Homologation of Alkenes to Carbonyl and Carboxylic Compounds
FULL PAPER
10.0 mmol, 300 equiv), and pyrrolidine (2.00 mL, 24.0 mmol, 1.50 equiv)
were added. The reaction mixture was warmed to 408C and stirred for
20 h at this temperature, and then an additional 4 h at room temperature.
The reaction was finished by the addition of aqueous H3PO4 (20%,
10 mL). After phase separation, the aqueous phase was extracted three
times with ethyl acetate and the combined organic phases were dried
over MgSO4. The solvent was removed in vacuo. Purification by flash
chromatography (silica gel, short column with CH2Cl2) furnished 793 mg
(80%) of the ester 5 as a colorless oil. 1H NMR (400.132 MHz, CDCl3):
d=0.88 (t, J=6.9 Hz, 3H), 1.24–1.31 (m, 10H), 1.41–1.48 (m, 2H), 2.20
(m, 2H), 3.72 (s, 3H), 5.79–5.84 (dt, J=15.7, 7.0 Hz, 1H), 6.93–7.01 ppm
(dt, J=15.7, 1.5 Hz, 1H); 13C{1H} NMR (100.626 MHz, CDCl3): d=24.2,
72.7, 28.1, 29.2, 29.3, 29.4, 31.9, 32.3, 51.5, 65.9, 120.9, 150.0, 167.3 ppm;
the analytical data match with those reported in literature.[40]
Typical procedure for the synthesis of a,b-unsaturated nitriles (Table 5,
11a–e, undec-2-enenitrile (11)): Under an atmosphere of argon, 1-octene
(314 mL, 2.00 mmol, 150 equiv) was added to a solution of 6-DPPon
(18.6 mg, 66.6 mmol, 5.00 equiv) and [RhACTHNUTRGNEG(NU acac)(CO)2] (3.40 mg,
13.3 mmol, 1.00 equiv) in THF (2 mL, 1m according to the alkene) at
room temperature in a flat-bottomed Schlenk tube. The argon atmos-
phere was replaced by synthesis gas (balloon). The reaction mixture was
stirred at room temperature and ambient pressure for 20 h. Subsequently,
the synthesis gas was removed over 20 min by bubbling argon through
the solution. At room temperature, nitrile acetic acid (187 mg,
2.20 mmol, 165 equiv) and pyrrolidine (2.00 mL, 0.02 mmol, 1.5 equiv)
were added and the reaction mixture was stirred at room temperature for
24 h. Then DBU (450 mL, 3.00 mmol, 225 equiv) was added and the reac-
tion mixture was stirred for an additional 24 h at room temperature. The
reaction was finished by the addition of aqueous NaOH (1m, up to
pH 11). After phase separation, the aqueous phase was extracted three
times with ethyl acetate and the combined organic phases were dried
over MgSO4. The solvent was removed in vacuo. Purification by flash
chromatography (silica gel, cyclohexane/ethyl acetate 20:1, Rf =0.45) fur-
nished 233 mg (70%) of the nitrile 11 as a colorless liquid. 1H NMR
(400.132 MHz, CDCl3): d=0.88 (t, J=6.9 Hz, 3H), 1.27–1.4 (m, 10H),
1.49–1.51 (m, 2H), 2.21 (tdd, J=7.0, 7.0, 1.7 Hz, 2H; trans), 2.42 (tdd, J=
7.4, 7.4, 1.4 Hz, 2H; cis), 5.31 (dt, J=11.0, 1.4 Hz, 1H; cis), 5.31 (dt, J=
16.3, 1.7 Hz, 1H; trans), 6.47 (dt, J=10.9, 7.7 Hz, 1H; cis), 6.72 ppm (dt,
J=16.3, 7.0 Hz; trans); 13C{1H} NMR (100.626 MHz, CDCl3): d=14.2,
22.7, 27.7, 28.3, 29.1, 29.2, 29.3, 31.9, 32.0, 33.4, 99.5, 116.2, 117.7, 155.4,
156.3 ppm; MS (EI, 70 eV): m/z (%): calcd for C11H19N: 165.28; found
164.2 (23) [MÀH]+, 150.1 (46) [MÀNH]+, 136.1 (100) [MÀCH3N]+,
122.1 (92) [MÀC3H7]+, 108.1 (32) [MÀC4H9]+, 94.1 (47) [MÀC5H11]+,
Typical procedure for the synthesis of b,g-unsaturated carboxylic acids
(Table 5, 6a–e, (E)-2-cyanoundec-2-enoic acid (6)): Under an atmosphere
of argon, 1-octene (785 mL, 5.00 mmol, 150 equiv) was added to a solu-
tion of 6-DPPon (64.7 mg, 167 mmol, 5.00 equiv) and [RhACHTUNGRTNEUNG(acac)(CO)2]
(8.50 mg, 33.0 mmol, 1.00 equiv) in THF (5 mL, 1m according to the
alkene) at room temperature in a flat-bottomed Schlenk tube. The argon
atmosphere was replaced by synthesis gas (balloon). The reaction mix-
ture was stirred at room temperature and ambient pressure for 20 h. Sub-
sequently, the synthesis gas was removed over 20 min by bubbling argon
through the solution. At room temperature malonic acid (520 mg,
5.00 mmol, 150 equiv) and DBU (1.50 g, 10.0 mmol, 300 equiv) were
added. The reaction mixture was stirred for 24 h at room temperature.
The reaction was finished by the addition of aqueous NaOH (1m, up to
pH 11). After phase separation, the aqueous phase was extracted three
times with ethyl acetate and the aqueous phase was acidified by adding
aqueous H3PO4 (20%, down to pH 2). This aqueous phase was extracted
three times with ethyl acetate and the combined organic phases were
dried over MgSO4. The solvent was removed in vacuo to furnish 688 mg
94.1 (47) [MÀC6H13]+, 80.1 (53) [MÀC6H13]+; HRMS: m/z: (CI, Cl
130 eV, 300 mA): calcd for C11H19N: 164.1440; found: 164.1439.
ACHTUNGTRENNUNG(NH3),
Procedure for the one-pot decarboxylative hydroformylation/decarboxy-
lative Knoevenagel reaction to (E)-dec-2-enoic acid (14) (Scheme 12):
Decarboxylative hydroformylation of (E)-oct-2-enoic acid (227 mg,
1.60 mmol) was carried out according to the literature procedure.[34] Sub-
sequently, the autoclave was depressurized and the synthesis gas was re-
moved over 20 min by bubbling argon through the solution. The solution
was cooled to 08C and malonic acid (167 mg, 1.60 mmol), pyridine
(259 mL, 253 mg, 3.20 mmol), and pyrrolidine (1.30 mg, 16.0 mmol) were
added. The reaction mixture was warmed to RT and stirred for 24 h at
this temperature (76% conversion of the Knoevenagel reaction). The re-
action was finished by the addition of aqueous H3PO4 (20%, 10 mL) at
08C. It was extracted three times with CH2Cl2, the combined organic
phases were dried (Na2SO4), and the solvent was removed in vacuo. Pu-
rification by chromatography (silica gel, petroleum ether/Et2O/AcOH
100:20:1) furnished 183 mg (67%) of the acid 14 as a colorless liquid.
1H NMR (400.132 MHz, CDCl3): d=0.88 (t, J=7.0 Hz, 3H); 1.17–1.38
(m, 8H); 1.41–1.56 (m, 2H); 2.23 (tdd, J=7.0, 7.0, 1.5 Hz, 2H), 5.82 (dt,
J=15.7, 1.5 Hz, 1H), 7.09 (dt, J=15.7, 7.0 Hz, 1H), 12.0 ppm (brs, 1H);
13C{1H} NMR (100.626 MHz, CDCl3): d=14.0, 22.5, 27.8, 29.0, 29.6, 31.6,
32.2, 120.5 (s, 1C; C2), 152.4 (s, 1C; C3), 172.3 ppm (s, 1C; COOH); the
analytical data match with those reported in the literature.[9f]
(75%) of the acid
6 as a
colorless solid. M.p. 48–508C; 1H NMR
(400.132 MHz, CDCl3): d=0.88 (t, J=5.8 Hz, 3H), 1.22–1.32 (m, 10H),
2.00–2.05 (m, 2H), 3.05–3.08 (m, 2H), 5.46–5.62 ppm (m, 2H);
13C{1H} NMR (100.613 MHz, CDl3): d=14.1, 22.7, 27.8, 29.1, 29.2, 29.3,
31.8, 32.4, 109.4, 113.1, 166.3, 166.4 ppm; MS (EI, 70 eV, 500 mA): m/z
(%): calcd for C12H19NO2: 209.14; found: 210.1 (19) [M+H]+, 166.1 (35)
[MÀCNÀOH]+, 164.1 (25) [MÀCO2H]+, 138.0 (58) [MÀCOOHÀCN]+;
HRMS (CI, ClACHTUNGTRENNUNG(NH3), 130 eV, 300 mA): m/z: calcd for C12H19NO2+NH4:
227.17595; found: 277.17580.
Typical procedure for the synthesis a-cyano acrylic acids (Table 5, 9a–e,
(E)-undec-3-enoic acid (9)): Under an atmosphere of argon, the alkene
(5.00 mmol, 150 equiv) was added to a solution of 6-DPPon (167 mmol,
5 equiv) and [RhACHTUNGTRENNUNG(acac)(CO)2] (33.0 mmol, 1 equiv) in THF (5 mL, 1m ac-
cording to the alkene) at room temperature. The argon atmosphere was
replaced by synthesis gas (balloon). The reaction mixture was stirred at
room temperature and ambient pressure for 20 h. Subsequently, the syn-
thesis gas was removed over 20 min by bubbling argon through the solu-
tion. At room temperature, nitrile acetic acid (486 mg, 5.5 mmol,
165 equiv) and pyrrolidine (4.00 mL, 50.0 mmol, 1.5 equiv) were added
and the reaction mixture was stirred at room temperature for 24 h. The
reaction was finished by the addition of aqueous NaOH (1m, up to
pH 11). After phase separation, the aqueous phase was extracted three
times with ethyl acetate and the aqueous phase was acidified by adding
aqueous H3PO4 (20%, down to pH 2). This aqueous phase was extracted
three times with ethyl acetate and the combined organic phases were
dried over MgSO4. The solvent was removed in vacuo to furnish 640 mg
Acknowledgements
(77%) of the acid
9 as a
colorless solid. M.p. 63–658C; 1H NMR
This work was supported by the DFG (International Research Training
Group: “Catalysts and Catalytic Reactions for Organic Synthesis”, GRK
1038) and the Alfried Krupp Foundation.
(400.132 MHz, CDCl3): d=0.88 (t, J=6.6 Hz, 3H), 1.27–1.36 (m, 10H),
1.53–1.61 (tt, J=7.2, 7.2 Hz, 2H), 2.57–2.62 (td, J=7.5, 7.5 Hz, 2H), 7.74
(t, J=7.9 Hz, 1H), 10.74 ppm (brs, 1H); 13C{1H} NMR (100.613 MHz,
CDl3): d=14.1, 22.7, 27.8, 29.1, 29.2, 29.3, 31.8, 32.4, 109.4, 113.1, 166.3,
166.4 ppm; MS (EI, 70 eV, 500 mA): m/z (%): calcd for C12H19NO2:
209.14; found: 210.1 (19) [M+H]+, 166.1 (35) [MÀCNÀOH]+, 164.1 (25)
[MÀCO2H]+, 138.0 (58) [MÀCOOHÀCN]+; HRMS (CI, Cl
ACHTUNGTNER(NUGN NH3),
130 eV, 300 mA): m/z: calcd for C12H19NO2+NH4: 227.17595; found:
277.17580.
Chem. Eur. J. 2010, 16, 3423 – 3433
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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