The stereochemistry of the reduction of cyclic enaminones

Article abstract of DOI:10.1007/s007060170060

The stereo- and regiochemistry of di-, tri-, and tetracyclic enaminones upon catalytic hydrogenation on Pd and Pt catalysts seems to be mainly a function of the catalyst and the medium. The highest stereoselectivity was observed for multiflorine on Pd/C in which 99% of equatorial alcohol were formed in this case, the formation of alcohols proceeds via a ketonic intermediate. On platinum, irrespective of the solvent used (EtOH, H₂O, AcOH, HCl), the hydrogenation reaction proceeds through ketonic (piperidone system) and dehydro (pyridone system) intermediates. In EtOH or H₂O solution, the dehydro product remains unchanged, whereas the ketonic intermediate is reduced to a mixture of epimeric alcohols. In HCl and acetic acid, both intermediates are hydrogenolyzed to a product with a methylene group, but the ketonic one is additionally reduced to a mixture of epimeric alcohols. Reductions with complex metal hydrides provide mixtures of epimeric alcohols with a predominance of equatorial orientation. The structures of products were determined by NMR spectroscopy and/or by GC-MS analysis.

Full text of DOI:10.1007/s007060170060

Monatshefte fuÈr Chemie 132, 973±984 (2001)
The Stereochemistry of the Reduction
of Cyclic Enaminones
Ã
Â
Faculty of Chemistry, Adam Mickiewicz University, PL-60780 Poznan, Poland
Waleria Wysocka and Anna Przybyø
Summary. The stereo- and regiochemistry of di-, tri-, and tetracyclic enaminones upon catalytic
hydrogenation on Pd and Pt catalysts seems to be mainly a function of the catalyst and the medium.
The highest stereoselectivity was observed for multi¯orine on Pd/C in which 99% of equatorial alcohol
were formed in this case, the formation of alcohols proceeds via a ketonic intermediate. On platinum,
irrespective of the solvent used (EtOH, H2O, AcOH, HCl), the hydrogenation reaction proceeds
through ketonic (piperidone system) and dehydro (pyridone system) intermediates. In EtOH or H2O
solution, the dehydro product remains unchanged, whereas the ketonic intermediate is reduced to a
mixture of epimeric alcohols. In HCl and acetic acid, both intermediates are hydrogenolyzed to a
product with a methylene group, but the ketonic one is additionally reduced to a mixture of epimeric
alcohols. Reductions with complex metal hydrides provide mixtures of epimeric alcohols with a
predominance of equatorial orientation. The structures of products were determined by NMR
spectroscopy and/or by GC-MS analysis.
Keywords. Multi¯orine; Seco-(11,12)-12,13-didehydromulti¯orine; 3,4-Didehydro-2-quinolizidone;
NMR; GC-MS.
Introduction
Recently, the enaminoketone moiety has received great attention because of its
usefulness in pharmacology [1, 2]. In continuation of our studies of the physical,
chemical, and biological properties of enaminoketones [3±7] we have studied the
stereochemistry of the reduction of some selected enaminones. Little is known on
the stereo- and regiochemistry of the reduction of the ꢀ-amino-vinyl ketone system,
and literature information, limited mostly to multi¯orine, is not well resolved
[8±11].
This paper reports new observations on the catalytic hydrogenation and complex
hydride reduction of multi¯orine (1) along with some preliminary results of
reduction of seco-(11,12)-12,13-didehydromulti¯orine (2) and 3,4-didehydro-2-
qinolizidone (3).
Ã
Corresponding author. E-mail: wysocka@main.amu.edu.pl

974
W. Wysocka and A. Przybyø
Results and Discussion
Multi¯orine (1) and seco-(11,12)-12,13-didehydromulti¯orine (2) were isolated
from L. albus [12, 13]. 3,4-Didehydro-2-quinolizidone (3) was obtained according
to the method described in literature [14±16]. Catalytic hydrogenation was carried
out in the presence of various catalysts (Adam's Pt, Pd/CaCO3, Pd/BaSO4, Pd/C)
and in different solvents (water (Pt), hydrochloric acid (Pt), glacial acetic acid (Pt),
ethanol (Pt, Pd/CaCO3, Pd/BaSO4, Pd/C)).
Reactions and Products
Reaction conditions and product distribution established for 1 are listed in Table 1.
In all experiments, the hydroxy derivative 4 was formed as the main product. In the
resulting post-hydrogenation mixture of 1 in aqueous solution and in absolute
ethanol (entries 1, 2), the didehydro product 7 was additionally formed (78 and
27%). Hydrogenation of 1 in HCl or glacial acetic acid resulted in the formation of
4 and sparteine (5), a product of hydrogenolysis, in ratios 1:1 (HCl) and 1:4
(CH3COOH).

Reduction of Cyclic Enaminones
975
Table 1. Catalytic hydrogenation and reduction with complex hydrides of multi¯orine (1) (yield in %
by GC-MS)
Entry
Catalyst
Medium
t/h
7
5
6
4b
4a
1
2
PtO2
PtO2
H2O
23
20
78
27
±
±
±
±
11
40
11
33
EtOH
(anhydrous)
1 M HCl
CH3COOH
(glacial)
EtOH
3
4
PtO2
PtO2
23
24
±
±
52
21
±
±
45
62
3
17
5
6
7
8
9
Pd/BaSO4
Pd/CaCO3
Pd/CaCO3
Pd/C
22 days
48
±
±
±
±
±
±
±
±
±
±
±
93
29
97
15
99
7
1
(anhydrous)
EtOH
70
±
(anhydrous)
EtOH
7 days
24
3
(anhydrous)
EtOH
85
±
±
(anhydrous)
EtOH
Pd/C
27 days
1
(anhydrous)
MeOH
10
11
12
NaBH4
NaBH4
LiALH4
0.5
1
±
±
±
±
±
±
±
90
88
57
10
12
13
CH2Cl2
±
Diethyl ether
(anhydrous)
Diethyl ether
(anhydrous)
THF
19
30
13
14
LiALH4
LiAlH4
43
24
±
±
±
±
±
±
81
77
19
23
In the presence of Pd/CaCO3, Pd/BaSO4, and Pd/C, the hydrogenation rate of 1
was very low, and it was possible to separate 4-oxosparteine (6) along with the
alcohols 4 after 48 h (Pd/CaCO3) and 24 h (Pd/C), whereas after 7 or 27 days only
the alcohols 4 were found (Table 1, entries 5±9). After separation from 5,6-
didehydromulti¯orine and/or sparteine, the TLC of the hydroxylic product 4
revealed only one spot. However, the 13C NMR spectrum of 4 proved the existence
of a mixture of two epimers. Two signals assigned to carbon C-4 bearing the
hydroxy group were observed (64.65 and 69.33 ppm). Separation of the epimers
by GC-MS was possible after conversion into the O-acetyl derivatives 8a and 8b
‡Á
under mild acetylation conditions ([M ]: m/z ˆ 292; Rt: 19 min 55 s (8a), 20 min
10 s (8b)).
Preparative separation of the 4-O-acetyl derivatives of hydroxysparteine was
achieved by short column chromatography [17] on Al2O3 with ethyl acetate/
methanol. Alkaline hydrolysis of 8a and 8b afforded two alcohols characterized by
a molecular mass of 250; they were assigned to the epimeric alcohols 4a, b.
The stereochemistry of 4a, b was established by analysis of their 13C and
1H NMR spectra (Tables 2 and 3) using two-dimensional techniques (HMQC,
DQF-COSY, NOESY, J-resolved spectroscopy) as well as by comparison of the
spectra with those of model compounds (13ꢁ-hydroxysparteine (ax) (9), 13ꢁ-

976
W. Wysocka and A. Przybyø
hydroxylupanine (ax) (10a), 13ꢀ-hydroxylupanine (eq) (10b) (Table 2)). The
structures of 4-oxosparteine (6) and 5,6-didehydromulti¯orine (7) were also
1
determined on the basis of their spectroscopic data (13C NMR, DEPT, H NMR,
HMQC, DQF-COSY; Tables 4 and 5).
The preliminary chromatographic investigation (TLC, GC-MS) of the products
resulting from catalytic hydrogenation of 2 and 3 (Tables 6 and 7) pointed to the
dominance of the equatorial alcohols. The hydrogenation of 2 and 3 on Pt in
aqueous solution resulted in the formation of alcoholic and dehydro products (48%
yield of dehydro moiety in the case of 2 (Table 6) and 58% for 3 (Table 7). In
ethanolic solution, the hydrogenation of 2 and 3 led to the dehydro products in 44
and 5% yield (Tables 6 and 7). In 1 M HCl solution, the hydrogenation of 6 and 7
gave seco-(11,12)-sparteine (15) and quinolizidine (17) along with the alcoholic
products 14 and 20a,b. Though TLC and GC-MS of 2 revealed only one product
1
with a hydroxy group, the 13C and H NMR spectra of 4-hydroxy-seco-(11,12)-
sparteine (14) proved it to be a mixture. However, attempts to separate it by
conversion into 4-acetyl- or 4-tert-butyl-dimethyl-silyl derivatives failed.

Reduction of Cyclic Enaminones
977
Table 2. 13C NMR chemical shifts of 13ꢁ-hydroxysparteine (ax) (9), 13ꢁ-hydroxylupanine (ax)
(10a), 13ꢀ-hydroxylupanine (eq) (10b), 4ꢀ-hydroxysparteine (ax) (4a), and 4ꢁ-hydroxysparteine (eq)
(4b) in CDCl3 (ppm from TMS)
Carbon
9a
10aa
10ba
4a
4b
2
3
56.2
25.7
24.7
29.3
66.5
33.1
27.4
35.6
61.7
57.2b
41.7
64.6b
32.8
49.2
43.2
171.0
32.9
19.6
26.6
60.8
31.6
27.3
34.2
46.8
57.0b
39.9
64.0b
32.4
49.2
52.4
171.8
33.0
19.6
26.7
58.7
32.6
27.4
34.5
46.9
61.3b
41.5
69.6b
33.8
51.5
53.0
52.58b
32.26
64.65b
35.85
59.17b
32.23
27.37
35.55
61.37
64.09
33.37
24.51
24.51
55.19
49.17
53.81b
34.43
69.33b
38.71
63.78b
32.74
27.14
35.89
60.94
64.30
35.02
24.78
25.71
55.38
53.25
4
5
6
7
8
9
10
11
12
13
14
15
17
a
Ref. [18]; b numbers in italics indicate the carbon atoms subject to the ꢂ-gauche effect
The reduction of 1 with NaBH4 (Table 1) was carried out both in methanol and
dichloromethane. It proceeded very smoothyl in 0.5 and 1 h, respectively, whereas
the reduction of 1 with LiAlH4 in diethyl ether or THF proceeded at a relatively
slower rate (43 and 24 h). Both the reactions with NaBH4 and LiAlH4 involved the
formation of 4-oxosparteine (6, Table 1, entries 12 and 14). The slow conversion of
1 to 4 proceeded via an intermediate metal enolate [10].
The chromatographic investigation (TLC, GC-MS) of the products of the
reduction of 2 and 3 with complex hydrides (Tables 6 and 7) proved that a mixture
of epimeric alcohols was formed in all cases. Thus, the reduction of 2 and 3 with
LiAlH4 and NaBH4 resulted in the formation of a mixture of 4ꢀ-hydroxy-seco-
(11,12)-12,13-didehydro-sparteine (16a) and 4ꢁ-hydroxy-seco-(11,12)-12,13-di-
dehydro-sparteine (16b) or 4ꢀ-hydroxy-quinolizidine (20a) and 4ꢁ-hydroxy-
quinolizidine (20b), respectively. They were separated as O-acetyl derivatives,
‡Á
‡Á
giving two peaks in the GC-MS (16a, b: m/z ˆ 292 [M ], 10%), 191 (89%), 112
(10%), 96 (100%), 58 (19%); 20a, b: m/z ˆ 197 ([M ], 22%), 138 (100%), 136
(40%), 108 (12%), 97 (9%), 55 (15%)).
Catalytic hydrogenation
As follows from the study of catalytic hydrogenation of di-, tri-, and tetracyclic
enaminoketones, regio- and stereoselectivity of these reactions depends mainly on
the kind of catalyst and the reaction medium used. The highest stereoselectivity of
catalytic hydrogenation was observed on palladium for 1 in which 99% (Pd/C), 97%
(Pd/CaCO3), and 93% (Pd/BaSO4) of the equatorial alcohol was formed. This
reaction proceeded at a relatively slow rate via the intermediate 6 (Table 1, entries 6

978
W. Wysocka and A. Przybyø: Reduction of Cyclic Enaminones
Table 3. 1H NMR chemical shifts and coupling constants of 4ꢀ-hydroxysparteine (4a) and 4ꢁ-
hydroxysparteine (4b) in CDCl3 (ppm from TMS)
Proton
4a
4b
ꢃH/ppm
J/Hz
ꢃH/ppm
J/Hz
2ꢀ=ax
2ꢁ=eq
3ꢁ=ax
3ꢀ=eq
4
2.78 (dd?)
2.39 (ddd?)
1.87 (ddd?)
1.76 (ddd?)
4.13 (dddd)
11.3, 10.9
2.00 (dd?)
2.72 (dd?)
1.85 (m)
11.6, 11.0
11.6, 3.0
11.3, 5.7, 3.5
13.7, 10.9, 2.9
13.7, 3.7, 2.9
2.9, 2.9, 2.9, 2.9
(Æ J ˆ 11:6)
13.8, 2.9, 2.9
13.8, 11.8, 2.9
11.8
1.51 (m)
11.0
3.57 (dddd)
11.0, 11.0, 4.6, 4.6
(Æ J ˆ 31:2)
5ꢁ=eq
5ꢀ=ax
6
1.37 (ddd)
1.64 (ddd)
2.26 (d??)
1.84 (dd)
2.09 (m)
1.14 (ddd)
1.52 (m)
2.59 (d?)
2.13 (dd?)
2.14 (m)
1.52 (m)
1.39 (m)
1.29 (m)
1.66 (m)
1.58 (m)
1.58 (m)
2.14 (m)
2.819 (ddd?)
2.50 (dd?)
2.41 (dd)
1.59 (m)
1.47 (ddd)
1.82 (ddd)
1.87 (m)
2.05 (dddd)
1.03 (dt)
1.49 (m)
2.59 (dd?)
1.99 (dd)
1.96 (m)
1.36 (m)
1.50 (m)
1.31 (m)
1.70 (m)
1.56 (m)
1.58 (m)
2.01 (m)
2.79 (ddd?)
2.27 (dd)
2.78 (d?)
11.1, 11.6, 11.0
11.6, 2.3, 2.2
4.6, 2.5
7
9.8, 2.8
8ꢁ=eqa
8ꢀ=axb
9
12.1
12.1, 4.0, 4.0, 1.95
12.1, 2.5, 2.5
12.1, 2.8, 2.8
10ꢁ=eq
10ꢀ=ax
11
10.8
10.9, 4.9
10.9, 2.6
10.1
10.8, 2.6
12ꢀ=ax
12ꢁ=eq
13ꢁ=ax
13ꢀ=eq
14ꢀ=ax
14ꢁ=eq
15ꢁ=ax
15ꢀ=eq
17ꢁ
11.1
11.1
10.3, 2.2
12.4
11.0
12.1, 4.1, 3.8
11.5, 5.2, 2.2
11.5, 9.8
11.0, 4.6, 1.34
11.3, 3.5
10.8
17ꢀ
a
Equatorial in ring B; b axial in ring B
and 8). The results indicate that the ꢀ-amino-vinyl-ketone is ®rst reduced at the
carbon-carbon double bond on palladium, desorbed from the catalyst (it was
possible to separate 4-oxo-sparteine on a preparative scale), reabsorbed, and then
reduced at the carbonyl group. Analysis of molecular models of 6 showed that the
A/B fragment of the molecule should be able to be adsorbed on the surface of the
catalyst on the ꢀ-side of the carbonyl group because of the diaxial interactions of
the hydrogen atoms on C-3 and C-5. Therefore, attachment of a hydrogen atom on
C-4 is favoured on the axial side, and the alcohol with the hydroxyl group in the
equatorial position is formed predominantly.
The catalytic hydrogenation of 1, 2, and 3 on platinum in ethanolic and aqueous
solutions drastically differs from that described in literature for 1 [8±11] and 1,10-
didehydro-2-quinolizidone [19, 20]. Rader et al. [20] have reported that the catalytic
hydrogenation of 1,10-didehydro-2-quinolizidone in ethanol gave a mixture of
epimeric alcohols (29% ax, 67% eq) as well as a hydrogenolysis product (4%), but

Table 4. a) 13C NMR chemical shifts of 4-oxosparteine (6) and sparteine (5) in CDCl3 and C6D6; b)
1H NMR chemical shifts and coupling constants of 4-oxosparteine (6) in C6D6 and CDCl3 (ppm from
TMS)
a)
Carbon
5 (CDCl3)
6 (CDCl3)
6 (C6D6)
2
3
56.2
25.9
24.9
29.4
66.5
33.0a
27.6
36.2a
62.0
64.4
34.7
24.7
25.9
55.4
53.6
54.95
41.59
209.58
44.7
55.04
41.62
206.74
44.63
65.06
32.84
26.51
36.39
60.59
64.13
34.96
25.4
4
5
6
65.13
32.49
26.35
35.65
60.52
64.27
34.37
24.81
25.66
55.49
52.74
7
8
9
10
11
12
13
14
15
17
26.38
55.69
53.04
a
Interchangeable
b)
6 (CDCl3)
J/Hz
6 (C6D6)
J/Hz
Proton
ꢃH/ppm
ꢃH/ppm
2ꢀ=ax
2ꢁ=eq
3ꢁ=ax
3ꢀ=eq
5ꢀ=ax
5ꢁ=eq
6
2.31
3.01
2.64
2.29
2.45
2.034
2.18
1.90
1.05
2.12
1.56
2.11
2.71
2.07
1.37
1.54
1.73
1.30
1.58
1.62
2.029
2.82
2.37
2.75
14.0
1.88
2.49
2.08
2.25
1.84
2.13
1.73
1.45
0.73
2.13
1.28
1.70
2.36
1.96
1.29
1.37
1.18
1.58
1.47
1.62
1.92
2.72
2.23
2.46
11.1
6.6, 2.2
14.0, 4.7
17.0
13.8, 2.2
17.0, 4.7
13.4
13.8, 6.6; 1.0
14.1, 12.2
14.1, 2.4
13.4, 3.0
3.0
12.2, 2.1; 3.3
7
4.1, 2.2
9.6, 2.2
9.6, 4.1
8ꢀ=axb
8ꢁ=eqa
9
11.8, 2.7
11.8, 2.0
5.0, 4.9, 2.7, 1.7
10.9, 2.7
10ꢀ=ax
10ꢁ=eq
11
10.8
10.8, 2.6
2.2
10.9, 4.9, 2.0
13.5, 3.1
12ꢀ=ax
12ꢁ=eq
13ꢁ=ax
13ꢀ=eq
14ꢀ=ax
14ꢁ=eq
15ꢁ=ax
15ꢀ=eq
17ꢁ
7.9, 3.1, 2.0
13.5, 9.5
13.5, 1.5
2.6
2.7
11.9, 4.0, 3.9
15.1, 2.6
4.0
11.5
11.2
11.5, 1.3
11.0
11.2, 4.0, 2.6
11.0, 3.5
11.0, 10.6
17ꢀ
11.0, 10.7
a
Equatorial in ring B; b axial in ring B

980
W. Wysocka and A. Przybyø
Table 5. 13C and 1H NMR chemical shifts of 5,6-didehydromulti¯orine (7) in CDCl3 (ppm from TMS)
Carbon
ꢃc/ppm
Proton
ꢃH/ppm
J/Hz
2
3
4
5
6
7
8
139.76
118.05
179.04
116.23
153.54
34.99
2
7.20
6.35
±
7.57
3
7.57, 2.78
±
±
5
6.18
±
2.78
±
±
7
2.91
2.02
1.75
2.06
3.92
4.13
2.93
1.89
1.12
1.49
1.90
1.16
1.61
2.75
2.68
2.49
3.36
2.8
21.19
8ꢁ=eqa
8ꢀ=axb
9
13.8, 1.3
13.8, 1.8
2.2, 1.68
12.7, 2.2, 1.05
12.7, 6.09
12.1, 2.2
9.2
9
32.79
57.57
10
10ꢁ=eq
10ꢀ=ax
11
11
12
63.17
22.34
12ꢁ=eq
12ꢀ=ax
13ꢁ=ax
13ꢀ=eq
14ꢁ=ex
14ꢀ=ax
15ꢁ=ax
15ꢀ=eq
17ꢁ
9.2
13
14
15
17
25.59
18.95
54.45
52.21
13.0, 3.5
13.0
12.1
12.1, 3.5
14.0, 12.1, 3.0
14.0, 1.9
10.9, 1.7
10.9, 2.8
17ꢀ
a
Equatorial in ring B; b axial in ring B
Table 6. Catalytic hydrogenation and complex hydride reduction of seco-(11,12)-12,13-didehydro-
multi¯orine (2; yield in %)
Entry
Condition
Medium
t/h
12
13
14
15
16a
16b
1
2
PtO2
PtO2
H2O
68
24
48
44
3
2
49
54
±
±
±
±
±
±
EtOH
(anhydrous)
1 M HCl
EtOH
3
4
PtO2
Pd/C
24
3
8
5
40
95
52
±
±
±
±
±
(anhydrous)
MeOH
5
6
NaBH4
LiAlH4
24
8
±
±
±
6
±
±
6
94
78
THF
16
only a mixture of epimeric alcohols (2% ax and 98% eq) in aqueous solution.
Â
Comin and Deloufeu [9] and Wolinska-Mocydlarz [11] have obtained only 4-
hydroxysparteine of undetermined con®guration from 1 under the same conditions.
According to our observations, catalytic hydrogenation of 1, 6, and 7 on
platinum, irrespectively of the reaction medium used (EtOH, H2O, AcOH, HCl),
proceeds via the formation of two intermediates including a system of ꢂ-piperidone

Reduction of Cyclic Enaminones
981
Table 7. Catalytic hydrogenation and complex hydride reduction of 3,4-didehydroquinolizidone-2
(3; yields in %)
Condition
Medium
t/h
17
18
20a
20b
PtO2
PtO2
H2O
56
58
±
±
58
5
6
36
75
EtOH
20
(anhydrous)
1 M HCl
MeOH
PtO2
24
19
50
±
±
±
3
47
82
NaBH4
18
(oxo derivative) or ꢂ-pyridone (dehydro derivative) (Tables 1, 6, 7). The inter-
mediates are formed simultaneously. Their presence was revealed by TLC already
after 15 min of reduction, apart from a mixture of the epimeric alcohols. The
dehydro product containing the ꢂ-pyridone system does not undergo further
reaction in media as EtOH or H2O, whereas the ꢂ-piperidone system of the oxo
derivative experiences a reduction to a mixture of epimeric alcohols. The amount of
the dehydro product formed from 1, 2, and 3 is different. In H2O, the amount of the
dehydro product reaches 78%, in EtOH 27%. The reduction of 6 in H2O leads to
48% of the dehydro product (EtOH: 44%) whereas the reduction of 7 in H2O gives
58% (EtOH: only 5%) of dehydro product. It is dif®cult to explain these differences.
In all these three compounds the N±C=C±C=O group is part of the rigid trans-
quinolizidine system. Repetition of the hydrogenation of 1, 2, and 3 for several
times always gave the same results. Most probably, the differences should be
interpreted as related to the molecule skeleton.
A chromatographic study of the hydrogenation of 1, 2, and 3 on platinum in HCl
and AcOH showed that in these media the intermediate containing the ꢂ-pyridone
system reacts to 5 if 1 is used, to 15 with 2, and to 17 in the case of 3. The
intermediate containing the ꢂ-piperidone moiety undergoes reduction and hydro-
genolysis to a mixture of epimeric alcohols and products including a methylene
group (5, 15, 17). Therefore, the formation of 5, 15, and 17 obviously proceed via
different pathways, i.e. through the intermediate with the ꢂ-pyridone system or that
with the ꢂ-piperidone system, in these two cases. The observations are consistent
Â
with the suggestions of Wolinskiej-Mocydlarz [11].
The hydrogenolysis of the ketonic product 6 (from 1) and, consequently, 13 and
19 from 2 and 3, takes place probably according to the same mechanism as is the
case with the isomers 13-oxo-sparteine (11) and 13-oxo-ꢁ-iso-sparteine [21]. An
attempt to obtain 7 on Pt and Pd from 1 without hydrogen in ethanolic or aqueous
solution failed. Dehydrogenation of 1 by other classical dehydrogenating agents
gave very poor results.
Reductions employing complex hydrides
The reduction of 1 and 2 by LiAlH4 and NaBH4 resulted in the formation of a
mixture of epimeric alcohols with a predominance of the epimer with an equatorial
hydroxy group (Tables 1 and 6). The process of reduction by LiAlH4 proceeds
rather slowly, so we were able to separate from 1 the intermediate product of 6. This

982
W. Wysocka and A. Przybyø
fact indicates that the initial hydride delivery to 1 (and, consequently, to 2 and 3)
occurs at C-4, resulting in an enolate form. This observation is in agreement with
the work of Goldberg et al. [10]. The predominating formation of the equatorial
alcohol is a consequence of the fact that steric approach control and product
development control would be expected to direct this reaction.
In order to perform conformational assignments for 4a, b, the NMR spectra of
these compounds were examined; the data are summarized in Tables 2 and 3.
NMR spectroscopy
Table 2 lists the 13C NMR chemical shifts of 4ꢀ- and 4ꢁ-hydroxysparteine (4a, b).
The signals were assigned by comparison with the spectra of compounds of similar
structure (13ꢁ-hydroxysparteine (9), 13ꢁ- (10a) and 13ꢀ-hydroxylupanine (10b)
[18]) and by comparing the spectra of 4a and 4b. The correctness of these
assignments was veri®ed by molecular model considerations of 4a, b and on the
basis of chemical the shifts of C-6 and C-2. The 13C NMR spectrum of the isomer
with the hydroxyl group in the axial position (4a) reveals up®eld shifts of 1.23
(C-2), 4.68 (C-4), and 4.61 (C-6) ppm relative to the positions of these signals in the
spectrum of 4b (Table 2). The up®eld shift of C-2 and C-6 is a result of a ꢂ-gauche
substituent effect [22±24]; in the case of C-4, the up®eld shift is similar as observed
in some related compounds [18].
1
A complete assignment of the H NMR spectra of 4a, b as well as the
determination of coupling constants was achieved by the analysis of HMQC
and DQF-COSY spectra (Table 3). Large coupling constants of H-4 (twice 11.0 Hz)
and a large value of the coupling constant sum Æ J ˆ 31:2 Hz (Table 3) and the
coupling of H-4 with axial protons at C-3 and C-5 prove the axial position of atom
H-4 and are in agreement with the equatorial position of the hydroxyl group on
C-4 in 4b [25]. On the other hand, low values of the vicinal coupling constants (four
times 2.9 Hz) and a low coupling constants sum of Æ J ˆ 11:7 Hz (Table 3) of the
relatively narrow signal of H-4 in 4a prove the axial position of the hydroxy group
at C-4. A similar relationship has been noted in the case of 14ꢁ-acetoxymatrine and
14ꢀ-acetoxymatrine [25].
The chemical shifts (1H, 13C) of 6 were assigned employing one- and two-
dimensional techniques in CDCl3 as well as by comparison with spectra of sparteine
1
(Table 4a). The coupling constants were obtained directly from the H NMR
spectrum of 6 in CDCl3 and C6D6 (Table 4b). The 1H and 13C chemical shifts of 7
(Table 5) and the corresponding coupling constants are in agreement with those
published previously [3, 26, 27].
Experimental
IR spectra were recorded with Perkin Elmer 580 and Bruker FTIR 113v spectrometers. 1H and
13C NMR spectra (including DEPT, DQF-COSY, HMQC, J-resolved spectroscopy) were recorded
in CDCl3 and in C6D6 on a Varian Unity 300 NMR spectrometer; chemical shifts are quoted relative
to internal TMS. GC-MS spectra were recorded on a JEOL IMSD-100 instrument connected with a
Varian Series 3300 gas chromatograph. Chromatography conditions: column: DB1 (0.25 mmÂ20 m);
carrier gas: He; split: 1:20; injector temperature: 260ꢀC; temperature program: 200ꢀC/1 min, 5 to

Reduction of Cyclic Enaminones
983
300ꢀC/10 min. Systems for TLC: (a) EtOH:CHCl3 ˆ 3:2, (b) Acetone:MeOH:NH3/MeOH ˆ 4:1:1,
(c) MeOH:ethyl acetate ˆ 1:4.
Plant material: The alkaloids 1 and 2 were isolated from Lupinus albus cv. BAC seeds [28] and
separated by short column chromatography with Kieselgel (Merck 70±230 mesh) and system (a)
according to a method described previously [17].
Catalytic hydrogenations were performed in a glass apparatus under slightly elevated pressure and
intense stirring with a magnetic stirrer. The processes were observed by TLC on silica gel; for their
development, system (b) was used. The ®nal products of hydrogenations and reduction reactions were
analyzed by GC-MS.
Catalytic hydrogenation: To a mixture of a proper amount of reduced PtO2 (0.01 g, 0.044 mmol),
5%Pd/BaSO4 (0.03 g), 5%Pd/CaCO3 (0.03 g), or 10% Pd/C (0.04 g), 0.02 g (0.08 mmol) substrate
dissolved in 2 cm3 of an adequate solvent were added. The reactions were performed until reduction
of the substrate and intermediate products was complete. After ®ltering off the catalyst, the solvent
was evaporated; the resulting mixture was dissolved in H2O and alkalized with KOH. The alkaloids
were extracted with diethyl ether and then with CH2Cl2. The products were analyzed by TLC using
system (b) and by GC-MS.
Hydride reduction: To the alkaloid dissolved in a proper amount of solvent the hydride was added
in 5-fold gravimetric excess relative to the substance. The reaction mixture was stirred at room
temperature until reduction of the substrate was complete. The excess of hydride was destroyed with
H2O or 1 N HCl, and the solvent was evaporated under reduced pressure. The residue was alkalized
with 25% KOH, extracted with diethyl ether and CH2Cl2, dried over MgSO4, and evaporated.
The hydroxylic products were converted to the O-acetyl derivatives by mixing 4 with acetic
anhydride and keeping it overnight. Then the mixture of 8a and 8b was analyzed by TLC (system (c))
and by GC-MS. Preparative separation of the 4-O-acetyl derivatives 8a, b was achieved by short
column chromatography [17] on Al2O3 or TLC (ICN Germany) with system (c). Alkaline hydrolysis
of acetylated compounds was achieved by heating overnight with 25% KOH.
5,6-Didehydromulti¯orine (7; C15H20N2O)
Crystallized from CH2Cl2/hexane; white needles; m.p.: 175±176ꢀC; [ꢁ]D20
ˆ
90ꢀ (EtOH); MS:
‡Á
m/z ˆ 244 ([M ], 100%), 163 (21%), 162 (59%), 146 (19%), 96 (46%); IR (KBr): ꢄ ˆ 1636, 1556,
1560, 2800±2600 (CHtrans) cm 1, NMR: Table 5.
4ꢁ-Acetoxysparteine (8b; C17H28N2O2)
‡Á
M.p.: 97±101ꢀC; [ꢁ]D20
ˆ
5:9ꢀ (EtOH); MS: m/z ˆ 292 ([M ], 46%), 251 (27%), 233 (28%), 195
(100%), 136 (38%), 135 (88%), 98 (42%), 96 (47%); IR (KBr): ꢄ ˆ 1736 (C=O), 979 (C±O), 2800±
1
2700 (CHtrans) cm
.
4ꢀ-Acetoxysparteine (8a; C17H28N2O2)
‡Á
Oil; [ꢁ]2D0
ˆ
4:6ꢀ (EtOH); MS: m/z ˆ 292 ([M ], 62%), 251 (49%), 233 (33%), 195 (94%), 136
(60%), 135 (100%), 98 (68%), 96 (47%); IR (®lm): ꢄ ˆ 1734 (C=O), 958 (C±O), (CHtrans) 2850±
1
2700 cm
.
4ꢁ-Hydroxysparteine (4b, C15H26N2O)
‡Á
M.p.: 74±75ꢀC (Ref. [10]: 67±72ꢀC); [ꢁ]2D0
ˆ
20:8ꢀ (EtOH); MS: m/z ˆ 250 ([M ], 29%), 209
(19%), 153 (100%), 136 (41%), 114 (46%), 98 (25%), 55 (20%); IR (KBr): ꢄ ˆ 3265±3427 (OH),
1
975.3 (C±O), 2880±2700 (CHtrans) cm
.

984
W. Wysocka and A. Przybyø: Reduction of Cyclic Enaminones
4ꢀ-Hydroxysparteine (4a; C15H26N2O)
‡Á
Oil; [ꢁ]2D0
ˆ
7:9ꢀ (EtOH); MS: m/z ˆ 250 ([M ], 29%), 209 (48%), 153 (100%), 136 (38%), 114
1
(58%), 98 (33%), 55 (6%); IR (®lm): ꢄ ˆ 3285±3470 (OH), 2880±2700 (CHtrans), 953.7 (C±O) cm
.
4-Oxosparteine (6; C15H24N2O)
‡Á
Light yellow oil; [ꢁ]D20
ˆ
27ꢀ (EtOH); MS: m=z ˆ 248 ([M ] 73%), 207 (14%), 151 (100%), 136
1
(76%), 112 (33%), 97 (60%), 55 (41%); IR (®lm): ꢄ ˆ 1724 (C=O), 2850±2700 (CHtrans) cm
;
NMR: Tables 4a, b.
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Received December 28, 2000. Accepted (revised) February 16, 2001