Crich and Rahaman
JOCArticle
N-[(2-Oxo-1,2,3,4-tetrahydroquinolin-3-yl)acetyl]piperidine
(21). Chromatographic purification over silica gel eluting with
4% methanol/dichloromethane afforded white needles in 82%
acrylate (82 mg, 0.37 mmol) were heated to reflux with
stirring in benzene (4 mL), and a mixture of thiophenol
(10 mg, 0.09 mmol) and AIBN (15 mg, 0.09 mmol) in benzene
(4 mL) was added over 7 h by syringe pump. Stirring was continued
for 3 h before the solvent was removed under vacuum and the
residue purified by chromatography over silica gel eluting with 4%
methanol/dichloromethane to afford a colorless oil in 68% yield:
1H NMR (500 MHz, CDCl3) δ 6.35 (s, 1H), 5.69 (br s, 1H), 5.67
(s, 1H), 4.20 (q, J=7.0 Hz, 2H), 3.45 (d, J=4.0 Hz, 1H), 3.44-3.28
(m, 2H), 3.09 (dd, J = 4.0, 17.0 Hz, 1H), 2.84-2.76 (m, 2H),
2.73 (dd, J = 7.5, 17.5 Hz, 1H), 2.04-1.98 (m, 1H), 1.92-
1.86 (m, 1H), 1.84-1.75 (m, 2H), 1.29 (t, J=7.2 Hz, 3H); 13C
NMR (125 MHz, CDCl3) δ 205.9, 174.1, 166.6, 134.6, 128.9,
61.2, 46.2, 44.1, 42.8, 37.7, 27.1, 22.4, 14.4; ESIHRMS
m/z calcd for C13H19NO4Na (M þ Na)þ 276.1212, found
276.1225.
3-(2-Oxo-2-phenylethyl)tetrahydro-2H-pyran-2-one (35). Thio-
oester 30 (36 mg, 0.1 mmol), PhB(OH)2 (19 mg, 0.15 mmol),
copper(I) thiophene-2-carboxylate (32 mg, 0.17 mmol), tris-p-
tolylphosphine (1.2 mg, 0.004 mmol), and bis(dibenzylideneace-
tone)palladium(0) (1.2 mg, 0.002 mmol) were mixed in dry THF
(5 mL) and heated to 55 °C with stirring for 60 h under N2 gas. The
solvent was removed under vacuum and the residue purified by
chromatography over silica gel eluting with 40% EtOAc/hexanes
toafford a colorlessoil in70% yield: 1H NMR (500 MHz, CDCl3)
δ 8.00 (d J = 7.5 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.48 (t,
J=7.7 Hz, 2H), 4.46 (t, J=5.7 Hz, 2H), 3.62 (dd, J=3.7, 18.2 Hz,
1H), 3.29 (dd, J=6.7, 18.2 Hz, 1H), 3.20-3.14 (m, 1H), 2.23-2.16
(m, 1H), 2.03-1.94 (m, 2H), 1.71-1.63 (m, 1H); 13C NMR (125
MHz, CDCl3) δ 197.7, 174.4, 136.8, 133.6, 128.9, 128.3, 68.9, 40.4,
35.8, 25.4, 22.7; ESIHRMS m/z calcdforC13H14O3Na (M þ Na)þ
241.0841, found 241.0820.
1
yield: mp 138.0-138.4 °C; IR (film) 1680 and 1634 cm-1; H
NMR (500 MHz, CDCl3) δ 7.67 (br s, 1H), 7.20-7.16 (m, 2H),
6.99 (t, J = 7.5 Hz, 1H), 6.73 (dd, J = 1.5, 7.5 Hz, 1H), 3.68-
3.62 (m, 1H), 3.58-3.40 (m, 3H), 3.24-3.14 (m, 3H), 2.83 (t, J =
15.2 Hz, 1H), 2.44-2.38 (m, 1H), 1.70-1.54 (m, 6H); 13C NMR
(125 MHz, CDCl3) δ 173.0, 169.1, 137.1, 128.5, 127.7, 124.1,
123.3, 115.0, 46.8, 43.1, 37.1, 33.2, 31.8, 29.9, 26.7, 25.8, 24.8;
m/z calcd for C16H20N2O2Na (M þ Na)þ 295.1422, found
295.1434.
General Procedure for Thioester Synthesis from the Radical
Adducts. TFA (5 mL) was added dropwise to a stirred solution
of thioanhydride (1 mmol) in dicholoromethane (20 mL) at 0 °C.
After the mixture was stirred for 40 min, toluene (5 mL) was
added and then removed under vacuum. Two further portions
of toluene (5 mL each) were added and stripped off under
vacuum, and the residue was dried under vacuum. For amino
thioanhydrides, the residue was dissolved in DMF (20 mL) and
cooled to 0 °C before 2,4,6-collidine (182 mg, 1.5 mmol) was
dropwise added and the mixture stirred for 1 h at 0 °C. For
hydroxy thioanhydrides, the residue was dissolved in DMF
(20 mL), and the reaction mixture was stirred overnight at room
temperature. For both amino thioanhydrides and hydroxy
thioanhydrides, the resulting reaction mixture was cooled to
0 °C, and alkyl iodide (4 mmol) in DMF (2 mL) was dropwise
added followed by triethylamine (102 mg, 1 mmol) followed by
stirring for 5 h at room temperature. The solvent was removed
under vacuum, the residue was dissolved in EtOAc (50 mL), and
the organic layer was successively washed with water and brine,
dried over Na2SO4, concentrated, and purified by silica gel
column chromatography.
General Procedure for Aldehyde Synthesis from S-Pentynyl-
thioesters. Thiophenol (34 mg, 0.30 mmol) and AIBN (10 mg,
0.06 mmol) in dry degassed benzene (3 mL) was dropwise added
to a refluxing solution of S-pentenylthioester (0.15 mmol) in dry
degassed benzene (3 mL) over 3 h. The reaction mixture was
stirred for an additional 6 h at reflux before the solvent was
removed under vacuum and the residue purified by column
chromatography over silica gel.
Acknowledgment. We thank the NIH (GM62160) for
partial support of this work.
Supporting Information Available: Complete experimental
details for the formation and characterization of compounds
1-6 and full characterization data for compounds 7-9, 11-20,
22-25, and 27-32. Copies of the 1H and 13C spectra of all
compounds. This material is available free of charge via the
Ethyl 2-Methylen-4-oxo-5-(2-oxopiperidin-3-yl)pentanoate (34).
Thioester 28 (44 mg, 0.184 mmol) and ethyl 2-(phenylthiomethyl)-
6796 J. Org. Chem. Vol. 74, No. 17, 2009