri, G.
Tetrahedron 1994, 50, 9831–9836; (g) Bartoli, G.; Bosco,
M.; Dalpozzo, R.; De Nino, A.; Iantorno, E.; Tagarelli,
A.; Palmieri, G. Tetrahedron 1996, 52, 9179–9186; (h)
Dalpozzo, R.; De Nino, A.; Bartoli, G.; Bosco, M.;
Sambri, L.; Marcantoni, E. J. Org. Chem. 1998, 63,
3745–3747; (i) Dalpozzo, R.; De Nino, A.; Miele, D.;
Procopio, A.; Bartoli, G. Heteroatom Chem. 2000, 11,
1–5.
5. (a) Bartoli, G.; Cimarelli, C.; Palmieri, G. J. Chem. Soc.,
Perkin Trans. 1 1994, 537–543; (b) Bartoli, G.; Cimarelli,
C.; Marcantoni, E.; Palmieri, G.; Petrini, M. J. Org.
Chem. 1994, 59, 5328–5335.
6. Greenhill, J. V. Chem. Soc. Rev. 1977, 6, 277–294.
7. (a) Bartoli, G.; Bosco, M.; Dalpozzo, R.; Marcantoni, E.;
Sambri, L. Chem. Eur. J. 1997, 3, 1941–1950; (b) Mar-
cantoni, E.; Cingolani, S.; Bartoli, G.; Bosco, M.; Sam-
bri, L. J. Org. Chem. 1998, 63, 3624–3630; (c)
Marcantoni, E.; Alessandrini, S.; Malavolta, M.; Bartoli,
G.; Bellucci, M. C.; Sambri, L.; Dalpozzo, R. J. Org.
1-butanol, 2b: lH 1.07–1.12 (bs, 2H, OH
3H, J=6.18 CH3CHNH), 1.49 (dt, 1H, J=10.82, 14.29
CHHCHOH), 1.67 (dt, 1H, J=2.07, 14.29 CH
2.42 (s, 3H, CH3NH), 2.82–2.92 (m, 1H, CH
(dd, 0.93H, J=1.93, 10.82 CH
6 , NH6 ), 1.09 (d,
6
6
6
HCHOH),
6 NH), 4.89
6
6
OH), 5.04 (dd, 0.07H,
J=3.09, 7.34), 7.21–7.37 (m, 5H, Ar). m/z (%): 179 (M+
3), 148 (4), 107 (5), 79 (6), 77 (8), 58 (100). Anal. calcd for
C11H17NO: C, 73.70; H, 9.56; N, 7.81. Found: C, 73.75;
H, 9.55; N, 7.80%. 3-N-(Ethylamino)-1-phenyl-1-butanol,
2c: lH 1.11 (d, 3H, J=6.03 CH3
J=7.38 CH3CH2NH), 1.11–1.15 (bs, 2H, OH
(dt, 0.88H, J=10.73, 14.42 CHHCHOH), 1.69 (dt,
0.88H, J=2.17, 14.42 CHHCHOH), 1.72 (ddd, 0.12H,
J=3.69, 6.71, 14.42 CHHCHOH), 1.84 (ddd, 0.12H,
J=3.36, 7.38, 14.42 CHHCHOH), 2.56 (dq, 1H, J=7.38,
11.41 CHHCH3), 2.87 (dq, 1H, J=7.38, 11.41
CHHCH3), 2.94–3.05 (m, 1H, CHNH), 4.91 (dd, 0.88 H,
J=2.01, 10.73 CHOH), 5.05 (dd, 0.12 H, J=3.36, 7.38),
6
CHNH), 1.12 (t, 3H,
6
6
, NH), 1.49
6
6
6
6
6
6
6
6
6
7.11–7.43 (m, 5H Ar). m/z (%): 193 (M+ 4), 107 (4), 79
(7), 77 (9), 72 (100). Anal. calcd for C12H19NO: C, 74.57;
H, 9.91; N, 7.25. Found: C, 74.60; H, 9.95; N, 7.20%.
3-N-(Isopropylamino)-1-phenyl-1-butanol, 2d: lH 1.10 (d,
3H, J=5.92 (CH
(CH3)2CHNH), 1.27 (d, J=3.98, 3H CH3), 1.48 (dt,
J=11.13, 14.49, 1H CHHCHOH), 1.64 (dt, J=2.34,
14.16, 1H CHHCHOH), 3.01–3.18 (m, 4H, CH(CH3)2,
CHNH, OH), 4.91 (dd, J=1.68, 10.44, 0.85H CHOH),
5.07 (m, 0.15H CH
OH). m/z (%): 207 (M+ 3), 120 (20),
6 3)2CHNH), 1.12 (d, 3H, J=5.41
6
6
6
6
6
6
6
6
6
105 (100), 77 (65). Anal. calcd for C13H21NO: C, 75.32;
H, 10.21; N, 6.76. Found: C, 75.40; H, 10.20; N, 6.70%.
3-N-(t-Butylamino)-1-phenyl-1-butanol, 2e: lH 1.13 (s, 3H

7444
G. Bartoli et al. / Tetrahedron Letters 43 (2002) 7441–7444
(CH3 3
(bs, 2H, OH
J=6.71 CH3CH), 1.47 (dt, 1H, J=11.06, 14.09
CHHCHOH), 1.69 (ddd, 1H, J=1.68, 3.02, 14.09
CHHCHOH), 3.14–3.22 (m, 1H, CHNH), 4.85 (dd,
0.78H, J=1.34, 11.06, CHOH), 5.07 (dd, 0.22H, J=2.35,
9.73, CH
OH), 7.18–7.41 (m, 5H, Ar). m/z (%): 221 (M+
13), 206 (35), 188 (6), 100 (73), 84 (100), 79 (22), 77 (23),
58 (43). Anal. calcd for C14H23NO: C, 75.97; H, 10.47; N,
6.33. Found: C, 76.00; H, 10.45; N, 6.35%. 3-Piperidinyl-
6
) C), 1.15 (d, 0.66H, J=7.04 CH3
6
CH), 1.10–1.22
6), 217 (40), 160 (100), 132 (35). Anal. calcd for
C16H27NO: C, 77.06; H, 10.91; N, 5.62. Found: C, 77.00;
H, 10.95; N, 5.65%. 2-N-(Isopropylamino)-6-methyl-4-hep-
6
, NH), 1.21 (s, 6H (CH3)3C), 1.27 (d, 2.34H,
6
6
6
6
tanol, 2m: lH 0.91 (d, 3H, J=6.78 CH3
J=6.78 CH3CH), 1.05 (d, 3H, J=6.17 (CH3 2
1.06 (d, 3H, J=5.85 CH3CH), 1.08 (d, 3H, J=6.24
(CH3)2CHNH), 1.10–1.28 (m, 1H, CH2CHCH3), 1.35–
1.45 (m, 3H, CHHCHOH, (CH3)2CHCH2), 1.51 (dt, 1H,
J=1.85, 14.18 CHHCHOH), 2.87–3.15 (m, 2H,
CHNHCH(CH3)2), 3.88–3.94 (m, 0.93H, CHOH), 3.98–
4.12 (m, 0.07H CH
OH). m/z (%): 187 (M+ 5), 172 (9),
6
CH), 0.92 (d, 3H,
6
6
6
) CHNH),
6
6
6
6
6
6
6
6
6
6
6
1-phenyl-1-butanol, 2h: lH 0.96 (d, 3H, J=6.81 CH3
1.22–1.85 (m, 14H (CH2)5, CH2CHOH, NH), 2.69–2.90
(m, 1H, CHNH), 4.90 (dd, 0.84H, J=2.28, 11.04,
CHOH), 5.14 (m, 0.16H, CH
6 CH),
6
6
6
6
130 (9), 86 (100), 72 (9), 44 (45). Anal. calcd for
C11H25NO: C, 70.53; H, 13.45; N, 7.48. Found: C, 70.50;
H, 13.50; N, 7.50%.
6
6
6 OH), 7.1–7.4 (m, 5H, Ar).
m/z (%): 233 (M+ 3), 112 (100). Anal. calcd for
C15H23NO: C, 77.21; H, 9.93; N, 6.00. Found: C, 77.20;
H, 9.90; N, 6.00%. 3-N-(Methylamino)-1-phenyl-5-methyl-
11. Maroni, P.; Cazaux, L.; Tisnes, P.; Zambetti, M. Bull.
Soc. Chim. Fr. 1980, 179–186.
12. Bartoli, G.; Marcantoni, E.; Petrini, M.; Sambri, L.
Chem. Eur. J. 1996, 2, 913–918.
1-hexanol, 2i: lH 0.81–0.96 (bs, 2H, OH
5.4H, J=5.94 (CH3)2CH), 1.02 (d, 0.6H, J=6.33
(CH3)2CH), 1.47 (dt, 1H, J=10.79, 14.52 CHHCHOH),
1.48–1.63 (m, 3H, (CH3)2CHCH2), 1.72 (dt, 1H, J=2.61,
14.52 CHHCHOH), 2.79–2.89 (m, 1H, CHNH), 2.43 (s,
3H, CH3NH), 4.89 (dd, 0.91H, J=2.23, 10.79 CHOH),
5.06 (dd, 0.09H, J=2.61, 8.56, CHOH), 7.21–7.40 (m,
6 , NH6 ), 0.91 (d,
6
13. All mass spectra associated to these peaks show aciluim
6
6
ion (R1CꢀO+) and retroaldol reaction ion [R1C(ꢁO)CH2
]
+
6
6
typical of a carbonyl compound rather than of an allyl
alcohol.
6
6
6
6
14. In our opinion, the formation of an enol ester borohy-
dride intermediate in analogy with the reported reduc-
tions of enaminoesters and b-hydroxybenzyl oximes
cannot be invoked. This intermediate should transfer
hydride to the carbonꢂcarbon double bond, but this
double bond appears electrophilic rather than nucle-
ophilic. Alternatively boron could link in the a-position
giving rise to a b-enaminoketone, whose reduction can
occur either intramolecularly or intermolecularly as in the
b-hydroxyketone system. Finally the water molecule,
which seems to be present also in ‘dry’ cerium chloride
could be the proton source which allows keto–enol tau-
tomerism, followed by reduction of the b-enaminoketone.
Intramolecular shift of a hydrogen atom from nitrogen to
oxygen atom is discarded because reduction occurs also
with N,N-dialkylamino derivatives (entry 8).
6
5H, Ar). m/z (%): 221 (M+ 2), 176 (24), 164 (37), 146 (34),
100 (93), 79 (20), 77 (30), 58 (100). Anal. calcd for
C14H23NO: C, 75.97; H, 10.47; N, 6.33. Found: C, 75.90;
H, 10.45; N, 6.30%. 3-N-(Methylamino)-1-phenyl-4-
methyl-1-pentanol, 2j: lH 0.78 (d, 3H, J=7.08
(CH
(m, 1H, (CH3)CH
2.41 (m, 1H, CHNH), 2.45 (s, 1H, (CH
0.85H, J=2.23, 10.79 CHOH), 5.10 (m, 0.15H, CH
6
3)2CH), 0.92 (d, 3H, J=7.08 (CH3 2
), 1.23–1.39 (m, 2H, CH2
3)NH), 4.86 (dd,
OH),
6
) CH), 0.83–0.97
6
6
CHOH), 2.30–
6
6
6
6
7.20–7.39 (m, 5H, Ar). m/z (%): 164 (M+−43, 46), 146
(20), 107 (23), 86 (22), 79 (22), 77 (19), 58 (100). Anal.
calcd for C13H21NO: C, 75.32; H, 10.21; N, 6.76. Found:
C, 75.30; H, 10.20; N, 6.80%. 3-N-(Isopropylamino)-1-
phenyl-5-methyl-1-hexanol, 2k: lH 0.88 (d, 3H, J=6.31
(CH
1.10 (d, 3H, J=6.32 (CH
(CH3)2CHNH), 1.27–1.65
CH2CHOH), 1.78–1.88 (m, 2H, (CH3)2CHCH2
3.05 (m, 4H, HNCH(CH3)2, CHNH, OH), 4.89 (dd,
0.89H, J=1.51, 10.52, CHOH), 5.07 (dd, 0.11H, J=2.8,
8.07 CH
OH), 7.21–7.44 (m, 5H, Ar). m/z (%): 249 (M+
6
3)2CHCH2), 0.90 (d, 3H, J=6.67 (CH3 2
3)2CHNH), 1.14 (d, 3H, J=5.96
(m, 3H, (CH3)2CH
), 2.85–
6 ) CHCH2),
15. Nazabadioko, S.; Pe´rez, J. R.; Brieva, R.; Gotor, V.
Tetrahedron: Asymmetry 1998, 9, 1597–1604.
16. (a) Carlier, P. R.; Moon-Lo, K.; Lo, M. M.-C.; Williams,
I. D. J. Org. Chem. 1995, 60, 7511–7517; (b) Gotor, V.;
Dehli, J. R.; Rebolledo, F. J. Chem. Soc., Perkin Trans.
1 2000, 307–309.
6
6
6 ,
6
6
6
6
6
6
6
6