Synthesis and conformational analysis of all eight diastereoisomers of 5-methylyohimbane

Article abstract of DOI:10.1002/1522-2675(200203)85:3<945::AID-HLCA945>3.0.CO;2-A

Some time ago, Siddiqui et al. proposed structure 1 for the naturally occurring indole alkaloid yohambinine, which they had isolated from Rauwolfia serpentina BENTH. In the present paper, enantioselective syntheses of all eight diastereoisomers endowed with the proposed 5-methylyohimbane structure are disclosed. However, none of the synthetically prepared compounds showed spectroscopic properties identical with those reported for the natural product yohambinine, which, therefore, must possess an altogether different constitutional formula. The ground-state conformations of the diastereoisomers 1, 14, 18, 19, 21, 22, 25, and 26 were deduced by spectroscopic methods, and the outcome was compared with the results of extensive force-field, semi-empirical, and ab-initio calculations.

Full text of DOI:10.1002/1522-2675(200203)85:3<945::AID-HLCA945>3.0.CO;2-A

Helvetica Chimica Acta Vol. 85 (2002)
945
Synthesis and Conformational Analysis of All Eight Diastereoisomers
of 5-Methylyohimbane
by Christian Lohse1), Richard Detterbeck2), Pierre Acklin3), and Hans-J¸rg Borschberg*
Laboratorium f¸r Organische Chemie der Eidgenˆssischen Technischen Hochschule, HCl, ETH-Hˆnggerberg,
CH-8093 Z¸rich
Some time ago, Siddiqui et al. proposed structure 1 for the naturally occurring indole alkaloid yohambinine,
which they had isolated from Rauwolfia serpentina Benth. In the present paper, enantioselective syntheses of
all eight diastereoisomers endowed with the proposed 5-methylyohimbane structure are disclosed. However,
none of the synthetically prepared compounds showed spectroscopic properties identical with those reported for
the natural product yohambinine, which, therefore, must possess an altogether different constitutional formula.
The ground-state conformations of the diastereoisomers 1, 14, 18, 19, 21, 22, 25, and 26 were deduced by
spectroscopic methods, and the outcome was compared with the results of extensive force-field, semi-empirical,
and ab-initio calculations.
1. Introduction. In 1987, Siddiqui et al. reported the isolation of a novel crystalline
monoterpenoid indole alkaloid from the roots of Rauwolfia serpentina Benth [3]. Its
molecular formula was shown to be C20H26N2 by combustion analysis, and this
composition was confirmed by high-resolution EI-MS. The unexpected presence of a
Me group at a tertiary C-atom was indicated by a doublet (d ˆ 1.12 ppm, d, J ˆ 6.7 Hz
1
(3 H)) in the H-NMR spectrum of yohambinine. The absence of Bohlmann bands in
the IR spectrum and the appearance of HÀC(3) as a broad singlet at 4.12 ppm in the
1H-NMR spectrum pointed to a cis-quinolizidine system for rings C and D. The
equatorial orientation of HÀC(5) (d ˆ 3.42 ppm, qdd, J ˆ 6.7, 5.3, 2.8 Hz)4) was
evident from the vicinal couplings with HÀC(6). The multiplicities of the deshielded
CH2 H-atoms at C(21) pointed to a b-orientation of HÀC(20) (J(HÀC(21a),
HÀC(20)) ˆ 12 Hz). The configuration at the remaining stereogenic center C(15)
was inferred to be a due to biogenetic reasons. Therefore, the structural formula 1 was
proposed for yohambinine (Scheme 1) [3].
Structure 1, devoid of any functional groups in ring E and presenting the former
carboxy group C(22) in a fully reduced form, is unique among the Yohimbine and seco-
Yohimbine alkaloids (for reviews, see [4]). Therefore, we set out to synthesize
yohambinine (1) in an enantioselective fashion according to the retrosynthetic plan
presented in Scheme 1. A disconnection along the dashed line leads to (R)-2'-
methyltryptamine (2), a known compound, readily prepared from l-tryptophane [5].
1
)
)
)
Taken in part from the Ph.D. thesis of C.L. [1].
2
3
Taken in part from the diploma thesis of R.D., on leave from the University of Erlangen (FRG) [2].
Author to whom correspondence regarding the various calculations should be addressed at Novartis
Pharma AG, WSJ-88.103, CH-4002 Basel.
4
)
In the cited paper, this signal was incorrectly interpreted as −ddd× [3].

946
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 1
The other building block, containing the remaining C-atoms including the intact ring E,
is represented by the chiral cyclohexane derivative (À)-3. This can be derived from the
known intermediate (À)-4 with established absolute configuration [6]) through Arndt-
Eistert synthesis. The original straightforward plan envisaged a Bischler-Napieralski
condensation to build ring C, followed by lactamization/reduction for the construction
of ring D.
2. Synthesis. The building block (À)-2 was prepared essentially according to
Repke and Ferguson [5] with some modifications [1][2] of the original procedure. The
preparation of the other half ((À)-3) was uneventful and, for reasons detailed below, we
prepared the optical antipode (‡)-3 as well. A similar reaction sequence was applied to
the optically pure cis-monoester (À)-5 [6] as well, but, surprisingly, the Arndt-Eistert
product 8 turned out to be optically inactive (Scheme 2). Control experiments showed
that the racemization occurred during the preparation of the acid chloride 7, a finding
that is in contrast with results reported by Turbanti et al. [7]. In many attempts, this
compound was invariably obtained in optically inactive form, and it repeatedly
furnished (Æ)-5 after hydrolysis. Among several possible intermediates in the step (À)-
5 ! (Æ)-7, the acylated oxonium ion I seems to be the only candidate that contains a
second-order element of symmetry.
The assembly of the seco-compound (À)-11 from the components (À)-2 and (À)-3
according to the protocol of Mukaiyama et al. [8] was straightforward (Scheme 3).
However, all attempts to lactamize this intermediate to 12 failed. Therefore, the
alternative route via amino alcohol (À)-13 was chosen. Gratifyingly, this intermediate
could be cyclized in good yield to (À)-14 by the method of Lange and Gottardo [9]. As
compound (À)-14 (normal yohimbane skeleton) represents the C(3)-epimer of the
alleged yohambinine structure (pseudo-type), it was equilibrated with (‡)-1 under

Helvetica Chimica Acta Vol. 85 (2002)
947
Scheme 2
a) (S)-2-Phenylethylamine, 2-chloro-1-methylpyridinium iodide, Bu3N, CH2Cl2, 2 h reflux. b) (COCl)2, 258. c) 1.
CH2N2, Et2O; 2. Ag2O, 1,4-dioxane/H2O.
acidic conditions to furnish a 2 :1 mixture in favor of the latter (for a discussion of the
mechanism, see [10]). Surprisingly, the properties of our synthetic (‡)-1 clearly did not
match the data reported for natural yohambinine [3] (see Table 1). As the straightfor-
ward nature of our synthetic approach undoubtedly led to compounds endowed with
the structures 14 and 1, we are forced to conclude that the originally proposed structural
formula for yohambinine is incorrect. Hoping to clarify the matter, we set out to
synthesize the remaining six diastereoisomers of 1, each of them in only one antipodal
form5).
The four isomers with unnatural (15R)-configuration were prepared from (À)-2 and
from (‡)-3 as shown in Scheme 4. With the same methodology as described above, we
obtained the ent-pseudo derivative (‡)-18, the optical antipode of the C(5)-epimer of 1.
The corresponding ent-normal compound (‡)-19 was prepared through equilibration
with (‡)-18 or reduction of lactam 17, which was isolated as a by-product in the
Bischler-Napieralski reaction, leading to (À)-16. When the latter was treated with
DIBAH, the imine (‡)-20 was obtained in low yield, which, upon reduction with
NaBH4, furnished a 1:4 mixture of (‡)-18 and of the D/E cis-fused diastereoisomer
(À)-21. This compound represents the ent-epiallo type, and it could be equilibrated with
the corresponding ent-allo derivative (‡)-22. As it turned out, none of the four
yohambinine-type alkaloids displayed in Scheme 5 was identical with the natural
product (see Table 1).
The two remaining isomers were prepared by combining (À)-2 with (Æ)-8 as shown
in Scheme 5. The resulting 1:1 mixture of the two amides 23 and 24 could not be
separated, but, after the standard transformation of this mixture, the resulting alkaloids
5
)
Only the four isomers derived from (À)-3 and from (‡)-5 represent alkaloids endowed with the natural
(15S)-configuration. The other four diastereoisomers were obtained in the antipodal (15R)-configuration
and are labelled with the prefix ent. However, this was not considered to cause serious problems for an
unambiguous identification of any of the latter compounds with natural yohambinine.

948
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 3
a) 2-Chloro-1-methylpyridinium iodide, Bu3N, CH2Cl2, 2 h reflux. b) POCl3, toluene, 3 h reflux. c) NaBH4,
MeOH/H2O. d) K2CO3, MeOH, 9 h reflux. e) LiAlH4, THF. f) PPh3, I2, imidazole, CH2Cl2, 15 h 258. g)
CF3COOH, 20 h 1008.
(À)-21 and the new isomer (À)-25 endowed with the allo skeleton were separated by
chromatography. The still missing epiallo isomer (‡)-26 was once more generated
through equilibration of (À)-25. Since neither of these 5-methylyohimbanes was
identical to natural yohambinine (Table 1), we have to conclude that the latter is not a
stereoisomer of 1, but, rather, it must possess an altogether different, as yet unknown
constitutional formula.

Helvetica Chimica Acta Vol. 85 (2002)
949
Scheme 4
a) 2-Chloro-1-methylpyridinium iodide, Bu3N, CH2Cl2, 2 h reflux. b) 1. POCl3, toluene, 3 h reflux; 2. NaBH4,
MeOH/H2O. c) 1. LiAlH4, THF, 18 h 258; 2. PPh3, I2, imidazole, CH2Cl2, 15 h 258. d) CF3COOH, 20 h 1008.
e) DIBAH, THF, 18 h 408. f) LiAlH4, THF, 18 h 258. g) NaBH4, MeOH/H2O.
3. Conformational Analysis.
The ground-state conformations of all eight 5-
methylyohimbanes were deduced through analyses of their spectral data. The following
features were most helpful in this respect: a) the axial or equatorial orientation of
HÀC(3) is readily apparent from the half-width and chemical shift of the respective
1
signal in the H-NMR spectrum; b) the presence of Bohlmann bands in the IR
spectrum indicates the presence of a trans-quinolizidine part system for rings C and D
with a least two a-H-atoms antiperiplanar to the lone-pair of N(4) [11]; c) the axial or
equatorial position of the Me group follows from its chemical shift in both the 1H-and
13C-NMR spectra (see Table 1 and 2). In the cases where rings D and E form a trans-
decalin system (compounds 1, 14, 18, and 19), the 1H-NMR spectra (500 MHz, CDCl3)
could be analyzed by first-order methods, and, in all cases, only the conformer
displayed in Fig. 1 could be discerned. However, in the cis-fused representatives 21, 22,
25, and 26, many signals in the 1H-and 13C-NMR spectra were considerably broadened
at 258, pointing to a dynamic process taking place within the NMR time-scale. Most
likely, this involves simultaneous N(4)-inversion and chair-chair transitions of rings D
and E. Recording of the spectra at 808 (300 MHz, C6D6) led to sharp signals in all cases,

950
Helvetica Chimica Acta Vol. 85 (2002)
Scheme 5
a) 2-Chloro-1-methylpyridinium iodide, Bu3N, CH2Cl2, 2 h reflux. b) 1. POCl3, toluene, 3 h reflux; 2. NaBH4,
MeOH/H2O; 3. LiAlH4, THF, 18 h 258; 4. PPh3; I2, imidazole, CH2Cl2, 15 h 258. c) CF3COOH, 20 h 1008.
Table 1. 1H-NMR Chemical-Shift Values d [ppm] (in CDCl3)
Compound Aa)
14
1
18
19
25
26
21
22
Type
normal pseudo
ent-pseudo ent-normal allo
epiallo
ent-epiallo ent-allo
HÀC(3)
HÀC(5)
4.12
3.42
3.30
2.57
2.71
2.60
7.50
7.12
7.17
7.36
1.30
2.03
1.10
0.92
1.63
1.24
1.68
1.25
1.68
1.01
1.55
1.25
1.75
3.12
1.24
4.42
3.32
3.12
2.35
7.50
7.12
7.17
7.36
1.73
2.06
0.90
1.03
1.68
1.14
1.68
1.25
1.68
0.76
1.50
1.34
2.36
2.54
1.26
4.46
3.30
2.64
2.66
7.48
7.11
7.15
7.35
1.81
2.01
0.87
1.03
1.67
1.12
1.67
1.23
1.67
0.76
1.50
1.25
2.05
2.65
1.36
3.53
3.34
3.14
2.52
7.45
7.07
7.12
7.29
1.34
2.00
1.16
1.07
1.70
1.29
1.75
1.29
1.75
1.02
1.62
1.41
2.39
2.72
1.01
2318
‡ 110
3.31
2.55
2.58
2.71
7.44
7.08
7.11
7.29
3.76
3.30
3.15
2.50
7.45
7.09
7.12
7.28
3.60
2.88
2.62
2.76
7.45
7.08
7.12
7.29
3.49
3.22
3.10
2.52
7.45
7.09
7.13
7.29
HaÀC(6) 3.54
HbÀC(6) 3.20
HÀC(9)
7.37
HÀC(10) 6.96
HÀC(11) 7.04
HÀC(12) 7.28
HaxÀC(14)
HeqÀC(14) 2.74
HÀC(15) 2.35
HaxÀC(16)
HeqÀC(16)
HaxÀC(17)
HeqÀC(17)
HaxÀC(18)
HeqÀC(18)
HaxÀC(19)
HeqÀC(19)
HÀC(20) 2.09
HaxÀC(21) 2.77
HeqÀC(21) 3.04
2.23
3.10
1.24
3.02
2.44
1.06
2.44
2.67
1.31
2.61
2.86
0.98
CH3(22)
M.p.
1.12
189 1908 1688
‡ 98
105 1078 788
À 165 ‡ 24 ‡ 5
152 1548 183 1868 122 1248 oil
À 134 ‡ 51 À 51 ‡ 123
[a]D
a) Data reported for natural yohambinine [3].

Helvetica Chimica Acta Vol. 85 (2002)
951
Table 2. 13C-NMR Chemical-Shift Values d [ppm] (in CDCl3 unless stated otherwise)
Compound
Type
14a)
1a)
18a)
19a)
25d)
26d)
21d)
22
normal
pseudo
ent-pseudo
ent-normal
allo
epiallo
ent-epiallo
ent-allo
C(2)
C(3)
134.4
61.0
132.2
47.6
133.7
56.4
134.3
53.0
135.5
60.6
134.5
47.2
135.7
56.2
134.7
52.9
C(5)
56.1
53.7
55.4
54.0
55.3
54.1
56.1
54.3
C(6)
30.8
21.9
24.6
28.5
31.2
22.1
23.7
26.4
C(7)
C(8)
C(9)
107.2
126.9
117.8
118.9
120.9
110.7
136.0
36.7
41.2
32.4
26.2
25.8
106.3
128.4
117.9
119.3
121.3
110.8
135.8
34.9
37.1
32.9
26.2
25.9
109.2
127.6
118.0
119.4
121.2
110.8
135.8
35.1
37.1
33.0
26.3
25.9
106.6
128.2
118.0
119.2
121.1
110.6
136.2
37.9
42.0
32.9
26.5
26.0
108.1
127.4
118.0
119.2
121.1
110.6
135.5
31.6
106.8
128.2
118.0
119.1
121.1
110.6
136.2
35.7
109.6
127.4
118.8
120.2
121.9
111.4
137.3
35.1
106.4
128.1
118.0
119.2
121.1
110.6
136.2
31.4
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)c)
C(18)c)
C(19)
C(20)
C(21)
C(22)
34.8b)
31.2
34.4b)
28.3
33.6b)
30.6
34.7b)
29.7
26.6
26.6
26.4
26.4
28.3
25.9
26.2
26.0
30.5
41.5
56.4
20.0
30.2
41.8
54.7
19.3
30.5
41.5
44.9
19.5
30.4
42.1
58.6
10.2
21.1
29.3
29.6
20.9
36.5b)
56.4
34.9b)
51.6
36.4b)
48.9
36.7b)
58.5
20.8
10.6
20.5
9.7
a) Assignments corroborated through HETCOR experiments. b)c) Respective assignments may be inter-
changed. d) In C6D6 at 808. Values reported for yohambinine: C(3): 50.42, C(15): 38.52, C(20): 41.21 [3].
which allowed a determination of the prevailing ground-state conformations (see
Fig. 2).
4. Calculations. Extensive calculations were performed to help us understand the
experiments and predict the most stable conformations of the different isomers.
Conformational analysis of all possible stereoisomers was performed in the continuum
model for CHCl3 with the AMBER* force field [12] in MacroModel [13], using the
truncated Newton conjugate gradient (TNCG) [14] as the minimizing method. In
accordance with the NMR observations, a single minimum-energy conformation was
found for isomers 1, 14, 18, and 19, two conformations were found for isomer 21 and 22,
and three conformations for isomers 25 and 26 within an energy window of 10 kcal
above the global minimum. Even though molecular-mechanics methods cannot be used
to compare energies of different molecules, they allow for ranging of conformers and
stereoisomeric structures. However, the result depends on the accuracy of the force
field for the calculated compounds. As we were not sure how well the AMBER*
parameters fit these indole alkaloids, we decided to verify the data with semi-empirical
methods. All low-energy conformations within a 10-kcal window were calculated with
the PM3 [15] and AM1 [16] Hamiltonians in Mopac 93 [17]. As it turned out, the
energies resulting from the force-field calculations strongly deviated from the semi-
empirically determined enthalpies of formation for the isomers, as well as for different

952
Helvetica Chimica Acta Vol. 85 (2002)
Fig. 1. Lowest-energy conformations of the four diastereoisomers of 5-methylyohimbane with trans-fused rings
D and E as calculated by PM3. Unlabelled substituents represent H-atoms.
conformations of each isomer. Some of the resulting low-energy conformations are
listed in Table 3.
To obtain more reliable energies, the calculations were repeated with more and
more sophisticated ab initio methods, although these are quite time-consuming for this

Helvetica Chimica Acta Vol. 85 (2002)
953
Table 3. Calculated Energy Minima (relative energies compared to 23, in kcal/mol)
Method Macromodel Mopaca)
Mopaca)
Gaussianb) Gaussianb) Gaussianb)
Gaussianb)
Type
Force field
Amber
Semi-empiric Semi-empiric HF-ab initio HF-ab initio RHF-ab initio DFT
AM1
PM3
6-31G
6-31G**
6-31G**PCM/ Becke-Lyp3
SCRF
(B3LYP)
Solvent CHCl3
in vacuo
in vacuo
in vacuo
in vacuo
CHCl3
in vacuo
1
14
18
19
19'
21
21'
22
25
26
26'
1.00
0.69
1.09
0.00
1.61
2.42
2.44
0.85
1.60
1.71
2.37
À 1.02
0.56
0.00
0.00
À 1.16
2.64
0.16
1.30
0.43
1.87
2.55
1.39
2.14
0.00
3.01
4.80
4.90
2.31
3.67
3.45
5.33
2.30
0.80
1.76
0.00
2.98
4.36
4.63
2.44
3.22
3.62
5.18
1.25
0.58
0.76
0.00
2.26
3.83
6.76
2.51
3.09
3.25
4.49
0.43
0.95
À 0.10
0.00
1.24
3.25
1.65
4.25
2.44
2.33
2.18
0.17
0.00
À 0.25
3.47
2.23
1.52
2.38
1.40
1.69
2.05
1.59
0.38
a) Hf.
b) Ground-state electronic and internuclear repulsion energy, neglecting 0-K residual vibration energy.
size of molecule. The conformational geometries determined by molecular mechanics
were used as starting points for Gaussian 94 [18]. In a first step, they were optimized on
6-31G level of theory. The relaxed geometries were taken as the basis for the
calculations at the 6-31G** level before applying the solvation model for CHCl3 at the
same level of theory. Finally the molecular-mechanics geometries were optimzed in
vacuo with density-functional theory, using the Becke-Lyp3 extension in Gaussian. The
relative enthalpy differences resulting from all these calculations are listed in Table 3,
where the relative enthalpy has been set to 0 for the minimal-energy conformation of
isomer 18. Interestingly, although the values of the relative enthalpies differ
substantially, the ranking of the different conformations of single diastereoisomers is
identical for all pure ab initio and the force-field calculations. This is not entirely so for
the density functionals and not at all the case for the semi-empirical energies.
Under thermodynamic control, the relative stabilities (DG8) of reaction products
can be determined from experimentally determined product ratios. This was possible
for all four pairs of C(3)-epimers, and the observed ratios of ca. 1:2 in favor of 14, 18,
22, and 16, respectively, translate into DDG8 values of less than 0.5 kcal/mol at 1108.
Even though the experimental differences in DG8 are not directly correlated with the
calculated differences in heat of formation (DHf 8), they seem to be best reflected by
the density-functional calculations (Becke-Lyp3). Whereas the Hartree-Fock DHf 8
values calculated in vacuo deviate substantially from the experimental values,
optimization in CHCl3 appears to improve the model.
We thank the Forschungskommission der ETH-Z¸rich and the Swiss National Science Foundation for
financial support.

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Helvetica Chimica Acta Vol. 85 (2002)
Fig. 2. Lowest-energy conformations of the four diastereoisomers of 5-methylyohimbane with cis-fused rings D
and E as calculated by PM3. Unlabelled substituents represent H-atoms. Formulae in square brackets represent
calculated, energetically higher lying conformers.

Helvetica Chimica Acta Vol. 85 (2002)
955
Fig. 2 (cont.)

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Helvetica Chimica Acta Vol. 85 (2002)
Experimental Part
General. See [19].
Calculations. All calculations were performed on Silicon Graphics Onyx, Power Challenge, and Indy.
MacroModel V. 5.0 [13] and the AMBER* force field [12] were used for all molecular-mechanics calculations.
To this end, 5000 conformations of each compound were generated according to the systematic Monte Carlo
procedure [20] and minimized in vacuo with the truncated Newton conjugate gradient (TNCG) method [14].
The resulting conformations were then relaxed in the GB/SA solvation model for CHCl3 [21] with the same
minimization method.
The global minima and all conformations within an energy window of 10 kcal above, found by the
molecular-mechanics method, were used as starting point for semi-empirical calculations. The DHf values were
calculated with Mopac 93 by means of both Hamiltonians AM1 [16] and PM3 [15].
The same set of conformations were optimized with HF methods in Gaussian 94 [18] on 6-31G and 6-31G**
theory levels. In addition, the resulting 6-31-G** geometries were used as starting points for ab initio solvation
calculation at the same level of theory. Furthermore, the original z-matrices were minimized with density
function theory on the Becke-Lyp3 level in Gaussian 94.
General Procedures. Method 1 [8]. To a stirred soln. of 1.2 equiv. of 2-chloro-1-methylpyridinium iodide
(Fluka, purum) in 8 ml of CH2Cl2 was added a soln. of 1 equiv. of (R)-3-(2-aminopropyl)indole ((À)-2) [5],
2.4 equiv. of Bu3N, and 1 equiv. of the designated carboxylic acid in 15 ml of CH2Cl2. The mixture was refluxed
for 1 h, cooled to 258, diluted with 100 ml of CH2Cl2, and extracted with 5% aq. HCl. The org. phase was dried
(Na2SO4), evaporated, and the residue was chromatographed (silca gel; hexane/AcOEt 1:1) to furnish the
desired amides.
Method 2. The amides obtained according to Method 1 were dissolved in POCl3 (1 mmol/ml) and refluxed
for 2 h. The resulting black mixture was evaporated (408/18 Torr), and the residue was poured onto ice. The
mixture was rendered basic by addition of 2n aq. NaOH soln. and extracted with CH2Cl2 (3Â). The org. phase
was dried (Na2SO4) and evaporated. The residue was chromatographed (silica gel; hexane/AcOEt, gradient 3 :1
to 1 :1) to furnish the desired 3,4-dihydro-b-carbolines.
Method 3. The intermediates obtained by Method 2 were dissolved in MeOH (0.5 mmol/ml, treated with
10 20 equiv. of NaBH4 and stirred for 16h at 258. After addition of 3 ml of 2n aq. NaOH soln., MeOH was
removed by evaporation (408/18 Torr), and the residue was extracted with CH2Cl2 (3Â). The org. phase was
dried (Na2SO4) and evaporated. The residue was chromatographed (silica gel; hexane/AcOEt 1 :1) to furnish
the desired 1,2,3,4-tetrahydro-b-carbolines.
Method 4. The intermediates obtained by Method 3 were dissolved in THF (5 ml/mmol) and added via
syringe to a suspension of 15 equiv. of LiAlH4 in 10 ml of THF at 08 under Ar. The mixture was stirred at 08 for
30 min and then refluxed for 16 h. After cooling to 08, sat. aq. NaHCO3 soln. was added dropwise until excess
reagent was decomposed. Most of the THF was removed in vacuo and the residue was rendered basic by
addition of 6n aq. NaOH soln. and extracted with Et2O (4Â). The org. phase was dried (Na2SO4) and
evaporated. The residue was chromatographed (silica gel; Et2O/hexane/MeOH/Et2NH 60 :40 :10 :3) to furnish
the desired primary alcohols.
Method 5 [9]. To a stirred suspension of 1.5 equiv. of polymer-bound Ph3P (Fluka, purum), 1.5 equiv. of
imidazole (Fluka, puriss.), and 1.5 equiv. of I2 (Fluka, purum) in 10 ml of CH2Cl2 was added a soln. of 1 equiv. of
the primary alcohol in 2 ml of CH2Cl2. After stirring at 258 for 15 h, the mixture was distributed between H2O
and CH2Cl2. The org. extracts were pooled, dried (Na2SO4), and evaporated. The residue was chromatographed
(silica gel; Et2O/hexane/MeOH/Et2NH 60 :40 :10 :3) to furnish the desired (5S)-5-methylyohimbanes.
Method 6. A soln. of the designated 5-methylyohimbane in CF3COOH (Fluka, puriss.) (0.05 mmol/ml) was
heated to 1108 under Ar for 18 h. The cold mixture was poured onto ice/H2O, rendered basic with 2n aq. NaOH
soln., and extracted with Et2O. The org. extracts were pooled, dried (Na2SO4), and evaporated. The residue was
chromatographed (silica gel; Et2O/hexane/MeOH/Et2NH, 60 :40 :10 :3) to furnish the starting material and the
desired C(3)-epimeric (5S)-5-methylyohimbane.
(‡)-(1S,2R)-2-(Methoxycarbonyl)cyclohexanecarboxylic Acid ((‡)-3). The compound (‡)-4 [6] (2.05 g,
11 mmol) was stirred with 2 equiv. of oxalyl chloride (Fluka, purum) for 40 min at 258. The excess reagent was
removed in vacuo at 258, and the oily residue was added to 150 ml of ethereal CH2N2. Stirring was continued
until no more N2 evolution was perceptible. After destruction of excess CH2N2 with the required amount of
AcOH, the mixture was evaporated and then dissolved in 40 ml of 1,4-dioxane (Fluka, puriss.). To this soln. was
added a suspension of 180 mg (0.78 mmol) of freshly precipitated Ag2O in 12 ml of H2O. The mixture was stirred
for 20 min at 608 and for 10 min at reflux. The cold mixture was filtered through CeliteTM and evaporated. The

Helvetica Chimica Acta Vol. 85 (2002)
957
residue was distributed between 1n aq. HCl soln. and Et2O. The combined org. extracts were dried (Na2SO4) and
evaporated to give 1.97 g (9.84 mmol, 89%) of crude (‡)-3, which was used for the next step without further
purification. Yellow oil. [a]D ˆ ‡39 (c ˆ 0.28, acetone). IR (CHCl3): 2930, 2860, 1720, 1450, 1430, 1370, 1255,
1160, 1110. 1H-NMR (300 MHz, CDCl3): 9.20 (br. s, 1 H); 3.63 (s, 3 H); 2.41 (dd, J ˆ 15.0, 3.3, 1 H); 2.20 2.04
(m, 3 H); 1.90 (m, 2 H); 1.74 (m, 2 H); 1.48 (qd, J ˆ 12.6, 3.5, 1 H); 1.26 (tt, J ˆ 12.6, 3.3, 2 H); 1.06 (qd, J ˆ 12.4,
3.9, 1 H). 13C-NMR (75 MHz, CDCl3): 179.2 (s); 178.1 (s); 51.8 (q); 48.9 (d); 39.6 (t); 35.9 (d); 31.6 (t); 30.0 (t);
‡
25.5 (t); 25.3 (t). EI-MS: 200 (0.3, M ), 182 (34), 168 (81), 150 (25), 122 (39), 100 (100), 81 (85).
(À)-(1R,2S)-2-(Methoxycarbonyl)cyclohexaneacetic Acid ((À)-3). Same procedure as above, starting with
(À)-4 [6], the optical purity of which having been shown to exceed 95% through an analysis ofthe 1H-NMR
spectrum of its (S)-phenethylamide derivative. Yield of (À)-3: 90%. [a]D ˆ À37 (c ˆ 0.35, acetone).
(Æ)-(1RS,2RS)-2-(Methoxycarbonyl)cyclohexaneacetic Acid ((Æ)-8). Same procedure as described above,
starting with (À)-5 [6]. Yield: 82%. [a]D ˆÆ 0 (c ˆ 0.4, acetone). IR (CHCl3): 3600 2300 (br.), 2920, 2860,
1720, 1680, 1440, 1300, 1120, 1035, 1000, 930, 870. 1H-NMR (200 MHz, CDCl3): 9.80 (br. s, 1 H); 3.64 (s, 3 H);
2.66 (m, 1 H); 2.40 (m, 2 H); 1.90 1.20 (m, 9 H).13C-NMR (50 MHz, CDCl3): 178.4 (s); 174.4 (s); 50.9 (q); 43.7
(d); 35.6 (t); 33.5 (d); 28.4 (t); 25.8 (t); 22.8 (t); 22.7 (t).
When the intermediate acid chloride (Æ)-7 ([a]D ˆÆ 0 (c ˆ 0.4, acetone) was hydrolyzed back to the half
1
ester 5, the isolated compound was racemic. This contention could be verified best by checking the H-NMR
(300 MHz, C6D6) of the derived (S)-phenethylamide 6, which showed two MeO signals of equal intensities
between 3.6 and 3.7 ppm, whereas the corresponding derivative of the starting material (À)-5 displayed only one
signal in this region.
(À)-(1R,2S)-Methyl 2-{N-[(1R)-2-(Indol-3-yl)-1-methylethyl]acetamido}cyclohexane-1-carboxylate ((À)-
9). Prepared from (À)-2 [5] and (À)-3 according to Method 1. Yield: 73%. M.p. 68 698 (foam). [a]D ˆ À44 (c ˆ
0.2, acetone). 1H-NMR (500 MHz, CDCl3): 8.34 (s, 1 H); 7.64 (dm, J ˆ 7.9, 1 H); 7.34 (ddd, J ˆ 8.0, 1.1, 0.7, 1 H);
7.17 (ddd, J ˆ 8.0, 7.0, 1.2, 1 H); 7.10 (ddd, J ˆ 8.0, 7.0, 1.10, 1 H); 7.02 (d, J ˆ 2.5, 1 H); 5.58 (br. d, J ˆ 8.2, 1 H);
4.37 (m, 1 H); 3.63 (s, 3 H); 2.96 (ddd, J ˆ 14.5, 6.0, 0.7, 1 H); 2.86 (ddd, J ˆ 14.4, 7.0, 0.6, 1 H); 2.16 (dd, J ˆ 13.8,
3.6, 1 H; 2.03 (td, J ˆ 11.5, 3.5, 1 H); 1.95 (m, 1 H); 1.83 (dd, J ˆ 13.8, 4.5, 1 H); 1.75 (dmd, J ˆ 13.4, 3.2, 1 H);
1.70 (dm, J ˆ 13.0, 1 H); 1.63 (dm, J ˆ 13.0, 1 H); 1.43 (tdd, J ˆ 13.0, 12.0, 3.5, 1 H); 1.21 (qt, J ˆ 13.0, 3.5, 1 H);
1.16 (d, J ˆ 6.6, 3 H); 1.11 (qt, J ˆ 13.0, 3.5, 1 H); 0.88 (tdd, J ˆ 13.0, 11.5, 3.6, 1 H). 13C-NMR (125 MHz,
CDCl3): 176.1 (s); 170.7 (s); 136.2 (s); 127.9 (s); 122.7 (d); 122.0 (d); 119.4 (d); 119.0 (d), 112.1 (s); 111.1 (d);
51.5 (q); 49.1 (d); 45.5 (d); 42.3 (t); 36.9 (d); 32.1 (t); 31.2 (t); 29.8 (t); 25.4 (t); 25.2 (t); 20.6 (q). HETCOR:
122.7/7.02; 122.0/7.17; 119.4/7.10; 119.0/7.64; 111.1/7.34; 51.5/3.63; 49.1/2.03; 45.5/4.37; 42.3/2.16 (expected cross-
peak with 1.83 missing), 36.9/1.95; 32.1/2.96 and 2.86; 20.6/1.16 (no significant cross-peaks for the remaining CH2
‡
groups). EI-MS: 356 (1, M ), 325 (1), 226 (1), 200 (2), 184 (3), 183 (24), 158 (20), 157 (100), 130 (26), 123 (10).
(‡)-(1R,2S)-Methyl 2-[(3,4-Dihydro-3-methyl-b-carbolin-1-yl)methyl]cyclohexane-1-carboxylate ((‡)-10).
Prepared from (À)-9 according to Method 2. Yield: 73%. M.p. 85 878 (foam). [a]D ˆ ‡33 (c ˆ 0.13, acetone).
1H-NMR (500 MHz, CDCl3): 9.94 (s, 1 H); 7.59 (dm, J ˆ 8.0, 1 H); 7.51 (dt, J ˆ 8.2, 0.9, 1 H); 7.27 (ddd, J ˆ 8.2,
7.0, 1.2, 1 H); 7.13 (ddd, J ˆ 8.0, 7.0, 1.0, 1 H); 3.88 (ddq, J ˆ 11.8, 7.0, 6.8, 1 H); 3.82 (s, 3 H); 2.99 (dd, J ˆ 16.2,
11.8, 1 H); 2.84 (ddd, J ˆ 12.8, 2.4, 1.4, 1 H); 2.61 (dd, J ˆ 16.2, 11.8, 1 H); 2.27 (td, J ˆ 11.5, 3.7, 1 H); 2.14
(dd, J ˆ 13.0, 11.0, 1 H); 2.09 1.95 (m, 2 H); 1.78 (dm, J ˆ 12.5, 1 H); 1.68 (dm, J ˆ 13.0, 1 H); 1.46 (d, J ˆ 6.8,
3 H); 1.39 1.25 (m, 2 H); 1.13 0.99 (m, 2 H). 13C-NMR (125 MHz, CDCl3): 178.5 (s); 158.2 (s); 136.8 (s);
128.2 (s); 125.5 (s); 124.0 (d); 119.8 (d); 119.6 (d); 115.7 (s); 112.4 (d); 53.9 (d); 52.1 (q); 49.1 (d); 42.4 (t); 36.6
(d); 30.9 (t); 30.6 (t); 26.3 (t); 25.7 (t); 25.2 (t); 22.3 (q). HETCOR: 124.0/7.27; 119.8/7.59; 119.6/7.13; 112.4/7.51;
53.9/3.88; 52.1/3.82; 49.1/2.27; 42.4/2.84 and 2.14; 36.6/1.98; 30.9/2.08 and 1.32; 30.6/1.95 and 1.02; 26.3/2.99 and
‡
2.61; 25.7/1.78 and 1.30; 25.2/1.68 and 1.06; 22.3/1.46. EI-MS: 338 (7, M ), 291 (3), 279 (7), 263 (4), 199 (15), 198
(100), 183 (22), 155 (20).
(À)-(1R,2S,1S)-Methyl 2-[(1,2,3,4-Tetrahydro-3-methyl-b-carbolin-1-yl)methyl]cyclohexane-1-carboxylate
((À)-11). Prepared from (‡)-10 according to Method 3. Yield: 70%. M.p. 1928. [a]D ˆ À187 (c ˆ 0.15, acetone).
UV (EtOH): 289 (2.82), 280 (2.87), 225 (3.50). IR (CHCl3): 3470, 3370, 3000, 2930, 2854, 1724, 1461, 1447, 1433,
1370, 1310, 1268, 1166, 1128. 1H-NMR (500 MHz, CDCl3): 8.17 (s, 1 H); 7.46 (dm, J ˆ 7.9, 1 H); 7.33 (dt, J ˆ 8.0,
0.8, 1 H); 7.14 (ddd, J ˆ 8.1, 7.1, 1.2, 1 H); 7.08 (ddd, J ˆ 7.8, 7.1, 1.1, 1 H); 4.21 (m, 1 H); 3.67 (s, 3 H); 3.04
(ddq, J ˆ 10.5, 3.9, 6.4, 1 H); 2.78 (ddd, J ˆ 15.1, 3.9, 1.9, 1 H); 2.37 (ddd, J ˆ 15.1, 10.5, 2.6, 1 H); 2.15 (ddd, J ˆ
12.0, 11.0, 3.5, 1 H); 2.12 (ddm, J ˆ 13.5, 3.0, 1 H); 2.02 (m, 1 H); 1.95 (ddd, J ˆ 13.0, 3.3, 1.6, 1 H); 1.77 (m, 2 H);
1.64 (m, 2 H); 1.48 (qd, J ˆ 12.5, 3.5, 1 H); 1.30 1.20 (m, 2 H); 1.32 (d, J ˆ 6.4, 3 H); 1.01 (qd, J ˆ 12.3, 3.5, 1 H).
NOE: a) irrad. at 4.21 (HÀC(3)) ! 8.17 (HÀN(1)), 3.04 (HÀC(5)), 2.12 (HeqÀC(16)), 2.02 (HÀC(15)), 1.64
(CH2(14)); b) irrad. at 3.04 (HÀC(5)) ! 4.21 (HÀC(3)), 2.78 HeqÀC(6), 1.32 (CH3(22)). 13C-NMR (125 MHz,
CDCl3): 176.9 (s); 136.4 (s); 136.02 (s); 127.5 (s); 121.3 (d); 119.2 (d); 117.9 (d); 110.8 (d); 109.7 (s); 51.6 (q); 50.7

958
Helvetica Chimica Acta Vol. 85 (2002)
(d); 50.3 (d); 50.1 (d); 40.6 (t); 34.9 (d); 31.5 (t); 30.7 (t); 30.2 (t); 25.5 (t), 25.4 (t); 22.7 (q). HETCOR: 121.3/
7.14; 119.2/7.08; 117.9/7.46; 110.8/7.33; 51.6/3.67; 50.7/4.21; 50.3/2.16; 50.1/3.04; 40.6/1.64; 34.9/2.02; 31.5/2.12 and
‡
1.01; 30.7/2.78 and 2.36; 30.2/1.95 and 1.48; 25.5/1.77 and 1.25; 25.4/1.77 and 1.25; 22.7/1.32. EI-MS: 340 (9, M ),
308 (13), 297 (16), 196 (11), 185 (100), 156 (26).
(À)-(1R,2S,1S)-{2-[(1,2,3,4-Tetrahydro-3-methyl-b-carbolin-1-yl)methyl]cyclohex-1-yl}methanol ((À)-13).
Prepared from (‡)-10 according to Method 4. Yield: 75%. M.p. 1258. [a]D ˆ À107 (c ˆ 0.09, acetone). UV
(EtOH): 290 (3.19), 282 (3.26), 226 (3.91). IR (CHCl3): 3620, 3470, 3000, 2960, 2920, 2850, 1460, 1447, 1380,
1309, 1270, 1144, 1123, 1086, 1045, 1009, 963. 1H-NMR (500 MHz, CDCl3): 8.31 (s, 1 H); 7.43 (dm, J ˆ 7.7, 1 H ) ;
7.25 (dt, J ˆ 7.9, 0.8, 1 H); 7.11 (ddd, J ˆ 7.9, 7.2, 1.2, 1 H); 7.06 (ddd, J ˆ 7.7, 7.2, 1.2, 1 H); 4.2 (m, 1 H); 3.68
(dd, J ˆ 11.5, 3.9, 1 H); 3.41 (dd, J ˆ 11.5, 3.1, 1 H); 3.06 (ddq, J ˆ 10.6, 4.0, 6.4, 1 H); 2.77 (ddd, J ˆ 15.3, 4.0, 1.8,
1 H); 2.39 (ddd, J ˆ 15.3, 10.6, 2.5, 1 H); 1.94 (dm, J ˆ 13.0, 1 H); 1.85 (m, 1 H); 1.75 1.65 (m, 3 H); 1.59 1.50
(m, 2 H); 1.37 (br. qd, J ˆ 12.4, 3.6, 1 H); 1.30 (d, J ˆ 6.4, 3 H); 1.26 1.20 (m, 2 H); 1.15 1.05 (m, 2 H).
13C-NMR (125 MHz, CDCl3): 136.1 (s); 136.0 (s); 127.4 (s); 121.4 (d); 119.3 (d); 118.0 (d); 110.8 (d); 109.1 (s);
64.5 (t); 52.1 (d); 50.3 (d); 45.0 (d); 38.7 (t); 35.0 (d); 33.1 (t); 30.5 (t); 30.0 (t); 26.2 (t); 26.1 (t); 22.5 (q).
HETCOR: 121.4/7.11; 119.3/7.05; 118.0/7.43; 110.8/7.25; 64.5/3.68 and 3.41; 52.1/4.12; 50.3/3.06; 45.0/1.10; 38.7/
1.85 and 1.55; 35.0/1.55; 33.1/1.94 and 1.05; 30.5/2.77 and 2.39; 30.0/1.72 and 1.37; 26.2/1.69 and 1.23; 26.1/1.69 and
‡
1.23; 22.5/1.30. EI-MS: 312 (3, M ), 294 (4), 198 (4), 186 (14), 185 (100), 156 (18).
(À)-(3S,5R,15S,20R)-5-Methylyohimbane ((À)-14). Prepared from (À)-13 according to Method 5. Yield:
78%. M.p. 1688 (foam). [a]D ˆ À165 (c ˆ 0.21, acetone). UV (EtOH): 290 (3.84), 283 (3.91), 222 (4.61). IR
(CHCl3): 3475, 3055, 3000, 2960, 2920, 2845, 2780, 1469, 1447, 1371, 1333, 1310, 1162, 1146, 1120, 1009, 982.
1H-NMR (500 MHz, CDCl3): 7.50 (dm, J ˆ 7.7, 1 H); 7.36 (dt, J ˆ 8.0, 0.9, 1 H); 7.17 (ddd, J ˆ 8.1, 7.1, 1.2, 1 H);
7.12 (ddd, J ˆ 7.7, 7.1, 1.1, 1 H); 3.30 (dm, J ˆ 11.7, 1 H); 3.12 (dd, J ˆ 11.0, 3.8, 1 H); 2.71 (m, 1 H); 2.60 (td, J ˆ
10.7, 2.4, 1 H); 2.57 (m, 1 H); 2.03 (dt, J ˆ 12.7, 3.1, 1 H); 1.75 (t, J ˆ 11.0, 1 H); 1.68 (m, 2 H); 1.63 (dm, J ˆ 12.6,
1 H); 1.55 (dm, J ˆ 12.9, 1 H); 1.30 (dt, J ˆ 12.5, 11.7, 1 H); 1.26 1.23 (m, 3 H); 1.24 (d, J ˆ 5.9, 3 H); 1.10
(qt, J ˆ 11.5, 3.4, 1 H); 1.01 (qd, J ˆ 12.0, 3.0, 1 H); 0.92 (qd, J ˆ 12.2, 3.2, 1 H). 13C-NMR (125 MHz, CDCl3):
136.0 (s); 134.4 (s); 126.9 (s); 120.9 (d); 118.9 (d); 117.8 (d); 110.7 (d); 107.2 (s); 61.0 (d); 56.4 (t); 56.1 (d); 41.5
(d); 41.2 (d); 36.7 (t); 32.4 (t); 30.8 (t); 30.5 (t); 26.2 (t); 25.8 (t); 20.0 (q). HETCOR: 120.9/7.12; 118.9/6.97;
117.8/7.35; 110.7/7.21; 61.0/3.30; 56.4/3.12 and 1.75; 56.1/2.57; 41.5/1.25; 41.2/1.10; 36.7/2.03 and 1.30; 32.4/1.63 and
1.02; 30.8: no cross-peaks with CH2(6) detectable; 30.5/1.56 and 0.92; 26.2/1.70 and 1.25; 25.8/1.70 and 1.25; 20.0/
‡
1.24. EI-MS: 294 (100, M ), 279 (40), 238 (17), 169 (9).
(‡)-(3R,5R,15S,20R)-5-Methylyohimbane ((‡)-1). Prepared from (À)-14 according to Method 6. M.p.
103 1078 (foam). [a]D ˆ ‡24 (c ˆ 0.24, acetone). UV (EtOH): 289 (3.78), 282 (3.85), 226 (4.54). IR (CHCl3):
3475, 3000, 2960, 2920, 2850, 1448, 1374, 1332, 1324, 1305, 1277, 1162, 1148, 1127, 1009. 1H-NMR (500 MHz,
CDCl3): 7.82 (s, 1 H); 7.50 (br. d, J ˆ 7.8, 1 H); 7.36 (dt, J ˆ 8.0, 0.9, 1 H); 7.17 (ddd, J ˆ 7.8, 7.0, 1.1, 1 H); 7.12
(ddd, J ˆ 8.0, 7.0, 1.0, 1 H); 4.42 (m, w1/2 ˆ 10, 1 H); 3.32 (quint., J ˆ 7.0, 1 H); 3.12 (ddd, J ˆ 16.0, 6.2, 2.6, 1 H);
2.54 (dd, J ˆ 11.1, 3.6, 1 H); 2.36 (dd, J ˆ 16.0, 1.8, 1 H); 2.35 (t, J ˆ 11.3, 1 H); 2.06 (dt, J ˆ 14.0, 2.8, 1 H); 1.73
(ddd, J ˆ 14.0, 12.4, 5.3, 1 H); 1.72 1.62 (m, 2 H); 1.50 (dm, J ˆ 13.0, 1 H); 1.34 (qt, J ˆ 11.1, 3.5, 1 H); 1.35 1.22
(m, 4 H, incl. 1.25 (d, J ˆ 7.0, 3 H)); 1.14 (m, 1 H); 1.03 (qd, J ˆ 12.8, 3.4, 1 H); 0.90 (qt, J ˆ 11.4, 3.2, 1 H); 0.76
(qd, J ˆ 12.8, 3.7, 1 H). 13C-NMR (125 MHz, CDCl3): 135.8 (s); 132.2 (s); 128.4 (s); 121.3 (d); 119.3 (d); 117.9
(d); 110.8 (d); 106.3 (s); 54.7 (t); 53.7 (d); 47.6 (d); 41.8 (d); 37.1 (d); 34.9 (t); 32.9 (t); 30.2 (t); 26.2 (t); 25.9 (t);
21.9 (t); 19.3 (q). HETCOR: 121.3/7.17; 119.3/7.12; 117.9/7.50; 110.8/7.36; 54.7/2.54 and 2.36; 53.7/3.32; 47.6/4.42;
41.8/1.25; 37.1/0.90; 34.9/2.06 and 1.73; 32.9/1.66 and 1.03; 30.2/1.50 and 0.76; 26.2/1.73 and 1.14; 25.9/1.66 and
‡
1.25; 21.9/3.32 and 2.36; 19.3/1.25. EI-MS: 294 (100, M ), 293 (72), 279 (55), 251 (33), 238 (54), 169 (82), 156
(54), 150 (98), 91 (72).
(‡)-(1S,2R)-Methyl 2-{N-[(1R)-2-(Indol-3-yl)-1-methylethyl]aceamido]cyclohexane-1-carboxylate ((‡)-
15). Prepared from (À)-2 and (‡)-3 according to Method 1. Yield: 73%. M.p. 72 748 (foam). [a]D ˆ ‡23
(c ˆ 0.16, acetone). UV (EtOH): 290 (3.00), 281 (3.02), 222 (3.81). IR (CHCl3): 3475, 3355, 3008, 2935, 2860,
1719, 1461, 1450, 1437, 1376, 1312, 1261, 1171, 1123, 1009. 1H-NMR (500 MHz, CDCl3): 8.33 (s, 1 H); 7.64
(dm, J ˆ 7.9, 1 H); 7.35 (dt, J ˆ 8.0, 0.9, 1 H); 7.18 (ddd, J ˆ 8.0, 7.0, 1.1, 1 H); 7.11 (ddd, J ˆ 8.0, 7.9, 1.1, 1 H); 7.01
(d, J ˆ 2.3, 1 H); 5.54 (br. d, J ˆ 8.1, 1 H); 4.36 (m, 1 H); 3.63 (s, 3 H); 2.95 (ddd, J ˆ 14.5, 5.9, 0.8, 1 H); 2.86
(ddd, J ˆ 14.5, 6.7, 0.6, 1 H); 2.17 (dd, J ˆ 13.5, 3.5, 1 H); 2.10 (ddd, J ˆ 12.0, 11.0, 3.5, 1 H); 1.96 1.86 (m, 2 H);
1.81 (dd, J ˆ 13.51, 9.0, 1 H); 1.77 1.68 (m, 2 H); 1.65 (m, 1 H); 1.43 (qd, J ˆ 12.5, 3.5, 1 H); 1.18 (m, 2 H); 1.16
(d, J ˆ 6.5, 3 H); 1.01 0.87 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 176.1 (s); 170.7 (s); 136.2 (s); 127.9 (s); 122.6
(d); 121.9 (d); 119.4 (d); 119.0 (d); 112.1 (s); 111.1 (d); 51.5 (q); 49.1 (d); 45.5 (d); 42.3 (t); 36.8 (d); 31.9 (t); 31.1
(t); 29.8 (t); 25.3 (t); 25.2 (t); 20.5 (q). HETCOR: 122.6/7.01; 121.9/7.18; 119.4/7.11; 119.0/7.64; 111.1/7.35; 51.5/
3.63; 49.1/2.10; 45.5/4.36; 42.3/2.17 and 1.81; 36.8/1.90; 31.9/2.95 and 2.86; 31.1/1.72 and 0.93; 29.8/1.86 and 1.43;

Helvetica Chimica Acta Vol. 85 (2002)
959
‡
25.3/1.62 and 1.18; 25.2/1.72 and 1.18; 20.5/1.16. EI-MS: 357 (76, [M ‡ 1] ), 325 (91), 200 (6), 187 (14), 186 (77),
183 (27), 158 (71), 157 (100), 130 (34), 123 (13).
(À)-(1S,2R,1S)-Methyl 2-[(1,2,3,4-Tetrahydro-3-methyl-b-carbolin-1-yl)methyl]cyclohexane-1-carboxylate
((À)-16). Prepared from (‡)-15 according to Method 2, followed by Method 3. Yield: 70%. M.p. 1128. [a]D
ˆ
À132 (c ˆ 0.12, acetone). IR (CHCl3): 3475, 3355, 3008, 2935, 2860, 1719, 1461, 1450, 1437, 1376, 1312, 1261,
1
1171, 1123, 1009. H-NMR (500 MHz, CDCl3): 8.99 (s, 1 H); 7.45 (dm, J ˆ 7.8, 1 H); 7.41 (dt, J ˆ 8.0, 0.8, 1 H);
7.15 (ddd, J ˆ 8.1, 7.1, 1.2, 1 H); 7.08 (ddd, J ˆ 7.8, 7.1, 1.1, 1 H); 4.04 (m, 1 H); 3.67 (s, 3 H); 3.13 (ddq, J ˆ 10.7,
4.2, 6.3, 1 H); 2.79 (ddd, J ˆ 15.2, 4.2, 1.9, 1 H); 2.41 (ddd, J ˆ 15.2, 10.7, 2.5, 1 H); 2.21 (ddd, J ˆ 11.9, 11.0, 3.7,
1 H); 2.13 (dm, J ˆ 13.5, 1 H); 2.02 (m, 1 H); 1.96 (m, 1 H); 1.86 1.77 (m, 3 H, incl. 1.82 (ddd, J ˆ 10.7, 8.1, 2.9,
1 H)); 1.51 (qd, J ˆ 12.7, 3.6, 1 H); 1.40 (ddd, J ˆ 12.8, 9.4, 3.3, 1 H); 1.36 1.29 (m, 5 H, incl. 1.32 (d, J ˆ 6.4,
3 H)); 1.06 (qd, J ˆ 12.3, 3.5, 1 H). 13C-NMR (125 MHz, CDCl3): 178.0 (s); 137.2 (s); 136.4 (s); 127.1 (s); 121.2
(d); 119.1 (d); 117.8 (d); 111.1 (d); 108.8 (s); 52.3 (d); 51.9 (q); 50.5 (d); 49.7 (d); 41.9 (t); 37.5 (d); 32.4 (t); 30.7
(t); 30.4 (t); 25.6 (t); 25.5 (t); 22.6 (q). HETCOR: 121.2/7.15; 119.1/7.08; 117.8/7.45; 111.1/7.41; 52.3/4.04; 51.9/
3.67; 50.5/3.13; 49.7/2.21; 41.9/1.82 and 1.40; 37.5/2.02; 32.4/2.13 and 1.06; 30.7/2.10 and 1.51; 30.4/2.79 and 2.41;
‡
25.6/1.82 and 1.31; 25.4/1.82 and 1.32; 22.6/1.33. EI-MS: 340 (13, M ), 297 (25), 196 (8), 185 (100), 156 (13).
(‡)-(3S,5R,15R,20S)-5-Methylyohimban-21-one ((‡)-17). Isolated as a by-product in 7% yield in the
above reaction leading to (À)-16. M.p. 187 1918 (subl.). [a]D ˆ ‡14 (c ˆ 0.1, acetone). IR (CHCl3): 3470, 3000,
2925, 2855, 1629, 1460, 1447, 1408, 1346, 1304. 1H-NMR (500 MHz, CDCl3): 7.80 (s, 1 H); 7.48 (dm, J ˆ 7.8, 1 H);
7.32 (dt, J ˆ 8.0, 0.8, 1 H); 7.18 (ddd, J ˆ 8.0, 7.1, 1.2, 1 H); 7.12 (ddd, J ˆ 7.8, 7.1, 1.1, 1 H); 5.55 (qd, J ˆ 7.0, 5.8,
1 H); 4.74 (m, 1 H); 2.99 (ddd, J ˆ 15.5, 5.8, 2.6, 1 H); 2.58 (dt, J ˆ 15.5, 1.3, 1 H); 2.47 (m, 1 H); 2.36 (ddm, J ˆ
10.0, 4.8, 1 H); 1.90 1.76 (m, 4 H); 1.63 (m, 2 H); 1.32 1.26 (m, 3 H); 1.19 (d, J ˆ 7.0, 3 H); 1.10 (m, 1 H).
13C-NMR (125 MHz, CDCl3): 170.8 (s); 136.4 (s); 132.2 (s); 127.6 (s); 122.1 (d); 119.7 (d); 118.4 (d); 110.8 (d);
107.2 (s); 49.2 (d); 47.5 (d); 42.5 (d); 36.7 (d); 35.8 (t); 33.2 (t); 27.7 (t); 26.3 (t); 26.2 (t); 25.6 (t); 17.1 (q). EI-MS:
‡
308 (100, M ), 293 (14), 279 (12), 183 (29), 168 (28), 156 (22).
(‡)-(3S,5R,15R,20S)-5-Methylyohimbane ((‡)-18). Prepared from (À)-16 according to Method 4, followed
by Method 5. Yield: 56%. M.p. 788 (foam). [a]D ˆ ‡5 (c ˆ 0.11, acetone). UV (EtOH): 289 (3.78), 282 (3.85),
226 (4.54). IR (CHCl3): 3475, 3000, 2960, 2920, 2850, 1459, 1447, 1382, 1310, 1305, 1269, 1154, 1143, 1120, 1009.
1H-NMR (500 MHz, CDCl3): 7.80 (s, 1 H); 7.48 (br. d, J ˆ 7.9, 1 H); 7.35 (dt, J ˆ 7.8, 1.0, 1 H); 7.15 (ddd, J ˆ 7.9,
7.1, 1.3, 1 H); 7.11 (ddd, J ˆ 7.8, 7.1, 1.2, 1 H); 4.46 (m, w1/2 ˆ 9.2, 1 H); 3.30 (m, 1 H); 2.70 2.56 (m, 3 H, incl.
2.65 ((dd, J ˆ 11.0, 2.7, 1 H)); 2.05 (t, J ˆ 11.0, 1 H); 2.01 (ddd, J ˆ 14.0, 3.3, 2.3, 1 H); 1.81 (ddd, J ˆ 13.9, 12.4,
5.3, 1 H); 1.70 1.60 (m, 3 H); 1.50 (dm, J ˆ 13.0, 1 H); 1.36 (d, J ˆ 6.8, 3 H); 1.28 1.09 (m, 3 H); 1.03
(br. qd, J ˆ 12.0, 3.1, 1 H); 0.87 (m, 1 H); 0.76 (qd, J ˆ 12.3, 3.5, 1 H). 13C-NMR (125 MHz, CDCl3): 135.8 (s);
133.7 (s); 127.6 (s); 121.2 (d); 119.4 (d); 118.0 (d); 110.8 (d); 109.2 (s); 56.4 (d); 55.4 (d); 44.9 (t); 41.5 (d); 37.1
(d); 35.1 (t); 33.0 (t); 30.5 (t); 26.3 (t); 25.9 (t); 24.6 (t); 19.5 (q). HETCOR: 121.2/7.15; 119.4/7.11; 118.0/7.48;
110.8/7.35; 56.4/4.46; 55.4/3.30; 44.9/2.65 and 2.05; 41.5/1.23; 37.1/0.87; 35.1/1.81 (only 1 cross-peak detectable);
‡
33.0/1.66 and 1.02; 30.5/1.51 and 0.76; 26.3/1.65 and 1.12; 24.6/2.65 and 2.63; 19.5/1.36. EI-MS: 294 (100, M ), 293
(70), 279 (40), 251 (30), 236 (17), 169 (14), 156 (11), 150 (15).
(‡)-(3S,5R,15R,20S)-5-Methylyohimbane ((‡)-19). Method A: Prepared from (‡)-18 according to
Method 6. Yield: 30% (and 62% of 18). M.p. 2318. [a]D ˆ ‡110 (c ˆ 0.13, acetone). UV (EtOH): 290 (3.82),
281 (3.90), 226 (4.57). IR (CHCl3): 3475, 3055, 3000, 2960, 2920, 2845, 2800, 2760, 1467, 1446, 1371, 1324, 1302,
1281, 1160, 1109, 1009. 1H-NMR (500 MHz, CDCl3): 7.68 (br. s, 1 H); 7.45 (br. d, J ˆ 7.8, 1 H); 7.29 (dm, J ˆ 8.0,
1 H); 7.12 (ddd, J ˆ 7.8, 7.1, 1.3, 1 H); 7.08 (ddd, J ˆ 8.0, 7.1, 1.1, 1 H); 3.53 (ddm, J ˆ 11.0, 1.8, 1 H); 3.34
(br. quint., J ˆ 6.6, 1 H); 3.15 (ddd, J ˆ 15.2, 5.9, 2.3, 1 H); 2.74 (dd, J ˆ 11.1, 3.8, 1 H); 2.53 (dt, J ˆ 15.2, 1.5,
1 H); 2.39 (t, J ˆ 10.9, 1 H); 2.00 (dt, J ˆ 12.1, 3.1, 1 H); 1.80 1.74 (m, 2 H); 1.70 (dm, J ˆ 13.0, 1 H); 1.62
(dm, J ˆ 13.0, 1 H); 1.41 (qt, J ˆ 11.8, 3.5, 1 H); 1.34 (q, J ˆ 11.7, 1 H); 1.32 1.22 (m, 2 H); 1.16 (qt, J ˆ 11.8, 3.4,
1 H); 1.07 (qd, J ˆ 12.0, 2.8, 1 H); 1.03 (m, 1 H); 1.01 (d, J ˆ 6.6, 3 H). 13C-NMR (125 MHz, CDCl3): 136.2 (s);
134.3 (s); 128.2 (s); 121.1 (d); 119.2 (d); 118.0 (d); 110.6 (d); 106.6 (s); 58.6 (t); 54.0 (d); 53.0 (d); 42.1 (d); 42.0
(d); 37.9 (t); 32.9 (t); 30.4 (t); 28.5 (t); 26.5 (t); 26.0 (t); 10.2 (q). HETCOR: 121.1/7.12; 119.2/7.12; 118.0/7.45;
110.6/7.29; 58.6/2.74 and 2.39; 54.0/3.34; 53.0/3.53; 42.1/1.41; 42.0/1.15; 37.9/2.00 and 1.34; 32.9/1.75 and 1.07; 30.4/
‡
1.61 and 1.03; 28.5/3.15 and 2.53; 26.5/1.75 and 1.26; 26.0/1.75 and 1.26; 10.2/1.01. EI-MS: 294 (100, M ), 293
(72), 279 (61), 251 (20), 238 (30), 169 (28), 156 (11).
Method B: From (‡)-17 according to Method 4. Yield: 94%.
(‡)-(3S,5R,15R)-5-Methylyohimb-20-ene ((‡)-20). To a soln. of 400 mg (1.18 mmol) of (À)-16 in 10 ml of
dry THF were added 3.7 ml of an 1m soln. of DIBAH in hexane (3 equiv.) under Ar. After stirring for 18 h at 408,
the mixture was distributed between 2n aq. NaOH soln. and CH2Cl2. The combined org. extracts were dried
(Na2SO4), evaporated, and chromatographed (silica gel; Et2O/hexane/MeOH/Et2NH, 60 :40 :10 :3) to give

960
Helvetica Chimica Acta Vol. 85 (2002)
115 mg (0.39 mmol, 33%) of (‡)-20 and starting material. M.p. 1938. [a]D ˆ ‡155 (c ˆ 0.10, acetone). UV: 290
(3.73), 282 (3.79), 226 (4.48). IR (CHCl3): 3470, 3060, 3000, 2920, 2850, 1661, 1460, 1448, 1431, 1397, 1311, 1270,
1260, 1175. 1H-NMR (500 MHz, CDCl3): 7.91 (br. s, 1 H); 7.49 (br. d, J ˆ 7.8, 1 H); 7.35 (dt, J ˆ 7.8, 0.8, 1 H); 7.17
(ddd, J ˆ 7.8, 7.2, 1.3, 1 H; 7.13 (ddd, J ˆ 7.8, 7.2, 1.1, 1 H); 5.95 (br. s, w1/2 ˆ 4, 1 H); 4.45 (br. s, w1/2 ˆ 9, 1 H); 3.34
(dqd, J ˆ 10.5, 6.8, 3.8, 1 H); 2.72 (ddd, J ˆ 15.0, 4.8, 1.2, 1 H); 2.56 (ddd, J ˆ 15.0, 10.5, 2.6, 1 H); 2.29 (m, 1 H);
2.07 (dm, J ˆ 13.6, 1 H); 1.96 (m, 2 H); 1.85 1.20 (m, 4 H); 1.45 (d, J ˆ 6.8, 3 H); 1.24 (m, 1 H); 1.24 (qd, J ˆ
13.0, 3.3, 1 H); 1.09 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 135.8 (s); 134.4 (s); 127.5 (s); 122.2 (d); 121.1 (d);
119.3 (d); 117.9 (d); 117.4 (s); 110.8 (d); 109.3 (s); 54.4 (d); 53.5 (d); 34.9 (t); 34.2 (t); 32.3 (t); 31.4 (d); 28.1 (t);
‡
‡
27.6 (t); 26.3 (t); 19.0 (q). CI-MS: 293 (100, [M ‡ 1] ), 292 (68, M ), 277 (32), 275 (15), 249 (17), 234 (18), 169
(11), 156 (14).
(À)-(3S,5R,15R,20R)-5-Methylyohimbane ((À)-21). Prepared from 100 mg (0.34 mmol) of (‡)-20
according to Method 3. The crude mixture was chromatographed (silica gel; Et2O/hexane/MeOH/Et2NH
60 :40 :10:3) to give 67 mg (67%) of (À)-21 and 15 mg (15%) of (‡)-18. Characterization of (À)-21: M.p. 122
1248. [a]D ˆ À51 (c ˆ 0.21, CHCl3). IR (CHCl3): 3630, 3475, 3055, 3005, 2965, 2920, 2850, 2800, 1463, 1448, 1371,
1
1337, 1312, 1288, 1275, 1260, 1158, 1111, 1074, 1013. H-NMR (500 MHz, CDCl3): sharp signals at: 7.70 (br. s,
1 H); 7.45 (br. d, J ˆ 7.6, 1 H); 7.29 (dm, J ˆ 7.8, 1 H); 7.12 (m, 1 H); 7.08 (m, 1 H); 2.44 (t, J ˆ 10.8, 1 H); 1.31
(q, J ˆ 6.1, 3 H); br. signals at: 3.60 (1 H); 2.88 (1 H); 2.75 2.60 (3 H); 2.10 1.40 (12 H). 1H-NMR (300 MHz,
C6D6, 808): 7.54 (m, 1 H); 7.22 7.1 (m, 3 H); 6.83 (br. s, 1 H); 3.58 (m, w1/2 ˆ 17, 1 H); 2.78 (dd, J ˆ 10.9, 3.5,
1 H); 2.70 2.55 (m, 3 H); 2.32 (dd, J ˆ 10.9, 9.6, 1 H); 1.92 (m, 1 H); 1.75-1.55 (m, 6 H); 1.50 1.20 (m, 5 H);
1.17 (d, J ˆ 5.9, 3 H). 13C-NMR (125 MHz, CDCl3): sharp signals at: 135.9 (s); 127.4 (s); 121.2 (d); 119.3 (d);
118.0 (d); 110.6 (d); 108.5 (s); 55.9 (d); 35.1 (d); 20.2 (q); br. signals at ca.: 135.0 (s); 55.0 (d); 49.1 (t); 36.3 (t);
33.2 (t); 30.8 (t); 29.5 (t); 26.3 (t); 21.9 (t). 13C-NMR (75 MHz, C6D6, 808): 137.3 (s); 135.7 (s); 127.4 (d); 121.9
(d); 120.2 (d); 118.8 (d); 111.4 (d); 109.6 (s); 56.2 (d); 56.1 (d); 48.9 (t); 36.4 (d); 35.1 (t); 33.6 (d); 30.6 (t); 29.6
‡
(t); 28.3 (t); 25.9 (t); 23.7 (t); 20.5 (q). EI-MS: 294 (100, M ), 293 (89), 279 (40), 251 (19), 238 (13), 236 (12), 183
(16), 169 (34), 156 (23), 150 (71), 143 (13), 130 (12).
(‡)-(3R,5R,15R,20R)-5-Methylyohimbane ((‡)-22). Prepared from (À)-21 according to Method 6. Yield:
52% (and 33% of 21). Yellow oil. [a]D 0 ‡ 123 (c ˆ 0.10, acetone). IR (CHCl3): 3475, 3055, 3000, 2960, 2920,
2855, 2800, 2760, 1464, 1446, 1373, 1325, 1308, 1285, 1162, 1109, 1008, 905. 1H-NMR (500 MHz, CDCl3): 7.77
(br. s, 1 H); 7.45 (br. d, J ˆ 7.8, 1 H); 7.29 (dm, J ˆ 7.8, 1 H); 7.13 (ddd, J ˆ 7.8, 7.2, 1.3, 1 H); 7.09 (ddd, J ˆ 7.8, 7.2,
1.1, 1 H); 3.49 (m, 1 H); 3.22 (br. quint., J ˆ 6.6, 1 H); 3.10 (ddd, J ˆ 15.0, 5.9, 2.3, 1 H); 2.86 (br. dd, J ˆ 11.5,
3.2, 1 H); 2.61 (br. dm, J ˆ 11.5, 1 H); 2.52 (dt, J ˆ 15.0, 1.4, 1 H); 1.98 1.85 (m, 2 H); 1.75 1.63 (m, 3 H);
1.60 1.52 (m, 2 H); 1.45 1.25 (m, 6 H); 0.98 (d, J ˆ 6.6, 3 H). 13C-NMR (125 MHz, CDCl3): sharp signals:
136.2 (s); 128.2 (s); 121.1 (d); 119.2 (d); 118.0 (d); 110.6 (d); 106.4 (s); 54.0 (d); 36.7 (d); 34.7 (d); 31.4 (t); 26.4
‡
(t); 26.2 (t); 26.0 (t); br. signals: 134.7 (s); 58.5 (t); 52.9 (d); 31.5 (t); 20.9 (t); 9.7 (q). EI-MS: 294 (100, M ), 293
(74), 279 (53), 251 (12), 238 (12), 170 (13), 169 (23), 156 (12), 150 (49).
1:1-Mixture of Methyl (1S,2S)-2-{N-[(1R)-2-(Indol-3-yl)-1-methylethyl]acetamido}cyclohexane-1-carbox-
ylate (23) and Methyl (1R,2R)-2-{N-[(1R)-2-(Indol-3-yl)-1-methylethyl]acetamidocyclohexane-1-carboxylate
(24). Prepared from (À)-2 and (Æ)-8 according to Method 1, followed by Method 2. Yield: 86%.
(À)-(3S,5R,15S,20S)-5-Methylyohimbane ((À)-25): Prepared from the 1:1 mixture 23/24 according to
Methods 3 5. Overall yield: 16% (and 16% of (À)-21). Slightly yellow needles. M.p. 152 1548 (dec.). [a]D
ˆ
À134 (c ˆ 0.28, CHCl3). IR (CHCl3): 3465, 3000, 2960, 2920, 2855, 2785, 2750, 1463, 1446, 1373, 1333, 1309, 1165,
1140, 1121, 1009. 1H-NMR (500 MHz, CDCl3): 7.77 (br. s, 1 H); 7.44 (br. d, J ˆ 7.7, 1 H); 7.29 (dt, J ˆ 7.7, 1.1,
1 H); 7.11 (ddd, J ˆ 7.7, 7.2, 1.3, 1 H); 7.08 (ddd, J ˆ 7.7, 7.2, 1.1, 1 H); 3.32 (m, 1 H); 3.10 (d, J ˆ 11.0, 1 H); 2.71
(m, 1 H); 2.62 2.50 (m, 2 H); 2.23 (dd, J ˆ 11.2, 3.2, 1 H); 2.00 1.30 (m, 12 H); 1.24 (d, J ˆ 6.0, 3 H). 1H-NMR
(300 MHz, C6D6, 808): aliphatic region: 3.08 (dm, J ˆ 8.2, 1 H); 3.01 (dd, J ˆ 11.0, 2.7, 1 H); 2.70 2.50 (m, 2 H);
2.42 (m, 1 H); 2.08 (dd, J ˆ 11.2, 3.3, 1 H); 1.98 (m, 1 H); 1.79 1.65 (m, 3 H); 1.60 1.52 (m, 3 H); 1.28 1.14
(m, 5 H); 1.10 (d, J ˆ 6.2, 3 H). 13C-NMR (125 MHz, CDCl3): sharp signals: 135.9 (s); 135.5 (s); 127.4 (s); 121.1
(d); 119.3 (d); 118.0 (d); 110.6 (d); 108.1 (s); 55.3 (d); 36.5 (d); 34.4 (d); 31.4 (t); 20.8 (q); br. signals: 60.6 (d);
56.4 (t); 31.5 (2t); 26.6 (2t); 21.1 (t). 13C-NMR (75 MHz, C6D6, 808): aliphatic region: 61.1 (d); 56.2 (t); 55.2 (d);
‡
37.1 (d); 34.8 (d); 31.69 (t); 31.63 (t); 31.5 (t); 26.8 (t); 26.6 (t); 21.1 (t); 20.6 (q). EI-MS: 294 (97, M ), 293 (75),
279 (41), 251 (15), 238 (15), 170 (23), 169 (33), 168 (21), 156 (26), 150 (100), 130 (13).
(‡)-(3R,5R,15S,20S)-5-Methylyohimbane ((‡)-26): Prepared from (À)-25 according to Method 6. Yield:
57% (and 34% of 25). M.p. 183 1868 (dec.). [a]D ˆ ‡51.4 (c ˆ 1.0, CHCl3). IR (CHCl3): 3470, 3055, 3000, 2950,
1
2920, 2850, 2780, 1462, 1446, 1368, 1320, 1311, 1280, 1256, 1153. H-NMR (400 MHz, CDCl3): 7.68 (br. s, 1 H);
7.45 (br. d, J ˆ 7.8, 1 H); 7.28 (dm, J ˆ 7.8, 1 H); 7.12 (ddd, J ˆ 7.8, 7.2, 1.3, 1 H); 7.09 (ddd, J ˆ 7.8, 7.2, 1.1, 1 H);
3.76 (m, 1 H); 3.30 (br. quint., J ˆ 6.6, 1 H); 3.15 (ddd, J ˆ 15.2, 5.9, 2.3, 1 H); 3.02 (br. t, J ˆ 11.2, 1 H); 2.50

Helvetica Chimica Acta Vol. 85 (2002)
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(br. d, J ˆ 15.2, 1 H); 2.44 (br. dd, J ˆ 11.2, 4.0, 1 H); 2.12 (br. m, 1 H); 1.95 1.70 (m, 5 H); 1.65 1.23 (m, 5 H);
1.06 (d, J ˆ 6.6, 3 H). 13C-NMR (100 MHz, CDCl3): sharp signals: 136.2 (s); 128.2 (s); 121.1 (d); 119.2 (d); 118.0
(d); 110.6 (d); 106.8 (s); 54.1 (d); 51.6 (t); 47.2 (d); 34.9 (d); 34.4 (d); br. signals: 134.5 (s); 35.7 (t); 31.5 (t); 29.3
‡
(t); 28.3 (t); 26.4 (2t); 22.1 (t); 10.6 (q). EI-MS: 294 (100, M ), 293 (79), 279 (46), 251 (12), 238 (12), 170 (16),
169 (28), 156 (15), 150 (70).
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Received January 5, 2002