Iodoalkene-based approach towards carboxamides of biological importance: aminocarbonylation of 2-iodobornene and 3-iodo-2- quinuclidene

Article abstract of DOI:10.2174/157017810790534048

The palladium-catalysed aminocarbonylation of 2-iodobornene and 3-iodo-2-quinuclidene, possessing iodo alkene functionality, resulted in the high-yielding synthesis of the corresponding carboxamide derivatives. The substrates were synthesised from camphor and 3-quinuclidone, respectively, via their hydrazones. The chemoselective homogeneous carbonylation reaction of synthetic value was carried out under mild reaction conditions. While the carbonylation of the 2- iodobornene was found to be a facile reaction with yields of synthetic interest, its isomer, 1-iodocamphene, formed in Wagner-Meervein rearrangement, remained intact under the same reaction conditions.

Full text of DOI:10.2174/157017810790534048

54
Letters in Organic Chemistry, 2010, 7, 54-60
Iodoalkene-Based Approach Towards Carboxamides of Biological
Importance: Aminocarbonylation of 2-Iodobornene and 3-Iodo-2-
quinuclidene
László Horváth, Andrea Petz and László Kollár*
Department of Inorganic Chemistry, University of Pécs, Hungary
Received May 22, 2009: Revised November 06, 2009: Accepted November 10, 2009
Abstract: The palladium-catalysed aminocarbonylation of 2-iodobornene and 3-iodo-2-quinuclidene, possessing iodo
alkene functionality, resulted in the high-yielding synthesis of the corresponding carboxamide derivatives. The substrates
were synthesised from camphor and 3-quinuclidone, respectively, via their hydrazones. The chemoselective homogeneous
carbonylation reaction of synthetic value was carried out under mild reaction conditions. While the carbonylation of the 2-
iodobornene was found to be a facile reaction with yields of synthetic interest, its isomer, 1-iodocamphene, formed in
Wagner-Meervein rearrangement, remained intact under the same reaction conditions.
Keywords: Iodoalkenes, aminocarbonylation, carbon monoxide, palladium, camphor, quinuclidene.
INTRODUCTION
to novel quinine and quinidine derivatives [9]. The oxidative
cyclization of a quinuclidine-3-carbonitrile derivative in the
presence of palladium acetate precursor resulted in novel
tetracyclic compounds [10]. The application of quinuclidine
[11] and especially its chiral Cinchona alkaloid derivatives in
asymmetric catalysis has been known for a long time [12].
Palladium-catalysed carbonylation reactions, carried out
in the presence of various nucleophiles like amines and
alcohols, belong to the most widely used homogeneous
catalytic reactions in synthetic chemistry [1]. There are a
number of applications concerning the synthesis of simple
building blocks and the functionalization of biologically
important skeletons [2]. Aminocarbonylation plays a special
role among these reactions, since those carboxamides which
are difficult to prepare via the conventional carboxylic
acid—carboxylic halide—carboxamide route (e.g. with
bulky substituents at the amide nitrogen) can be synthesised
from easily available starting materials [3]. In addition to the
enol-triflates and aryl triflates, the corresponding iodo
analogues, iodoalkenes and iodoaromatics have been used
for aminocarbonylation reaction. The homogeneous catalytic
synthesis of unsaturated carboxamides or aryl carboxamides
with various structures has been published also in our group
[4,5].
The easy availability of the starting parent ketones
(camphor, 1 and quinuclidone, 6) prompted us to investigate
their homogeneous catalytic functionalization reactions. As
derivatives of major interest, carboxamides were the target
compounds. In this paper, the palladium-catalysed
aminocarbonylation of the corresponding iodoalkenes was
carried out.
RESULTS AND DISCUSSION
Synthesis of 2-iodobornene (3) and 3-iodo-2-quinuclidene
(8)
The above two iodoalkenes have been synthesised by
using the conventional ketoneꢀhydrazoneꢀiodoalkene route
[13,14]. Since several modifications were done concerning
the experimental details, full description of the procedure
and characterization is given in the Experimental. The
ketones, (±)-camphor (1) and 3-quinuclidone (6) were
transferred to the corresponding hydrazones, 2 and 7,
respectively. Their reaction with iodine, in the presence of
TMG (N,N,N’,N’-tetramethylguanidine) furnished the two
iodoalkenes, 3 and 8, with the expected structure (Figs. (1,
2)). However, the reaction of 2 resulted in a further iodo-
isomer, 4 via Wagner-Merwein rearrangement. The two
isomers (3 and 4), formed in ca. 30/70 ratio, were separated
by repeated column chromatography.
In spite of the importance of the functionalization of a
bornene skeleton, to the best of our knowledge, a single
example for the use of 2-iodobornene is known. Behaving
both as reagent and substrate in Heck self-condensation, 2-
iodobornene was dimerized with a formal elimination of an
iodine molecule [6].
More homogeneous catalytic reactions are known for the
synthesis of quinuclidine derivatives. A palladium-catalysed
domino reaction was developed for the synthesis of
neosarpagine and other quinuclidine-related alkaloids [7]. 3-
Vinyl-quinuclidine was synthesised in an intramolecular
palladium-mediated allylic alkylation [8]. Cross-coupling
reactions (Heck and Sonogashira reactions) provide access
Aminocarbonylation of 3 and 8
*Address correspondence to this author at the Department of Inorganic
Chemistry, University of Pécs and MTA-PTE Research Group for Chemical
Sensors, H-7624 Pécs, Ifjúság u. 6.; Hungary; Tel: 0036-72-503600; Fax:
0036-72-501527; E-mail: kollar@ttk.pte.hu
The two iodoalkenes, 3 and 8, were reacted with tert-
butylamine (a), aniline (b), piperidine (c), morpholine (d),
1570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

Bornene and Quinuclidene Carboxamides
Letters in Organic Chemistry, 2010, Vol. 7, No. 1
55
Fig. (1). The synthesis of camphor-based ‘iodovinyl’ substrates 3 (and 4) and their aminocarbonylation.
methyl glycinate (e), methyl alaninate (f), methyl
phenylalaninate (g), methyl prolinate (h) and methyl valinate
(i) under atmospheric carbon monoxide in the presence of in
situ generated palladium(0)-triphenylphosphine catalysts
(Figs. 1, 2)). Palladium(II) acetate was used as catalytic
precursor and reduced to highly active low-ligated Pd(0)
complexes as described previously in detail [15,16]. The
phosphine ligand, PPh3 was added in twofold excess to
palladium. One of the two phosphine ligands is oxidized to
the corresponding phosphine oxide while Pd(II) was reduced
to Pd(0). The other PPh3 is coordinated to Pd(0) resulting in
coordinatively unsaturated reactive catalytic species.
The corresponding carboxamides (5a-h and 9a-i) were
formed with high chemoselectivity and isolated in moderate
to good yields except for 5b (Table 1). The low reactivity of
the less basic arylamine (b) in carbonylation reactions was
detected also earlier [17]. It is worth noting that even no
traces of 2-ketocarboxamides, due to double carbon
monoxide insertion, was detected when the catalytic
mixtures were analysed by GC-MS.
The ‘iodo-allyl’ isomer, 4, containing a tertiary iodide
fragment, did not show any reactivity under the same
reaction conditions. Thus, even if the mixture of the two
isomers, 3 and 4 were used in carbonylations, the latter
compound remained unreacted during even more severe
o
reaction conditions (40 bar, 50 C). Similarly, no reaction
was
observed
also
by
using
dppf
(1,1’-
bis(diphenylphosphino)ferrocene) instead of PPh3. In this
way, the separation of 4 from the carboxamides (5a-h),
obtained in complete aminocarbonylation of 3, proved to be
a facile step. As its synthetic consequence, the isolation of 3
prior to aminocarbonylation is not necessary.
The formation of the amide products 5a-h can be
rationalized on the basis of a simplified reaction mechanism
(Fig. (3)). The oxidative addition of the substrate (3) to
palladium(0) complexes (PdLn, where
L stands for
triphenylphosphine and solvent donor ligands), formed in
situ from palladium(II)-acetate and triphenylphosphine,
resulted in the corresponding iodo-palladium-alkenyl
intermediate (A). Carbon monoxide is coordinated to Pd(II)
as terminal carbonyl ligand (B), which is inserted into the
palladium-alkenyl bond resulting in the corresponding
palladium-acyl complex (C). The latter compound acts as a
highly reactive acylating agent of the amines. From the other
side, the reaction of C with the amine nucleophile furnishes
the amide products (5) and the hydrido-iodo-palladium-
complex. The latter compound undergoes reductive
Fig. (2). The synthesis of 3-iodo-2-quinuclidene 8 and its
aminocarbonylation.

56 Letters in Organic Chemistry, 2010, Vol. 7, No. 1
Horváth et al.
Table 1. Aminocarbonylation of Iodoalkenes 3 and 8 with Various Aminesa
Entry
Substrate
Amine
Isolated Yieldc (Amide) [%]
1
2
3
3
3
3
3
3
3
8
8
8
8
8
8
8
8
t-BuNH2b (a)
anilineb (b)
78 (5a)
53 (5b)
80 (5d)
77 (5e)
85 (5f)
83 (5g)
74 (5h)
80 (9a)
84 (9c)
85 (9d)
76 (9e)
81 (9f)
79 (9g)
72 (9h)
77 (9i)
3
morpholineb (d)
GlyOMe (e)
AlaOMe (f)
PheOMe (g)
ProOMe (h)
t-BuNH2b (a)
piperidineb (c)
morpholineb (d)
GlyOMe (e)
AlaOMe (f)
PheOMe (g)
ProOMe (h)
ValOMe (i)
4
5
6
7
8
9
10
11
12
13
14
15
aReaction conditions: 0.025 mmol Pd(OAc)2; 0.05 mmol PPh3, 10 mL DMF; 0.5 mL Et3N; amine/substrate=1.1/1 (unless otherwise stated); reaction temperature: 50oC, conversions
were higher than 98% in all cases except for 5b (78%).
bamine/substrate=3/1.
cYields are based on the corresponding substrate (3 or 8).
elimination of HI on the influence of triethylamine resulting
in the ‘starting’ palladium(0) catalytic species.
reaction tolerates various N-nucleophiles such as simple
primary or secondary amines as well as amino acid methyl
esters. The results are rationalized in terms of
a
homogeneous catalytic reaction which takes into account the
intermediacy of Pd(0)-Pd(II) catalytically active species.
EXPERIMENTAL
General Procedures
1H and 13C NMR spectra were recorded in CDCl3 on a
Varian Inova 400 spectrometer at 400.13 MHz and 100.62
MHz, respectively. Chemical shifts ꢀ are reported in ppm
relative to CHCl3 (7.26 and 77.00 ppm for 1H and 13C,
respectively). Elemental analyses were measured on a 1108
Carlo Erba apparatus. Samples of the catalytic reactions were
analysed with an Agilent 6890N GC-5975 MSD system
fitted with a capillary column HP-1-MS.
(±)-Camphor, 1 and 3-quinuclidone hydrochloride, 6, as
well as the amines including amino acid esters were
purchased from Aldrich and were used as obtained.
Substrates 3 and 8 were synthesised in a two-step synthesis
13,
according to modified conventional synthetic procedures
14
Fig. (3). The simplified reaction mechanism for the formation of
amides 5a-h.
by using the corresponding keto derivatives (1 and 6,
respectively) as starting material. Due to several differences
related to the original procedure the preparations of the
iodoalkene substrates are detailed below.
CONCLUSIONS
Novel carboxamido-camphene and -quinuclidene
derivatives were synthesised in moderate to high isolated
yields, respectively. Iodoalkenes, easily available from the
corresponding natural ketone derivatives, were used as
substrates for the palladium-catalysed functionalization. The
Synthesis of 2-iodobornene (3)
(±)-Camphor (1) (30.4 g, 0.2 mol), freshly distilled
hydrazine hydrate (98%, 40 g, 0.8 mol) and acetic acid (12.0
g, 0.2 mol) in absolute ethanol (300 mL) were heated for 17

Bornene and Quinuclidene Carboxamides
Letters in Organic Chemistry, 2010, Vol. 7, No. 1
57
hours under reflux. After completion of the reaction, ethanol
and acetic acid were distilled off. The residue was distilled
by using a condenser warmed continuously with water
(90oC). The row hydrazone (2) obtained by this method was
used in the next step without further purification.
NaHCO3 (20 mL), brine (20 mL), dried over Na2SO4 and
concentrated to a yellow waxy material or a thick oil.
Chromatography (silica, EtOAc/CHCl3 or EtOAc/CH2Cl2,
for exact eluent composition see Characterization) yielded
the desired carboxamides (5a-h).
To a stirred solution of 1,1,3,3-tetramethylguanidine
(TMG, 6.1 mL, 47.9 mmol) and camphor hydrazone (2) (2.3
g, 13.7 mmol) in diethyl ether (50 mL), the solution of iodine
(7.3 g, 60.8 mmol) in diethyl ether (60 mL) was added
dropwise between 0-15oC by using an ice-bath. After the
addition was complete, the mixture was stirred for 24 h.
Then the TMG-salt (TMG.HI) was filtered off and the etheral
solution was washed with 10% aqueous HCl (3x100 mL),
water (100 mL), saturated aqueous NaHCO3 (2x50 mL),
saturated aqueous Na2S2O3 (50 mL) and water (50 mL)
again. The oily liquid iodoalkene (3) was purified by column
chromatography (Silicagel 60, n-hexane) to yield a dark
yellow viscous material. It was used for carbonylation
experiments without further purification. Yield: 0.72 g; 20 %
(3); 1.40 g, 39% (4).
Aminocarbonylation of 8 Carried Out at Normal
Pressure
To carry out the catalytic carbonylation of 8, the
procedure described above was used. However, there were
some differences in the work-up procedure of the reaction
mixture. Thus, the residue obtained after evaporation was
dissolved in chloroform (20 mL), washed with water (20
mL) only, then purified by chromatography (silica,
EtOAc/CHCl3 1/1) yielding the desired carboxamides (9a-i).
Characterization of the Products
1
2-Iodo-7,7,1-trimethyl-bicyclo[2,2,1]-2-heptene (3): H-
NMR(CDCl3) ꢀ: 6.39 (d, 3.0 Hz, 1H, =CH); 2.35 (br s, 1H,
CH); 1.70-1.80 (m, 1H, CHaHb); 1.58-1.65 (m, 1H, CHaHb);
1.39-1.43 (m, 1H, CHaHb); 1.00-1.06 (m, 1H, CHaHb); 0.96
(s, 3H, CH3); 0.84 (s, 3H, CH3); 0.82 (s, 3H, CH3). 13C-NMR
(CDCl3)ꢀ: 143.0; 106.8; 58.0; 55.7; 54.7; 30.7; 25.2; 20.3;
19.5; 15.2. IR (KBr, (cm-1)): 1670 (ꢁ-C=C). MS m/z (rel.int.
%): 262 (100), 247 (43), 234 (9), 219 (9), 135 (39), 107 (67),
91 (70). Analysis calculated for C10H15I (262.13): C, 45.82;
H, 5.77; Found: C, 45.70; H, 5.51. Rf (EtOAc/CHCl3 1/1)
0.92; highly viscous orange material.
Synthesis of 3-iodo-2-quinuclidene (8)
3-Quinuclidone hydrochloride (6) (8.05 g, 0.05 mmol),
freshly distilled hydrazine hydrate (98%, 10 g, 0.2 mol) and
acetic acid (3.0 g, 0.05 mol) in absolute ethanol (100 mL)
were heated for 4 hours under reflux. Ethanol and acetic acid
were distilled off and the residue was evaporated to dryness.
The row product (2) obtained by this method was used in the
next step without further purification.
1-Iodo-3,3-dimethyl-2-methylene-bicyclo[2,2,1]-heptane
(4): H-NMR(CDCl3) ꢀ: 5.18 (s, 1H, =CHaHb); 4.81 (s, 1H,
To a stirred solution of 1,1,3,3-tetramethylguanidine
(TMG, 46.0 g, 0.4 mmol) and quinuclidone hydrazone (7)
(8.75 g, 0.05 mol) in diethyl ether (200 mL), the solution of
iodine (25.5 g, 0.11 mol) in diethyl ether (200 mL) was
added dropwise to let the ether boil. The TMG-salt
(TMG.HI) was filtered off and the residue was kept at 90-
95oC for 1.5 h. Iced water (200 mL) was added and extracted
with n-hexane (3x100 mL). The hexane solution was washed
with saturated aqueous Na2S2O3 (3x50 mL), saturated
aqueous NaHCO3 (3x50 mL), and water (100 mL). After the
evaporation of hexane, a brown crystalline material was
obtained that was used for carbonylation experiments
without further purification. Yield: 8.97 g; 76.2 %.
1
=CHaHb); 2.18-2.30 (m, 2H); 1.58-1.90 (m, 4H); 1.12 (s, 3H,
CH3); 1.08 (s, 3H, CH3); 0.80-0.85 (m, 1H). 13C-NMR
(CDCl3)ꢀ: 165.0; 105.6; 49.9; 46.3; 45.5; 43.0; 41.7; 29.9;
26.7; 26.2.166.7; 146.7; 136.7; 56.5; 54.4; 51.8; 51.0; 31.4;
29.0; 25.0; 19.4; 19.1; 11.6. IR (KBr, (cm-1)): 1670 (ꢁ-C=C).
MS m/z (rel.int. %): 262 (70), 247 (3), 219 (39), 135 (100),
107 (94), 93 (99), 91 (98). Analysis calculated for C10H15I
(262.13): C, 45.82; H, 5.77; Found: C, 45.75; H, 5.60. Rf
(EtOAc/CHCl3 1/1) 0.90; highly viscous orange material.
2-(N-tert-Butylcarboxamido)-7,7,1-trimethyl-
1
bicyclo[2,2,1]-2-heptene (5a): H-NMR(CDCl3) ꢀ: 6.24 (d,
3.2 Hz, 1H, =CH); 5.40 (br s, 1H, NH); 2.34 (br s, 1H, CH);
1.87 (m, 1H, CHaHb); 1.58 (m, 1H, CHaHb); 1.37 (s, 9H,
tBu); 1.26 (m, 1H, CHaHb); 1.20 (s, 3H, CH3); 1.00 (m, 1H,
CHaHb); 0.80 (s, 3H, CH3); 0.78 (s, 3H, CH3). 13C-NMR
(CDCl3)ꢀ: 166.7; 146.7; 136.7; 56.5; 54.4; 51.8; 51.0; 31.4;
29.0; 25.0; 19.4; 19.1; 11.6. IR (KBr, (cm-1)): 3304 (NH);
1638 (CON). MS m/z (rel.int. %): 235 (88), 220 (19), 179
(25), 164 (100), 162 (56), 135 (90). Analysis calculated for
C15H25NO (235.37): C, 75.55; H, 10.71; N, 5.95; Found: C,
75.40; H, 10.85; N, 5.79. Rf (CHCl3) 0.71; off-white solid,
m.p. 132-133oC.
Aminocarbonylation of 3 Carried Out at Normal
Pressure
In a typical experiment a solution of Pd(OAc)2 (5.6 mg,
0.025 mmol), PPh3 (13.1 mg, 0.05 mmol), 0.5 mmol
substrate (3) , 1.5 mmol tert-butylamine (or 0.55 mmol
further amines) were dissolved in 10 mL DMF under argon.
Triethylamine (1.0 mL) was added to the homogeneous
yellow solution and the atmosphere was changed to carbon
monoxide. The colour changed to dark red. The reaction was
conducted for 20 hours at 50oC. Some metallic palladium
was formed at the end of the reaction which was filtered. (A
sample of this solution was immediately analysed by GC-
MS.) The mixture was then concentrated and evaporated to
dryness. The residue was dissolved in chloroform (20 mL)
and washed with water (20 mL). The organic phase was
thoroughly washed twice with 5% HCl (20 mL), saturated
2-(N-Phenylcarboxamido)-7,7,1-trimethyl-bicyclo[2,2,1]-
2-heptene (5b): 1H-NMR(CDCl3) ꢀ: 7.54 (d, 8.0 Hz, 2H, Ph-
ortho); 7.35 (br s, 1H, NH); 7.30 (t, 8.0 Hz, 2H, Ph-meta);
7.07 (t, 8.0 Hz, 1H, Ph-para); 6.53 (d, 2.8 Hz, 1H, =CH);
2.43 (br s, 1H, CH); 1.95 (m, 1H, CHaHb); 1.63 (m, 1H,
CHaHb); 1.30 (m, 1H, CHaHb); 1.29 (s, 3H, CH3); 1.03 (m,

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Letters in Organic Chemistry, 2010, Vol. 7, No. 1
Horváth et al.
1H, CHaHb); 0.82 (s, 3H, CH3); 0.80 (s, 3H, CH3). 13C-NMR
(CDCl3)ꢀ: 164.7; 146.0; 139.2; 138.2; 129.0; 123.9; 119.6;
56.5; 54.8; 52.1; 31.3; 25.0; 19.4; 19.1; 11.6. IR (KBr, (cm-
1)): 3266 (NH); 1649 (CON). MS m/z (rel.int. %): 255 (48),
240 (8), 163 (100), 135 (45). Analysis calculated for
C17H21NO (255.36): C, 79.96; H, 8.29; N, 5.49; Found: C,
79.80; H, 8.44; N, 5.23. Rf (CHCl3) 0.69; off-white solid,
m.p. 150-151oC.
128.4; 127.0; 56.8/56.6; 54.3; 52.7/52.6; 51.9/51.8; 38.0;
31.3/31.4; 24.8/24.9; 19.4/19.3; 19.0/19.1; 11.7/11.6. IR
(KBr, (cm-1)): 1736 (COO); 1640 (CON); 1585 (C=C). MS
m/z (rel.int. %): 341 (30), 326 (3), 162 (100), 147 (38), 135
(36). Analysis calculated for C21H27NO3 (341.45): C, 73.87;
H, 7.97; N, 4.10; Found: C, 73.67; H, 8.04; N, 4.02. Rf
(CHCl3) 0.91; yellow waxy material.
2-(N,N-((1-Metoxycarbonyl)-pentan-1,4-diyl)-
2-(N,N-(3-oxa-penta-1,5-diyl)-carboxamido)-7,7,1-
trimethyl-bicyclo[2,2,1]-2-heptene (5d): 1H-NMR (CDCl3)
ꢀ: 5.98 (d, 3.3 Hz, 1H, =CH); 3.50-3.70 (m, 8H,
2xOCH2CH2); 2.42 (t, 3.3 Hz, 1H, CH); 1.85 (m, 1H,
CHaHb); 1.60 (m, 1H, CHaHb); 1.43 (m, 1H, CHaHb); 1.09 (s,
3H, CH3); 1.02 (m, 1H, CHaHb); 0.82 (s, 3H, CH3); 0.80 (s,
3H, CH3). 13C-NMR (CDCl3)ꢀ: 167.6; 142.7; 136.2; 67.1;
55.9; 55.6; 52.6; 47.0 (br); 42.1 (br); 31.8; 25.2; 19.6; 19.1;
11.1. IR (KBr, (cm-1)): 1632 (CON); 1582 (C=C). MS m/z
(rel.int. %): 249 (100), 234 (70), 220 (33), 163 (84), 162
(75), 135 (82). Analysis calculated for C15H23NO2 (249.35):
C, 72.25; H, 9.30; N, 5.62; Found: C, 72.07; H, 9.51; N,
5.40. Rf (CHCl3) 0.86; yellow waxy material.
carboxamido)-7,7,1-trimethyl-bicyclo[2,2,1]-2-heptene (5h):
1H-NMR(CDCl3) ꢀ: 6.22/6.10 (br s, 1H, =CH); 4.46 (m, 1H,
NHCH); 3.67 (s, 3H, OCH3); 3.50-3.65 (m, 2H, NCH2); 2.39
(br s, 1H, CH); 0.85-2.25 (m, 8H, 4xCH2); 1.05 (s, 3H, CH3);
0.81 (s, 3H, CH3); 0.79 (s, 3H, CH3). 13C-NMR (CDCl3)ꢀ:
171.8; 162.8; 144.1/143.9; 138.1/136.4; 58.6/57.3; 56.5;
55.2; 52.0; 48.7; 47.2; 31.5; 29.2; 25.4; 24.5; 19.8; 19.1;
11.2. IR (KBr, (cm-1)): 1733 (COO); 1660 (CON); 1582
(C=C). MS m/z (rel.int. %): 291 (42), 276 (14), 232 (13),
162 (100), 147 (36), 134 (44). Analysis calculated for
C17H25NO3 (291.39): C, 70.07; H, 8.65; N, 4.81; Found: C,
69.91; H, 8.69; N, 4.55. Rf (CHCl3) 0.71; yellow waxy
material.
1
2-(N-(Metoxycarbonylmethyl)-carboxamido)-7,7,1-
trimethyl-bicyclo[2,2,1]-2-heptene (5e): H-NMR(CDCl3) ꢀ:
3-Iodo-2-quinuclidene (8): H-NMR(CDCl3) ꢀ: 6.74 (br.
1
s, 1H, =CH); 2.78-2.88 (m, 2H, CH2); 2.70 (br. s, 1H, CH);
2.55-2.67 (m, 2H, CH2); 1.55-1.72 (m, 4H, 2xCH2). 13C-
NMR (CDCl3)ꢀ: 148.7; 101.0; 48.8 (double intensity); 40.2;
28.2 (double intensity). IR (KBr, (cm-1)): 1672 (ꢁ-C=C). MS
m/z (rel.int. %): 235 (12), 127 (3); 108 (100); 79 (10).
Analysis calculated for C7H10IN (235.07): C, 35.77; H, 4.29;
N, 5.96; Found: C, 35.52; H, 4.49; N, 5.84. Rf
(EtOAc/CHCl3 1/1) 0.43; bright yellow oily liquid (at RT),
pale yellow crystals (at -5 oC).
3-(N-tert-butylcarboxamido)-2-quinuclidene (9a): 1H-
NMR (CDCl3) ꢀ: 7.02 (br. s, 1H, =CH); 6.66 (br. s, 1H, NH);
3.12 (br. s, 1H, CH); 2.94-3.03 (m, 2H, CH2); 2.52-2.63 (m,
2H, CH2); 1.65-1.73 (m, 2H, CH2); 1.41-1.53 (m, 2H, CH2);
1.39 (s, 9H, tBu). 13C-NMR (CDCl3)ꢀ: 164.3; 144.7; 143.0;
51.4; 48.8 (double intensity); 28.9 (double intensity); 27.6;
26.6. IR (KBr, (cm-1)): 3314 (NH); 1639 (CON); 1602
(C=C). MS m/z (rel.int. %): 208 (100), 151 (80); 136 (73);
124 (44); 108 (65). Analysis calculated for C12H20N2O
(208.30): C, 69.19; H, 9.68; N, 13.45; Found: C, 69.02; H,
9.55; N, 13.28. Rf (EtOAc/CHCl3 1/1) 0.41; brown waxy
solid.
6.45 (d, 3.2 Hz, 1H, =CH); 6.23 (br s, 1H, NH); 3.90-4.05
(m, 2H, NCH2); 3.68 (s, 3H, OCH3); 2.35 (br s, 1H, CH);
1.92 (m, 1H, CHaHb); 1.55 (m, 1H, CHaHb); 1.20 (m, 1H,
CHaHb); 1.18 (s, 3H, CH3); 0.93 (m, 1H, CHaHb); 0.72 (s,
3H, CH3); 0.71 (s, 3H, CH3). 13C-NMR (CDCl3)ꢀ: 170.7;
166.7; 144.6; 139.5; 56.6; 54.4; 52.2; 51.9; 40.9; 31.3; 24.8;
19.3; 19.1; 11.6. IR (KBr, (cm-1)): 1756 (COO); 1645
(CON); 1583 (C=C). MS m/z (rel.int. %): 251 (11), 236 (4),
220 (3), 162 (100), 147 (62), 134 (46). Analysis calculated
for C14H21NO3 (251.33): C, 66.91; H, 8.42; N, 5.57; Found:
C, 66.80; H, 8.57; N, 5.32. Rf (CHCl3) 0.74; yellow solid,
m.p. 104-106oC.
2-(N-(1-Metoxycarbonylethyl)-carboxamido)-7,7,1-
1
trimethyl-bicyclo[2,2,1]-2-heptene (5f): H-NMR(CDCl3) ꢀ:
6.46/6.44 (d, 3.3 Hz, 1H, =CH); 6.18 (br s, 1H, NH); 4.62
(qi, 7.0 Hz, 1H, NHCH); 3.73/3.75 (s, 3H, OCH3); 2.40 (br s,
1H, CH); 1.90 (m, 1H, CHaHb); 1.60 (m, 1H, CHaHb);
1.40/1.42 (d, 7.2 Hz, 3H, CHCH3); 1.20 (m, 1H, CHaHb);
1.19/1.21 (s, 3H, CH3); 1.01 (m, 1H, CHaHb); 0.80/0.81 (s,
3H, CH3); 0.79/0.78 (s, 3H, CH3). 13C-NMR (CDCl3)ꢀ:
173.9; 166.1; 144.8; 139.3/139.2; 56.7; 54.4; 52.4; 51.9;
47.7/47.6; 31.4; 24.9; 19.4; 19.1; 18.8/18.7; 11.7. IR (KBr,
(cm-1)): 1743 (COO); 1655 (CON); 1581 (C=C). MS m/z
(rel.int. %): 265 (16), 250 (4), 162 (100), 147 (61), 134 (42).
Analysis calculated for C15H23NO3 (265.35): C, 67.90; H,
8.74; N, 5.28; Found: C, 67.77; H, 8.59; N, 5.02. Rf (CHCl3)
0.77; yellow waxy material.
3-(N,N-pentan-1,5-diylcarboxamido)-2-quinuclidene
(9c): H-NMR(CDCl3) ꢀ: 6.01 (br. s, 1H, =CH); 3.50 (br. s,
1
4H, NCH2); 2.92-3.03 (m, 2H, CH2); 2.87 (br. s, 1H, CH);
2.55-2.65 (m, 2H, CH2); 1.46-1.73 (m, 10H, 5xCH2) 13C-
NMR (CDCl3)ꢀ: 167.5; 142.9; 141.0; 48.8 (double
intensity); 48.0 (br); 43 (br); 40.9; 29.1 (double intensity);
28.0; 26.0 (br); 24.6. IR (KBr, (cm-1)): 1632 (CON), 1603
(C=C). MS m/z (rel.int. %): 220 (100), 191 (41); 178 (21);
164 (26); 151 (42); 136 (70); 108 (95). Analysis calculated
for C13H20N2O (220.31): C, 70.87; H, 9.15; N, 12.72; Found:
C, 70.72; H, 9.01; N, 12.50. Rf (EtOAc/CHCl3 1/1) 0.62;
brown waxy solid.
2-(N-(1-Metoxycarbonyl-2-phenyl-ethyl)-carboxamido)-
7,7,1-trimethyl-bicyclo[2,2,1]-2-heptene
(5g):
1H-
NMR(CDCl3) ꢀ: 7.20-7.30 (m, 3H, Ph-meta+Ph-para); 7.08
(d, 7.2 Hz, 2H, Ph-ortho); 6.42/6.35 (d, 3.3 Hz, 1H, =CH);
6.05 (br s, 1H, NH); 4.92 (m, 1H, NHCH); 3.73/3.72 (s, 3H,
OCH3); 3.08-3.22 (m, 2H, PhCH2); 2.37/2.39 (br s, 1H, CH);
1.88 (m, 1H, CHaHb); 1.59 (m, 1H, CHaHb); 1.22 (m, 1H,
CHaHb); 1.18 (s, 3H, CH3); 0.98 (m, 1H, CHaHb); 0.80 (s,
3H, CH3); 0.79 (s, 3H, CH3). 13C-NMR (CDCl3)ꢀ: 172.2;
166.0/165.9; 144.8/144.7; 139.6/139.4; 136.1/136.0; 129.4;
3-(N,N-(3-oxa-penta-1,5-diyl)-carboxamido)-2-
quinuclidene (9d): 1H-NMR(CDCl3)ꢀ: 6.62 (br. s, 1H,
=CH); 3.55-3.65 (two overlapping br. s, 8H, N(CH2CH2)2O);
2.90-3.03 (m, 2H, CH2); 2.87 (br. s, 1H, CH); 2.52-2.62 (m,

Bornene and Quinuclidene Carboxamides
Letters in Organic Chemistry, 2010, Vol. 7, No. 1
59
2H, CH2); 1.62-1.72 (m, 2H, CH2); 1.50-1.60 (m, 2H, CH2).
13C-NMR (CDCl3)ꢀ: 168.0; 143.8; 142.5; 67.1 (double
intensity); 49.0 (double intensity); 48.5 (br); 43.0 (br); 29.3;
28.5 (double intensity). IR (KBr, (cm-1)): 1630 (CON); 1604
(C=C). MS m/z (rel.int. %): 222 (100), 193 (14); 180 (5);
166 (3); 153 (6); 136 (81); 108 (74). Analysis calculated for
C12H18N2O2 (222.29): C, 64.84; H, 8.16; N, 12.60; Found: C,
64.70; H, 8.28; N, 12.36. Rf (EtOAc/CHCl3 1/1) 0.57; light
brown waxy solid.
3-(N-1-methoxycarbonyl-2-methyl-propyl-carboxamido)-
2-quinuclidene (9i): H-NMR(CDCl3) ꢀ: 7.12 (br. s, 1H,
1
=CH); 6.27 (br. d, 7.2 Hz, 1H, NH); 4.60 (m, 1H, CHCOO);
3.72 (s, 3H, OCH3); 3.40 (m, 1H, CH(CH3)2); 3.30-3.40 (m,
2H, CH2); 2.92-3.01 (m, 2H, CH2); 1.65-1.75 (m, 2H, CH2);
1.62-1.72 (m, 2H, CH2); 0.95 (d, 7.2Hz, 3H, CHCH3); 0.91
(d, 7.2Hz, 3H, CHCH3). IR (KBr, (cm-1)): 3305 (NH); 1741
(COO); 1630 (CON). MS m/z (rel.int. %): 266 (36), 207
(20); 152 (24); 136 (100); 108 (65). Analysis calculated for
C14H22N2O3 (266.34): C, 63.14; H, 8.33; N, 10.52; Found: C,
63.01; H, 8.50; N, 10.38. Rf (EtOAc/CHCl3 1/1) 0.50;
yellowish brown waxy solid.
3-(N-methoxycarbonylmethyl-carboxamido)-2-
1
quinuclidene (9e): H-NMR(CDCl3) ꢀ: 8.20 (br. t, 6.5 Hz,
1H, NH); 7.38 (br. s, 1H, =CH); 3.84 (d, 6.5 Hz, 1H,
CH2COO); 3.51 (s, 3H, OCH3); 3.47 (br s, 1H, CH); 3.30-
3.42 (m, 2H, CH2); 2.89-3.00 (m, 2H, CH2); 1.85-1.92 (m,
2H, CH2); 1.50-1.60 (m, 2H, CH2). 13C-NMR (CDCl3)ꢀ:
170.1; 163.1; 142.3; 133.2; 52.3; 50.1; 41.9; 41.2; 40.7; 26.4;
23.9. MS m/z (rel.int. %): 224 (100), 182 (10); 165 (16); 136
(50); 108 (86). IR (KBr, (cm-1)): 3314 (NH); 1740 (COO);
1673 (NCO). Analysis calculated for C11H16N2O3 (224.26):
C, 58.91; H, 7.19; N, 12.49; Found: C, 58.82; H, 7.11; N,
12.31. Rf (EtOAc/CHCl3 1/1) 0.45; yellow solid, m.p. 142-
144oC.
ACKNOWLEDGEMENT
The authors thank the Hungarian Research Fund (OTKA
NI61591, CK78553) and the Joint Project of the European
Union - Hungarian National Development Program (GVOP-
3.2.1-2004-04-0168/3) for the financial support and Johnson
Matthey for the generous gift of palladium(II) acetate.
REFERENCES
3-(N-1-methoxycarbonylethyl-carboxamido)-2-
quinuclidene (9f): H-NMR(CDCl3) ꢀ: 8.15 (br. s, 1H, NH);
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Skoda-Földes, R.; Kollár, L. Synthetic applications of palladium
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1
7.66 (br. s, 1H, =CH); 4.52 (qi, 1H, CHCH3); 3.66 (s, 3H,
OCH3); 3.47 (br s, 1H, CH); 3.30-3.42 (m, 2H, CH2); 2.92-
3.02 (m, 2H, CH2); 1.85-1.92 (m, 2H, CH2); 1.62-1.72 (m,
2H, CH2); 1.46 (d, 7.2Hz, 3H, CHCH3) 13C-NMR (CDCl3)ꢀ:
173.2; 162.8; 142.0; 135.1; 52.3; 49.3; 48.6; 45.9; 41.1; 26.1;
24.5; 17.4. IR (KBr, (cm-1)): 3311 (NH); 1741 (COO); 1670
(NCO). MS m/z (rel.int. %): 238 (100), 210 (10); 179 (24);
151 (30); 136 (98); 108 (84). Analysis calculated for
C12H18N2O3 (238.29): C, 60.49; H, 7.61; N, 11.76; Found: C,
60.33; H, 7.73; N, 11.48. Rf (EtOAc/CHCl3 1/1) 0.48; brown
waxy solid.
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3-(N-1-methoxycarbonyl-2-phenyl-ethyl-carboxamido)-
2-quinuclidene (9g): 1H-NMR(CDCl3) ꢀ: 8.01 (br. d, 6.0 Hz,
1H, NH); 7.01-7.18 (m, 6H, =CH+Ph); 4.62 (m, 1H,
CHCOO); 3.52 (s, 3H, OCH3); 3.28-3.35 (m, 2H, CH2); 3.24
(br. s, 1H, CH); 2.90-3.01 (m, 2H, CH2); 1.73-1.84 (m, 2H,
CH2); 1.42-1.51 (m, 2H, CH2). 13C-NMR (CDCl3)ꢀ: 171.9;
161.5; 142.0; 136.7; 134.7; 129.2; 128.3; 126.7; 54.2; 52.2;
49.3; 40.2 (double intensity); 37.2; 26.2; 24.2. IR (KBr, (cm-
1)): 3310 (NH); 1742 (COO); 1637 (CON). MS m/z (rel.int.
%): 314 (29), 255 (10); 152 (47); 136 (100); 108 (54).
Analysis calculated for C18H22N2O3 (314.38): C, 68.77; H,
7.05; N, 8.91; Found: C, 68.55; H, 7.25; N, 8.79. Rf
(EtOAc/CHCl3 1/1) 0.72; brown waxy solid.
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3.05-3.20 (m, 7H, CH+ NCH2 + 2xCH2); 1.70-2.25 (m, 8H,
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7.63; N, 10.60; Found: C, 63.50; H, 7.76; N, 10.37. Rf
(EtOAc/CHCl3 1/1) 0.52; yellowish red waxy solid.
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