Synthetic transformation of abietic acid I. Addition of Dienophiles

Article abstract of DOI:10.1007/PL00000088

Addition of acetylene dicarboxylic acid dimethylester to abietic acid is an en-reaction. The structure of the resulting product was determined. Compounds formally derived from addition of acetylene to levopimaric acid have been synthesized. By a retro-Die

Full text of DOI:10.1007/PL00000088

Monatshefte fuÈr Chemie 129, 297±308 (1998)
Synthetic Transformation of Abietic Acid I.
Addition of Dienophiles
Ernst Haslinger and Dieter Hofnera
Ã
Institute of Pharmaceutical Chemistry, University of Graz, A-8010 Graz, Austria
Summary Addition of acetylene dicarboxylic acid dimethylester to abietic acid is an en-reaction.
The structure of the resulting product was determined. Compounds formally derived from addition of
acetylene to levopimaric acid have been synthesized. By a retro-Diels-Alder reaction, the B-ring is
cleaved and an aromatic system is formed. Diels-Alder addition of 2-chloroacrylonitrile to abietic
acid gives a tetracyclic ꢀ-chloronitrile (10). Further transformations of this product are described.
Keywords. Abietic acid; En-reaction of acetylenedicarboxylic acid; 2-Chloroacrylonitrile; retro-
Diels-Alder reaction.
È
È
Synthetische Umwandlung des Abietinsauregerusts. Addition von Dienophilen
È È
Zusammenfassung. Die Addition von Acetylendicarbonsaure an Abietinsaure ist eine En-Reaktion.
È
Die Struktur des Reaktionsprodukts wurde aufgeklart. Formale Dien-Addukte von Acetylen an
È È È È
Laevopimarsaure konnen durch oxidative Decarboxylierung des Abietinsaure-Fumarsaure-Addukts
È
und Decarbony-Decarboxylierung des Maleinsaureanhydrid-Addukts hergestellt werden. Durch
retro-Diels-Alder-Reaktion wird anschlieûend der B-Ring unter Bildung aromatischer Produkte
È È
geoffnet. Das Ketenaquivalent 2-Chloracrylnitril liefert als Dien-Addukt ein tetracyclisches
ꢀ-Chlornitril (10), das in verschiedener Weise weiter umgesetzt werden kann.
Introduction
Diels-Alder addition of maleic acid anhydride to abietic acid (1) at elevated
temperature is very well known and routinely used during industrial utilization of 1
[1]. The product, maleopimaric acid, is formed by addition of the dienophile to
levopimaric acid (3), which is ®rst generated by isomerization of the double bond
system of 1 [2]. Sandermann [3] studied the addition of acetylene dicarboxylic acid
dimethyl ester to 1. The structure he deduced for the product (2) was corroborated
by the fact that pyrolysis of 2 did not give a volatile product. Therefore, he
assumed a retro-Diels-Alder reaction resulting in product 4.
ÐÐÐÐ
* Corresponding author
a
Present address: CU Chemie Uetikon, Raiffeisenstr. 4, D-77933 Lahr, Germany

298
E. Haslinger and D. Hofner
Scheme 1
Results and Discussion
Addition of acetylene dicarboxylic acid dimethyl ester
We have studied the addition of acetylene dicarboxylic acid dimethyl ester to 5
under the same conditions as described Sandermann [3]. After 3 h at 190ꢀC, no,
residual educt (5) could be detected. After column chromatography, 6 was obtained
in 60% yield. The structure was established by NOE experiments. Irradiating the
resonance of the ole®nic proton gave enhancements of the signals of H-5, H-7, and
H-14, proo®ng that the ole®nic hydrogen is in close spatial proximity to these
protons. Therefore, we concluded that the con®guration of the double bond is Z and
that the vinyl substituent is in ꢀ-position. Variation of the reaction conditions
(temperature, time, or molar ratio of the educts) always lead to the same product.
We therefore conclude that compound 4 has the structure given for 6 and that the
addition of acetylene dicarboxylic acid dimethyl ester is an en-reaction. The
acetylene molecule is the enophile and approaches 5 from the ꢀ-side. Z-
con®guration of the double bond in 6 indicates that the course of the reaction is
concerted.

Diels-Alder Reactions of Abietic Acid
299
Synthesis of diene adducts formally derived from acetylene
To obtain compounds which are formally acetylene adducts on levopimaric acid we
tried a decarbony-decarboxylation of maleopimaric acid (8) [4, 5] with bis-
(triphenylphosphine)-nickel dicarbonyl at 200ꢀC.
Scheme 2
At this temperature, a retro-Diels-Alder reaction is also induced, and the
primary product is in turn converted to the aromatic compound 9. The
bisdecarboxylation of the fumaric acid adduct (7) [5±7] affords the retro-Diels-
Alder aromate 9 in 8% yield. The mass spectrum of 9 has its base peak at
m/z ˆ 133. This ion, an isopropyl substituted tropylium ion, is formed by cleavage
at the benzyl position. COSY correlations were observed connecting the aromatic
proton H-12 with H-17 and H-7. CH3-20 has small couplings to the ole®nic
hydrogens H-9 and H-8trans
.
Addition of ketene equivalents
[4‡2] addition of ketene equivalents [8] to 5 and further transformation of the
primary product should give access to tricyclic molecules with an oxo function
which in turn can be used as starting materials for further synthetic transforma-
tions. 2-Chloroacrylonitrile has high reactivity and regioselectivity and has been
used previously to produce ꢀ-chloronitrile adducts which can be easily converted
to ketones by KOH in DMSO [9±14]. Addition of 2-chloroacrylonitrile to 5 gave 10
in moderate yield which shows an IR absorption at 2237 cmꢁ1 (stretching vibration
of nitrile). The El-MS exhibits a molecular ion at m/z ˆ 403 and a base peak at

300
E. Haslinger and D. Hofner
Scheme 3
m/z ˆ 316 as the result of a retro-Diels-Alder fragmentation. The high ®eld shift of
CH3-20 (ꢁ ˆ 0.61 ppm) is induced by the anisotropy of the double bond between
C-13 and C-14. The ꢀ-orientation of the nitrile group in 10 was determined by
X-ray crystallography.
Treatment of 10 with KOH in DMSO gave ± after usual workup and
esteri®cation of the acid with diazomethane ± ketone 11 (40%) and pyrazoline 13
(22%). 11 shows a typical ketocarbonyl resonance at ꢁ ˆ 212.9 ppm in the 13C
NMR spectrum. In the IR spectrum of compound 13 we found the nitrile
absorption at 2230 cmꢁ1 and the -N ˆ N-stretching vibration at 1562 cmꢁ1 [15].
We assume that 13 was formed by addition of the 1,3-dipole diazomethane to the
double bond of 12 during workup. Using KOH in ethanol improved the yield of 11,
and no pyrazoline was observed. Upon thermolysis, compound 13 yields the
cyclopropane derivative 14 (51%) and the aromatic compound 16 (39%) which is
probably formed by a retro-Diels-Alder reaction from intermediate 15 which could
not be isolated. The mechanism of thermal decomposition of 1-pyrazolines is not
entirely clear; besides ionic intermediates which are shown in Scheme 4, radical
intermediates are also discussed in the literature [15±17].

Diels-Alder Reactions of Abietic Acid
301
Scheme 4
Ring cleavage by oxime rearrangement
The oxime 17 was obtained in quantitative yield by re¯uxing 11 and
hydroxylamine hydrochloride in EtOH over solid NaOH [18]. The Z-oxime is
formed exclusively as could be shown by an NOE correlation between the HON-
proton and H-7. We planned to introduce a nitrogen function in the terpene
skeleton via a Beckmann rearrangement of the corresponding tosylate [19±21]. 17
Scheme 5

302
E. Haslinger and D. Hofner
was treated with an excess of tosylchloride in dry pyridine until no educt could be
detected. The product obtained in 85% yield turned out to be the 12-cyanomethyl
derivative of abietic acid (18).
Treatment of 17 with 72% sulfuric acid [22] or polyphosphoric acid
trimethylsilyl-ester [23] (both reagents have been used to induce Beckmann
rearrangements) also gave nitrile 18 in nearly quantitative yield. We assume that
the tert-allylkation shown in Scheme 5 is more stable than the carbenium ion which
is formed via the Beckmann rearrangement; therefore, nitrile formation is the main
reaction path. The con®guration at C-12 was derived from the proton resonance of
H-12. Couplings to both H-21 (3J ˆ 10.8 Hz and 4.4 Hz) and two couplings to the
protons in position 11 (3J ˆ 4.7 Hz and 1.9 Hz) can be observed. This indicates that
H-12 and H-11 are not in an antiperiplanar arrangement. From the reaction
mechanism one can also deduce on ꢀ-orientation of the cyanomethyl substituent.
We therefore assign R con®guration to C-12.
Further investigations are in progress to clarify how the tetracyclic compounds
10 and 11 can be used as synthons for stereoselective terpene syntheses.
Experimental
Analytical methods
Preparative thin layer chromatography: Chromatotron Harrison Research, 1 mm Kieselgel 60 PF254
(Merck) with gypsum; column chromatography (CC): Kieselgel 60 (Merck) (70±230 mesh), pore-
Ê
diameter 60 A; thin layer chromatography (TLC): TLC plates (Machery-Nagel) Alugram SIL G/
UV254 and Polygram SIL G/UV254 Kieselgel 60 F254 0.2 mm 200Â200 mm; solvents frequently used:
cyclohexane (CH) and AcOEt; the substances were detected in UV light at 254 nm and by spraying
with molybdatophosphoric acid or methanol/sulfuric acid (9:1) and subsequent heating. Melting
points: melting point apparatus SM-LUX (Leitz), uncorrected; optical rotation: polarimeter 241 MC
(Perkin Elmer); IR spectra: Perkin-Elmer IR spectrometer 883; UV/Vis: Lambda 17 UV/Vis-
spectrometer (Perkin Elmer); NMR spectra: Bruker AC 200 and AMX 500 (300 K), 5 mm tubes,
solvent resonance as internal standard. Before NOE experiments were performed, dissolved oxygen
was removed by bubbling Ar through the solutions. 1H and 13C resonances were assigned using 1H,
1H and 1H, 13C correlation spectra (sometimes optimized for small CH couplings) and are numbered
as given in the formulas. MS: Varian MAT 711 spectrometer (70 eV electron impact and ®eld
desorption); elementary analyses: Laboratory for Microanalysis, Institute for Physical Chemistry of
the University of Vienna, and Sektion Analytik of the University of Ulm; autoclave: laboratory
autoclave, model HR 200 (Berghof).
Abietic acid methyl ester (5)
5 was obtained as given in the literature [22].
Dimethyl-(10R-(10ꢀ,40aꢂ,90ꢀ(Z)))-10-methoxycarbonyl-10, 40a-dimethyl-70-(1-methylethyl)-
10,20,30,40,40a,90,100,100a-octahydro-90-phenanthrene-1,2-ethylendicarboxylate (6)
A solution of 6.1 g (19 mmol) 5 in 13.5 g (95 mmol) acetylene dicarboxylic acid dimethyl ester was
gradually heated to 210ꢀC during 25 h under 80 bar Ar in an autoclave. The pressure went up to
115 bar. After cooling, the Ar pressure was released and the dark resin was dissolved in CH2Cl2. This

Diels-Alder Reactions of Abietic Acid
303
solution was washed with H2O and dried over Na2SO4. Evaporation and puri®cation by CC over
silica (CH/AcOEt ˆ 1:1) gave 5.2 g 5 as a colourless oil (yield: 60%).
Rf ˆ 0.31 (CH/AcOEt ˆ 9:1), 0.58 (CH/AcOEt ˆ 1:1); [ꢀ]2D0 ˆ ‡24.7 (c ˆ 0.5, CHCl3); IR (neat):
ꢃ ˆ 2951 (m), 1728 (vs), 1434 (m), 1251 (s), 1166 (m) cmꢁ1; UV (MeOH): ꢄmax (lg ") ˆ 217
1
(4.156), 265 (3.237) nm; H NMR (C6D6): ꢁ ˆ 1.05 (s, 3H, 20-H), 1.12 (d, J ˆ 6.9 Hz, 6 H, 16-H,
17-H), 1.30 (s, 3H, 19-H), 1.34 (m, 1 H, 1-Hax), 1.51 (m, 1 H, 3-Heq), 1.3±1.6 (m, 2H, 2-H), 1.71
(d, J ˆ 14.0 Hz, 1H, 6-Heq), 1.89 (m, 1H, 3-Hax), 1.98 (m, 1H, 6-Hax), 2.11 (m, 1H, 1Heq), 2.44 (dd,
J ˆ 12.3 Hz, J ˆ 1.8 Hz, 1H, 5-H), 2.66 (sept, J ˆ 6.9 Hz, 1H, 15-H), 3.26 (s, 3H, 27-H), 3.63 (s, 6H,
25-H, 26-H), 4.04 (d, J ˆ 7.3 Hz, 1H, 7-Heq), 5.50 (d, J ˆ 1.1 Hz, 1H, 22-H), 6.99 (d, Jmeta ˆ 2.0 Hz,
1 H, 14-H), 7.07 (dd, Jortho ˆ 8.2 Hz, Jmeta ˆ 2.0 Hz, 1H, 12-H), 7.17 (d, Jortho ˆ 8.2 Hz, 1H, 11-H)
ppm; 13C NMR (C6D6): ꢁ ˆ 17.0 (q, C-19), 18.8 (t, C-2), 23.9 (q, C-16/C-17), 24.1 (q, C-17/C-16),
25.2 (C-6 u. C-20), 33.7 (d, C-15), 36.2 (t, C-3), 37.5 (s, C-10), 38.2 (t, C-1), 39.9 (d, C-5), 43.6 (d,
C-7), 47.6 (s, C-4), 51.1 (q, C-27), 51.9 (q, C-25/C-26), 52.0 (q, C-26/C-25), 122.9 (d, C-22), 124.9
(d, C-11), 125.8 (d, C-12), 129.2 (d, C-1), 133.1 (s, C-8), 146.6 (s, C-13), 148.4 (s, C-9), 155.3 (s, C-
‡
21), 165.6 (s, C-24), 169.0 (s, C-23), 177.5 (s, C-18) ppm; MS (FD): m/z (%) ˆ 456 (100) [M ]; MS
(70 eV): m/z (%) ˆ 456 (28), 424 (100), 350 (36), 321 (29), 175 (26), 43 (23); C27H36O6 (456.6);
calc.: C 71.03, H 7.95; found: C 71.21, H 7.96.
13-(1-Methylethyl)-17, 18-dinoratis-13-ene-4-methoxycarbonyl-15ꢀ, 16ꢂ-dicarboxylic acid (7)
7 was obtained from 5 as described in the literature [4±6].
Methyl 13-(1-methylethyl)-17, 18-dinoratis-13-ene-4, 15ꢂ, 16ꢂ-tricarboxylic acid-15,
16-anhydride-4-carboxylate (8)
8 was prepared from 5 according to the literature [4, 24].
Methyl-(1R-(1ꢀ, 2ꢂ, 3ꢀ)-1,3-dimethyl-2-(2-(3-(1-methylethyl)-phenyl)-ethyl)-3-vinyl-
1-cyclohexane-carboxylate (9)
a) 840 mg (2.0 mmol) 8 were dissolved in 6 ml triglyme and stirred under Ar at 220ꢀC. Within 22 h,
1.6 g (2.5 mmol) bis-(triphenylphosphino)nickel dicarbonyl were added in small portions. After
removing the solvent, a residue was obtained which was re¯uxed in 12 ml EtOH/CCl4 (1:1) for 1 h.
The solvents were evaporated and the residue was puri®ed by CC over silica (CH/AcOEt ˆ 30:1).
Yield: 160 mg 9 (23%), colourless oil.
b) A mixture of 800 mg (1.8 mmol) 7, 500 mg (3.5 mmol) Cu2O, 560 mg (3.6 mmol) 2,20-
bipyridyl, 200 mg glass powder, and 5 ml dry quinolin under Ar was heated to 200ꢀC for 7 h. After
cooling it was poured in 2 N HCl, ®ltered, and extracted three times with Et2O. The combined
organic phases were washed twice with 2 N HCl and twice with H2O and dried over Na2SO4. The
solvent was evaporated and the residue puri®ed by CC over silica (CH/AcOEt ˆ 30:1); yield: 50 mg
9 (8%) as a colourless oil.
Rf ˆ 0.36 (CH/AcOEt ˆ 30:1); [ꢀ]2D0 ˆ ꢁ13.8 (c ˆ 0.03, CHCl3); IR (neat): ꢃ ˆ 2957 (s), 1728
(vs), 1460 (m), 1243 (m), 1139 (w) cmꢁ1; UV (MeOH): ꢄmax (lg ") ˆ 212 (3.788), 259 (2.774) nm;
1H NMR (CDCl3): ꢁ ˆ 0.98 (s, 3H, 20-H), 1.20 (d, J ˆ 6.9 Hz, 6H, 18-H, 19-H), 1.22 (s, 3H, 21-H),
1.31 (m, 2H, 1-H), 1.3±1.7 (m, 2H, 6-H), 1.4±1.6 (m, 2H, 2-H), 1.45 (m, 1H, 3-Heq), 1.77 (m, 1H, 3-
Hax), 1.92 (dd, J ˆ 6.1 Hz, J ˆ 4.1 Hz, 1H, 5-H), 2.38 (m, 2H, 7-H), 2.82 (sept, J ˆ 6.9 Hz, 1H, 17-H),
3.63 (s, 3H, 23-H), 4.89 (dd, J ˆ 17.3 Hz, J ˆ 1.2 Hz, 1H, 8-Htrans), 4.93 (dd, J ˆ 10.9 Hz, J ˆ 1.2 Hz,
1H, 8-Hcis), 5.69 (dd, J ˆ 17.3 Hz, J ˆ 10.9 Hz, 1H, 9-H), 6.89 (dt, Jortho ˆ 7.7 Hz, 2 Jmeta ˆ 1.4 Hz,
1H, 14-H/16-H), 6.91 (br s, 1H, 12-H), 6.99 (dt, Jortho ˆ 7.7 Hz, 2ÂJmeta ˆ 1.4 Hz, 1H, 16H/14H),
7.14 (td, 2Jortho ˆ 7.7 Hz, Jpara ˆ 0.9 Hz, 1H, 15-H) ppm; 13C NMR (CDCl3): ꢁ ˆ 18.0 (t, C-2), 18.7

304
E. Haslinger and D. Hofner
(q, C-21), 19.4 (q, C-20), 24.0 (q, C-18, C-19), 30.7 (t, C-6), 34.1 (d, C-17), 36.4 (t, C-3), 36.9 (t, C-
7), 38.2 (t, C-1), 40.8 (s, C-10), 46.6 (s, C-4), 47.8 (d, C-5), 51.7 (q, C-23), 110.9 (t, C-8), 123.7 (d,
C-14/C-16), 125.7 (d, C-16/C-14), 126.5 (d, C-12), 128.2 (d, C-15), 143.0 (s, C-11), 148.9 (s, C-13),
‡
150.6 (d, C-9), 179.3 (s, C-22) ppm; MS (70 eV): m/z (%) ˆ 342 (52) [M ], 282 (42), 185 (50), 146
(92), 133 (100), 117 (66), 81 (46), 41 (47); C23H34O2 (342.5); calc.: C 80.66, H 10.01; found: C
80.45, H 9.98.
Methyl-(4ꢀ, 15ꢂ)-15-chloro-15-cyano-13-(1-methylethyl)-17,19-dinoratis-13-en-4-carboxylate (10)
A mixture of 7.1 g (22 mmol) 5, 9.7 g (111 mmol) 2-chloroacrylonitrile, and a few mg of
thiodiphenylamine were heated in an autoclave under Ar to 170ꢀC for 15 h. A brown oil was
obtained which was dissolved in 300 ml CH2Cl2. 50 g silica were added, and the solvent was
evaporated. The cooled silica was moistened with CH/AcOEt (9:1), brought on top of a column
containing 300 g silica, and eluted with CH/AcOEt ˆ 9:1.
Yield: 3.1 g 10 (39%); white crystals (petrol ether); m.p.: 133±134ꢀC. Suitable crystals for an X-
ray analysis were obtained from AcOEt. Crystal data: orthorhombic, space group P212121, lattice
constants: a ˆ 11.49(1), b ˆ 16.47(1), c ˆ 12.04 (1)A; Z ˆ 4; Dcalc: ˆ 1.178 g/cm3, Dmeasd: ˆ 1.17 g/
Ê
cm3; ꢅ ˆ 1.48 cmꢁ1
.
Rf ˆ 0.34 (CH/AcOEt ˆ 9:1); [ꢀ]2D0 ˆ ꢁ83.9 (c ˆ 0.1, CHCl3); IR (KBr): ꢃ ˆ 2932 (s), 2237 (w),
1730 (vs), 1448 (m), 1244 (s), 1185 (m) cmꢁ1; UV (MeOH): ꢄmax (lg ") ˆ 206 (3.720) nm; 1H NMR
(CDCl3): ꢁ ˆ 0.61 (s, 3H, 20-H), 0.99 (td, 2ÂJ ˆ 12.8 Hz, J ˆ 3.9 Hz, 1H, 1-Hax), 1.02 (d, J ˆ 6.9 Hz,
3H, 18-H/19-H), 1.03 (d, J ˆ 6.9 Hz, 3H, 19-H/18-H), 1.14 (s, 3H, 21-H), 1.18 (m, 1H, 11-Hꢂ), 1.26
(m, 1H, 6-Heq), 1.40 (m, 1H, 1-Heq), 1.48 (m, 1H, 6-Hax), 1.52 (m, 1H, 3-Heq), 1.59 (m, 1H, 11 Hꢀ),
1.72 (m, 1H, 3-Hax), 1.73 (m, 1H, 7-Hax), 1.77 (m, 1H, 5-H), 1.80 (dd, J ˆ 9.5 Hz, J ˆ 5.7 Hz, 1H,
9-H), 1.98 (dt, J ˆ 14.1 Hz, J ˆ 3.0 Hz, J11ꢂ,16ꢂ ˆ 3.0 Hz, 1H, 16-Hꢂ), 2.23 (ddd, J ˆ 13.4 Hz,
J ˆ 3.6 Hz, J ˆ 3.0 Hz, 1H, 7-Heq), 2.35 (sept, J ˆ 6.9 Hz, J14;17 ˆ 1.3 Hz, 1H, 17-H), 2.56 (dd,
J ˆ 14.1 Hz, J ˆ 2.3 Hz, 1H, 16-Hꢀ), 2.57 (br s, 1H, 12-H), 3.65 (s, 3H, 24-H), 5.31 (br s, 1H, 14-H)
ppm; 13C NMR (CDCl3): ꢁ ˆ 15.9 (q, C-20), 16.9 (q, C-21), 17.1 (t, C-6), 20.1 (q, C-18/C-19), 20.2
(q, C-19/C-18), 21.6 (d, C-6), 27.1 (t, C-11), 32.6 (C-7, C-12), 32.7 (d, C-17), 36.5 (t, C-3), 37,9
(t, C-1), 38.0 (s, C-10), 46.1 (s, C-8), 47.1 (s, C-4), 47.5 (t, C-16), 48.9 (d, C-5), 49.8 (d, C-9), 51.9
(q, C-24), 65.2 (s, C-15), 120.5 (s, C-23), 121.7 (d, C-14), 149.7 (s, C-13), 178.8 (s, C-22) ppm;
‡
‡
MS (70 eV): m/z (%) ˆ 405 (16) [(M‡2) ], 403 (43) [M ], 316 (100), 187 (46), 146 (62), 121 (37),
91 (31), 43 (19); C24H34ClNO2 (404.0); calc.: C 71.35, H 8.48, N 3.47; found: C 71.29, H 8.48,
N 3.52.
Methyl-(4ꢀ)-13-(1-methylethyl)-15-oxo-17,19-dinoratis-13-en-4-carboxylate (11)
A hot saturated solution of 2.8 g (50 mmol) KOH was added to a solution of 2.0 g (5.0 mmol) 10 in
EtOH. The mixture became brown and was re¯uxed for 25 h. After evaporation of the solvent, a
yellow oil was obtained. 10 ml ice-cold H2O was added, and the mixture was acidi®ed with 2 N
H2SO4 and extracted three times with Et2O. The combined organic phases were dried over Na2SO4,
and an ethereal diazomethane solution was added until a yellow colour persisted. After evaporation
and CC over silica (CH/AcOEt ˆ 9:1), 1.3 g 11 (71%) were obtained as yellow crystals. Further
puri®cation for characterization: sublimation at 100ꢀC/0.1 torr.
M.p.: 97±98ꢀC; Rf ˆ 0.27 (CH/AcOEt ˆ 9:1), 0.34 (CH/AcOEt ˆ 5:1); [ꢀ]2D0 ˆ ‡170.6 (c ˆ 0.05,
CHCl3); IR (KBr): ꢃ ˆ 2954 (s), 1720 (vs), 1466 (m), 1236 (s), 1101 (m) cmꢁ1, UV (MeOH):
ꢄ
max (lg ") ˆ 216 (3.394), 297 (2.491) nm; 1H NMR (CDCl3): ꢁ ˆ 0.70 (s, 3H, 20-H), 0.94 (m, 1H, 1-
Hax), 0.99 (d, J ˆ 6.8 Hz, 3H, 18-H/19-H), 1.00 (d, J ˆ 6.8 Hz, 3H, 19-H/18-H), 1.13 (s, 3H, 21-H),
1.17 (m, 1H, 6-Heq), 1.39 (m, 1H, 11-Hꢂ), 1.4±1.5 (m, 2H, 2-H), 1.45 (m, 1H, 1-Heq), 1.48 (m, 1H, 6-
Hax), 1.49 (m, 1H, 3-Heq), 1.53 (m, 1 H, 9-H), 1.66 (m, 1H, 5-H), 1.68 (m, 1 H, 3-Hax), 1.69 (m, 1H,

Diels-Alder Reactions of Abietic Acid
305
7-Hax), 1.72 (m, 1H, 11-Hꢀ), 1.91 (m, 1H, 7-Heq), 1.94 (dt, J ˆ 18.1 Hz, J ˆ 3.1 Hz, J11ꢂ,16ꢂ ˆ 3.1 Hz,
1H, 16-Hꢂ), 2.01 (dd, J ˆ 18.1 Hz, J ˆ 2.1 Hz, 1H, 16-Hꢀ), 2.33 (sept, J ˆ 6.8 Hz, J14;7 ˆ 1.3 Hz, 1H,
17-H), 2.80 (m, 1H, 12-H), 3.62 (s, 3H, 23-H), 5.26 (d, J ˆ 0.7 Hz, 1H, 14-H) ppm; 13C NMR
(CDCl3): ꢁ ˆ 15.8 (q, C-20), 16.8 (q, C-21), 17.1 (t, C-2), 20.0 (q, C-18/C-19), 20.1 (q, C-19/C-18),
21.2 (t, C-6), 27.7 (t, C-11), 28.5 (t, C-7), 32.8 (d, C-17), 34.0 (d, C-12), 36.6 (t, C-3), 38.2 (s, C-10)
38.5 (t, C-1), 40.4 (t, C-16), 47.2 (s, C-4), 48.9 (d, C-5), 49.5 (d, C-9), 51.9 (q, C-23), 52.2 (s, C-8),
120.6 (d, C-14), 152.7 (s, C-13), 179.0 (s, C-22), 212.9 (s, C-15) ppm; MS (70 eV): m/z (%) ˆ 358
‡
(27) [M ], 316 (100), 299 (55), 239 (54), 187 (13), 146 (92), 121 (68), 91 (72), 41 (42); C22H34O3
(358.5); calc.: C 77.05, H 9.56; found: C 77.06, H 9.57.
(3aR-(3aꢀ,3bꢂ,5aꢀ,6ꢀ,9aꢂ,9bꢀ,11ꢂ,11aꢀ))-3a-Cyano-6, 9a-dimethyl-12-(1-methylethyl)-
3a,3b,4,5,5a,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-3b,11-etheno-1H-phenanthro-
[1,2-c]pyrazol (13)
To a solution of 910 mg (2.25 mmol) 10 in 18 ml dry oxygen free DMSO under Ar, a hot saturated
solution of 630 mg (11.2 mmol) KOH in H2O was added and this mixture was stirred at 50ꢀC for
10 h. After cooling, 20 ml ice-cold H2O and 2 N H2SO4 were added and the mixture was extracted
three times with Et2O. The combined organic phases were washed with brine, dried over Na2SO4,
and an ethereal solution of diazomethane was added until a yellow colour persisted. After
evaporation of the solvent and CC over silica (CH/AcOEt ˆ 9:1), 90 mg 10, 320 mg 11, and 200 mg
(22%) 13 were obtained.
13: White crystals, m.p.: 126ꢀC (decomp); Rf ˆ 0.15 (CH/AcOEt ˆ 9:1), 0.21 (CH/AcOEt ˆ 5:1);
[ꢀ]2D0 ˆ ‡87.7 (c ˆ 0.1, CHCl3); IR (KBr): ꢃ ˆ 2944 (s), 2230 (w), 1721 (vs), 1562 (m), 1448 (m),
1238 (s), 1193 (m) cmꢁ1; UV (MeOH): ꢄmax (lg ") ˆ 203 (3.714), 325 (2.209) nm; 1H NMR (CDCl3):
ꢁ ˆ 0.53 (s, 3H, 20-H), 0.92 (d, J ˆ 6.8 Hz, 3H, 18-H/19-H), 0.93 (d, J ˆ 6.8 Hz, 3H, 19-H/18-H),
1.00 (m, 1H, 1-Hax), 1.10 (m, 1H, 11-Hꢂ), 1.11 (s, 3H, 21-H), 1.23 (m, 1H, 6-Heq), 1.3±1.5 (m, 2H,
2-H), 1.34 (m, 1H, 1-Heq), 1.47 (m, 1H, 3-Heq), 1.53 (m, 1H, 6-Hax), 1.59 (m, 1H, 11-Hꢀ), 1.78 (m,
1H, 3-Hax), 1.90 (m, 1H, 9-H), 2.11 (sept, J ˆ 6.8 Hz, J14;11 ˆ 1.2 Hz, 1H, 17-H), 2.3±2.5 (m, 2H,
7-H), 2.37 (m, 1H, 16-H), 2.50 (br s, 1H, 12-H), 3.63 (s, 3H, 25-H), 4.19 (dd, J ˆ 18.9 Hz, J ˆ 3.6 Hz,
1H, 24-Hꢂ), 4.52 (dd, J ˆ 18.9 Hz, J ˆ 9.3 Hz, 1H, 24-Hꢀ), 5.09 (br s, 1H, 14-H) ppm; 13C NMR
(CDCl3): ꢁ ˆ 15.9 (q, C-20), 16.7 (q, C-21), 16.9 (t, C-2), 19.7 (q, C-18/C-19), 20.6 (q, C-19/C-18),
21.3 (t, C-6), 26.6 (d, C-11), 32.9 (d, C-7), 33.5 (d, C-17), 36.4 (t, C-3), 36.8 (d, C-12), 37.6 (s,
C-10), 37.7 (t, C-1), 42.5 (d, C-16), 44.0 (s, C-8), 46.9 (s, C-4), 48.66 (d, C-5), 48.73 (d, C-9), 51.9
(q, C-25), 84.0 (t, C-24), 98.4 (s, C-15), 118.0 (s, C-23), 123.2 (d, C-14), 148.1 (s, C-13), 178.7 (s,
‡
C-22) ppm; MS (FD): m/z (%) ˆ 381 (100) [(M ± N2) ], 316 (4); C25H35N3O2 (409.6); calc.:
C 73.30, H 8.61, N 10.26; found: C 73.27, H 8.61, N 10.30.
Methyl-(4ꢀ,8ꢀ,12ꢀ,13R,14S)-14-cyano-16-(1-methylethyl)-13,14-methano-17,19-dinoratis-
15-en-4-carboxylate (14) and Methyl-(1R-(1ꢀ,2ꢂ,3ꢀ))-2-(2-(2-cyano-3-methyl-5-
(1-methylethyl))-phenyl)-ethyl)-1,3-dimethyl-3-vinyl-1-cyclohexanecarboxylate (16)
110 mg (0.27 mmol) 13 were heated under medium vac. (ca. 25 torr) to 140ꢀC for 2 h. CC over silica
(CH/AcOEt ˆ 9:1) gave 52 mg (50%) 14 as white crystals.
M.p.: 144±145ꢀC; Rf ˆ 0.22 (CH/AcOEt ˆ 9:1); [ꢀ]D20 ˆ ‡100.8 (c ˆ 0.1, CHCl3); IR (KBr):
ꢃ ˆ 2946 (s), 2225 (m), 1727 (vs), 1464 (m), 1243 (s), 1158 (m) cmꢁ1; UV (MeOH): ꢄmax
(lg ") ˆ 204 (3.671) nm; 1H NMR (CDCl3): ꢁ ˆ 0.54 (s, 3H, 20-H), 0.68 (m, 2H, 24-H), 0.93 (d, J ˆ
6.8 Hz, 6H, 18-H, 19-H), 0.98 (m, 1H, 1-Hax), 1.10 (m, 1H, 6-Heq), 1.10 (m, 1H, 11-Hꢂ), 1.10 (s, 3H,
21-H), 1.3±1.5 (m, 2H, 2-H), 1.34 (m, 1H, 1-Heq), 1.45 (m, 1H, 3-Heq), 1.49 (m, 1H, 6-Hax), 1.55 (m,
1H, 16-H), 1.62 (m, 1H, 11-Hꢀ), 1.69 (m, 1H, 9-H), 1.7±2.0 (m, 2H, 7-H), 1.72 (m, 1H, 3-Hax), 1.80

306
E. Haslinger and D. Hofner
(m, 1H, 5-H), 2.16 (sept, J ˆ 6.8 Hz, J14;17 ˆ 1.2 Hz, 1H, 17-H), 2.71 (br s, 1H, 12-H), 3.63 (s, 3H,
25-H), 5.01 (br s, 1H, 14-H) ppm; 13C NMR (CDCl3): ꢁ ˆ 11.7 (t, C-24), 15.9 (s, C-15), 16.4 (q,
C-20), 16.8 (q, C-21), 17.1 (t, C-2), 20.0 (q, C-18/C-19), 20.2 (q, C-19/C-18), 21.7 (t, C-6), 22.0 (d,
C-16), 27.2 (t, C-11), 32.2 (d, C-17), 33.1 (d, C-12), 33.8 (t, C-7), 36.5 (t, C-3), 37.6 (s, C-10), 38.1
(t, C-1), 39.6 (s, C-8), 47.2 (s, C-4), 48.9 (d, C-5), 51.9 (q, C-25), 52.1 (d, C-9), 121.4 (d, C-14),
‡
123.4 (s, C-23), 144.3 (s, C-13), 179.0 (s, C-22) ppm; MS (70 eV): m/z (%) ˆ 381 (100) [M ], 321
(48), 306 (29), 171 (51), 81 (44), 55 (51), 41 (66); C25H35NO2 (381.6); calc.: C 78.69, H 9.25, N
3.67; found: C 78.52, H 9.30, N 3.59.
16: 40 mg (39%); colourless oil; Rf ˆ 0.42 (CH/AcOEt); [ꢀ]2D0 ˆ ꢁ11.4 (c ˆ 0.1, CHCl3); IR
(neat): ꢃ ˆ 2960 (s), 2218 (m), 1727 (vs), 1606 (m), 1459 (m), 1258 (s), 1245 (s) cmꢁ1 ; UV (MeOH):
1
ꢄmax (Ig ") ˆ 249 (3.452), 279 (3.229), 288 (3.268) nm; H NMR (CDCl3): ꢁ ˆ 1.03 (s, 3H, 20-H),
1.21 (d, J ˆ 6.9 Hz, 6H, 18-H, 19-H), 1.26 (s, 3H, 21-H), 1.35 (m, 1H, 1-Heq), 1.43 (m, 1H, 6-H),
1.45 (m, 1H, 1-Hax), 1.5±1.6 (m, 2H, 2-H), 1.51 (m, 1H, 3-Heq), 1.59 (m, 1H, 6-H), 1.80 (m, 1H, 3-
Hax), 2.03 (dd, J ˆ 5.7 Hz, J ˆ 4.6 Hz, 1H, 5-H), 2.47 (s, 3H, 24-H), 2.60 (m, 2ÂJ ˆ 11.9±13.3 Hz,
J ˆ 5.4 Hz, 1 H, 7-H), 2.69 (m, 2ÂJ ˆ 11.9±13.3 Hz, J ˆ 5.4 Hz, 1H, 7-H), 2.84 (sept, J ˆ 6.9 Hz, 1H,
17-H), 3.69 (s, 3H, 25-H), 4.94 (dd, J ˆ 17.5 Hz, J ˆ 0.9 Hz, 1 H, 8-Htrans), 4.96 (dd, J ˆ 10.8 Hz,
J ˆ 0.9 Hz, 1 H, 8-Hcis), 5.72 (dd, J ˆ 17.5 Hz, J ˆ 10.8 Hz, 1H, 9-H), 6.86 (s, 1H, 12-H), 6.94 (s, 1H,
14-H) ppm; 13C NMR (CDCl3): ꢁ ˆ 17.9 (t, C-2), 18.7 (q, C-21), 19.4 (q, C-20), 20.8 (q, C-24),23.51
(q, C-18/C-19), 23.46 (q, C-19/C-18), 29.8 (t, C-6), 35.5 (d, C-17), 35.5 (t, C-7), 36.4 (t, C-3), 38.0
(t, C-1), 40.6 (s, C-10), 46.6 (s, C-4), 47.5 (d, C-5), 51.9 (q, C-25), 110.0 (s, C-15), 111.2 (t, C-8),
117.4 (s, C-23), 124.8 (d, C-12), 125.6 (d, C-14), 142.1 (s, C-16), 147.2 (s, C-11), 150.2 (d, C-9),
‡
153.6 (s, C-13), 179.1 (s, C-22) ppm; MS (70 eV): m/z (%) ˆ 381 (100) [M ], 321 (30), 172 (29),
136 (28), 81 (37), 41 (33); C25H35NO2 (381.6); calc.: C 78.69, H 9.25, N 3.67; found: C 78.50, H
9.22, N 3.55.
Methyl-(4ꢀ,15Z)-15-hydroximino-13-(1-methylethyl)-17,19-dinoratis-13-en-4-carboxylate (17)
To a solution of 310 mg (0.86 mmol) 11 in 15 ml EtOH, a conc. aqueous solution of 310 mg
(4.5 mmol) H2NOH Á HCl and 390 mg solid NaOH were added. This mixture was re¯uxed for 7 h.
After cooling it was diluted with 20 ml ice-cold water, acidi®ed with 2 N H2SO4, and extracted three
times with Et2O. The combined organic phases were dried over Na2SO4, and a solution of
diazomethane in ether was added. Evaporation and CC over silica with CH/AcOEt (2:1) afforded
colourless crystals.
Yield: 310 mg 17 (92%); m.p.: 73±75ꢀC; Rf ˆ 0.45 (CH/AcOEt ˆ 2:1); [ꢀ]2D0 ˆ ‡74.5 (c ˆ 0.1,
CHCl3); IR (KBr): ꢃ ˆ 3283 (m), 2928 (s), 1728 (vs), 1460 (m), 1258 (s), 1076 (m) cmꢁ1; UV
1
(MeOH): ꢄmax (lg ") ˆ 205 (3.901) nm; H NMR (CDCl3): ꢁ ˆ 0.64 (s, 3H, 20-H), 0.89 (m, 1H,
1-Hax), 0.98 (d, J ˆ 6.8 Hz, 3H, 18-H/19-H), 0.99 (d, J ˆ 6.8 Hz, 3H, 19-H/18-H), 1.13 (s, 3H, 21-H),
1.17 (m, 1H, 6-Heq), 1.25 (m, 1 H, 11-Hꢂ), 1.35±1.55 (m, 2H, 2-H), 1.40 (m, 1H, 1-Heq), 1.48 (m,
1H, 3-Heq), 1.50 (m, 1H, 6-Hax), 1.54 (m, 1 H, 9-H), 1.62 (ddd, J ˆ 12.8 Hz, J ˆ 10.0 Hz, J ˆ 2.4 Hz,
1H, 11-Hꢀ), 1.69 (m, 1 H, 3-Hax), 1.69 (m, 1H, 5-H), 1.83 (dt, J ˆ 13.5 Hz, 2ÂJ ˆ 3.2 Hz, 1H, 7-Heq),
1.94 (td, 2ÂJ ˆ 13.5 Hz, J ˆ 4.6 Hz, 1H, 7-Hax), 2.13 (dt, J ˆ 17.8 Hz, J ˆ 3.2 Hz, J11ꢂ;16ꢂ ˆ 3.2 Hz,
1H, 16-Hꢂ), 2.26 (dd, J ˆ 17.8 Hz, J ˆ 2.3 Hz, 1H, 16-Hꢀ), 2.30 (sept, J ˆ 6.8 Hz, J14;11 ˆ 1.2 Hz, 1H,
17-H), 2.74 (br s, 1H, 12-H), 3.63 (s, 3H, 23-H), 5.35 (br s, 1H, 14-H), 8.45 (br s, 1H, NOH) ppm;
13C NMR (CDCl3): ꢁ ˆ 16.0 (q, C-20), 16.8 (q, C-21), 17.0 (t, C-2), 20.2 (q, C18/C-19), 20.3 (q, C-
19/C-18), 21.5 (t, C-6), 27,7 (t, C-11), 30.3 (t, C-7), 31.8 (t, C-16), 32.7 (d, C-17), 33.2 (d, C-12),
36.6 (t, C-3), 38.0 (s, C-10), 38.2 (t, C-1), 44.0 (s, C-8), 47.3 (s, C-4), 49.3 (d, C-5), 51.8 (d, C-9),
51.9 (q, C-23), 122.5 (d, C-14), 151.5 (s, C-13), 166.5 (s, C-15), 179.2 (s, C-22) ppm; MS (70 eV):
‡
m/z (%) ˆ 373 (100) [M ], 356 (69), 330 (42), 296 (77), 181 (52), 139 (70), 121 (93), 43 (41);
C23H35NO3 (373.5); calc.: C 73.96, H 9.44, N 3.75; found: C 73.92, H 9.50 N 3.73.

Diels-Alder Reactions of Abietic Acid
307
Methyl-(1R-(1ꢀ,4aꢂ,4bꢀ,6ꢀ))-6-(cyanomethyl)-1,4a-dimethyl-7-(1-methylethyl)-
1,2,3,4,4a,4b,5,6,10,10a-decahydro-1-phenanthrene-carboxylate (18)
A mixture of 160 mg (0.43 mmol) 17 and 210 mg (1.10 mmol) TsCl in 8 ml abs. pyridine was stirred
under Ar for 3 days, diluted with 30 ml H2O, and extracted three times with Et2O. The combined
organic phases were washed with 2 N H2SO4, NaHCO3, and H2O, dried over Na2SO4, and
evaporated. The crude product was air sensitive and puri®ed by prep. TLC under Ar (CH/
AcOEt ˆ 3:1).
Yield: 160 mg 18 (85%); colourless air sensitive oil; Rf ˆ 0.53 (CH/AcOEt ˆ 3:1); IR (KBr):
ꢃ ˆ 2950 (s), 2245 (w), 1726 (vs), 1432 (m), 1246 (s), 1148 (m) cmꢁ1; 1H NMR (CDCl3): ꢁ ˆ 0.81 (s,
3H, 20-H), 1.01 (d, J ˆ 6.9 Hz, 3H, 16-H/17-H), 1.05 (d, J ˆ 6.9 Hz, 3H, 17-H/16-H), 1.17 (m, 1H,
1-Hax), 1.24 (s, 3H, 19-H), 1.42 (m, 1H, 11-Hax), 1.5±1.6 (m, 2H, 2-H), 1.62 (m, 1H, 3-Heq), 1.76
(m, 1H, 3-Hax), 1.80 (m, 1 H, 6-Heq), 1.87 (m, 1H, 1-Heq), 1.95 (m, 1H, 11-Heq), 2.06 (m, 1H, 9-H),
2.06 (m, 1H, 6-Hax), 2.07 (m, 1H, 5-H), 2.19 (sept, J ˆ 6.9 Hz, 1H, 16-H), 2.32 (dd, J ˆ 17.0 Hz,
J ˆ 10.8 Hz, 1H, 21-H), 2.50 (ddd, J ˆ 17.0 Hz, J ˆ 4.4 Hz, J11ax;21 ˆ 0.7 Hz, 21-H), 2.62 (m, 1H,
12-H), 3.63 (s, 3H, 23-H), 5.45 (m, 1H, 7-H), 5.82 (br s, 1H, 14-H) ppm; 13C NMR (CDCl3):
ꢁ ˆ 13.9 (q, C-20), 16.9 (q, C-19), 18.0 (t, C-2), 21.2 (t, C-21), 21.4 (q, C-16/C-17), 22.8 (q, C-17/C-
16), 25.9 (t, C-6), 26.4 (t, C-11), 32.5 (d, C-15), 34.3 (s, C-10), 34.5 (d, C-12), 37.2 (t, C-3), 38.1 (t,
C-1), 44.6 (d, C-9), 45.4 (d, C-5), 46.6 (s, C-4), 51.8 (q, C-23), 118.8 (s, C-22), 123.6 (d, C-7), 124.7
(d, C-14), 133.9 (s, C-8), 144.2 (s, C-13), 178.7 (s, C-18) ppm; MS (FD): m/z (%) ˆ 403 (1)
‡
‡
‡
‡
[(M‡48) ], 387 (3) [(M‡32) ], 371 (23) [(M‡16) ], 355 (100) [M ]; C23H33NO2 (355.5).
Acknowledgements
This work was supported by Krems Chemie AG, Krems a. d. Donau, Austria. We are grateful to Dr.
E. Prantz and Dr. W. Streicher (Krems Chemie) for stimulating discussions, to Dr. G. Schmidtberg
(University of Ulm) for recording the mass spectra, and to Mrs. M. Lang (University of Ulm) for the
elementary analyses.
References
Â
[1] Barendrecht W, Lees LJ, Hercules BV (1972) In: Bertholome E, Biekert E, Hellmann H,
È
Ley H (eds) Ullmanns Ezyklopadie der technischen Chemie, 4th edn, vol 12. Verlag Chemie,
Weinheim, p 525
[2] Sandermann W (1941) Chem Ber 74: 154
È
[3] Sandermann W, Hohn R (1943) Chem Ber 76: 1257
[4] Langlois N, Gastambide B (1965) Bull Soc Chim Fr 2966
[5] Zalkow LH, Brannon DR (1964) J Org Chem 29: 1296
[6] Ayer WA, McDonnald CE (1965) Can J Chem 43: 1429
[7] Halbrook NJ, Lawrence RV (1958) J Am Chem Soc 80: 368
[8] Evans DA, Scott WL, Truesdale LK (1972) Tetrahedron Lett 121
[9] Freeman PK, Balls DM, Brown DJ (1968) J Org Chem 33: 2211
[10] Corey EJ, Weinshenker NM, Schaaf TK, Huber W (1969) J Am Chem Soc 91: 5675
[11] Brown ED, Lilley TJ (1975) J Chem Soc Chem Commun 39
[12] Goering, HL, Chang C-S (1975) J Org Chem 40: 2565
[13] Brown ED, Clarkson R, Leeney TJ, Robinson GE (1974) J Chem Soc Chem Commun 642
[14] Corey EJ, Koelliker U, Neuffer J (1971) J Am Chem Soc 93: 1489
[15] van Auken TV, Rinehart KL (1962) J Am Chem Soc 84: 3736
È
[16] von Auwers K, Konig F (1932) Liebigs Ann Chem 496: 252
[17] Wendisch D (1971) In: Methoden der organischen Chemie (Houben-Weyl), Bd 413. Thieme,
Stuttgart, p 45

308
E. Haslinger and D. Hofner: Diels-Alder Reactions of Abietic Acid
[18] Metzger H (1968) In: Methoden der organischen Chemie (Houben-Weyl), 4. Au¯., Bd 1014.
Thieme, Stuttgart, p 60
[19] Tsuda K, Hayatsu R (1956) J Am Chem Soc 78: 4107
[20] Grieco PA, Flynn DL, Zelle RE (1984) J Am Chem Soc 106: 6414
[21] Paquette LA, Varadarajan A, Bay E (1984) J Am Chem Soc 106: 6702
[22] Tietze L-F, Eicher Th (1981) Reaktionen und Synthesen im org.-chem. Praktikum. Thieme,
Stuttgart, p 123
[23] Imamoto T, Yokoyama H, Yokoyama M (1981) Tetrahedron Lett 22: 1803
[24] Ruzicka L, Ankersmit PJ, Frank B (1932) Helv Chim Acta 15: 1285
Received October 8, 1997. Accepted October 14, 1997