Cyclopalladate complex of 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonane

Article abstract of DOI:10.1007/s11172-016-1610-x

A new (C,N,N)-pincer cyclopalladate unsymmetrical complex of 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonane (3-benzyl-7-methylbispidine) was synthesized and characterized. Catalytic performance of this complex was examined in the Heck and Suzuki reactions and in the norbornene hydroarylation.

Full text of DOI:10.1007/s11172-016-1610-x

Russian Chemical Bulletin, International Edition, Vol. 65, No.10, pp. 2479—2484, October, 2016
2479
Cyclopalladate complex of
3ꢀbenzylꢀ7ꢀmethylꢀ3,7ꢀdiazabicyclo[3.3.1]nonane
L. A. Bulygina, N. S. Khrushcheva, A. S. Peregudov, and V. I. Sokolov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: stemos@ineos.ac.ru
A new (C,N,N)ꢀpincer cyclopalladate unsymmetrical complex of 3ꢀbenzylꢀ7ꢀmethylꢀ3,7ꢀ
diazabicyclo[3.3.1]nonane (3ꢀbenzylꢀ7ꢀmethylbispidine) was synthesized and characterized.
Catalytic performance of this complex was examined in the Heck and Suzuki reactions and
in the norbornene hydroarylation.
Key words: bispidines, palladacycles, catalysts, Heck reaction, Suzuki reaction, hydroarylꢀ
ation, norbornene.
Since the synthesis of the first compound with the
3,7ꢀdiazabicyclo[3.3.1]nonane (bispidine) framework in
1930,1 these compounds, especially chiral, were actively
studied. In this field, two directions were particularly fruitꢀ
ful: the use in pharmacology and the use as the polydenꢀ
tate Nꢀligands for organometallic chemistry.2 Bispidines
similarly to their synthetic precursors bispidones are capaꢀ
ble of formation of stable coordination complexes with
transitions metals, for instance, with palladium.3 It was of
interest whether these bicyclic compounds can be applied
as the ligands for the synthesis of palladacycle complexes.
The aim of the present work is the study of the reacꢀ
tions of the 3,7ꢀdiazabicyclo[3.3.1]nonane derivative with
palladation agents and examination of the structures of
the synthesized products. First of all, it was necessary to
synthesize the model compound with an appropriate strucꢀ
ture. For cyclopalladation to occur, a suitable substituent
at one nitrogen atom is the benzyl group, while the nature
of the substituent at the second nitrogen atom is insignifiꢀ
cant. The reactions of such derivative with the palladation
agent can follow three directions.
The first direction is the formation of the coordination
complex with Pd, either intraꢀ (A) or intermolecular (A´).
The second route is the formation of dimeric (C,N)ꢀcyꢀ
clopalladate with chloride bridges (B). The third direction
is the formation of monomeric (C,N,N)ꢀcyclopalladate
with metal atom coordinated with two nitrogens, namely,
pincer unsymmetrical complex (C).
Furthermore, to study the cyclopalladation we syntheꢀ
sized another model compound with the 3ꢀazabiꢀ
cyclo[3.3.1]nonane skeleton, i.e., the bispidine analog with
only one nitrogen atom. This derivative is able to produce
only complexes of the D and E types.
ly, we intended to synthesize 3ꢀbenzylꢀ7ꢀmethylꢀ3,7ꢀ
diazabicyclo[3.3.1]nonane (1) (Scheme 1).
Numerous examples of monoꢀNꢀsubstituted bispidine
synthesis comprise a double Mannich reaction between
amine, ketone, and paraformaldehyde followed by the
carbonyl group reduction. These approaches can be diꢀ
vided into two groups. The first group includes the direct
syntheses; in these methods the substituents at the nitroꢀ
gen atoms are defined by the starting ketones and amines.
The second group consists of the synthetic methods toꢀ
wards bispidines with protecting groups at either one or
both nitrogen atoms, which could be further replaced by
the required substituents. Although the direct synthesis of
The methyl group was chosen as the substituent at the
second nitrogen atom in the model bispidine. Consequentꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2479—2484, October, 2016.
1066ꢀ5285/16/6510ꢀ2479 © 2016 Springer Science+Business Media, Inc.

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Bulygina et al.
Scheme 1
Scheme 2
Reagents and conditions: i. (CH2O)x, AcOH, MeOH, 60 °C;
ii. NH2NH2•H2O, KOH, diglyme, 140 °C; iii. 1) HCl, PriOH,
2) CH2O, NaBH(OAc)3, THF; iv. 1) Na2PdCl4, AcONa•3 H2O,
MeOH, 2) (AcO)2Pd, toluene, 3) Li2PdCl4, AcONa•3H2O,
MeOH.
Reagens and conditions: i. 1) Me3SiCl, 2) 5 M HCl, 100 °C;
ii. NH2NH2•H2O, KOH, diglyme, 140 °C; iii. 1) Na2PdCl4,
AcONa•3H2O, MeOH, 2) (AcO)2Pd, toluene or AcOH,
3) Li2PdCl4, AcONa•3H2O, MeOH.
Bispidine 1 was palladated (see Scheme 1) with either
lithium/sodium tetrachloropalladate in the presence of
sodium acetate or palladium acetate at heating in toluene.
Reactions with all palladation agents produce the same
palladacycle 6. Bispidine 1 reacts with sodium tetrachloꢀ
ropalladate in the presence of sodium acetate to give prodꢀ
uct 6 in 35% yield. Heating compound 1 with palladium
acetate in toluene followed by treatment with lithium chloꢀ
ride produces 6 in 51% yield. The highest isolated yield of
complex 6 equal to 80% was achieved by the reaction of 1
with lithium tetrachloropalladate and sodium acetate.
The presence of the C—Pd bond in the synthesized comꢀ
plex 6 was confirmed by the NMR spectroscopy.
In the 1H spectrum, the total integral intensity of aromatic
protons corresponds to the disubstituted phenyl ring and
the 13C NMR spectrum exhibits a new signal of a quaternaꢀ
ry C atom at δ 144.52. This chemical shift is in good agreeꢀ
ment with the known9 data for the C atom bonded to the
palladium atom. Moreover, cyclopalladation causes the corꢀ
compound 1 was reported,4 we decided to synthesize this
compound via intermediate 3ꢀbenzylꢀ7ꢀ(tertꢀbutyloxycarbꢀ
onyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]nonane (5). This route is
longer but yet has some advantages. First, in contrast to
bicycle 1 compound 5 as its precursor 3ꢀbenzylꢀ7ꢀ(tertꢀ
butyloxycarbonyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]nonaneꢀ9ꢀone
(4) can be easily purified by chromatography. Second,
compound 5 is a universal building block whose Bocꢀ
protecting group can be replaced not only with the methyl
group but also with other appropriate substituents. Ketone 4
is synthesized from NꢀBocꢀpiperidinꢀ4ꢀone (2), benzylꢀ
amine (3), and paraformaldehyde by the double Mannich
reaction and purified by silica gel chromatography (see
Scheme 1). Reduction of the carbonyl group of ketone 4
under Kishner—Wolff conditions5 produces NꢀBocꢀN´ꢀ
benzylbispidine 5. Replacement of the NꢀBoc group by
the Me group gives pure target compound 1.
The second model ligand, 3ꢀbenzylꢀ3ꢀazabiꢀ
cyclo[3.3.1]nonane (10), was synthesized as shown in
Scheme 2.
1
responding changes in the H NMR spectrum of the aroꢀ
matic ring from fiveꢀspin system of the phenyl group to the
fourꢀspin system characteristic of the orthoꢀdisubstituted
phenyl moiety. The C(12)H, C(13)H, and C(14)H protons
show upfield shift, while the C(15)H proton adjacent to the
metal atom shows the downfield shift (Scheme 3, Table 1).
Consequently, the signals of the C(12), C(13), and C(14)
atoms are shifted upfield and the signals of the C(11) and
C(15) atoms are shifted downfield. The C(16) atom bonded
to Pd experiences the greatest downfield shift. Similar
changes in the chemical shifts on going from the ligand to
complex were observed for other palladacycles.9a,c
Synthesis of cyclic ketone 9 from cyclohexanone (7),
benzylamine 3, and paraformaldehyde has been previousꢀ
ly described;6,7 however, product 9 was obtained in a
very low yield (7%)6 or its laborious isolation caused the
low yield.7 Only recently, chlorotrimethylsilaneꢀpromotꢀ
ed double Mannich annulation of ketones using N,Nꢀ
bisꢀ(methoxymethyl)benzylamine as an aminoalkylating
agent was elaborated.8 This procedure allowed synthesis
of 3ꢀbenzylꢀ3ꢀazabicyclo[3.3.1]nonaneꢀ9ꢀone (9) from 7
and 8 in 70% yield.

Palladacycle of 3ꢀbenzylꢀ7ꢀmethylbispidine
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 10, October, 2016
2481
Scheme 3
are somewhat larger (J = 5.2 Hz) than for the similar
couplings between antiꢀoriented protons C(2)H2,
C(4)H2 and C(1)H, C(5)H (J = 3.6 Hz). The signals of
the protons C(2)H2, C(4)H2 and C(6)H2, C(8)H2 syn
oriented to the protons C(1)H and C(5)H are slightly
broadened and resonate as a doublet with 2J(Ha,Hs) =
10.8 Hz. The C(9)H2 protons form the AB system with
2J(Ha,Hs) = 12 Hz.
In the case of complex 6, the spectral pattern showing
the diastereotopic CH2 groups is preserved. Note that the
geminal spinꢀspin coupling constants for the pairs of proꢀ
tons C(2)H2, C(4)H2 and C(6)H2, C(8)H2 increase slightly
(from 10.8 to 12.4 Hz) and the vicinal spinꢀspin coupling
constants decrease. On going from ligand 1 to complex 6,
the majority of the protons of the alkyl substituents beꢀ
come deshielded. The strongest deshielding (up to
0.76 ppm) is found for the protons adjacent to both nitroꢀ
gen atoms of the ligand. The exception is the C(6)H2 and
C(8)H2 protons oriented anti to the C(1)H and C(5)H
protons that are slightly more shielded (0.06 ppm) than
those in ligand 1.
A comparison of the 13C NMR spectra of complex 6
and ligand 1 reveals the lowꢀfield shifts of the 13C nuclei of
the alkyl groups of 3ꢀbenzylꢀ7ꢀmethylꢀ3,7ꢀdiazabiꢀ
cyclo[3.3.1]nonane fragment in 6. The deshielding effects
on the C atoms adjacent to the nitrogen atoms are most
remarkable being nearly the same (6—7 ppm) for the
C(2)/C(4) atoms and the methyl C(17) atom, somewhat
lower (1.4 ppm) for the C(6)/C(8) atoms, and the highest
(12 ppm) for the methylene C(10) atoms of the benzyl
group, which can be ascribed to the electronic effect of
the Pdꢀcontaining fragment. Similar lowꢀfield shifts were
However, these data were insufficient for unambiguꢀ
ous attribution of the structure of compound 6 to either
dimeric (C,N)ꢀpalladacycle B bearing the chloride bridgꢀ
es or monomeric (C,N,N)ꢀpalladacycle with metal atom
coordinated with two nitrogen atoms.
To clarify the structure of the synthesized palladacyꢀ
cle, we performed the detailed analysis of the 1H and 13
C
NMR spectra of ligand 1 and complex 6 using correlation
experiments (COSY, HMQC, and HMBC). From the
NMR spectral data (see Scheme 3 and Table 1), the folꢀ
lowing conclusions were drawn.
All protons of the CH2 groups of 3ꢀbenzylꢀ7ꢀmethylꢀ
3,7ꢀdiazabicyclo[3.3.1]nonane 1 are diastereotopic. The
protons C(2)H2, C(4)H2 and C(6)H2, C(8)H2 oriented
anti with respect to the protons C(1)H and C(5)H resoꢀ
nate as the doublet of doublets due to spinꢀspin coupling
between each other and with the protons C(1)H and
C(5)H. Vicinal spinꢀspin coupling constants between the
anti oriented protons C(6)H2, C(8)H2 and C(1)H, C(5)H
Table 1. 1Ha and 13Cb NMR spectra of ligand 1 and complex 6
Position
Ligand 1
Complex 6
δH (J/Hz)
δ
δH (J/Hz)
δ
C
C
(Δδ, ppm)c
1, 5
2, 4
1.95 (br.s, 2 H)
29.39
57.74
2.19 (br.s, 2 H)
30.05 (0.66)
64.45 (6.71)
2.35 (dd, 2 H, 2J = 10.8, 3J = 3.6);
2.80 (br.d, 2 H, 2J = 10.8)
2.41 (dd, 2 H, 2J = 10.8, 3J = 5.2);
2.76 (br.d, 2 H, 2J = 10.8)
1.45 (d), 1.57 (AB system, 2 H, 2J = 12.0)
3.57 (br.s, 2 H)
2.77 (dd, 2 H, 2J = 12.4, 3J = 1.8);
3.98 (d, 2 H, 2J = 12.4)
2.35 (dd, 2 H, 2J = 12.4, 3J = 2.3);
3.52 (d, 2 H, 2J = 12.6)
1.70 (dd), 1.75 (AB system, 2 H, 2J = 12.8)
4.11 (s, 2 H)
6, 8
59.67
61.05 (1.38)
9
29.71
63.04
31.63 (1.92)
75.10 (12.06)
146.95 (7.98)
120.11 (–8.85)
124.26 (–3.79)
125.08 (–1.53)
136.40 (8.35)
144.52 (15.56)
52.65 (6.00)
10
11
12
13
14
15
16
17
—
138.97
128.96
128.05
126.61
128.05
128.96
46.65
—
7.40 (d, 1 H, 3J = 7.6)
7.32 (t, 1 H, 3J = 7.8)
7.28 (t, 1 H, 3J =7.6)
6.84 (d, 1 H, 3J = 7.3)
6.96 (t, 1 H, 3J = 7.3)
6.90 (t, 1 H, 3J = 7.2)
7.77 (dd, 1 H, 3J = 7.8)
—
7.32 (t, 1 H, 3J = 7.8)
7.40 (d, 1 H, 3J = 7.6)
2.28 (s, 3 H)
2.61 (s, 3 H)
a At 600 MHz.
b At 151 MHz.
c Difference between chemical shifts of the 13C atoms of ligand 1 and complex 6.

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Bulygina et al.
observed for the methylene 13C nuclei adjacent to the
nitrogens of the only described3c metal cyclic bispidine
complex, i.e., cycloplatinate complex F, with respect to
the parent free ligand.
cases, palladium black rapidly precipitated from the reacꢀ
tion mixtures and in some cases a palladium mirror was
formed on the flask walls. No individual products were
isolated. Thus, it can be concluded that 3ꢀbenzylꢀ3ꢀ
azabicyclo[3.3.1]nonane 10 bearing one nitrogen atom reꢀ
acts with the palladation agents producing unstable pallaꢀ
dates, which rapidly decompose releasing the metal.
In contrast to compound 10, 3ꢀbenzylꢀ7ꢀmethylꢀ3,7ꢀ
diazabicyclo[3.3.1]nonane 1 forms stable (C,N,N)ꢀpincer
cyclopalladium complex 6, whose stability is ensured by
coordination of the Pd atom with two nitrogen atoms.
The catalytic performance of the synthesized palladaꢀ
cycle 6 was preliminary estimated on several model C—C
bond forming reactions (Scheme 4).
The Suzuki reaction of 4ꢀbromoanizole with phenylꢀ
boronic acid catalyzed by complex 6 proceeds under mild
conditions producing compound 13 in 85% yield. The
Heck reaction between ethyl acrylate and 4ꢀbromoanisole
in the presence of 6 gives compound 14 in 56% yield.
Reductive arylation of norbornene with iodobenzene catꢀ
alyzed by complex 6 carried out under standard conditions
leads to product 15 in 99% yield. The obtained yields are
in accord with the data of the similar experiments involvꢀ
ing the same haloarenes and performed under comparable
conditions but with other palladacycles as the catalysts.10
For complex F, insignificant deshielding (0.4 ppm) of
the C(6)/C(8) and much stronger deshielding (8—9 ppm)
of the C(2)/C(4) and C(13) atoms were found.
Furthermore, deshielding of the 13C nuclei bonded to
the nitrogen atoms of the alkyl groups upon the N—Pd
coordination are known. Thus, the lowꢀfield shifts of the
C atoms bonded to nitrogen atoms were observed for
platinum N,N´ꢀdiallylbispidine complexes: a marked shift
(nearly 10 ppm) for the allylic C atoms and less pronounced
coordination shift for the C atoms of the bispidine
framework.3c
These NMR spectral data indicate that the metal atom
coordinates with electron pairs of both nitrogen atoms;
therefore, the complex has the structure of monomeric
(C,N,N)ꢀpalladacycle 6. Note that in dimeric (C,N)ꢀcyꢀ
clopalladate only characteristic 13C nuclei adjacent to one
nitrogen atom should be deshielded.
We attempted synthesis of coordination Pd complex
by the reaction of ligand 1 with sodium/lithium tetrachloꢀ
ropalladate in the absence of the sodium acetate. Howevꢀ
er, even under these conditions the major product was
palladacycle 6 and the coordination complex was detected
(1H NMR spectroscopy) as a minor impurity. Only once
Scheme 4
1
we were able to isolate it pure. According to H and 13C
NMR spectral data, the isolated compound is a coordinaꢀ
tion complex containing two molecules of the ligand and
1.6 molecules of carbonic acid per one Pd atom (miꢀ
croanalysis data). For this complex, we conventionally
attributed structure 11.
Apparently, upon storage, diamine 1 transforms into
stable carbonates, which are preserved in complex 11. This
significantly decreases the solubility of complex 11 in comꢀ
mon organic solvents and facilitates its isolation pure reꢀ
moving the more soluble impurities by washings with aceꢀ
tone and diethyl ether avoiding aqueous workꢀup. It should
be emphasized that to the best of our knowledge all coorꢀ
dination bispidineꢀderived metal complexes were syntheꢀ
sized using ligands symmetrically substituted on the nitroꢀ
gen atoms.
Palladation of bicyclic ligand 10 was attempted with
sodium/lithium tetrachloropalladate in the presence or
absence of sodium acetate in toluene or acetic acid. In all
Reagents and conditions: i. 6, PhB(OH)2, K2CO3, MeOH,
H2O, 55 °C, 5 h; ii. 6, CH2=CHCO2Et, K2CO3, DMF, 140 °C,
5 h; iii. 6, norbornene, HCOOH, Et3N, DMSO, 65 °C, 5 h.

Palladacycle of 3ꢀbenzylꢀ7ꢀmethylbispidine
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 10, October, 2016
2483
solution to pH 12, extracted with CHCl3, dried with Na2SO4, and
the solvent was removed in vacuo. The residue was dissolved in THF
(50 mL) and 37% aqueous formaldehyde (1.5 mL, 20 mmol) was
added followed by portionwise addition of sodium triacetoxyboroꢀ
hydride (6.4 g, 30 mmol). After 5 h stirring, the reaction mixture
was diluted with water, treated with aqueous NaOH to pH 12,
extracted with diethyl ether, and the solvent was removed in vacuo.
The residue was dissolved in diethyl ether and dried with Na2SO4.
Removal of the solvent and drying under vacuum afforded 2.3 g
(97%) of product 1. 1H and 13C NMR spectral data are summarized
in Table 1.
In summary, palladacycle 6 is stable and can serve as
an efficient catalyst for the C—C bond forming reactions.
It is of note that small amounts of palladium black are
formed during all studied reactions. Formation and interꢀ
conversion of different palladium species during the cataꢀ
lytic process is a general feature of palladacycle catalytic
systems lacking phosphorus.11
Experimental
3ꢀBenzylꢀ3ꢀazabicyclo[3.3.1]nonanꢀ9ꢀone (9).8 To a solution
of compound 8 (10 g, 0.051 mol) in MeCN (50 mL), Me3SiCl
(9.7 mL, 0.077 mol) was added dropwise. After 15 min stirring,
cyclohexanone 7 (5.3 mL) was added dropwise and the mixture was
stirred for 5 h. Then the reaction mixture was concentrated, diluted
with water (25 mL), treated with concentrated HCl (25 mL), and the
mixture was refluxed with stirring for 1 h. After cooling, a 12 M
aqueous NaOH solution was added to pH 10, the mixture was
extracted with AcOEt, dried with Na2SO4, and the solvent was
removed in vacuo. The residue was dissolved in AcOEt—hexane
(1 : 4), filtered through a short silica gel layer (elution with
AcOEt—hexane, 1 : 4), and concentrated to give 8.1 g (70%) of
product 9. 1H NMR (400 MHz, CDCl3) δ:6 1.56 (m, 1 H); 2.04
(m, 2 H); 2.18 (m, 2 H); 2.37 (br.s, 2 H); 2.58 (d, 2 H, J =
= 11.7 Hz); 3.00 (m, 1 H); 3.18 (d, 2 H, J = 11.0 Hz); 3.49 (s, 2 H);
7.23—7.43 (m, 5 H). 13C NMR (101 MHz, CDCl3), δ (cf. Ref. 6):
21.38; 34.75; 47.88; 60.42; 62.23; 127.13; 128.41; 128.68; 138.69;
218.75.
3ꢀBenzylꢀ3ꢀazabicyclo[3.3.1]nonane (10). A stirred mixture of
compound 9 (8.1 g, 0.035 mol), hydrazine hydrate (9.7 mL,
0.2 mol), and diglyme (60 mL) was heated to 70 °C and treated with
KOH (13.4 g, 0.24 mol). The reaction mixture was heated at 140 °C
for 6 h, cooled to 80 °C, treated with water (150 mL), and stirred for
15 min. After cooling to room temperature, the mixture was exꢀ
tracted with hexane, dried with Na2SO4, filtered through a short
silica gel layer (elution with AcOEt—hexane, 5 : 95) to give 3.8 g
(51%) of product 10. Found (%): C, 83.67; H, 9.83; N, 6.50.
C15H21N. Calculated (%): C, 83.60; H, 9.78; N, 6.42. 1H NMR
(400 MHz, CDCl3), δ: 1.52—1.91 (m, 9 H); 2.29 (d, 2 H, J =
= 10.9 Hz); 2.73—2.89 (m, 1 H); 2.95 (d, 2 H, J =
= 10.6 Hz); 3.43 (s, 2 H); 7.24—7.32 (m, 1 H); 7.33—7.43 (m, 4 H).
13C NMR (101 MHz, CDCl3), δ: 22.61; 29.71; 31.51; 34.41;
59.92; 64.26; 126.57; 128.15; 128.71; 139.89.
1
H and 13C NMR spectra of compounds 1, 6, and 11 were
recorded with a Bruker AvanceTM 600 spectrometer at working
frequencies of 600.22 and 150.93 MHz, respectively. H NMR
1
spectra of the other compounds were obtained with Brukerꢀ
Avance 400 and BrukerꢀAvance 300 instruments at working freꢀ
quencies of 400.13 and 300.61 MHz, respectively. The chemical
shifts are given in the δ scale and were measured relative to the
residual proton signal (1H) of the solvent (CDCl3 or CD2Cl2) or
the solvent signal (13C) and recounted with respect to Me4Si.
2D NMR experiments (COSY, HMQC, and HMBC) were perꢀ
formed using the Bruker standard pulse sequences.
N,NꢀBis(methoxymethyl)benzylamine (8) was synthesized
as earlier described.8
3ꢀBenzylꢀ7ꢀ(tertꢀbutoxycarbonyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]ꢀ
nonanꢀ9ꢀone (4).5 A solution of NꢀBocꢀ4ꢀpiperidone 2 (10 g,
0.05 mol), Nꢀbenzylamine 3 (5.45 mL, 0.05 mol), and AcOH
(2.86 mL, 0.05 mol) in MeOH (80 mL) was added dropwise to a
stirred suspension of paraformaldehyde (6 g, 0.2 mol) in MeOH
(80 mL) at 60 °C. After addition was completed, the mixture was
heated for 6 h, cooled down, diluted with water, extracted with
CH2Cl2, dried with Na2SO4, and the solvent was removed
in vacuo. Purification of the residue by silica gel column chroꢀ
matography (elution with AcOEt—hexane, 1 : 4) afforded 12.1 g
(74%) of product 4. 1H NMR (400 MHz, CDCl3), δ: 1.53 (s, 9 H);
2.39—2.60 (m, 2 H); 2.66—2.86 (m, 2 H); 3.10—3.68 (m, 6 H);
4.47 (d, 1 H, J = 13.6 Hz); 4.64 (d, 1 H, J = 13.4 Hz); 7.17—7.56
(m, 5 H). 13C NMR (75 MHz, CDCl3), δ: 28.58; 47.56; 49.77;
50.46; 58.69; 59.03; 61.82; 80.07; 127.25; 128.33; 128.75; 137.44;
154.76; 213.64.
3ꢀBenzylꢀ7ꢀ(tertꢀbutoxycarbonyl)ꢀ3,7ꢀdiazabicyclo[3.3.1]ꢀ
nonane (5).5 A stirred mixture of compound 4 (12.1 g, 0.037 mol),
hydrazine hydrate (9 mL, 0.184 mol), and diglyme (60 mL) was
heated to 70 °C, treated with KOH (14.5 g, 0.259 mol), and
heated at 140 °C for 6 h. After cooling to 80 °C, the mixture was
diluted with water (150 mL), stirred for 15 mL, cooled to room
temperature, extracted with hexane, dried with Na2SO4, and
filtered through a short silica gel layer (elution with AcOEt—
hexane, 1 : 4) to give 7.7 g (66%) of product 5. 1H NMR
(400 MHz, CDCl3), δ: 1.54 (s, 9 H); 1.61—1.70 (m, 2 H); 1.81
(br.s, 1 H); 1.89 (br.s, 1 H); 2.17—2.25 (m, 2 H); 2.91—3.17
(m, 4 H); 3.32 (d, 1 H, J = 13.6 Hz); 3.46 (d, 1 H, J = 13.5 Hz);
4.02 (d, 1 H, J = 13.1 Hz); 4.18 (d, 1 H, J = 13.1 Hz); 7.21—7.36
(m, 5 H). 13C NMR (75 MHz, CDCl3), δ: 28.60; 28.86; 31.05;
47.45; 48.28; 58.60; 58.90; 63.38; 78.59; 126.49; 127.93; 128.44;
138.89; 154.94.
Chloro[2ꢀ(3ꢀmethylꢀ3,7ꢀdiazabicyclo[3.3.1]nonanꢀ3ꢀylmethyl)ꢀ
phenylꢀC,N,N]palladium (6). Method A. To a solution of Na2PdCl4
(0.2888 g, 1.0 mmol) and AcONa•3H2O (0.1334 g, 1.0 mmol)
in
a mixture of MeOH (30 mL) and water (10 mL),
a solution of ligand 1 (0.226 g, 1.0 mmol) in MeOH (10 mL) was
added. After 6 h stirring, the mixture was filtered through a
Celite pad (elution with MeOH, then CHCl3) and the solvent
was removed in vacuo. The residue was diluted with water,
extracted with chloroform, dried with Na2SO4, and the solvent was
removed in vacuo. The residue was washed with acetone and dried to
give 0.1264 g (35%) of complex 6.
Method B. A suspension of ligand 1 (0.1663 g, 0.7 mmol) and
palladium acetate (0.1623 g, 0.7 mmol) in toluene (30 mL) was
heated at 60 °C for 6 h and concentrated. The residue was treatꢀ
ed with lithium chloride (0.1484 g, 3.5 mmol) in EtOH (30 mL),
the mixture was stirred at room temperature for 3 h, filtered
through a Celite pad (elution with MeOH, then CHCl3), and
3ꢀBenzylꢀ7ꢀmethylꢀ3,7ꢀdiazabicyclo[3.3.1]nonane (1).4
A solution of compound 5 (3.3 g, 10 mmol) in PriOH (30 mL)
was carefully treated with concentrated HCl (15 mL). The mixꢀ
ture was stirred for 5 h, diluted with water, treated with a NaOH

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Bulygina et al.
concentrated. The residue was diluted with water, extracted with
CHCl3, dried with Na2SO4, and the solvent was removed
in vacuo. The residue was washed with acetone and dried to give
0.1340 g (51%) of complex 6.
Reaction of norbornene with iodobenzene (hydroarylation of
norbornene). Norbornene (0.28 g, 3.4 mmol), iodobenzene (0.204 g,
1 mmol), formic acid (0.11 mL, 3 mmol), and triethylamine (0.53 mL,
3.8 mmol) were sequentially added to DMSO (5 mL) with stirring
followed by addition of complex 6 (0.5 mol.%) after 5 min stirring.
The mixture was stirred at 65 °C for 5 h, diluted with water, extractꢀ
ed with petroleum ether, dried with Na2SO4, and concentrated.
Purification of the residue by silica gel column chromatography
(elution with petroleum ether) afforded 0.168 g (99%) of compound
15. Product 15 was identified using 1H NMR spectral data, which
are in agreement with the previously published.14
Method C. A suspension of palladium chloride (0.1724 g,
0.9 mmol) and lithium chloride (0.0811 g, 1.9 mmol) in MeOH
(15 mL) was refluxed for 1 h. After cooling to room temperature,
the obtained solution of lithium tetrachloropalladate was treated
dropwise with a solution of ligand 1 (0.2091 g, 0.9 mol) and
AcONa•3H2O (0.1224 g, 0.9 mmol) in MeOH (5 mL). The
reaction mixture was stirred at room temperature for 5 h, filtered
through a Celite pad (elution with MeOH and CHCl3), and
concentrated. The residue was diluted with water, extracted with
CHCl3, dried with Na2SO4, and the solvent was removed
in vacuo. The residue was washed with acetone and dried to give
0.2680 g (80%) of complex 6. Found (%): C, 48.38; H, 5.51;
N, 7.39; Cl, 10,06. C15H21ClN2Pd. Calculated (%): C, 48.53;
H, 5.70; N, 7.55; Cl, 9.55. 1H and 13C NMR spectral data are
summarized in Table 1.
Dichlorobis(3ꢀbenzylꢀ7ꢀmethylꢀ3,7ꢀdiazabicyclo[3.3.1]ꢀ
nonaneꢀN,N)palladium(II) dihydrocarbonate (11). To a solution
of Na2PdCl4 (0.1786 g, 0.61 mmol) in MeOH (12 mL), a soluꢀ
tion of ligand 1 (0.1337 g, 0.58 mmol) in MeOH (10 mL)
was added. The mixture was stirred for 6 h and then kept for
16 h. The mixture was filtered through a Celite pad (elution
with MeOH) and concentrated. The residue was dissolved in
CHCl3, the precipitated NaCl was filtered off. The filtrate was
concentrated, the precipitate was collected, washed with
acetone and diethyl ether, and dried to give 0.0935 g (44%)
of complex 11. Found (%): C, 51.22; H, 6.28; N, 7.91.
C30H44Cl2N4Pd•1.6H2CO3. Calculated (%): C, 51.48; H, 6.45;
N, 7.60. 1H NMR (600 MHz, CD2Cl2), δ: 1.72 (d, 1 H, J =
= 13.1 Hz); 1.85 (d, 1 H, J = 13.1 Hz); 2.18 (s, 2 H); 2.60 (d, 2 H,
J = 11.6 Hz); 3.07 (m, 5 H); 3.49 (d, 2 H, J = 11.4 Hz); 3.93
(d, 2 H, J = 11.9 Hz); 4.02 (s, 2 H); 7.32 (t, 1 H, J = 7.2 Hz); 7.37
(t, 2 H, J = 7.4 Hz); 7.45 (d, 2 H, J = 7.3 Hz). 13C NMR (151 MHz,
CD2Cl2), δ: 28.42; 30.02; 45.57; 56.47; 60.15; 61.64; 127.65;
128.40; 130.29; 135.00.
Reaction of phenylboronic acid with 4ꢀbromoanisole (the Suꢀ
zuki reaction). To a stirred mixture of MeOH (8 mL) and water
(4 mL), phenylboronic acid (0.183 g, 1.5 mmol), 4ꢀbromoaniꢀ
sole (0.187 g, 1 mmol), and K2CO3 (0.276 g, 2 mmol) were
added. After 5 min stirring, complex 6 (0.5 mol.%) was added.
The reaction mixture was heated at 55 °C for 5 h, diluted with
water, extracted with CHCl3, dried with Na2SO4, and concenꢀ
trated. Purification of the residue by silica gel column chromaꢀ
tography (elution with petroleum ether—CHCl3, 8 : 1) afforded
0.156 g (85%) of 4ꢀmethoxybiphenyl 13. Compound 13 was idenꢀ
tified using 1H NMR spectral data, which are in agreement with
the previously published.12
Reaction of 4ꢀbromoanisole with ethyl acrylate (the Heck reacꢀ
tion). 4ꢀBromoanisole (0.935 g, 5 mmol), ethyl acrylate (0.75 g,
7.5 mmol), and K2CO3 (1.38 g, 10 mmol) were sequentially added
to DMF (5 mL) with stirring followed by addition of complex 6
(0.5 mol.%) after 5 min stirring. The mixture was stirred at 140 °C
for 5 h, diluted with water, extracted with CHCl3, dried with
Na2SO4, and concentrated. Purification of the residue by silica gel
column chromatography (elution with petroleum ether—AcOEt,
9 : 1) afforded 0.545 g (56%) of ethyl 4ꢀmethoxycinnamate 14. Comꢀ
pound 14 was identified using 1H NMR spectral data, which are in
agreement with the previously published.13
References
1. C. Mannich, P. Mohs, Ber. Dtsch. Chem. Ges., 1930, 63, 608.
2. M. Breuning, M. Steiner, Synthesis, 2008, 2841.
3. (a) D. S. C. Black, G. B. Deacon, M. Rose, Tetrahedron,
1995, 51, 2055; (b) A. Gogoll, C. Johansson, A. Axen,
H. Grennberg, Chem. Eur. J., 2001, 7, 396; (c) H. Cui,
R. Goddard, K.ꢀR. Pörschke, Organometallics, 2011, 30, 6241.
4. P.ꢀW. Phuan, J. C. Ianni, M. C. Kozlowski, J. Am. Chem.
Soc., 2004, 126, 15473.
5. V. Haridas, S. Sadanandan, Y. K. Sharma, S. Chinthalapalli,
A. Shandilya, Tetrahedron Lett., 2012, 53, 623.
6. J. A. Lowe, S. E. Drozda, S. McLean, D. K. Bryce, R. T.
Crawford, R. M. Snider, K. P. Longo, A. Nagahisa,
M. Tsuchiyat, J. Med. Chem., 1994, 37, 2831.
7. A. I. Moskalenko, V. I. Boev, Russ. J. Org. Chem. (Engl.
Transl.), 2009, 45, 472 [Zh. Org. Khim., 2009, 45, 481].
8. A. P. Mityuk, A. V. Denisenko, O. P. Dacenko, O. O. Gryꢀ
gorenko, P. K. Mykhailiuk, D. M. Volochnyuk, O. V. Shishꢀ
kin, A. A. Tolmachev, Synthesis, 2010, 493.
9. (a) A. A. Watson, D. A. House, P. J. Steel, J. Organomet.
Chem., 1986, 311, 387; (b) O. N. Gorunova, K. J. Keuseꢀ
man, B. M. Goebel, N. A. Kataeva, A. V. Churakov, L. G.
Kuzmina, V. V. Dunina, I. S. Smoliakova, J. Organomet.
Chem., 2004, 689, 2382; (c) A. V. Kuchin, Ya. A. Gur´eva,
L. L. Frolova, I. N. Alekseev, O. A. Zalevskaya, Russ. Chem.
Bull. (Int. Ed.), 2013, 62, 745 [Izv. Akad. Nauk, Ser. Khim.,
2013, 745].
10. (a) J. Ma, X. Cui, B. Zhang, M. Song, Y. Wu, Tetrahedron,
2007, 63, 5529; (b) D. Zim, A. S. Gruber, G. Ebeling,
J. Dupont, A. L. Monteiro, Organic. Lett., 2000, 2, 2881;
(c) D. A. Alonso, C. Najera, M. C. Pacheco, Adv. Synth.
Catal., 2002, 344, 172; (d) J. Bravo, C. Cativiela, R. Navarꢀ
ro, E. P. Urriolabeitia, J. Organomet. Chem., 2002, 650, 157.
11. (a) I. P. Beletskaya, A. V. Cheprakov, J. Organomet. Chem.,
2004, 689, 4055; (b) V. P. Ananikov, I. P. Beletskaya, Orgaꢀ
nometallics, 2012, 31, 1595; (c) A. S. Sigeev, A. S. Pereguꢀ
dov, A. V. Cheprakov, I. P. Beletskaya, Adv. Synth. Catal.,
2015, 357, 417.
12. Y. Cheng, X. Gu, P. Li, Org. Lett., 2013, 15, 2664.
13. B. Mu, T. Li, W. Xu, G. Zeng, P. Liua, Y. Wu, Tetrahedron,
2007, 63, 11475.
14. X.ꢀY. Wu, H.ꢀD. Xu, F.ꢀY. Tang, Q.ꢀL. Zhou, Tetrahedron:
Asymmetry, 2001, 12, 2565.
Received September 15, 2015;
in revised form May 13, 2016