Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives

Article abstract of DOI:10.1002/open.201500187

A selective synthesis of 7-or 14-nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α-hydroxy-15,16-dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(trifluoromethyl)aniline yield the subsequent 7α-, 7β-and 14αnitrogen-containing diterpenoids. The reaction with 2-nitroaniline, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenylsulfamide, or tert-butyl carbamate proceeds with the formation of 7α-nitrogen-substituted diterpenoids as the main products.

Full text of DOI:10.1002/open.201500187

DOI: 10.1002/open.201500187
Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic
Amination Reaction of Isopimaric Acid Derivatives**
Mariya A. Timoshenko,[a, b] Yurii V. Kharitonov,[a, b] Makhmut M. Shakirov,[a]
Irina Yu. Bagryanskaya,[a, b] and Elvira E. Shults*[a, b]
A selective synthesis of 7- or 14-nitrogen containing tricyclic di-
terpenoids was completed according to a strategy in which
the key step was the catalyzed direct allylic amination of
methyl 14a-hydroxy-15,16-dihydroisopimarate with a wide va-
riety of nitrogenated nucleophiles. It was revealed that the se-
lectivity of the reaction depends on the nature of nucleophile.
The catalyzed reaction of the mentioned diterpenoid allylic al-
cohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(tri-
fluoromethyl)aniline yield the subsequent 7a-, 7b- and 14a-
nitrogen-containing diterpenoids. The reaction with 2-nitroani-
line, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenyl-
sulfamide, or tert-butyl carbamate proceeds with the formation
of 7a-nitrogen-substituted diterpenoids as the main products.
Introduction
Isopimaric acid (1) (Figure 1) is a widely available tricyclic diter-
penoid well represented in the resin of conifers of the genera
Pinus, Larix, and Picea.[1] It exhibits interesting biological and
pharmaceutical properties such as antimicrobial,[2] antiviral,[3]
antiallergenic,[4] and anti-inflammatory[5] activities. Renewed in-
terest in this natural compound started with the discovery of
pimaranes belonging to a class of potent potassium-channel
(BK channel) openers.[6] Openers of these channels have
emerged as potentially useful agents in the therapy of various
diseases associated with both the central nervous system and
smooth muscle system, such as acute stroke, epilepsy, psycho-
ses, erectile dysfunction, arterial hypertension, asthma, and
bladder hyperactivity. As primary regulators of neuronal excita-
bility, potassium (K+) channels have been a major research
focus in drug discovery and development.[7] Thus, there is now
significant interest in the preparation of isopimaric acid deriva-
tives to possibly enhance or alter its biological activity. Oxida-
tive[8,9] and isomeric[10] transformations of 1 in addition to sev-
eral modifications of the carboxyl group[11,12] have already
been described. Accordingly, in light of new isopimaranes con-
taining a nitrogen substituent in the diterpenoid core, we
became interested in the targeted preparation of isopimaric
acid derivatives through allylic amination reaction of its acces-
sible derivatives.
Figure 1. Substrate scope.
The substitution reaction of allylic alcohols with diverse nu-
cleophiles has become an extremely useful tool for the con-
struction of carbonÀheteroatom bonds. The direct use of allylic
alcohols as substrates, with the hydroxy group as the leaving
group and water as the only side product, allows this to be
a green reaction with good atom economy.[13] In order to acti-
vate the hydroxy functionality as a leaving group, Brønsted
acids such as phosphotungstic acid,[14] calix[4]resorcinarene sul-
fonic acid,[15] or triflic acid[16] and Lewis acids such as transition
metal complexes or salts from FeIII,[16] BiIII,[17] MoVI,[18] AgI,[19]
AuIII,[20] and AuI[19,21] have been used as catalysts. Gold catalysts
have recently gained much attention in organic transforma-
tions. Reactions catalyzed by gold generally proceed under
mild conditions without exclusion of water and oxygen. Both
AuIII and AuI salts have already been shown to activate allylic
alcohols under mild conditions.
[a] M. A. Timoshenko, Y. V. Kharitonov, M. M. Shakirov, I. Y. Bagryanskaya,
E. E. Shults
Laboratory of Medicinal Chemistry, Novosibirsk Institute of Organic Chemis-
try, Siberian Branch, Russian Academy of Sciences, Lavrentyev Avenue, 9
630090 Novosibirsk (Russia)
E-mail: schults@nioch.nsc.ru
[b] M. A. Timoshenko, Y. V. Kharitonov, I. Y. Bagryanskaya, E. E. Shults
Chemical and Physical Departments, Novosibirsk State University
Pirogova St. 2, 630090 Novosibirsk (Russia)
[**] This article is part of the Virtual Issue “Nature-Inspired Organic Chemistry”
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/open.201500187. Included: 13C NMR data of
the synthesized compounds (Tables S1–S4), X-ray crystal data (Tables S5,
1
S6), and copies of H NMR and 13C NMR spectra.
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons
Attribution-NonCommercial License, which permits use, distribution and
reproduction in any medium, provided the original work is properly
cited and is not used for commercial purposes.
In this paper we present a comparative study about the al-
lylic amination reaction of methyl 14a-hydroxy-15,16-dihydro-
isopimarate (2)[9] with different nitrogenated compounds (sub-
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stituted anilines, benzenesulfonamide, tert-butyl carbamate)
sults are summarized in Table 2. The completion of the reac-
tion was increased to 92%, and the amination products 12, 13,
and 15 compose an over yield of 85% with 6 mol% catalyst
loading (Table 2, Entries 1 and 2). The yield of compound 15—
the product of allylic amination of allylic alcohol 14—was also
increased. Exactly the same % conversion was obtained when
the reaction was conducted with the catalytic system com-
posed of 2% AuCl3À6% AgOTf (Table 2, Entry 3). However, the
reaction was more selective for the formation of 7a-(3-nitroani-
lino)-substituted diterpenoid (the ratio of 12:13 was changed
from 4.7:1 to 6.4:1). In the case
using gold catalysts.
Results and Discussion
The reaction between methyl 14a-hydroxy-15,16-dihydroisopi-
marate (2) and 2-nitroaniline (3) was studied using AuCl3,
.
TsOH, or BF3 Et2O at room temperature in acetonitrile
(Scheme 1, Table 1). The first experiment was carried out with
2 mol% of AuCl3 as catalyst giving the expected product 4 in
of employing the mentioned
catalyst
in
nitromethane,
a
better % conversion and
higher isolated yield of the ami-
nation product (overall yield of
91%) than in acetonitrile was
obtained (Table 2, Entry 4). We
were pleased to find that the 7-
hydroxydihydrosandaracopimaric
acid derivative 14 in this case
was not formed.
Scheme 1. Amination of methyl 14a-hydroxy-15,16-dihydroisopimarate (2) with 2-nitroaniline (3). Reagents and
conditions: a) catalyst, CH3CN, rt, 24 h. Catalysts and yields are given in Table 1
AgOTf-catalyzed direct amina-
tion of primary alcohols was
previously described by Shree-
dar et al.[22] In the presence of
this active catalyst, compound 2
reacted with aniline 9 with the
formation of the amination
products with an overall yield of
68%. The amination reaction of
alcohol 2 was considerably pro-
Table 1. Direct amination of dihydroisopimarate 2 with 2-nitroaniline (3).
Yield [%]
Entry
Catalyst
Compound 4
Compound 5
Compound 6
Compound 7
1
2
3
AuCl3
TsOH
BF3 OEt2
90
24
–
2
24
28
–
2
6
–
8
23
.
90% yield (Table 1, entry 1). When TsOH was used as catalyst,
even with 10 mol% loading, only 24% of the compound 4 was
obtained. Additionally, diterpenoid dienes 5, 6, and methyl 7-
(4-amino-3-nitrophenyl)-15,16-dihydrosandaracopimarate
(7)
.
were isolated. In the case of employing of BF3 Et2O as catalyst
(10 mol%), the amination product formation was not ob-
served; only dienes 5 and 6 and the product of electrophilic
substitution reaction, 7, were obtained.
We further explored the reactivity of 2 with 4- and 3-nitro-
substituted anilines 8 and 9 under the conditions mentioned
above (Table 1, Entry 1). We found that the interaction of allylic
alcohol 2 with anilines 8 and 9 under the AuCl3 catalyst was
not so effective compared with 3. In the reaction of 2 with 4-
nitroaniline (8), amination products at the C(7) (compound 10,
74% yield) and C(14) position (compound 11, 19% yield) were
isolated (Scheme 2).
Scheme 2. AuCl3-catalyzed amination of compound 2 with 4-nitroaniline (8).
Reagents and conditions: a) AuCl3 (2 mol%), CH3CN, rt, 24 h, 10: 74%, 11:
19%.
moted also by the addition of AgBF4 (Table 2, Entry 6), while
using AgBF4 only resulted in lower reactivity; moreover, a differ-
ent selectivity of the formation of 7a- and 7b-compounds 12
and 13 (ratio 6.4:1 and 8.5:1) was observed as a function of
the used Ag-salt catalyst (Table 2, Entries 5 and 6). Several ex-
amples of stereoselective direct amination reaction of alcohols
were described by using AuI-salt catalysts.[19] We found that in
the considered reaction with PPh3AuCl, the catalyst was inac-
tive, but by employing PPh3AuCl/AgBF4 or PPh3AuCl/AgOTf
catalysts, the amination reaction proceeded with moderate
yield and conversion of allylic alcohol 2 (Table 2, Entry 7,8). In-
creasing of the AgOTf content in the catalytic system provided
Amination of alcohol 2 with 3-nitroaniline (9) in the pres-
ence of 2 mol% of catalyst proceeds smoothly to give the de-
sired product 12 only in 24% yield. The 7b-(3-nitroanilino)-
15,16-dihydrosandaracopimarate (13), the allylic alcohol 14,
and 14a-(3-nitroanilino)-15,16-dihydroisopimarate (15) were
also isolated. The over-all conversion of this reaction was only
at 76% (Scheme 3, Table 2, Entry 1). A further search for more
effective catalysts of this reaction was conducted, and some re-
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the conversion of compound 2.
Ph3PAuOTf, generated in situ
from Ph3PAuCl and AgOTf, was
found to be the best catalyst for
the direct amination reaction of
methyl 14-hydroxy-15,16-dihy-
droisopimarate (2). The best
condition involved the use of
a 1:3 mixture of AuI complex
and AgOTf (Table 2, Entry 9), but
the stereoselectivity of forma-
tion of 7a-(3-nitroanilino)-substi-
tuted derivative 12 (ratio 12/13
of 4.5:1) was lower than with
the use of the AuCl3ÀAgOTf cat-
alyst (Entries 3,4).
Table 2. Catalyzed amination of isopimarate 2 with 3-nitroaniline (9).
Entry
Catalyst (concentration)
[mol%]
Yield [%][a]
13
Conversion
[%]
12
14
15
1
2
3
4[b]
5
6
7
8
9
AuCl3 (2)
AuCl3 (6)
AuCl3 (2)ÀAgOTf (6)
AuCl3 (2)ÀAgOTf (6)
AgOTf (6)
24
52
51
63
45
34
38
32
41
6
11
8
9
7
4
8
5
9
14
5
9
0
13
8
14
15
6
13
22
18
19
16
12
15
12
16
76
92
92
100
87
62
77
80
96
AgBF4 (4)
[PPh3AuCl] (2)ÀAgBF4(4)
[PPh3AuCl] (2)ÀAgOTf(2)
[PPh3AuCl] (2)ÀAgOTf(6)
[a] Isolated yields. [b] Reaction was performed in CH3NO2.
With the optimized conditions
in hand (2 mol% AuCl3À6 mol%
AgOTf in either nitromethane or
acetonitrile), we then extended
the scope to various amines by
amination of compound 2 with
anilines 16–21 in this catalytic
system (Scheme 4, Table 3). The
results revealed that all the de-
sired 7a-anilino-15,16-dihydro-
sandaracopimaric acid deriva-
tives 22–27 could be obtained
in high yields (48–81%). We
found that the reaction of 2
with 2-bromoaniline 16 in
CH3NO2 proceeds with the for-
mation of a mixture of amina-
tion reaction product 22 and
electrophilic substitution reac-
tion products 28 and 29
(Table 3, entry 1). Using acetoni-
trile as a solution gave the pos-
sibility to exclude the reaction
of electrophilic substitution. Al-
lylic amination in this case pro-
ceeds with lower selectivity;
amination products 22, 30, and
31, were isolated with yields of
39, 19, and 16% accordingly.
Additionally, compound 14 and
dienes 5 and 6 were also isolat-
ed. The allylic amination reac-
tion of 2 with anilines 17, 18,
and 20 with a strong electron-
withdrawing group in o- or p-
position to the amino group
was performed in acetonitrile;
by using nitromethane as a solu-
tion, dienes 5 and (or) 6 were
obtained as the main products.
Reactions of 2 with o-,p-disubsti-
Scheme 3. Optimization of reaction conditions. Reagents and conditions: a) catalyst, CH3CN, rt, 24 h. Catalysts, sol-
vents, and yields are given in Table 2
Scheme 4. Reaction of alcohol 2 with anilines catalyzed by AuCl3ÀAgOTf. Reagents and conditions: a) AuCl3–
AgOTf, solvent, rt, 24 h; b) AuCl3ÀAgOTf, CH3NO2, rt, 24 h. Solvents and yields are given in Table 3
Table 3. Direct allylic amination of alcohol 2 with anilines catalyzed by AuCl3ÀAgOTf.
Entry
Aniline
Solvent
Isolated compounds (yield) [%]
1
2
3
4
5
6
7
16
16
17
18
19
20
21
CH3NO2
CH3CN
CH3CN
CH3CN
CH3NO2
CH3CN
CH3NO2
22 (53); 28 (10); 29 (6)
22 (39); 30 (19); 31 (16); 14 (13); 5 (2); 6 (1)
23 (52); 6 (14)
24 (81); 5 (5); 6 (3)
25 (48); 32 (20); 33 (13); 5 (2); 6 (2)
26 (70); 34 (14); 35 (7); 14 (6)
27 (67); 36 (11)
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tuted nitroanilines 17 or 18 in acetonitrile proceed selectively
with the formation of 7a-anilinosubstituted derivatives 23 and
24, respectively (Table 3, Entries 3 and 4); compound 17 dis-
played lower reactivity in the amination reaction.
By the reaction of compound 2 with 3-substituted aniline 19
in nitromethane, amination products 25, 32, and 33 were ob-
tained with the overall yield of 81%; however, the reaction
proceeded with lower selectivity (Table 3, Entry 5). The p-sub-
stituted anilines 20 and 21 afforded the desired amination
products 26, 34, and 35, or 27 and 36, respectively, in good
overall yields (Entries 6 and 7).
Scheme 6. Reaction of alcohol 2 with benzenesulfonamide (41). Reagents
and conditions: a) 2% AuCl3À6% AgOTf, CH3CN, rt, 24 h, 42: 41%, 5/6: 18%
(2:1 ratio).
In light of the results obtained from the optimization of re-
action parameters, we decided to further explore the reaction
of allylic alcohol 2 using different nitrogenated nucleophiles.
Compound 2 was submitted to the direct amination with the
more basic N-methyl-4-nitroaniline (37) (Scheme 5). On the
contrary, this reaction in acetonitrile gave rise to the corre-
sponding 7b-amination product 38 (18% yield). Besides dienes
5 (31% yield) and 6 (3% yield), a biditerpenoid derivative 39
Scheme 7. Reaction of alcohol 2 with tert-butyl carbamate (43). Reagents
and conditions: a) 2% AuCl3À6% AgOTf, CH3NO2, rt, 24 h, 65%; b) HCl,
MeOH, 90%.
Above mentioned experi-
ments of the reaction of 14a-hy-
droxydihydroisopimarate 2 with
anilines 3, 8, 9, 16–21, 37, ben-
zenesulfonamide (41), and tert-
butyl carbamate (43) under the
gold catalysts proceeded due to
a carbocation intermediate in-
volved in the process. In addi-
tion to direct allylic amination
reaction, the skeletal transforma-
tion of the diterpenoid 2, as
well as reactions with CÀH and
OÀH nucleophiles, were per-
formed. Furthermore, the key
tricyclic carbocation might be
Scheme 5. Amination of alcohol 2 with N-methyl-4-nitroaniline (37). Reagents and conditions: a) 2% AuCl3À
6%AgOTf, CH3CN, rt, 24 h, 38: 18%, 39: 15%, 5: 31%, 6: 3% ; b) 2% AuCl3À6% AgOTf, CH3NO2, rt, 24 h, 10/40
(1:1 ratio): 46%, 5: 38%.
generated in several isomeric
forms (by thermodynamic and
sterical access) prior to the ami-
nation reaction, because the a-
(15% yield) was isolated. Quite interestingly, the reaction of
compound 39 with 4-nitroaniline (8) in nitrometane proceeds
with the formation of two amination products at the C(7) posi-
tion—compounds 10 and 40 (ratio, 1:1; 46% yield), apart from
the diene 5 (38% yield) (Scheme 5).
The reaction of allylic alcohol 2 with benzenesulfonamide
(41) was also taken into account (Scheme 6). Firstly, the diter-
penoid allylic benzenesulfonamide 42 was obtained in 41%
yield when acetonitrile was used as the solvent. In addition,
dienes 5 and 6 were isolated in 18% yield in approximately
a 2:1 ratio. When the reaction was performed in nitromethane,
diene 5 was obtained as the main product.
and b-amination products could be formed. Moreover, a rear-
rangement of the allylic alcohol catalyzed by a Lewis acid
could also have an obvious impact on this reaction. In order to
confirm this, allylic alcohol 2 was allowed to react under reac-
tion conditions identical to those described above (Table 2, En-
tries 1 and 4) in the presence of AuCl3 in acetonitrile or AuCl3À
AgOTf in nitromethane, and without any nucleophile
(Scheme 8). Under AuCl3 action in acetonitrile, the main trans-
formations of 2 included the rearrangement into 14 and the
formation of the diterpenoid ether 39 (64% conversion). By
Reaction of alcohol 2 with tert-butyl carbamate 43 in nitro-
methane proceeded with the formation of compound 44 as
the only isolable product (65% yield) (Scheme 7). Acidic hy-
drolysis of 44 smoothly led to the methyl 7a-amino-15,16-dihy-
drosandaracopimarate (45).
Scheme 8. Transformations of alcohol 2 in the reaction conditions.
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the action of AuCl3ÀAgOTf in CH3NO2, compound 2 was trans-
formed into isopimara-6(7),8(14)-diene and isopimara-
5
Scheme 9. Reaction of alcohol 14 with with 3-nitroaniline (9). Reagents and
6(7),8(9)-diene 6. Interestingly, in these conditions, com-
pound 6 was stable and was not isomerized.
conditions: a) 2% AuCl3À6% AgOTf, CH3CN, rt, 24 h, 12: 51%, 13: 15%, 15:
7%.
Finally, and with the aim of gaining more knowledge about
the amination reaction of the diterpenoid 2, the allylic alcohol
14 was also made to undergo a direct allylic amination reac-
tion using 3-nitroaniline (9) as a nucleophile under the opti-
mized reaction conditions (Table 2, Entry 3). After the reaction
time, compounds 12, 13, and 15 were obtained in the 51, 15,
and 7% yields, respectively (Scheme 9). The same trend in
product formation was observed in the amination of allylic al-
cohol 2 (Table 2, Entry 3). These results point out that the
mechanism for this reaction is probably through a nucleophilic
SN1-type process.
27, and 36 were established by X-ray structure analysis. The re-
fined molecules are shown in Figure 2. The X-ray data of com-
pounds and selected hydrogen bond parameters for com-
pounds 24 and 27 are presented in Tables S5 and S6, respec-
tively, in the Supporting Information.
The bond lengths and bond angles are the same as the stat-
istical values.23 An envelope-like conformation of the cyclohex-
ene ring C5–C10 of 5 could be characterized by the C10 atom
deviation from the plane of the rest of the atoms, which was
equal to 0.762(2) (the standard deviation from the mean plane
was 0.018 Š). The other cyclohexene ring of 5 had a half-chair
conformation: C11 and C12 atoms deviated from C9ÀC8=C14À
C13 fragment plane by À0.441(4) and 0.290(4) Š, respectively
(with standard deviations of 0.002 Š). An envelope-like confor-
mation of the cyclohexene rings of 24 and 27 could be charac-
terized by C12-atom deviation from the rest of the atomic
plane, equal to 0.649(3) Š for 24 and 0.646(5) Š for 27 (stan-
dard deviations of 0.015 Š for 24 and 0.030 Š for 27). The cy-
The composition and structure of the synthesized com-
pounds were confirmed by infrared (IR) and UV/Vis spectrosco-
1
py, H and 13C NMR, mass spectrometry (MS), and X-ray data
1
for compounds 5, 24, 27, and 36. The H and 13C NMR spectra
of all synthesized compounds agreed with their structures and
contained one set of characteristic signals for the tricyclic diter-
penoid core and the corresponding substituents. The 13C NMR
spectra are given in Tables S1–S4 in the Supporting Informa-
tion. The configuration of the
substituent at C7 of the synthe-
sized dihydrosandaracopimaric
acid derivatives was unequivo-
cally established from 1H NMR
data. The H7 proton in the
1H NMR spectra of the 7a-substi-
tuted derivatives 4, 7, 10, 12,
22–27, 28, 29, 42, 44, and 45
appeared as a doublet of dou-
blets (dd), broad doublet, or
broad singlet at 3.39–4.16 ppm,
indicating the axial disposition
of the substituent. The H7
proton in the spectra of com-
pounds 13, 31, 33, 35, 38, and
40 appeared as a dd with Jax-ax
of 12.2–11.9 Hz and Jax-eq of
2.3–3.0 Hz, indicating the equa-
torial disposition of the aniline
substituent. The signals for
atom H14 in dihydroisopimaric
acid derivatives 11, 15, 30, 32,
34, and 36 are found in the
range of 3.43–3.57 ppm. The rel-
ative configuration of the sub-
stituent at the C14 position was
confirmed by Nuclear Overhaus-
er Effect spectroscopy (NOESY)
spectral data (NOE appeared for
H14 and C17-methyl signals; no
NOE-effect was observed be-
tween H14 and H9 protons). The
structures of compounds 5, 24,
Figure 2. Structures of molecules 5, 24, 27, and 36 in the crystals.
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clohexene rings of two crystalographically independent mole-
cules of 36 had a half-chair conformation: for one molecule,
C5 and C10 atoms deviated from the C9ÀC8=C14ÀC13 frag-
ment plane by À0.520(5) and 0.329(5) Š, respectively (with
standard deviations of 0.015 Š). For the other molecule, the C5
and C10 atoms deviated from the C9ÀC8=C14ÀC13 fragment
plane by À0.394(4) and 0.420(4) Š, respectively (with standard
deviations of 0.009 Š).
The crystal structure of 24 was stabilised by a large number
of CÀH···O1 and CÀH···O2 short intermolecular contacts and
the N1ÀH···O3 hydrogen bond. In addition to the H-bond, the
C3ÀH···p interaction with the phenyl ring were observed,
showing an atom-to-centroid distance of 2.65 Š. The crystal
structure of 27 was stabilised by the many CÀH···O2, CÀH···O3,
and CÀH···O5 short intermolecular contacts. Atoms N1 and N2
were are not involved in the intermolecular interactions be-
cause of the very short intramolecular N1···N2 and N1···O3 con-
tacts. The two crystalographically independent molecules of 36
formed dimers by N1ÀH···O2 and N1ÀH···O3 hydrogen bonds.
In addition to the H-bond, the crystal structure of 36 was stabi-
lized by CÀH···O1 short intermolecular contact. Interestingly,
there weren’t any short intermolecular contacts in the crystal
structure of 5, but, in turn, the O1 and O2 atoms were engag-
ed in the CÀH···O intramolecular interactions (Table S6 in the
Supporting Information).
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We have demonstrated that the gold-catalyzed amination of
methyl 14a-hydroxy-15,16-dihydroisopimarate with substituted
anilines, benzenesulfonamide, or tert-butyl carbamate produ-
ces good to excellent yields of nitrogen-containing tricyclic di-
terpenoids, which are extremely useful synthetic intermediates
in the construction of biologically important compounds. The
stereochemical result of the reaction is dependent on the
nature of the nucleophile.
Experimental Section
The experimental details for each compound, including the full
1
chemical names, physical characteristics, and 13C NMR, H NMR, IR,
UV/Vis, and MS data are available in the Supporting Information.
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Acknowledgements
This work was supported in part by the Russian Science Founda-
tion (Grant No. 14-13-00822) and the Russian Foundation for
Basic Research (Project 15-03-06546).
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Keywords: allylic amination reaction · diterpenoids · gold
catalysis · pimaranes · stereoselectivity
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Received: September 9, 2015
Published online on October 28, 2015
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