Formic acid catalyzed rearrangement of thevinols (=4,5-epoxy-3,6-dimethoxy-α,17-dimethyl-6,14-ethenomorphinan-7-methanols) and their vinylogous analogues: Effects of 5β-methyl substitution

Article abstract of DOI:10.1002/hlca.200390185

In a limited number of cases, 14-alkenylcodeinones (=14-alkenyl-7,8-didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ones) can be obtained by formic acid treatment of thevinols (=4,5-epoxy-3,6-dimethoxy-α,17-dimethyl-6,14-ethenomorphinan-7-methanols), b

Full text of DOI:10.1002/hlca.200390185

Helvetica Chimica Acta Vol. 86 (2003)
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Formic Acid Catalyzed Rearrangement of Thevinols (ˆ4,5-Epoxy-3,6-
dimethoxy-a,17-dimethyl-6,14-ethenomorphinan-7-methanols) and Their
Vinylogous Analogues: Effects of 5b-Methyl Substitution
by Peter Grundta), Fernando Martinez-Bermejob), John W. Lewisa), Stephen M. Husbands*a)
a) Department of Pharmacy and Pharmacology, University of Bath, Bath, BA27AY, UK
b) School of Chemistry, University of Bristol, Bristol, BS81TS, UK
In a limited number of cases, 14-alkenylcodeinones (ˆ14-alkenyl-7,8-didehydro-4,5-epoxy-3-methoxy-17-
methylmorphinan-6-ones) can be obtained by formic acid treatment of thevinols (ˆ4,5-epoxy-3,6-dimethoxy-
a,17-dimethyl-6,14-ethenomorphinan-7-methanols), but under these conditions the equivalent 14-alkenyl-7,8-
dihydrocodeinones undergo further rearrangement (Scheme 1 and Table). Introduction of a 5b-methyl group
allows the 18,19-dihydrothevinol precursors to be rearranged to 14-alkenyl-7,8-dihydrocodeinones, but similar
manipulation of the vinylogues of these thevinols is generally unable to prevent full rearrangement to 5,14-
bridged thebainone derivatives.
Introduction.
The indolomorphinan-3,14-diol structure 1 provided the first
nonpeptide d-selective opioid receptor antagonist naltrindole (1a) and the selective d-
partial agonist oxymorphindole (1b) [1][2]. Following investigations of 14-(alkylamino)
and 14-(acylamino) derivatives [3], our interest in 14-substituted indolomorphinan-3-
ols turned to 14-alkyl derivatives, of which only one 6a has been reported (6a ˆ NIH
10889); it had high affinity for d-opioid receptors and good selectivity for d over m and k
[4].
The thevinols (ˆ4,5-epoxy-3,6-dimethoxy-a,17-dimethyl-6,14-ethenomorphinan-7-
methanols) 2, orvinols 3, and their 18,19-dihydro analogues 4 and 5 are important series
of opioid ligands from which etorphine (3a), a veterinary immobilizing agent, and
buprenorphine (5b), a clinical analgesic and agent for treatment of opioid abuse, have
been developed [5][6]. The 14-alkenylcodeinones (ˆ14-alkenyl-7,8-didehydro-4,5-
epoxy-3-methoxy-17-methylmorphinan-6-ones) 9 (see below, Scheme 1), which were
among several sets of acid-catalyzed-rearrangement products of the thevinols 7 [7][8],
provided the precursor 9c for 6a and also the precursor 9a for the 3-methoxyindolo-
morphinan 6b [9]. Though other syntheses of 14-alkyl-7,8-dihydrocodeinones have
been reported [10][11], they are long and low-yielding. From the reaction of thevinols
with formic acid, only three alkenylcodeinones, 9a c, have been reported [7][12], so
that opportunities for the synthesis of 14-alkylindolomorphinans have been limited.
The major problem limiting the availability of stable 14-alkenylcodeinones is that
they are prone to further acid-catalyzed rearrangement, which, in the case of the 7,8-
dihydrocodeinone analogues 15 (see Scheme 1), prohibits their isolation; the products
of formic acid treatment of the dihydrothevinols 13b,c were 5,14-bridged dihydrothe-
bainone derivatives 17b,c (see Scheme 1) [7]. We hypothesized that introduction of a
5b-methyl group into the dihydrothevinols such as in 14a c should suppress cyclization

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of the 14-alkenyl side chain to C(5) and allow the isolation of the 14-alkenyldihy-
drocodeinones 16a c rather than 18a c (Scheme 1).
The only other thevinol to have produced an alkenylcodeinone structure is
vinylthevinol 7d, giving in this case the 14-dienylcodeinone 9d on brief heating with
formic acid. This base was rapidly converted in cold 2n HCl to the furanocodide 19a
and, in hot HCl solution, to the bridged thebainone derivative 11d [13] (Scheme 1). It
was, thus, of interest to prepare further examples of the vinylthevinols, particularly the
secondary alcohol analogue, in the hope of giving access to a range of 14-
Scheme 1a)
a) See Table for obtained products.

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2289
dienylcodeinones and, thence, to 14-alkyldihydrocodeinones. Again, for this purpose,
14b-methyl-substituted thevinols 8 should give precursors 10 rather than the bridged 12
(Scheme 1).
Results and Discussion. Scheme 2 shows the chemistry used for the preparation of
the new thevinols and thevinol analogues. The starting materials were thebaine ((5a)-
6,7,8,14-tetradehydro-4,5-epoxy-3,6-dimethoxy-17-methylmorphinan; 20) and 5b-
methylthebaine (21) [14], which were treated with prop-2-enal to give the Diels
Alder adducts 22 (R1 ˆ H) and 23 (R1 ˆ H). Analogous Diels Alder reactions with
methyl vinyl ketone afforded 22 (R1 ˆ Me) and 23 (R1 ˆ Me) [15]. Adducts 22 (R1 ˆ
H) and 23 (R1 ˆ H, Me) were hydrogenated to give the corresponding 18,19-dihydro
derivatives 24. Reaction of thevinone 22 (R1 ˆ Me) with Grignard reagents (R2MgBr)
was shown by Bentley et al. [16] to be stereoselective, giving single diastereoisomers 7
(R1 ˆ Me). Though similar stereoselectivity was claimed for the formation of the
secondary thevinols 7 (R1 ˆ H) from the Grignard reaction with aldehyde 22 (R1 ˆ H),
no experimental details were given [16]. In our hands, the reported general procedure
with 24 (R1 ˆ R3 ˆ H) and PhMgBr gave approximately equal quantities of the
diastereoisomers 13a (R1 ˆ R3 ˆ H, R2 ˆ Ph) and 13i (R1 ˆ Ph, R2 ˆ R3 ˆ H). However,
we found that, by conducting the reaction of 23 or 24 at À 788, single diastereoisomers
of the secondary alcohols, i.e. 7e g, 8a,c,f,g, and 14a,c were produced in moderate to
very good yields (Table). Their configurations at the exocyclic C(a) were defined by
analogy with the previous work [16]. The benzylidene-substituted secondary alcohols
7h and 8h were prepared from thevinones 22 and 23 (Scheme 3) by base-catalyzed
condensation with benzaldehyde via the benzylidene ketones 25 and 26, respectively,
which were reduced by L-Selectride.
In the present investigation of the action of formic acid on the thevinols and
analogues, the standard conditions used were to reflux the substrate with anhydrous
formic acid until all had been transformed (TLCmonitoring). This reaction time was
eventually standardized as four hours. In the case of the secondary vinyl alcohol 7e, the
Scheme 2
i) C HˆCHCHO or CH2ˆCHC(O)Me. ii) H2, Pd/C. iii) R2MgBr or PhLi.
2

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Scheme 3
i) LDA, C6H5CHO. ii) L-Selectride.
Table. Yields ofThevinols 7, 8, and 14 from Thevinals and of Products from Their Treatment with Formic Acid
Thevinolsa)
R1
Yield [%]
Product(s)b)
Yield [%]
R2
C
R3
R1
R2
R3
7e
7f
H
H
ˆCHH
H
H
H
H
H
H
H
Me
Me
Me
Me
56
84
81
27a
11f (19b)
11g
11h
10f
12g
12h (10h)
10a
16a
10c
CH2ˆC
H
H
H
H
H
H
H
H
H
61
34 (29)
59
2
MeCHˆCH
Me2CˆCH
PhCHˆC
MeCHˆC
Me2CˆC
PhCHˆC
Ph
Ph
Me
Me
MeCHˆCH
Me2CˆCH
PhCHˆCH
MeCHˆC
Me2CˆC
PhCHˆCH
Ph
Ph
Me
Me
H
H
H
7g
H
c
7h
8f
H
H
H
)
71
Me
75
H
H
Me
43
8g
H
Me
81
Me
63
42 (12)
78
8h
8a
H
H
Mec)
91
Me
Me
Me
Me
Me
14a
8c
14c
H
Me
Me
46
84
86
54
65
54
Me
Me
16c
a) From thevinals. b) From thevinols and HCOOH. c) Formed by an alternative route, see Scheme 3.
only product was the formate ester 27a. Though secondary thevinols, e.g., 2c and 4c,
gave only formate esters when reacted with formic acid [17], nepenthol (7a) was
converted to nepenthene (9a) in good yield under these conditions [12] due to the ease
of formation of the intermediate benzylic carbocation 28a. A similar facilitation of ring
opening of 7e via the allylic carbocation 28b might have been expected. The propenyl
alcohol 7f rearranged in the presence of formic acid to a mixture of the pyrano-
derivative 19b and the thebainone derivative 11f (Table), isomeric with the rearrange-
ment products 19a and 11d from vinylthevinol 7d [13]. Further substitution of the vinyl
group such as in 7g increased the reactivity with formic acid resulting in conversion to
the thebainone derivative 11g in good yield; this also applied to the benzylidene
analogue 7h (Table). Thus, the secondary vinylogous thevinols 7e h proved not to be a
good source of 14-dienylcodeinones 9e h. The only success in suppressing the
formation of the 4-hydroxy derivatives in this series was in the case of the 5b-methyl-
substituted propenyl alcohol 8f, which gave 43% of the dienylcodeinone 10f. The
principal products from 8g and 8h were 12g and 12h, respectively, but, in the latter case,
a small amount of the dienylcodeinone 10h was also isolated (Table).
The 5b-methylnepenthol (8a) and 5b,20-dimethylthevinol (8c) gave with formic
acid good yields of the 5b-methylalkenylcodeinones 10a and 10c, respectively, as

Helvetica Chimica Acta Vol. 86 (2003)
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expected since nepenthol (7a) and methylthevinol (7c) behaved similarly [7][12].
However, the 18,19-dihydro analogues 14a and 14c both gave over 50% yields of the
5b-methylalkenyldihydrocodeinones 16a and 16c (Table), respectively, whereas 13a
and 13c yielded only the 4-hydroxy derivatives 17a and 17c, respectively [7].
Comparison of the reactivity on formic acid treatment of the vinylogous thevinols
7f h with the equivalent thevinols 2c, 7c and 7a, respectively, shows that the vinylogues
are substantially more active. Whereas 2c gave only the formate ester 27b [17], 7f was
rearranged to 19b and 11f. Rearrangement of 7c stopped at the alkenylcodeinone stage
[7], whereas 7g gave only the 4-hydroxy derivative 11g, and comparison of 7a with 7h is
similar. The greater reactivity of the vinylogues was also manifested in the 5b-methyl
series where introduction of the 5-methyl group did not prevent formation of the 4-
hydroxy derivatives 12g and 12h from 8g and 8h, respectively.
The product-determining factor in these rearrangements is the reactivity of the 14-
alkenylcodeinones vs. the vinylogous dienylcodeinones. It was proposed by Bentley et
al. [7] that conversion of the 14-alkenylcodeinones 9a c to the bridged thebainones
11a c was initiated by protonation of the epoxy O-atom followed by fission of the
epoxy bridge and Markownikov addition of the C(5) carbocation 29 (R3 ˆ H) to the
alkenyl-side-chain CˆCbond ( Scheme 4). The greater reactivity of the dienylcodei-
nones can, thus, be attributed to the greater migratory aptitude of the dienyl side chain
in 9g,h related to the greater stability of the 5,14-bridged carbocations 30b,d.
The effect of introducing a 5b-methyl group into the alkenyl codeinones 9a,c (R3 ˆ
H) and dienylcodeinones 9b,d (R3 ˆ H) on the reaction sequence shown in Scheme 4
Scheme 4

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would not be inhibitory. Indeed, the tertiary carbocation 29 (R3 ˆ Me), if formed as a
discrete species in the epoxy-bridge opening, would be stabilized compared to the
secondary carbocation 29 (R3 ˆ H) formed from 9, which would have a rate-enhancing
effect. If however, the epoxy opening and formation of the 5,14-bridge were concerted
processes, so that the new bridge was formed from the b-face as the epoxy bridge was
fissioned, the steric inhibitory effect of the 5b-methyl group would be a greater factor.
It is possible that the mechanisms for converting the dienylcodeinones and alkenylco-
deinones into the bridged thebainones are different. The ionic mechanism in Scheme 4
could be dominant for the more extensively conjugated dienyl series whereas for the
alkenyl series the concerted mechanism could be of greater importance.
This view is supported by the effect of the 5b-methyl group in allowing the isolation
of 14-alkenyldihydrocodeinones 16a and 16c from the acid-catalyzed rearrangement of
the dihydrothevinols. It is evident that the factors governing acid-catalyzed rearrange-
ments in these bridged-ring systems are very finely balanced.
This work was supported by NIDA Grants DA 00254 and DA 07315.
Experimental Part
1. General. Anh. THF, DMF, CH2Cl2, and MeOH were purchased from Aldrich, HPLC-solvent-grade
CHCl3 and MeOH from Merck, and all other solvents used were GPR (general-purpose reagent) grade and
from Merck or Fisher Scientific. Chemicals were purchased from Aldrich, Fluka, Lancaster, and Across chemical
companies. Column chromatography (CC): silica gel 60 (35 70 mm); FC ˆ flash chromatography. NMR
Spectra: Jeol 270 (270 (1H) and 67.8 MHz (13C)). Jeol Lambda-300 (300 (1H) and 75 MHz (13C)), or Jeol EX-400
(400 (1H) and 101 MHz (13C)) spectrometers; chemical shifts (d) in ppm, coupling constants J in Hz. MS:
electron ionization (EI) at 70 eV, VG AutoSpec instrument, equipped with a Fisons autosampler; HR ˆ high
resolution.
2. Carboxaldehydes and Ketones 22 24 and Methanols 13a/13i. (5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-
17-methyl-6,14-ethenomorphinan-7-carboxaldehyde (22; R1 ˆ R3 ˆ H). Thebaine (20; 2.5 g, 8.0 mmol), prop-2-
enal (7.5 ml, 0.11 mol), and benzene (50 ml) were refluxed for 16 h. Benzene and unreacted prop-2-enal were
evaporated and the crude white-yellow foam was purified by CC (MeOH/CH2Cl2 95 :5): 22 (R1 ˆ H) (quant.).
Light yellow solid. Rf (MeOH/CH2Cl2 90 :10) 0.69. IR (CHCl3): 1722. 1H-NMR (270 MHz, CDCl3): 1.48
(dd, J ˆ 5.3, 13.1, HaÀC(8)); 2.38 (s, MeN); 2.75 (m, H ÀC(7)); 2.83 (dd, J ˆ 9.5, 13.1, HbÀC(8)); 3.61
(s, MeOÀC(6)); 3.82 (s, MeOÀC(3)); 4.64 (d, J ˆ 1.4, HÀbC(5)); 5.58 (d, J ˆ 8.6, HÀC(19)); 5.88 (d, J ˆ 8.6,
HÀC(18)); 6.55 (d, J ˆ 8.2, HÀC(1)); 6.64 (d, J ˆ 8.2, HÀC(2)); 9.41 (d, J ˆ 3.8, CHOÀC(7)). 13C-NMR
(67.8 MHz, CDCl3): 22.5; 26.6; 33.1; 42.9; 43.4; 45.4; 47.3; 49.7; 52.6; 56.5; 60.0; 80.8; 93.4; 113.4; 119.5; 126.6;
‡
‡
127.9; 133.6; 137.0; 141.9; 147.9; 201.6. EI-MS: 367 (100, M ). HR-EI-MS: 367.1783 (C22H25NO4 ; calc. 367.1783).
(5a,6a,7a,14a)-4,5-Epoxy-18,19-dihydro-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-carboxalde-
hyde (24; R1 ˆ R3 ˆ H). A soln. of 22 (R1 ˆ R3 ˆ H) (1.31 g, 3.58 mmol) in EtOH (20 ml) was added to 10% Pd/C
in EtOH (3 ml), and the mixture hydrogenated under 1 atm at r.t. for 1 h. The catalyst was removed by filtration
through Celite and the solvent evaporated: 24 (R1 ˆ R3 ˆ H) (quant.). White solid. Rf (AcOEt/hexane 7.2 :2.5)
0.35, Rf (MeOH/CH2Cl2 90 :10) 0.58. IR (CHCl3): 1721s (CHˆO). 1H-NMR (270 MHz, CDCl3): 2.32 (s, MeN);
3.12 (d, J ˆ 18.5, HbÀC(10)); 3.48 (d, J ˆ 4.6, HaÀC(9)); 3.51 (s, MeOÀ(6)); 3.88 (s, MeOÀC(3)); 4.59 (d, J ˆ
2.2, HÀC(5)); 6.61 (d, J ˆ 8.1, HÀC(1)); 6.73 (d, J ˆ 8.1, HÀC(2)); 9.91 (d, J ˆ 3.8, 1 H, CHOÀC(7)).
13C-NMR (67.8 MHz, CDCl3): 19.9; 22.0; 26.6; 28.5; 35.1; 35.5; 43.5; 45.2; 48.6; 51.6; 56.7; 61.4; 77.4; 92.2; 114.0;
‡
‡
119.3; 128.3; 132.1; 141.8; 146.7; 203.0. EI-MS: 369 (100, M ). HR-EI-MS: 369.1936 (C22H27NO4 ; calc.
369.1940).
(aS,5a,6a,7a,14a)- and (aR,5a,6a,7a,14a)-4,5-Epoxy-18,19-dihydro-3,6-dimethoxy-17-methyl-a-phenyl-
6,14-ethenomorphinan-7-methanol (13a and 13i, resp.). At r.t., 24 (R1 ˆ R3 ˆ H) (1.30 g, 3.54 mmol) was
treated with phenylmagnesium bromide in toluene for 24 h. The crude product was purified by CC (MeOH/
CH2Cl2 98 :2): 13i (0.72 g, 45%) and 13a (0.56 g, 35%).

Helvetica Chimica Acta Vol. 86 (2003)
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Data of 13a: Rf (MeOH/CH2Cl2 95 :5) 0.63. IR (CHCl3): 3401 (br., OH). 1H-NMR (270 MHz, CDCl3): 2.17
(s, MeÀN); 3.05 (d, J ˆ 18.7, HbÀC(10)); 3.62 (s, MeOÀC(6)); 3.88 (s, MeOÀC(3)); 4.55 (d, J ˆ 1.3, HÀC(5));
4.75 (d, J ˆ 8.9, HÀC(a)); 5.70 (s, OHÀC(a)); 6.58 (d, J ˆ 8.1, HÀC(1)); 6.73 (d, J ˆ 8.1, HÀC(2)); 7.37
(m, Ph). 13C-NMR (67.8 MHz; CDCl3): 17.7; 21.9; 32.2; 35.3; 41.8; 43.3; 45.1; 52.5; 56.8; 61.2; 70.2; 79.9; 94.8;
‡
114.1; 115.3; 119.2; 125.3; 127.3; 128.1; 128.4; 129.3; 132.4; 141.8; 142.2; 146.6. EI-MS: 447 (88, M ). HR-EI-MS:
‡
447.2404 (C28H31NO4 ; calc. 447.2409).
Data of 13i: Rf (MeOH/CH2Cl2 5 :95) 0.50. IR (CHCl3): 3411 (br., OHÀC(a)). 1H-NMR (270 MHz,
CDCl3): 2.28 (s, MeN); 3.05 (d, J ˆ 18.7, HbÀC(10)); 3.51 (s, MeOÀC(6)); 3.86 (s, MeOÀC(3)); 4.20 (d, J ˆ 2.0,
HÀC(5)); 5.92 (s, OHÀC(a)); 6.58 (d, J ˆ 8.1, HÀC(1)); 6.74 (d, J ˆ 8.1, HÀC(2)); 7.35 (m, Ph). 13C-NMR
(67.8 MHz; CDCl3): 17.6; 20.3; 25.6; 32.2; 35.3; 35.9; 42.4; 43.4; 45.3; 50.9; 56.5; 61.1; 70.0; 79.9; 92.5; 113.6;
‡
115.0; 118.9; 119.1; 126.8; 127.7; 128.0; 128.2; 132.0; 141.7; 144.8; 147.0. EI-MS: 447 (100, M ). HR-EI-MS:
‡
447.2402 (C28H31NO4 ; calc. 447.2409).
(5a,6a,7a,14a)-4,5-Epoxy-18,19-dihydro-3,6-dimethoxy-5,17-dimethyl-6,14-ethenomorphinan-7-carboxal-
dehyde (24; R1 ˆ H, R3 ˆ Me). A mixture of (5a,6a,7a,14a)-4,5-epoxy-3,6-dimethoxy-5,17-dimethyl-6,14-
ethenomorphinan-7-carboxaldehyde (23; R1 ˆ H, R3 ˆ Me) [18] (2.02 g, 7.04 mmol) in AcOEt (150 ml) and
10% Pd/C(0.51 g) was refluxed under 11 atm of H 2 for 30 h. After filtration over Celite and solvent evaporation,
the residue was purified by recrystallization from EtOH: 1.04 g (51%) of 24 (R1 ˆ H, R3 ˆ Me). Solid. Rf
(AcOEt) 0.45. IR (CHCl3): 1722. 1H-NMR (270 MHz, CDCl3): 0.77 (td, J ˆ 11.9, 3.4, 1 H); 1.06 1.27 (m, 2 H);
1.59 (m, HaÀC(8)); 1.65 (s, MeÀC(5)); 1.85 (m, 1 H); 2.01 2.22 (m, 2 H); 2.24 2.56 (m, 4 H); 2.32 (s, MeN);
2.67 2.78 (m, HÀC(7), HbÀC(8)); 3.10 (d, J ˆ 9.5, 1 H); 3.47 (s, MeOÀC(6)); 3.85 (s, MeOÀC(3)); 6.56
(d, J ˆ 8.0, HÀC(1)); 6.71 (d, J ˆ 8.2, HÀC(2)); 9.98 (s, C HOÀC(7)). 13C-NMR (75 MHz, CDCl3): 16.3; 19.3;
22.2; 25.6; 28.0; 29.5; 36.8; 43.4; 45.1; 46.3; 51.5; 52.5; 56.6; 61.9; 78.9; 98.2; 113.5; 118.8; 128.7; 133.4; 141.3;
‡
‡
145.5; 204.8 (CHOÀC(7)). EI-MS: 383 (50, M ). HR-EI-MS: 383.2081 (C23H29NO4 ; calc. 383.2096).
1-[(5a,6a,7a,14a)-4,5-Epoxy-18,19-dihydro-3,6-dimethoxy-5,17-dimethyl-6,14-ethenomorphinan-7-yl]etha-
none (24; R1 ˆ R3 ˆ Me). A suspension of 3.3 g (8.4 mmol) 1-[(5a,6a,7a,14a)-4,5-epoxy-3,6-dimethoxy-5,17-
dimethyl-4,5-epoxy-6,14-ethenomorphinan-7-yl]ethanone [18] (23; R1 ˆ R3 ˆ Me) and 10% Pd/C(1.78 g) in
EtOH (100 ml) was hydrogenated at 508 and 60 psi for 2 days. The catalyst was removed by filtration over Celite
and the crude mixture purified by FC(AcOEt/CH 2Cl2 gradient): 2.63 g (77%) of 24 (R1 ˆ R3 ˆ Me). Solid. Rf
1
(AcOEt) 0.26. IR (film): 1712. H-NMR (270 MHz, CDCl3): 0.71 (m, 1 H); 1.32 1.44 (m, 2 H); 1.59 (dd, J ˆ
13.0, 2.4, 1 H); 1.65 (s, MeÀC(5)); 1.70 (dd, J ˆ 17.8, 4.6, 1 H); 1.74 (m, 1 H); 2.08 (m, 1 H); 2.22 2.33 (m, 2 H);
2.24 (s, 3 H); 2.28 (s, 3 H); 2.45 2.54 (m, 2 H); 2.68 (d, J ˆ 6.6, 1 H); 3.07 3.16 (m, 2 H); 3.37 (s, 3 H); 3.85
(s, 3 H); 6.55 (d, J ˆ 8.2, HÀC(1)); 6.70 (d, J ˆ 8.3, HÀC(2)). 13C-NMR (67.8 MHz, CDCl3): 16.27; 17.56; 22.30;
28.57; 29.77; 29.8; 34.17; 36.69; 43.43; 45.33; 46.97; 50.53; 52.21; 56.62; 61.89; 78.87; 98.49; 113.50; 118.74; 129.12;
‡
‡
133.63; 141.39; 145.66; 211.90 (COCH3). EI-MS: 397 (100, M ). HR-EI-MS: 397.2252 (C24H31NO4 ; calc.
397.2253).
3. General Procedure for the Synthesis of the Alcohols 7, 8, and 14 Required as Starting Materials for the
Acid-Catalyzed Rearrangements: (aS,5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-5,17-dimethyl-a-phenyl-6,14-
ethenomorphinan-7-methanol (8a). A soln. of 1.7m PhLi in cyclohexane (5.0 ml, 8.5 mmol) was added to a
stirred soln. of (5a,6a,7a,14a)-4,5-epoxy-3,6-dimethoxy-5,17-dimethyl-6,14-ethenomorphinan-7-carboxalde-
hyde (23; R1 ˆ H, R3 ˆ Me) (0.68 g, 1.7 mmol) at À 788 in anh. THF (35 ml), and the mixture was allowed to
warm to r.t. within 16 h. The volatiles were removed in vacuo, and the residue was purified by FC(AcOEt/
CH2Cl2 gradient). 701 mg (91%) of 8a as a single isomer (1H-NMR). Rf (AcOEt) 0.57. IR (film): 3445.
1H-NMR (270 MHz, CDCl3, selected signals): 1.29 (dd, J ˆ 11.9, 5.3, 1 H); 1.63 (s, MeÀC(5)); 1.89 (td, J ˆ 12.5,
5.9, 1 H); 2.29 (s, MeN); 3.09 (d, J ˆ 6.6, 1 H); 3.21 (d, J ˆ 18.5, 1 H); 3.80 (s, 3 H); 3.81 (s, 3 H); 5.27 (d, J ˆ 1.3,
CHÀC(7)); 5.46 (d, J ˆ 8.9, HÀC(19)); 6.10 (d, J ˆ 8.9, HÀC(18)); 6.46 (d, J ˆ 8.3, HÀC(1)); 6.61 (d, J ˆ 8.3,
HÀC(2)); 7.11 7.28 (m, Ph). 13C-NMR (67.8 MHz, CDCl3): 16.26; 22.59; 24.89; 29.18; 43.39; 44.16; 45.54;
46.26; 48.43; 54.74; 56.76; 60.55; 71.08; 82.33; 100.36; 113.52; 118.74; 125.34; 125.91; 126.51; 127.98; 128.76;
‡
‡
135.64; 136.76; 141.44; 143.79. EI-MS: 459 (62, M ), 352 (100). HR-EI-MS: 459.2423 (C28H33NO4 ; calc.
459.2410).
(aS,5a,6a,7a,14a)-4,5-Epoxy-18,19-dihydro-3,6-dimethoxy-5,17-dimethyl-a-phenyl-6,14-ethenomorphin-
an-7-methanol (14a) [18]. From PhLi and (5a,6a,7a,14a)-4,5-epoxy-18,19-dihydro-3,6-dimethoxy-5,17-dimeth-
yl-6,14-ethenomorphinan-7-carboxaldehyde (24; R1 ˆ H, R3 ˆ Me): 14a (46%). Rf (AcOEt) 0.59. IR (CHCl3):
3437. 1H-NMR (400 MHz, CDCl3): 0.69 (m, 1 H); 1.26 (m, 1 H); 1.51 (m, 1 H); 1.55 (s, MeÀC(5)); 1.70
(m, 1 H); 1.76 (m, 2 H); 1.95 (td, J ˆ 12.7, 5.9, 1 H); 2.08 (dd, J ˆ 11.7, 5.9, 1 H); 2.18 2.29 (m, 3 H); 2.26
(s, MeN); 2.38 (m, 1 H); 2.65 (d, J ˆ 6.4, 1 H); 3.07 (d, J ˆ 18.1, 1 H); 3.53 (s, 3 H); 3.86 (s, 3 H); 5.37
(s, C HÀC(7)); 6.52 (d, J ˆ 7.9, HÀC(1)); 6.69 (d, J ˆ 8.3, HÀC(2)); 7.18 7.38 (m, Ph). 13C-NMR (101 MHz,

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Helvetica Chimica Acta Vol. 86 (2003)
CDCl3): 16.32; 18.56; 22.26; 25.80; 29.21; 29.81; 37.02; 43.45; 45.14; 45.43; 46.82; 52.46; 56.72; 62.18; 70.90; 77.97;
99.51; 113.5; 118.44; 125.89; 126.71; 128.15; 129.30; 133.95; 141.27; 145.59; 146.03. EI-MS: 461 (85). HR-EI-MS:
‡
461.2561 (C29H35NO4 ; 461.2566).
(aR,5a,6a,7a,14a)-4,5-Epoxy-a-ethenyl-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-methanol (7e).
From ethenylmagnesium bromide and (5a,6a,7a,14a)-4,5-epoxy-3,6-dimethoxy-17-methyl-6,14-ethenomor-
phinan-7-carboxaldehyde (22; R1 ˆ R3 ˆ H): 7e (56%). Rf (AcOEt) 0.39. IR (film): 3458. 1H-NMR (270 MHz,
CDCl3): 1.14 (dd, J ˆ 12.9, 7.3, 1 H); 1.84 (m, 1 H); 1.99 (m, 1 H); 2.06 (m, 1 H); 2.31 2.56 (m, 3 H); 2.37
(s, MeN); 2.76 (dd, J ˆ 12.8, 9.2, 1 H); 3.14 3.25 (m, 2 H); 3.66 (s, 3 H); 3.82 (s, 3 H); 4.35 (m, C HÀC(7)); 4.56
(d, J ˆ 1.0, HÀC(5)); 5.06 (dt, J ˆ 10.6, 1.7, Htrans of CH2ˆCH); 5.20 (ddd, J ˆ 17.2, 2.0, 1.7, Hcis of CH2ˆCH) 5.45
(d, J ˆ 8.9, HÀC(19)); 5.79 (ddd, J ˆ 17.2, 10.6, 5.3, CH2ˆCH); 5.86 (d, J ˆ 8.6, HÀC(18)); 6.51 (d, J ˆ 8.3,
HÀC(2)); 6.62 (d, J ˆ 7.9, HÀC(1)). 13C-NMR (67.8 MHz, CDCl3): 22.35; 26.92; 33.64; 42.53; 42.98; 43.54;
45.59; 47.43; 53.61; 56.78; 60.07; 71.71; 81.54; 96.30; 113.79; 114.56; 119.27; 126.37; 128.38; 134.2; 135.78; 138.90;
‡
141.84; 148.29. EI-MS: 395 (43). HR-EI-MS: 395.2104 (C24H29NO4 ; calc. 395.2097).
(aR,5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-17-methyl-a-(prop-1-enyl)-6,14-ethenomorphinan-7-metha-
nol (7f). From (prop-1-enyl)magnesium bromide and 22 (R1 ˆ R3 ˆ H): 7f (84%), 1:1 mixture of (E)- and (Z)-
isomers. Rf (AcOEt) 0.28. 1H-NMR (400 MHz, CDCl3; selected signals): 1.67 (m, 3 H); 3.38 (s, 3 H); 3.65, 3.69
(2s, 3 H); 3.82 (s, 3 H); 4.31, 4.72 (2m, 1 H); 4.56, 4.57 (2s, 1 H); 5.44, 5.45 (2d, J ˆ 8.8, HÀC(19)); 5.84, 5.85
(2d, J ˆ 8.8, HÀC(18)); 6.52 (d, J ˆ 8.3, HÀC(1)); 6.62 (d, J ˆ 8.3, HÀC(2)). 13C-NMR (101 MHz, CDCl3):
13.39; 17.74; 22.26; 26.77; 26.98; 33.57; 33.64; 42.55; 42.59; 42.89; 42.94; 43.52; 45.57; 47.38; 53.34; 53.41; 56.63;
60.01; 60.03; 66.20; 71.36; 81.35; 81.59; 95.88; 113.49; 119.20; 125.39; 126.11; 126.41; 126.46; 128.3; 131.15;
‡
131.82; 134.13; 135.63; 135.86; 141.74; 141.76; 148.20. EI-MS: 409 (100, M ), 338 (58). HR-EI-MS: 409.2253
‡
(C25H31NO4 ; calc. 409.2253).
(aR,5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-17-methyl-a-(2-methylprop-1-enyl)-6,14-ethenomorphinan-7-
methanol (7g). From (2-methylprop-1-enyl)magnesium bromide and 22 (R1 ˆ R3 ˆ H): 7g (81%). Rf (AcOEt)
0.34. IR (film): 3484. 1H-NMR (270 MHz, CDCl3): 1.67 1.69 (m, Me2C); 1.83 (m, 1 H); 1.94 2.08 (m, 2 H);
2.34 2.47 (m, 2 H); 2.40 (s, MeN); 2.54 (m, 1 H); 2.76 (dd, J ˆ 12.7, 9.4, 1 H); 3.17 3.26 (m, 2 H); 3.67 (s, 3 H);
3.82 (s, 3 H); 4.58 (d, J ˆ 1.0, 1 H); 4.66 (d, J ˆ 8.9, 1 H); 5.17 (d, J ˆ 9.2, 1 H); 5.46 (d, J ˆ 8.9, HÀC(19)); 5.84
(d, J ˆ 8.9, HÀC(18)); 6.53 (d, J ˆ 7.9, HÀC(1)); 6.63 (d, J ˆ 7.9, HÀC(2)). 13C-NMR (101 MHz, CDCl3): 18.36;
22.33; 25.96; 26.70; 33.64; 42.54; 43.02; 43.59; 45.68; 47.43; 53.19; 56.67; 60.15; 67.08; 81.35; 95.54; 113.49; 119.23;
‡
125.65; 126.75; 128.31; 133.97; 134.19; 135.79; 141.84; 148.29. EI-MS: 423 (100, M ). HR-EI-MS: 423.2410
‡
(C26H33NO4 ; calc. 423.2410).
(aR,5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-5,17-dimethyl-a-(2-methylprop-1-enyl)-6,14-ethenomorphin-
an-7-methanol (8g). From (2-methylprop-1-enyl)magnesium bromide and 23 (R1 ˆ H, R3 ˆ Me): 8g (81%). Rf
1
(AcOEt) 0.21. IR (film): 3419. H-NMR (270 MHz, CDCl3, selected signals): 1.06 (dd, J ˆ 12.9, 6.7, 1 H); 1.60
(s, 3 H); 1.62 (d, J ˆ 1.2, 3 H); 1.65 (d, J ˆ 1.2, 3 H); 1.99 (m, 1 H); 2.16 (m, 1 H); 2.36 (s, MeN); 2.52 (m, 1 H);
2.73 (m, 1 H); 3.73 (s, 3 H); 3.78 (s, 3 H); 3.82 (d, J ˆ 7.2, 1 H); 4.52 (dd, J ˆ 9.4, 2.2, 1 H); 5.08 (dt, J ˆ 9.4, 1.3,
1 H); 5.38 (d, J ˆ 8.9, 1 H); 6.02 (d, J ˆ 8.9, 1 H); 6.45 (d, J ˆ 8.2, 1 H); 6.58 (d, J ˆ 8.2, 1 H). 13C-NMR
(67.8 MHz, CDCl3): 16.26; 18.29; 22.52; 25.91; 26.88; 29.36; 43.48; 43.94; 44.14; 45.68; 48.38; 54.62; 56.62; 60.52;
68.46; 83.58; 100.40; 113.21; 118.63; 125.41; 125.99; 128.74; 133.44; 135.50; 135.67; 141.35; 147.54. EI-MS: 437
‡
‡
(65, M ), 352 (100), 248 (99). HR-EI-MS: 437.2564 (C27H35NO4 ; calc. 437.2566).
(aR,5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-5,17-dimethyl-a-(prop-1-enyl)-6,14-ethenomorphinan-7-
methanol (8f). From (prop-1-enyl)magnesium bromide and 23 (R1 ˆ H, R3 ˆ Me): 8f (75%), 1 :1 mixture of
(E)- and (Z)-isomers. Rf (AcOEt) 0.31. 1H-NMR (400 MHz, CDCl3, selected signals): 1.61 (m, 3 H); 2.36
(s, 3 H); 3.72, 3.74 (2s, 3 H); 3.80 (s, 3 H); 4.19, 4.61 (2m, 1 H); 5.39 (d, J ˆ 8.8, 1 H); 5.40 (d, J ˆ 9.8, 1 H); 5.46,
5.51 (2m, 1 H); 6.01 (d, J ˆ 8.8, 1 H); 6.02 (d, J ˆ 9.3, 1 H); 6.47 (d, J ˆ 8.3, 1 H); 6.58, 6.59 (2d, J ˆ 8.3, 1 H).
13C-NMR (101 MHz, CDCl3): 13.23; 16.14; 16.17; 17.63; 22.41; 22.43; 26.91; 27.09; 29.19; 29.27; 30.20; 43.35;
43.74; 43.79; 45.53; 48.23; 48.25; 54.47; 56.52; 60.37; 60.47; 67.41; 72.84; 83.62; 83.77; 100.18; 100.22; 113.16;
118.55; 118.57; 124.92; 125.20; 125.33; 125.42; 128.55; 131.39; 132.06; 135.21; 135.31; 135.34; 135.6; 141.22;
‡
‡
141.24; 147.39. EI-MS: 423 (51, M ), 352 (70), 234 (100). HR-EI-MS: 423.2407 (C26H33NO4 ; calc. 423.2410).
(5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-a,5,17-trimethyl-6,14-ethenomorphinan-7-methanol (8c). From
methylmagnesium bromide and 23 (R1 ˆ R3 ˆ Me) at r.t.: 8c (84%). Rf (AcOEt) 0.32. IR (film): 3494 (OH).
1H-NMR (270 MHz, CDCl3): 0.77 (dd, J ˆ 12.9, 7.6, 1 H); 0.99 (s, 3 H); 1.05 (s, 3 H); 1.67 (s, 3 H); 1.70 (m, 1 H);
1.96 (dd, J ˆ 12.9, 5.9, 1 H); 2.17 (d, J ˆ 8.4, 1 H); 2.32 2.45 (m, 2 H); 2.37 (s, MeN); 2.55 (dd, J ˆ 11.6, 5.0,
1 H); 2.82 (dd, J ˆ 12.9, 9.6, 1 H); 3.06 (d, J ˆ 6.6, 1 H); 3.24 (d, J ˆ 18.8, 1 H); 3.76 (s, 3 H); 3.79 (s, 3 H); 4.94
(s, 1 H); 5.36 (d, J ˆ 8.9, 1 H); 6.01 (d, J ˆ 8.9, 1 H); 6.48 (d, J ˆ 8.0, 1 H); 6.61 (d, J ˆ 8.2, 1 H). 13C-NMR
(67.8 MHz, CDCl3): 16.39; 22.47; 25.49; 28.79; 29.64; 30.72; 43.38; 43.76; 45.57; 47.77; 48.19; 54.58; 56.59; 60.39;

Helvetica Chimica Acta Vol. 86 (2003)
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73.58; 86.11; 100.40; 113.27; 118.61; 124.84; 128.65; 134.50; 135.47; 141.28; 147.45. EI-MS: 412 (23), 411 (72), 353
‡
(33), 352 (84), 222 (100). HR-EI-MS: 411.2426 (C25H33NO4 ; calc. 411.2410).
(5a,6a,7a,14a)-4,5-Epoxy-18,19-dihydro-3,6-dimethoxy-a-5,17-trimethyl-6,14-ethenomorphinan-7-metha-
nolmorphinan (14c). From methylmagnesium bromide and 24 (R1 ˆ R3 ˆ Me) at r.t.: 14c (86%). Rf (AcOEt)
0.29. IR (film): 3422. 1H-NMR (400 MHz, CDCl3); 0.79 (m, 1 H); 1.24 1.42 (m, 2 H); 1.26 (s, 3 H); 1.36
(s, 3 H); 1.71 (s, 3 H); 1.97 2.07 (m, 3 H); 2.27 (m, 1 H); 2.55 (m, 1 H); 2.84 2.96 (m, 2 H); 3.04 3.11
(m, 2 H); 3.24 (d, J ˆ 19.0, 1 H); 3.49 3.62 (m, 3 H); 3.52 (s, 3 H); 3.87 (s, 3 H); 4.87 (s, 1 H); 6.65 (d, J ˆ 8.2,
1 H); 6.80 (d, J ˆ 7.8, 1 H); 9.98 (br. s, 1 H). 13C-NMR (67.8 MHz, CDCl3): 16.69; 17.62; 24.96; 25.39; 28.09;
30.15; 30.31; 32.44; 37.69; 42.90; 45.56; 46.21; 46.81; 52.18; 56.66; 63.62; 74.18; 81.22; 98.37; 114.97; 119.49;
123.87; 130.92; 142.59; 146.35. EI-MS: 414 (54), 413 (75), 419 (51), 380 (39), 355 (37), 354 (100). HR-EI-MS:
‡
413.2572 (C25H35NO4 ; calc. 413.2566).
4. Alcohols 7h and 8h from 25 and 26, resp. 1-[(5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-17-methyl-6,14-
ethenomorphinan-7-yl]-3-phenylprop-2-en-1-onae (25). A soln. of 22 (R1 ˆ Me, R3 ˆ H) (1.18 g, 3.1 mmol) in
anh. THF (25 ml) was added at À 788 to a soln. of lithium diisopropylamide (LDA; 0.34 g, 3.2 mmol) in anh.
THF (50 ml), and the mixture was allowed to warm to 08 within 2 h. Benzaldehyde (0.34 g, 3.2 mmol) was added
to the soln. and the mixture was stirred overnight at r.t. The volatiles were evaporated, and the residue was
purified by FC(AcOEt/CH 2Cl2 1:5): 598 mg (41%) of 25. Colorless solid. Rf (AcOEt) 0.81. IR (film): 1682.
1H-NMR (270 MHz, CDCl3): 1.53 (dd, J ˆ 19.5, 12.9, 1 H); 1.89 (m, 1 H); 2.05 (m, 1 H); 2.37 (s, MeN); 2.40
2.53 (m, 3 H); 2.99 (dd, J ˆ 12.7, 9.4, 1 H); 3.19 (dd, J ˆ 9.6, 6.6, 1 H); 3.21 (m, 1 H); 3.26 (d, J ˆ 10.9, 1 H); 3.59
(s, 3 H); 3.83 (s, 3 H); 4.65 (d, J ˆ 1.3, 1 H); 5.62 (d, J ˆ 8.9, 1 H); 5.98 (d, J ˆ 8.9, 1 H); 6.54 (d, J ˆ 7.9, 1 H);
6.63 (d, J ˆ 7.9, 1 H); 6.88 (d, J ˆ 15.8, 1 H); 7.35 7.40 (m, 3 H); 7.51 7.57 (m, 3 H). 13C-NMR (67.8 MHz,
CDCl3): 22.52; 30.28; 33.58; 43.31; 43.51; 45.55; 47.46; 49.33; 53.65; 56.79; 60.08; 81.89; 95.64; 113.91; 119.39;
126.15; 126.38; 128.33; 128.77; 128.83; 130.20; 134.21; 134.91; 135.67; 141.77; 141.91; 148.19; 199.36. EI-MS: 470
‡
(26), 469 (81), 454 (12), 338 (29), 311 (42), 294 (35), 131 (100), 103 (45). HR-EI-MS: 469.2246 (C30H31NO4 ;
calc. 469.2253).
(aR,5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-17-methyl-a-(2-phenylethenyl)-6,14-ethenomorphinan-7-
methanol (7h). A soln. of 1m L-Selectride in THF (0.75 ml, 0.75 mmol) was added at À 788 to a soln. of 25
(347 mg, 0.73 mmol) in anh. THF (20 ml), and the mixture was stirred at À 788 for 2 h. The mixture was treated
with sat. NH4Cl soln. (10 ml) and extracted with CHCl3 (3 Â 10 ml). The combined org. extract was dried
(MgSO4) and evaporated and the residue purified by FC(AcOEt): 323 mg (91%) of 7h as a single isomer
1
(1H-NMR). Rf (AcOEt) 0.24. IR (film): 3425. H-NMR (270 MHz, CDCl3): 0.89 (m, 1 H); 1.87 (dd, J ˆ 12.9,
2.0, 1 H); 2.46 (s, MeN); 2.44 2.69 (m, 2 H); 2.84 (dd, J ˆ 3.2, 9.3, 1 H); 3.18 (d, J ˆ 18.9, 1 H); 3.16 3.27
(m, 2 H); 3.48 (s, 3 H); 3.70 (s, 3 H); 4.04 (t, J ˆ 8.2, 1 H); 4.62 (d, J ˆ 1.3, 1 H); 4.98 (br. s, 1 H); 5.54 (d, J ˆ 8.9,
1 H); 5.99 (d, J ˆ 8.6, 1 H); 6.12 (dd, J ˆ 15.8, 7.6, 1 H); 6.50 6.58 (m, 2 H); 6.65 (d, J ˆ 7.92, 1 H); 7.16 7.32
‡
‡
(m, 3 H); 7.38 (m, 2 H). EI-MS: 471 (100, M ). HR-EI-MS: 472.2410 (C30H33NO4 ; calc. 471.2422).
1-[(5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-5,17-dimethyl-6,14-ethenomorphinan-7-yl]-3-phenylprop-2-
en-1-one (26). As described for 25 with 23( R1 ˆ R3 ˆ Me) and benzaldehyde: 26 (78%). Rf (AcOEt) 0.35. IR
(film): 1685. 1H-NMR (270 MHz, CDCl3): 1.57 (dd, J ˆ 13.0, 5.4, 1 H); 1.69 (m, 1 H); 1.73 (s, 3 H); 2.05
(m, 1 H); 2.35 (s, MeN); 2.39 2.61 (m, 3 H); 2.78 (dd, J ˆ 12.7, 9.7, 1 H); 3.14 3.24 (m, 3 H); 3.61 (s, 3 H); 3.79
(s, 3 H); 5.54 (d, J ˆ 8.9, 1 H); 6.05 (d, J ˆ 8.9, 1 H); 6.50 (d, J ˆ 8.2, 1 H); 6.62 (d, J ˆ 8.2, 1 H); 6.85 (d, J ˆ 16.1,
1 H); 7.33 7.38 (m, 3 H); 7.46 (d, J ˆ 15.9, 1 H); 7.54 (m, 2 H). 13C-NMR (67.8 MHz, CDCl3): 16.15; 22.61;
28.49; 28.98; 43.31; 44.05; 45.44; 48.09; 50.05; 54.53; 56.49; 60.46; 83.67; 99.6; 113.26; 118.58; 124.34; 127.52;
‡
127.94; 128.45; 128.49; 129.70; 134.89; 135.11; 135.57; 140.43; 141.35; 147.19; 199.62. EI-MS: 483 (46, M ), 294
‡
(75), 131 (100). HR-EI-MS: 483.2399 (C31H33NO4 ; calc. 483.2410).
(aR,5a,6a,7a,14a)-4,5-Epoxy-3,6-dimethoxy-5,17-dimethyl-a-(2-phenylethenyl)-6,14-ethenomorphinan-7-
methanol (8h). As described for 7h, with 26 and L-Selectride: 8h 87%. Rf (AcOEt) 0.37. IR (film): 3431.
1H-NMR (270 MHz, CDCl3): 0.83 (dd, J ˆ 13.4, 5.3, HaÀC(8)); 1.65 (s, MeÀC(5)); 1.67 (m, HaÀC(16)); 2.01
(ddd, J ˆ 12.8, 5.9, HbÀC(16)); 2.10 (m, HbÀC(7)); 2.31 (s, MeN); 2.34 2.42 (m, HaÀC(10), HaÀC(15)); 2.51
(dd, J ˆ 11.4, 5.1, HbÀC(15)); 2.65 (dd, J ˆ 13.4, 9.7, HbÀC(8)); 3.02 (d, J ˆ 6.6, 1 H); 3.21 (d, J ˆ 18.7, HÀC(9));
3.79 (s, 3 H); 3.81 (s, 3 H); 3.98 (m, C HÀ(7)); 5.36 (s, OH); 5.51 (d, J ˆ 9.2, HÀC(19)); 6.06 6.12
(m, HÀC(18), PhCHˆCH); 6.48 6.51 (m, HÀC(1), PhCHˆCH); 6.62 (d, J ˆ 8.1, HÀC(2)); 7.21 (m, 1 H);
7.29 (m, 2 H); 7.37 (m, 2 H). 1H,1H-NOESY (CDCl3, selected cross-peaks): 0.83 (HaÀC(8))/3.98 (CHÀC(7));
0.83 (HaÀC(8))/6.06 6.12 (HÀC(18), PhCHˆCH); 2.10 (m, HbÀC(7))/2.65 (HbÀC(8)); 2.65 (HbÀC(8))/
6.06 6.12 (HÀC(18), PhCHˆCH); 3.98 (CHÀC(7))/6.48 6.51 (HÀC(1), PhCHˆCH). 13C-NMR (67.8 MHz,
CDCl3): 16.52; 22.52; 28.91; 29.07; 43.43; 43.62; 44.24; 45.54; 47.71; 55.03; 56.58; 60.47; 76.30; 86.48; 100.14;

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Helvetica Chimica Acta Vol. 86 (2003)
113.10; 118.92; 124.77; 126.58; 127.50; 128.42; 128.48; 129.91; 132.35; 135.68; 136.83; 136.87; 141.52; 147.00. EI-
‡
‡
MS: 485 (75, M ), 352 (100), 296 (93). HR-EI-MS: 485.2551 (C31H35NO4 ; calc. 485.2566).
5. General Procedure for the Acid-Catalyzed Rearrangements: (5a,14b)-7,8-Didehydro-4,5-epoxy-3-
methoxy-5,17-dimethyl-14-[(2E,4E)-5-phenylpenta-2,4-dienyl]morphin-2-en-6-one (10h) and (5b,14b,18E)-7,8-
Didehydro-4-hydroxy-3-methoxy-5,17-dimethyl-18-(3-phenylprop-2-enylidene)-5,14-ethanomorphinan-6-one
(12h) from 8h. A soln. of 8h (0.49 g, 1.0 mmol) in formic acid (5 ml) was heated to 1008 for 4 h. After this time,
most of the volatiles were evaporated. The residue was basified with ammonia and extracted with CHCl2 (3 Â
10 ml). The combined extract was washed with H2O (10 ml) and brine (10 ml) and dried (MgSO4) and the crude
mixture purified by FC(AcOEt/CH 2Cl2 1 :5, then AcOEt gradient): 54 mg (12%) of 10h and 190 mg (42%) of
12h.
Data of 10h: Rf (AcOEt) 0.69. IR (film): 1678. 1H-NMR (270 MHz, CDCl3, selected signals): 1.50 (m, 1 H);
1.70 (s, 3 H); 2.11 (m, 1 H); 2.37 (s, MeN); 2.60 (m, 1 H); 3.05 3.16 (m, 2 H); 3.78 (s, MeOÀC(3)); 5.74
(m, 1 H); 6.06 (d, J ˆ 10.4, HÀC(8)); 6.25 6.80 (m, 9 H); 7.17 7.39 (m, 4 H). 13C-NMR (67.8 MHz, CDCl3):
17.49 (q, MeÀC(5)); 21.29 (t); 25.89 (t); 39.92 (t); 42.82 (q, MeN); 44.53 (s); 45.87 (t); 47.25 (s); 56.37; 58.85;
92.75 (s, C(5)); 113.31 (d); 119.25 (d); 126.20 (d); 126.36 (d); 126.46 (d); 127.44 (s); 127.57 (d); 128.58 (d); 128.70
(d); 131.44 (d); 132.65 (s); 134.76 (d); 137.16 (s); 142.00 (s); 143.85 (s); 155.50 (d, C(8)); 196.89 (s, C(6)). EI-MS:
‡
‡
453 (100, M ). HR-EI-MS: 453.2305 (C30H31NO3 ; calc. 453.2304).
1
Data of 12h: Rf (AcOEt) 0.58. IR (film): 3504, 1678. H-NMR (270 MHz, CDCl3; selected signals): 1.90
(s, MeÀC(5)); 2.11 (td, J ˆ 12.2, 3.6, 1 H); 2.38 (s, MeN); 2.46 (m, 1 H); 2.78 (dd, J ˆ 18.8, 5.9, 1 H); 3.26 (d, J ˆ
18.5, 1 H); 3.80 (s, MeOÀC(3)); 5.70 (d, J ˆ 9.6, HÀC(7)); 6.05 (s, OHÀC(4)); 6.40 (d, J ˆ 10.9, 2.0,
PhCHˆCHCH); 6.49 (d, J ˆ 15.5, PhCHˆCHCH); 6.59 (d, J ˆ 8.6, HÀC(2)); 6.62 (d, J ˆ 8.3, HÀC(1)); 6.76
(d, J ˆ 9.9, HÀC(8)); 6.85 (dd, J ˆ 15.1, 10.9, PhCHˆCHCH); 7.16 7.27 (m, Ph). 13C-NMR (67.8 MHz,
CDCl3): 15.04 (q, MeÀC(5)); 25.81 (t); 29.51 (t); 33.47 (t); 42.99 (q, MeN); 46.04 (t, C(16)); 50.17 (s); 54.27 (s);
56.10; 56.42; 65.96 (C(5)); 108.33 (d); 118.33 (d); 126.30 (s); 126.35 (d); 126.65 (d); 127.35 (d); 128.33 (d); 128.59
(d); 128.84 (d); 132.01 (s); 132.16 (d); 137.69 (s); 143.66 (s); 144.69 (s); 146.64 (s); 153.35 (d, C(8)); 196.57
‡
‡
(s, C(6)). EI-MS: 453 (100, M ). HR-EI-MS: 453.2304 (C30H31NO3 ; calc. 453.2304) 453.2299.
(aR,5a,6a,7a,14a)-4,5-Epoxy-a-ethenyl-3,6-dimethoxy-17-methyl-6,14-ethenomorphinan-7-methanol For-
mate (27a) from 7e. Yield 61 %. Rf (AcOEt) 0.67. IR (film): 1723. 1H-NMR (270 MHz, CDCl3): 1.85
(m, 1 H); 1.93 2.04 (m, 2 H); 2.31 2.62 (m, 3 H); 2.40 (s, MeN); 2.82 (m, 1 H); 3.18 3.25 (m, 2 H); 3.62
(s, 3 H); 3.82 (s, 3 H); 4.52 (d, J ˆ 0.98, 1 H); 5.17 (d, J ˆ 7.8, 1 H); 5.20 (d, J ˆ 14.2, 1 H); 5.41 (d, J ˆ 8.8, 1 H);
5.62 5.82 (m, 3 H); 6.52 (d, J ˆ 8.3, HÀC(1)); 6.62 (d, J ˆ 8.3, HÀC(2)); 7.99 (s, OC HO). 13C-NMR
(75.5 MHz, CDCl3): 22.39 (t); 26.69 (t); 33.49 (t); 41.00 (d); 42.62 (s); 43.52 (q); 45.63 (t); 47.09 (s); 53.23
(q); 56.64 (q); 60.11 (d); 72.18 (d); 79.63 (s); 95.81 (d, C(5)); 113.52 (d); 116.55 (t, C HˆCH2); 119.26 (d); 126.62
‡
(d); 127.96 (s); 134.03 (s); 134.04 (d); 134.91 (d); 141.83 (s); 148.2 (s); 160.4 (d, OCHO). EI-MS: 423 (100, M ),
‡
338 (94), 248 (90). HR-EI-MS: 423.2043 (C25H29NO5 ; calc. 423.2046).
(5b,14b,18E)-7,8-Didehydro-4-hydroxy-3-methoxy-17-methyl-18-(3-methylbut-2-enylidene)-5,14-ethano-
morphinan-6-one (11g) from 7g. Yield 59%. Rf (AcOEt): 0.61. IR (film): 3268, 1678. 1H-NMR (270 MHz,
CDCl3): 1.27 (m, 1 H); 1.75 (s, 3 H); 1.78 (s, 3 H); 1.90 (m, 1 H); 2.05 (m, 1 H); 2.20 (d, J ˆ 16.8, HaÀC(16));
2.37 (s, MeN); 2.41 (m, 1 H); 2.71 (m, 1 H); 3.11 3.21 (m, 2 H); 3.42 (m, HbÀC(16)); 3.80 (s, MeOÀ(3)); 4.27
(s, HÀC(5)); 5.69 (dd, J ˆ 9.7, 1.5, HÀC(7)); 5.73 (br. s, OHÀC(4)); 5.84 (d, J ˆ 11.5, Me2CˆCHCH); 6.55
6.64 (m, HÀC(1), HÀC(2), Me2CˆCHCH); 6.80 (d, J ˆ 9.6, HÀC(8)). 1H,1H-NOESY (CDCl3; selected cross-
peaks): 2.20 (HaÀC(16))/5.84 (Me2CˆCHCH); 3.42 (HbÀC(16))/5.84 (Me2CˆCHCH); 4.27 (HÀC(5))/6.55
6.64 (HÀC(1), HÀC(2), Me2CˆCHCH). 13C-NMR (101 MHz, CDCl3): 18.35; 24.80; 26.28; 30.76; 32.37; 43.18;
45.91; 49.29; 49.55; 55.88; 56.60; 67.13 (s, C(5)); 108.44 (d, Me2CˆCHCH); 118.03 (d, C(2)); 122.46
(d, Me2CˆCHCH); 125.21 (d, C(1)); 125.69 (s); 128.52 (d, C(7)); 131.00 (s); 135.51 (s); 135.72 (s); 143.12
‡
(s); 144.55 (s); 154.98 (d, C(8)); 196.94 (s, C(6)). EI-MS: 391 (100, M ), 230 (71). HR-EI-MS: 391.2153
‡
(C25H29NO3 ; calc. 391.2147).
(5b,14b,18E)-7,8-Didehydro-4-hydroxy-3-methoxy-17-methyl-18-(but-2-enylidene)-5,14-ethanomorphinan-
6-one (11f) and (5a,6a,7a,14a)-6,7-Didehydro-6,7-dihydro-3-methoxy-6',17-dimethyl-6'H-pyrano[2',3':6,7]-
6,14-ethenomorphinan (19b) from 7f. Data of 11f: Yield 34%. Rf (AcOEt) 0.62. IR (film): 3432 (OH), 1673
1
(CˆO). H-NMR (270 MHz, CDCl3): 1.47 (m, 1 H); 1.75 (m, 3 H); 1.89 (m, 1 H); 2.05 (m, 1 H); 2.21 (d, J ˆ
16.6, HaÀC(19)); 2.37 (s, MeN); 2.41 (m, 1 H); 2.71 (m, 1 H, HaÀC(10)); 3.11 3.19 (m, HÀC(9), HbÀC(10));
3.43 (m, HbÀC(19)); 3.78 (s, MeOÀC(3)); 4.22 (s, HÀC(5)); 5.62 5.73 (m, HÀC(7), MeCHˆCHCH); 5.75
(s, OHÀC(4)); 6.08 (ddd, J ˆ 15.1, 10.8, 1.5, MeCHˆCHCH); 6.38 (d, J ˆ 10.8, MeCHˆCHCH); 6.56 6.62
(m, HÀC(1), HÀC(2)); 6.81 (d, J ˆ 9.8, HÀC(8)). 13C-NMR (67.8 MHz, CDCl3): 18.38 (q, MeÀC(5)); 24.76
(t, C(10)); 30.69 (t); 32.34 (t); 43.13 (q, MeN); 45.85 (t); 49.26 (s); 49.54 (s); 55.85 (q, MeO); 56.53 (d, C(9));

Helvetica Chimica Acta Vol. 86 (2003)
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66.86 (d, C(5); 108.45 (d, C(2)); 117.99 (d, C(1)); 125.59 (s); 128.51 (d); 128.66 (d); 128.88 (d); 129.40 (d); 130.93
‡
(s); 136.06 (s); 143.08 (s); 144.52 (s); 154.93 (d, C(8)); 196.78 (s, CˆO). EI-MS: 377 (100, M ), 230 (54). HR-
‡
EI-MS: 377.1989 (C24H27NO3 ; calc. 377.1991).
Data of 19b: Yield 29%. Rf (AcOEt) 0.57. 1H-NMR (400 MHz, CDCl3): 0.94 (dd, J ˆ 12.5, 6.9, HÀC(8));
1.36 (d, J ˆ 6.9, MeÀC(6)); 1.85 (m, 1 H); 2.00 (dd, J ˆ 4.0, 2.0, 1 H); 2.23 (m, HÀC(7)); 2.35 2.44 (m, 2 H);
2.37 (s, MeN); 2.51 (m, 1 H); 3.07 3.24 (m, HbÀC(8), HÀC(9), HbÀC(10)); 3.83 (s, MeOÀC(3)); 4.38 (d, J ˆ
1.3, HÀC(5)); 4.51 (m, HÀC(6')); 5.41 (d, J ˆ 8.9, HÀC(19)); 5.48 (m, HÀC(5')); 5.61 (m, HÀC(4')); 5.80
(d, J ˆ 8.9, HÀC(18)); 6.49 (d, J ˆ 7.9, HÀC(1)); 6.62 (d, J ˆ 7.9, HÀC(2)). 13C-NMR (67.8 MHz, CDCl3): 22.34
(t, C(10)); 23.05 (MeÀC(6')); 32.41 (d, C(7)); 32.77 (t, C(8)); 33.57 (t); 42.68 (s); 43.58 (q, MeN), 45.67 (t);
46.92 (s); 56.93 (q, MeOÀC(3)); 60.09 (d, C(9)); 68.65 (d, C (6')); 76.62 (s); 96.74 (d, C(5)); 114.04 (C(2));
118.93 (C(1)); 128.21 (s); 128.54 (C(5')); 128.93 (C(4')); 130.15 (C(18)); 134.51 (s); 135.73 (C(19)); 141.89 (s);
148.77 (s). EI-MS: 377 (100), 362 (29), 202 (78). HR-EI-MS: 377.1997 (C24H27NO3‡, calc. 377.1991).
(5b,14b,18E)-7,8-Didehydro-4-hydroxy-3-methoxy-5,17-dimethyl-18-(3-methylbut-2-enylidene)-5,14-etha-
nomorphinan-6-one (12g) from 8g. Yield 63%. Rf (AcOEt) 0.58. IR (film): 3511 (OH), 1678 (CˆO). 1H-NMR
(400 MHz, CDCl3): 1.54 (m, 1 H); 1.75 (s, 3 H); 1.78 (s, 3 H); 1.82 (m, 1 H); 1.87 (s, 3 H); 2.05 (td, J ˆ 12.2, 3.4,
1 H); 2.26 (dd, J ˆ 16.6, 1.5, 1 H, HaÀC(16)); 2.37 (s, MeN); 2.42 (m, 1 H); 2.79 (dd, J ˆ 18.6, 5.9, 1 H); 3.08
(d, J ˆ 5.9, 1 H); 3.19 (d, J ˆ 18.6, 1 H); 3.58 (d, J ˆ 16.1, HbÀC(16)); 3.78 (s, MeOÀC(3)); 5.67 (d, J ˆ 9.3,
HÀC(7)); 5.87 (m, HÀC(19)); 6.07 (br. s, OHÀC(4)); 6.41 (m, HÀC(18)); 6.57 (d, J ˆ 8.3, HÀC(1)); 6.62
(d, J ˆ 7.8, HÀC(2)); 6.72 (d, J ˆ 9.8, HÀC(8)). 13C-NMR (67.8 MHz, CDCl3): 15.19 (q); 18.41 (q); 25.71 (t);
26.39 (q); 29.39 (t); 33.02 (t); 43.01 (q, MeN); 46.04 (t, C(16)); 50.02 (s); 54.14 (s); 56.00; 56.31; 65.51 (s, C(5));
108.09 (d, C(2)); 118.21 (d, C(1)); 122.70 (d); 124.46 (d); 126.40 (s); 128.66 (d); 132.09 (s); 135.45 (s); 142.29 (s);
‡
143.57 (s); 144.54 (s); 153.47 (C(8)); 197.22 (C(6)). EI-MS: 405 (100, M ), 230 (56). HR-EI-MS: 405.2306
‡
(C26H31NO3 ; calc. 405.2304).
(5a,14b)-4,5-Epoxy-3-methoxy-5,17-dimethyl-14-(3-methylbut-2-enyl)morphinan-6-one (16c) from 14c.
Yield 54%. Rf (AcOEt) 0.67. IR (film): 1720 (CˆO). 1H-NMR (270 MHz, CDCl3): 1.29 (m, 1 H); 1.41
(m, 1 H); 1.54 (m, 1 H); 1.63 (s, 3 H); 1.72 (m, 1 H); 1.74 (s, 3 H); 1.76 (s, 3 H); 2.11 (m, 1 H); 2.17 2.29
(m, 3 H); 2.31 (s, MeN); 2.51 2.62 (m, 2 H); 2.81 (d, J ˆ 5.1, 1 H); 3.04 (d, J ˆ 18.3, 1 H); 3.57 (dd, J ˆ 14.1, 7.9,
1 H, Me2CˆCHCH2); 3.88 (s, MeOÀC(3)); 5.17 (m, Me2CˆCHCH2); 6.58 (d, J ˆ 8.1, HÀC(1)); 6.65 (d, J ˆ
8.1, HÀC(2)). 13C-NMR (101 MHz, CDCl3): 17.56 (q); 18.07 (q); 20.03 (t); 25.96 (t); 26.23 (q); 26.55 (t); 26.63
(t); 35.79 (t); 41.09 (s); 43.04 (q, MeN); 45.82 (t, C(16)); 49.88 (s); 56.39; 59.44; 95.46 (s, C(5)); 113.33 (d, C(2));
119.00 (d); 119.44 (d); 126.86 (s); 131.18 (s); 134.79 (s); 142.42 (s); 144.40 (s); 212.36 (s, C(6)). EI-MS: 381
‡
(100), 244 (99), 189 (39). HR-EI-MS: 381.2305 (C24H31NO3 ; calc. 381.2304).
(5a,14b)-7,8-Didehydro-4,5-epoxy-3-methoxy-5,17-dimethyl-14-(3-methylbut-2-enyl)morphinan-6-one
(10c) from 8c. Yield: 65%. Rf (AcOEt) 0.68. IR (film): 1678 (CˆO). 1H-NMR (270 MHz, CDCl3): 1.46
(m, 1 H); 1.66 (s, 3 H); 1.72 (s, 3 H); 1.73 (s, 3 H); 2.00 (dd, J ˆ 12.9, 7.2, 1 H, Me2CˆCHCH2); 2.19 2.31
(m, 3 H); 2.35 (s, MeN); 2.58 (m, 1 H); 3.07 3.12 (m, 2 H); 3.64 (dd, J ˆ 12.5, 8.9, 1 H, Me2CˆCHCH2); 3.79
(s, MeOÀC(3)); 5.11 (t, J ˆ 7.9, Me2CˆCHCH2); 6.03 (d, J ˆ 10.2, HÀC(7)); 6.56 (d, J ˆ 8.2, HÀC(1)); 6.63
(d, J ˆ 8.2, HÀC(2)); 6.70 (d, J ˆ 10.2, HÀC(8)). 13C-NMR (101 MHz, CDCl3): 17.50 (q); 17.97 (q); 21.25 (t);
25.85 (t); 26.05 (q); 35.09 (t); 42.85 (q, MeN); 44.41 (s); 45.85 (t); 47.26 (s); 56.36; 58.81; 92.85 (s, C(5)); 113.24
(d); 118.37 (d); 119.13 (d); 126.58 (s); 130.66 (d, C(7)); 132.87 (s); 135.66 (s); 141.96 (s); 143.85 (s); 156.24
‡
(d, C(8)); 196.91 (s, C(6)). EI-MS: 379 (100). HR-EI-MS: 379.3147 (C24H29NO3 ; calc. 379.2147).
(5a,14b)-7,8-Didehydro-4,5-epoxy-14-(hexa-2,4-dienyl)-3-methoxy-5,17-dimethylmorphinan-6-one (10f)
from 8f. Yield 43%. Rf (AcOEt) 0.57. IR (film): 1679 (CˆO). 1H-NMR (270 MHz, CDCl3): 1.46 (m, 1 H);
1.70 (s, 3 H); 1.74 (d, J ˆ 8.8, 3 H); 2.05 (dd, J ˆ 12.2, 7.3, 1 H, MeCHˆCHCHˆCHCH2); 2.19 2.33 (m, 3 H);
2.36 (s, MeN); 2.57 (m, 1 H); 3.09 3.14 (m, 2 H); 3.67 (dd, J ˆ 12.3, 8.5, 1 H, MeCHˆCHCHˆCHCH2); 3.79
(s, MeOÀC(5)); 5.47 (m, MeC HˆCHCHˆCHCH2); 5.64 (m, MeC HˆCHCHˆCHCH2); 6.02 6.14
(m, HÀC(7), MeCHˆCHCHˆCHCH2); 6.56 (d, J ˆ 8.3, HÀC(1)); 6.62 (d, J ˆ 8.3, HÀC(2)); 6.66 (dd, J ˆ
10.2, 3.4, HÀC(8)). 13C-NMR (75 MHz, CDCl3): 17.35 (q); 17.94 (q); 21.14 (t); 25.74 (t); 39.5 (t); 42.66 (q); 44.28
(s); 45.74 (t); 47.08 (s); 56.23 (d); 58.61 (q); 92.64 (s, C(5)); 113.11 (d, C(2)); 119.09 (d, C(1)); 124.78 (d, C(19));
126.39 (d, MeCHˆCHCHˆCHCH2); 128.41 (d); 130.74 (d); 131.09 (d); 132.59 (s); 134.54 (d); 141.84 (s);
‡
143.71 (s); 155.61 (d, C(8)); 196.76 (s, C(6)). EI-MS: 391 (100, M ), 244 (99), 243 (93). HR-EI-MS: 391.2148
‡
(C25H29NO3 ; calc. 391.2147).
(5b,14b,18E)-7,8-Didehydro-4-hydroxy-3-methoxy-17-methyl-18-(3-phenylprop-2-enylidene)morphinan-6-
one (11h) from 7h. Yield 71%. Rf (AcOEt) 0.69. IR (film): 3340 (OH), 1678 (CˆO). 1H-NMR (270 MHz,
CDCl3): 1.51 (m, 1 H); 1.92 (m, 1 H); 2.07 (m, 1 H); 2.35 (m, 1 H); 2.39 (s, MeN); 2.43 (m, 1 H); 2.73 (dd, J ˆ
18.6, 5.8, 1 H); 3.15 (m, 1 H); 3.19 (d, J ˆ 12.2, 1 H); 3.56 (dd, J ˆ 16.7, 2.1, 1 H); 3.78 (s, MeO); 4.34

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(s, HÀC(5)); 5.71 (dd, J ˆ 9.6, HÀC(7)); 5.79 (s, OHÀC(4)); 6.49 (d, J ˆ 15.5, PhCHˆCHCH); 6.55 6.64
(m, HÀC(1), HÀC(2), PhCHˆCHCH); 6.76 6.88 (m, HÀC(8), PhCHˆCHCH); 7.14 7.40 (m, Ph). 1H,1H-
NOESY (CDCl3; selected crosspeaks): 4.34 (s, HÀC(5))/6.55 6.64 (HÀC(1), HÀC(2), PhCHˆCHCH).
13C-NMR (67.8 MHz, CDCl3): 24.79 (t); 30.82 (t); 32.82 (t); 43.12 (q, MeN); 45.85 (t, C(16)); 49.45 (s); 49.59 (s);
55.90 (q, MeO); 56.57 (d, C(10)); 67.41 (d, C(5)); 108.62 (d); 118.06 (d); 125.53 (s); 126.24 (d); 126.31 (d);
127.38 (d); 128.55 (d); 128.63 (d); 128.76 (d); 130.91 (s); 132.05 (d); 137.55 (s); 140.05 (s); 143.14 (s); 144.61 (s);
‡
‡
154.92 (d); 196.24 (s, C(6)). EI-MS: 439 (100, M ). HR-EI-MS: 439.2155 (C29H29NO3 ; calc. 439.2147).
(5a,14b)-7,8-Didehydro-4,5-epoxy-3-methoxy-5,17-dimethyl-14-(3-phenylprop-2-enyl)morphinan-6-one
(10a) from 8a. Yield 78%. Rf (AcOEt) 0.64. IR (film): 1678 (CˆO). 1H-NMR (270 MHz, CDCl3): 1.51
(m, 1 H); 1.74 (s, 3 H); 2.16 2.38 (m, 3 H); 2.36 (m, 1 H,PhCHˆCHCH2); 2.40 (s, MeN); 2.62 (m, 1 H); 3.14
(d, J ˆ 18.7, 1 H); 3.19 (d, J ˆ 5.3, 1 H); 3.80 (s, MeO); 3.85 (m, 1 H, PhCHˆCHCH2); 6.09 (d, J ˆ 10.1,
HÀC(7)); 6.17 (m, PhCHˆCHCH2); 6.51 (d, J ˆ 15.8, PhCHˆCCHCH2); 6.56 (d, J ˆ 8.3, HÀC(1)); 6.63
(d, J ˆ 8.3, HÀC(2)); 6.71 (d, J ˆ 10.1, HÀC(8)); 7.20 7.37 (m, Ph). 13C-NMR (67.8 MHz, CDCl3): 17.50
(q, MeÀC(5)); 21.38 (t); 26.00 (t); 40.08 (t); 42.83 (q, MeN), 44.61 (s); 45.96 (t); 47.39 (s); 56.58; 58.99; 92.81
(s, C(5)); 113.76 (d, C(2)); 119.29 (d, C(1)); 124.34 (d); 126.12 (d); 126.55 (s); 127.42 (d); 128.61 (d); 131.13 (d);
132.79 (s); 134.24 (d); 137.22 (s); 142.11 (s); 144.03 (s); 155.32 (d, C(8); 196.88 (s, C(6)). EI-MS: 427 (100), 244
‡
(58), 243 (82). HR-EI-MS: 427.2156 (C28H29NO3 ; calc. 427.2147).
(5a,14b)-4,5-Epoxy-3-methoxy-5,17-dimethyl-14-(3-phenylprop-2-enyl)morphinan-6-one (16a) from 14a.
Yield 54%. Rf (CH2Cl2/MeOH 90 :10) 0.79. IR (CHCl3): 1721 (CˆO). 1H-NMR (300 MHz, CDCl3): 1.65
(s, MeÀC(5)); 2.42 (s, MeN); 2.50 (dd, J ˆ 8.2, 13.5, 1 H, PhCHˆCHCH2); 3.00 (d, J ˆ 6.8, HÀC(9)); 3.10
(d, J ˆ 18.3, HbÀC(10)); 3.78 (dd, J ˆ 7.6, 13.5, 1 H, PhCHˆCHCH2); 3.86 (s, MeOÀC(3)); 6.25
(m, PhC HˆCHCH2); 6.55 (d, J ˆ 15.4, PhCHˆCHCH2); 6.62 (d, J ˆ 8.3, HÀC(1)); 6.67 (d, J ˆ 8.3,
HÀC(2)); 7.35 (m, Ph). 13C-NMR (75 MHz, CDCl3): 17.5 (MeÀC(5); 20.2; 25.9; 26.5; 31.6; 35.4; 41.1; 43.0;
46.0; 49.6; 56.4; 59.7; 95.3 (C(5)); 113.5; 119.1; 125.4; 126.0; 127.3; 128.6; 130.8; 133.3; 137.3; 142.5; 144.4; 212.0
‡
(C(6)). EI-MS: 429 (100). HR-EI-MS: 429.2291 (C28H31N1O3 ; calc. 429.2303).
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Received October 28, 2002