Palladium-catalyzed reactions of allyl acetates with N-substituted 4-trimethylstannyl-1,2,3,6-tetrahydropyridines

Full text of DOI:10.1134/S1070428013120269

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 12, pp. 1848–1850. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © A.I. Moskalenko, V.I. Boev, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 12, pp. 1863–1865.
SHORT
COMMUNICATIONS
Palladium-Catalyzed Reactions
of Allyl Acetates with N-Substituted 4-Trimethylstannyl-
1,2,3,6-tetrahydropyridines
A. I. Moskalenkoa and V. I. Boevb
a Lipetsk State Pedagogical University, ul. Lenina 42, Lipetsk, 398020 Russia
e-mail: kaf_himii@lspu.lipetsk.ru
b Russian State Agrarian University, Moscow, Russia
Received June 21, 2013
DOI: 10.1134/S1070428013120269
Palladium-catalyzed cross-coupling reactions are
widely used in organic synthesis [1]. Diversity of reac-
tants that could be involved in cross-coupling reactions
ensures purposeful synthesis of organic molecules with
a required structure. In the present communication we
report on the reactions of previously obtained N-sub-
stituted 4-trimethylstannyl-1,2,3,6-tetrahydropyridines
I and II [2] with a number of allyl acetates III–VII,
including those containing natural alcohol residues
(geraniol, nerol, and farnesol). The reactions were
carried out according to modified procedures [3, 4]
with the use of tris(dibenzylideneacetone)palladium(0)
[Pd2(dba)3] [5], ethyl(diisopropyl)amine, and anhy-
drous lithium chloride as catalytic system in N-methyl-
pyrrolidin-2-one (NMP) at 50–55°C. We thus isolated
in high yields the corresponding N-protected (Cbz,
Boc) 1,2,3,6-tetrahydropyridine derivatives VIII–XIII
containing unsaturated hydrocarbon substituents in the
4-position, which attract interest as potential biologi-
cally active substances [6] and building blocks for
organic synthesis (Scheme 1).
zoic acid in methylene chloride to produce a mixture
of diastereoisomeric mono- and diepoxides XIV and
XV. The Boc protection was readily removed from
compound XV by treatment of the latter with tri-
methylsilyl trifluoromethanesulfonate, the epoxide
rings being conserved, and the subsequent addition of
acetic anhydride to the reaction mixture afforded the
corresponding N-acetyl derivative XVI (Scheme 2).
1,2,3,6-Tetrahydropyridines VIII–XIII (general
procedure). To a mixture of 0.23 g (0.243 mmol) of
Pd2(dba)3 and 0.42 g (9.9 mmol) of anhydrous lithium
chloride we added under stirring in an argon atmo-
sphere in succession 2.2 mmol of allyl acetate III–VII
in 6 mL of N-methylpyrrolidin-2-one, 2.16 mmol of
pyridine derivative I and II in 6 mL of NMP, and
0.75 mL (5 mmol) of ethyl(diisopropyl)amine. The
resulting dark red mixture was stirred for 10 min,
heated for 3–8 h at 50–55°C (TLC), cooled, and
filtered through a thin layer of celite, the precipitate
was washed on a filter with 60 mL of ethyl acetate, the
filtrate was poured into 100 mL of a saturated solution
of ammonium chloride, the mixture was stirred for
10 min, the organic layer was separated, and the aque-
Compound VIII was oxidized at both endocyclic
and exocyclic double bonds with 3-chloroperoxyben-
Scheme 1.
R
Pd2(dba)3, Et(i-Pr)2N
LiCl, NMP
Me3Sn
R
O
R'
+
N
N
R'
O
Me
Cbz (Boc)
Cbz (Boc)
I, II
III–VII
VIII–XIII
I, X, XII, XIII, Cbz = PhCH2OC(O); II, VIII, IX, XI, Boc = t-BuOC(O); II, VIII, R = R′ = H; IV, IX, R = R′ = Me; V, X, XI, R = Me,
R′ = (E)-Me2C=CHCH2; VI, XII, R = Me, R′ = (Z)-Me2C=CHCH2; VII, XIII, R = Me, R′ = (E,E)-Me2C=CHCH2CH2C(Me)=CHCH2.
1848

PALLADIUM-CATALYZED REACTIONS OF ALLYL ACETATES
1849
Scheme 2.
O
O
H2C
3-ClC6H4CO3H
O
+
VIII
N
N
Boc
Boc
XIV
XV
O
(1) Me3SiOSO2CF3, NEt3
(2) Ac2O
O
XV
N
Ac
XVI
ous layer was extracted with ethyl acetate (2×50 mL).
The extracts were combined with the organic phase,
washed with two portions of water and with brine, and
dried over sodium sulfate. The solvent was removed
under reduced pressure, and the residue was subjected
to column chromatography on silica gel using hexane–
ethyl acetate (5:1 to 3:1) as eluent.
7.27–7.37 m (5H, Harom). Mass spectrum, m/z (Irel, %):
354.11 (18.2) [M + H]+, 310.21 (100) [M – 44 + H]+,
218.18 (15.6) [M – 136 + H]+. Found, %: C 78.02;
H 8.57; N 4.03. C23H31NO2. Calculated, %: C 78.15;
H 8.85; N 4.12. M 353.24.
tert-Butyl 4-[(2E)-3,7-dimethylocta-2,6-dien-1-
yl]-3,6-dihydropyridine-1(2H)-carboxylate (XI).
Yield 92%, light yellow oily substance. IR spectrum, ν,
tert-Butyl 4-allyl-3,6-dihydropyridine-1(2H)-
carboxylate (VIII). Yield 79%, light yellow oily sub-
stance. IR spectrum, ν, cm–1: 1686 (C=O), 1636, 1625
1
cm–1: 1685 (C=O), 1636, 1628, 1617 (C=C). H NMR
spectrum, δ, ppm: 1.48 s (9H, t-Bu), 1.62 s (6H, CH3),
1.73 s (3H, CH3), 1.98–2.05 m (6H, CH2), 2.71 d (2H,
CH2, J = 8.8 Hz), 3.48 t (2H, NCH2, J = 7.4 Hz), 3.85 s
(2H, NCH2), 5.08 t (1H, CH=, J = 9.2 Hz), 5.13 t (1H,
CH=, J = 9.4 Hz), 5.34 s (1H, CH=). Mass spectrum,
m/z (Irel, %): 320.24 (36.7) [M + H]+, 264.18 (100)
[M – 57 + 2H]+, 220.30 (58.8) [M – 101 + 2H]+.
Found, %: C 75.04; H 10.36; N 4.58. C20H33NO2. Cal-
culated, %: C 75.28; H 10.43; N 4.45. M 319.48.
1
(C=C). N NMR spectrum, δ, ppm: 1.48 s (9H, t-Bu),
2.02 s (2H, CH2), 2.73 d (2H, CH2C=, J = 8.3 Hz),
3.47 t (2H, NCH2, J = 7.4 Hz), 3.83 s (2H, NCH2),
5.02 d (2H, CH2=C, J = 9.6 Hz), 5.31 s (1H, 5-H),
5.78 m (1H, CH=C). Mass spectrum, m/z (Irel, %):
224.26 (100) [M + H]+, 168.18 (23.4) [M – 57 + 2H]+.
Found, %: C 69.74; H 9.17; N 6.12. C13H21NO2. Cal-
culated, %: C 69.96; H 9.42; N 6.28. M 223.31.
tert-Butyl 4-(3-methylbut-2-en-1-yl)-3,6-dihydro-
pyridine-1(2H)-carboxylate (IX). Yield 83%, light
yellow oily substance. IR spectrum, ν, cm–1: 1685
(C=O), 1632, 1620 (C=C). 1H NMR spectrum, δ, ppm:
1.49 s (9H, t-Bu), 1.67 s (3H, CH3), 1.72 s (3H, CH3),
2.03 m (2H, CH2), 2.71 m (2H, CH2C=), 3.45 t (2H,
NCH2, J = 7.8 Hz), 3.82 s (2H, NCH2), 5.30 s (1H,
5-H), 5.73 m (1H, CH=C). Mass spectrum, m/z
(Irel, %): 252.31 (5.2) [M + H]+, 196.25 (100) [M –
57 + 2H]+, 152.37 (18.4) [M – 101 + 2H]+. Found, %:
C 71.67; H 10.08; N 5.43. C15H25NO2. Calculated, %:
C 71.73; H 10.23; N 5.64. M 251.42.
Benzyl 4-[(2Z)-3,7-dimethylocta-2,6-dien-1-yl]-
3,6-dihydropyridine-1(2H)-carboxylate (XII). Yield
76%, light yellow oily substance. IR spectrum, ν, cm–1:
1695 (C=O), 1637, 1625 (C=C). 1H NMR spectrum, δ,
ppm: 1.54 s (3H, CH3), 1.58 s (3H, CH3), 1.67 s (3H,
CH3), 2.05 m (6H, CH2), 2.69 t (2H, CH2, J = 7.8 Hz),
3.46 t (2H, NCH2, J = 7.8 Hz), 3.81 s (2H, NCH2),
5.05–5.17 m (4H, OCH2, CH=), 5.31 s (1H, CH=),
7.24–7.46 m (5H, Harom). Mass spectrum, m/z (Irel, %):
354.28 (100) [M + H]+, 310.32 (21.4) [M – 44 + H]+.
Found, %: C 77.96; H 8.63; N 3.84. C23H31NO2. Cal-
culated, %: C 78.02; H 8.85; N 4.12. M 353.24.
Benzyl 4-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-
3,6-dihydropyridine-1(2H)-carboxylate (X). Yield
76%, light yellow oily substance. IR spectrum, ν, cm–1:
1694 (C=O), 1638, 1624 (C=C). 1H NMR spectrum, δ,
ppm: 1.61 s (6H, CH3), 1.72 s (3H, CH3), 2.03 m (6H,
CH2), 2.70 d (2H, CH2, J = 8.7 Hz), 3.56 t (2H, NCH2,
J = 7.5 Hz), 3.97 s (2H, NCH2), 5.12 d (1H, CH=, J =
9.6 Hz), 5.17 m (3H, OCH2, CH=), 5.36 s (1H, CH=),
Benzyl 4-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-
trien-1-yl]-3,6-dihydropyridine-1(2H)-carboxylate
(XIII). Yield 89%, yellow oily substance. IR spectrum,
ν, cm–1: 1697 (C=O), 1643, 1631, 1624 (C=C).
1H NMR spectrum, δ, ppm: 1.50–1.68 m (12H, CH3),
1.97–2.05 m (10H, CH2), 2.62 d (2H, CH2, J = 9.3 Hz),
3.47 t (2H, NCH2, J = 7.6 Hz), 3.81 s (2H, NCH2),
5.12 d (1H, CH=, J = 9.6 Hz), 5.01–5.12 m (5H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 12 2013

MOSKALENKO, BOEV
1850
OCH2, CH=), 5.38 s (1H, CH=), 7.26–7.37 m (5H,
XV and 0.41 g (4 mmol) of triethylamine in 6 mL of
anhydrous methylene chloride, maintaining the tem-
perature not higher than 20°C. The mixture was stirred
for 25 h (TLC), 0.41 g of triethylamine in 6 mL of
methylene chloride and 0.61 g (6 mmol) of acetic
anhydride were added in succession, and the mixture
was stirred for 3 h. It was then poured into 20 mL of
a saturated aqueous solution of sodium hydrogen
carbonate, the organic phase was separated, and the
aqueous phase was extracted with 30 mL of methylene
chloride. The extract was combined with the organic
phase and dried over Na2SO4, the solvent was removed
under reduced pressure, and the residue was purified
by chromatography on silica gel using ethyl acetate as
eluent. Yield 0.26 g (66%), colorless thick oily sub-
stance which slowly crystallized. IR spectrum, ν, cm–1:
1701 (C=O), 920, 867 (oxirane). 1H NMR spectrum, δ,
ppm: 1.70–2.08 m (7H, CH2, CH3), 2.51 m (1H, CH),
2.78 m (1H, CH), 2.96–3.04 m (2H, NCH2), 3.45–
3.69 m (2H, NCH2), 3.81–4.03 m (2H, OCH2). Mass
spectrum, m/z (Irel, %): 198.31 (100) [M + H]+. Found,
%: C 60.73; H 7.41; N 6.95. C10H15NO3. Calculated,
%: C 60.84; H 7.60; N 7.10. M 197.24.
H
arom). Mass spectrum, m/z (Irel, %): 422.30 (100) [M +
H]+, 378.34 (12.4) [M – 44 + H]+. Found, %: C 79.63;
H 9.18; N 3.42. C28H39NO2. Calculated, %: C 79.84;
H 9.36; N 3.38. M 421.62.
tert-Butyl 6-allyl-7-oxa-3-azabicyclo[4.1.0]hep-
tane-3-carboxylate (XIV) and tert-butyl 6-(oxiran-
2-yl)methyl-7-oxa-3-azabicyclo[4.1.0]heptane-3-car-
boxylate (XV). A mixture of 1.34 g (6 mmol) of
compound VIII and 15 mL of anhydrous methylene
chloride was cooled to 0°C, 2.58 g (15 mmol) of
3-chloroperoxybenzoic acid was added under stirring,
and the mixture was stirred for 50 h at room tem-
perature (until initial diene VIII disappeared). The
mixture was filtered, the filtrate was washed with three
portions of 7% aqueous potassium hydroxide and with
water and dried over Na2SO4, the solvent was removed
under reduced pressure, and the residue was subjected
to chromatography on silica gel to isolate first mono-
epoxide XIV (eluent ethyl acetate–hexane, 1:5) and
then diepoxide XV (ethyl acetate).
Compound XIV. Yield 23%, colorless oily sub-
stance. IR spectrum, ν, cm–1: 1686 (C=O), 1628
1
The IR spectra were recorded on a Specord 75 IR
(C=C), 873 (oxirane). H NMR spectrum, δ, ppm:
1
spectrometer from thin films. The H NMR spectra
1.48 s (9H, t-Bu), 1.78–1.91 m (2H, CH2), 2.37 d (2H,
H2CC=, J = 8.1 Hz), 3.06 t (2H, NCH2, J = 7.5 Hz),
3.48 m (1H, NCH), 3.58 d (1H, NCH, J = 7.8 Hz),
3.88 br.s (1H, OCH), 5.08–5.15 d (2H, CH2=, J =
9.8 Hz), 5.73 m (1H, CH=). Mass spectrum, m/z
(Irel, %): 240.19 (88.4) [M + H]+, 184.26 (100) [M –
57 + 2H]+, 140.39 (52.3) [M – 101 + 2H]+. Found, %:
C 65.03; H 8.56; N 5.67. C13H21NO3. Calculated, %:
C 65.17; H 8.78; N 5.85. M 239.31.
were measured on a Varian Mercury Plus-400 spec-
trometer (400 MHz) from solutions in CDCl3 (VIII,
IX, XI, XIV–XVI) or DMCO-d6 (X, XI, XIII);
hexamethyldisiloxane was used as internal standard.
The mass spectra (atmospheric pressure chemical
ionization) were obtained on a Thermo Finnigan
Surveyor MSQ instrument (USA).
REFERENCES
Compound XV. Yield 37%, colorless thick oily
substance. IR spectrum, ν, cm–1: 1685 (C=O), 921, 870
1. Tsuji, J., Palladium Reagents and Catalysts. Innovations
in Organic Synthesis, Chichester: Wiley, 1995, p. 549.
1
(oxirane). H NMR spectrum, δ, ppm: 1.48–1.52 m
(9H, t-Bu), 1.71–2.05 m (4H, CH2), 2.48 m (1H, CH),
2.75 m (1H, CH), 2.98–3.07 m (2H, NCH2), 3.47–
3.71 m (2H, NCH2), 3.78–4.01 m (2H, OCH2). Mass
spectrum, m/z (Irel, %): 256.16 (18.4) [M + H]+, 200.17
(25.2) [M – 57 + 2H]+, 156.33 (100) [M – 101 + 2H]+.
Found, %: C 60.84; H 8.17; N 5.32. C13H21NO4. Cal-
culated, %: C 61.10; H 8.23; N 5.48. M 255.31.
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