Yoshikazu Mori and Masahiko Seki
FULL PAPERS
MS m/z [MÀH]À: calcd. for C26H30N2O3S: 450.1977, found:
(s, 3H),2.46–2.40 (m, 2H), 2.43 (q, J=7.3 Hz, 2H),2.35–2.31
(m, 2H), 1.66–1.55 (m, 4H), 1.05 (t, J=7.3 Hz, 3H).
450.1966.
Propiophenone (3e):[18] Yield: 85%; IR (ATR): nmax
=
1
1685 cmÀ1; H NMR (CDCl3): d=7.99–7.95 (m, 2H), 7.58–
7.52 (m, 1H), 7.49–7.43 (m, 2H), 3.01 (q, J=7.2 Hz, 2H),
1.23 (t, J=7.2 Hz, 3H).
Use of PdACHTREUNG(OAc)2 (Table 4, entry 5)
1-Oxo-1-(3-chlorophenyl)propane (3f):[19] Yield: 83%; IR
To a suspension of zinc dust (3.57 g, 54.6 mmol) in a mixed
solvent of THF (7.0 mL) and toluene (4.7 mL) was added
bromine (0.72 mL, 14.0 mmol) below 408C for 5 min. After
the mixture was stirred at 258C for 30 min, it was warmed
(ATR): nmax =1682 cmÀ1 1H NMR (CDCl3): d=7.95–7.92
;
(m, 1H), 7.86–7.82 (m, 1H), 7.55–7.50 (m, 1H), 7.40 (t, J=
8.0 Hz, 1H),2.98 (q, J=7.2 Hz, 2H), 1.23 (t, J=7.2 Hz, 3H).
1-Oxo-1-(3-thienyl)propane (3g):[20] Yield: 57%; IR
up to 508C, and ethyl 5-iodopentanoate
4
(7.16 g,
1
(ATR): nmax =1670 cmÀ1; H NMR (CDCl3): d=8.04 (dd, J=
28.0 mmol) was added at 50–558C for 30 min. The mixture
was stirred at the same temperature for 1 h and cooled
down to 308C. To the mixture were added thiolactone 1a
2.9, 1.3 Hz, 1H), 7.55 (dd, J=5.1, 1.3 Hz, 1H),7.31 (dd, J=
5.1, 2.9 Hz, 1H), 2.92 (q, J=7.3 Hz, 2H), 1.21 (t, J=7.3 Hz,
3H).
(6.77 g, 20.0 mmol), toluene (9.3 mL), PdCATHRE(UGN OAc)2 (4.5 mg,
0.02 mmol) and DMF (1.7 mL, 22.0 mmol), and the mixture
was stirred at 30–358C for 20 h. The mixture was cooled
down to 58C, and 3N HCl (21 mL) was added to the mix-
ture below 208C. The mixture was stirred at 258C for
30 min and was filtered. To the filtrate was added AcOEt
(30 mL), and the organic layer was warmed up to 458C and
evaporated. A part of the residue was analyzed by HPLC
(L-Column, MeCN/THF/0.03M phosphate buffer (K2HPO4/
KH2PO4 =1:1)=40:8:52, 408C, 1 mLminÀ1, 254 nm). The
assay yield of 5 was determined to be 90%. The residue was
purified by silica gel column chromatography (toluene/
AcOEt=15:1) to give 5 as a slightly yellow oil; yield: 7.87 g
(87%). The spectroscopic data of the product were in com-
plete accordance with those described above.
(3aS,4Z,6aR)-2-[1,3-Dibenzyl-2,3,3a,4,6,6a-hexahydro-2-
oxo-1H-thienoACTHRE[UNG 3,4-d]imidazol-4-ylidene]-ethane (6): Mp 89–
918C; [a]1D8: +255.1 (c, 0.5, MeOH); IR (ATR): nmax =1687,
1
1650 cmÀ1; H NMR (CDCl3): d=7.38–7.24 (m, 10H), 5.52
(q, J=6.7 Hz, 1H), 4.97 (d, J=16 Hz, 1H), 4.82 (d, J=
15 Hz, 1H), 4.27 (d, J=7.7 Hz, 1H), 4.21 (d, J=15 Hz, 1H),
4.11–4.06 (m, 1H), 4.03 (d, J=16 Hz, 1H),3.02–2.92 (m,
2H),1.71 (d, J=6.7 Hz, 3H); 13C NMR (CDCl3): d=158.9,
137.7, 137.2, 137.1 (4 s), 128.6, 128.5, 128.0,127.9, 127.5,
127.2, 121.3, 64.4, 59.1 (9d), 46.4, 44.7, 36.9 (3t), 16.8 (q);
SIMS: m/z=351 (M+1); anal. calcd for C21H22N2OS: C
71.97, H 6.33, N 7.99; found: C 71.87, H 6.35, N 8.03.
Assessment of Behavior of Pd in the Fukuyama
Coupling of Thiolactone 1a with Et2Zn 2b (Figure 2)
Typical Procedure for the Synthesis of Ketones 3b–g
by the Reaction of Thiol Esters 1b–h with Et2Zn in
the Presence of Pd/C
Into a suspension of zinc dust (584 mg, 8.93 mmol) in THF
(8.0 mL) and toluene (8.0 mL) was added dropwise bromine
(0.229 mL, 4.46 mmol) at <328C. Thiolactone 1a (1.51 g,
4.46 mmol) was then added to the mixture at 208C followed
by Pd/C D1 (5 wt.%, 475 mg, 0.223 mmol) and toluene
(3.2 mL). Into the mixture was added dropwise Et2Zn 2b
(1.0M hexane solution, 4.46 mL, 4.46 mmol) at <328C fol-
lowed by DMF (1.7 mL). The mixture was warmed up to
35–408C. A sample (4 mL) was periodically taken from the
reaction mixture by syringe with a thick needle under stir-
ring. A part of the sample was transferred to the flask. To
the flask was added 3N HCl and the mixture was stirred at
558C until the alcohol formed was completely dehydrated
into the corresponding olefin. To the flask was added ethyl
acetate and the organic layer was analyzed by HPLC to de-
termine the conversion (L-Column, MeCN/THF/0.03M
phosphate buffer (K2HPO4/KH2PO4 =1:1)=40:8:52, 408C,
1-(4-Methoxyphenyl)-3-oxopentane (3b): Into a suspension
of zinc dust (584 mg, 8.93 mmol) in THF (2.5 mL) and tolu-
ene (2.5 mL) was added dropwise bromine (0.23 mL,
4.46 mmol) at<308C. Thiol ester 1b (1.00 g, 4.46 mmol) in
toluene (1 mL) was then added to the mixture at 208C fol-
lowed by Pd/C D1 (20 wt.%, 123 mg, 0.23 mmol). Into the
mixture was added dropwise Et2Zn (1.1M toluene solution,
Aldrich, 4.05 mL, 4.46 mmol) at under 258C followed by
DMF (1.7 mL). The mixture was stirred at 208C for 17 h.
Into the suspension was carefully added 18% aqueous HCl
(10 mL) at<308C to dissolve excess zinc dust. The mixture
was filtered and the filtrate was separated. The resulting or-
ganic phase was washed three times with water, dried over
anhydrous MgSO4 and evaporated. The residue was purified
by silica gel column chromatography (hexane to hexane/
AcOEt=30/1) to afford ethyl ketone 3b as a yellow oil;
À1
1 m Lm in , 254 nm). The remaining sample was transferred
to a test tube. Allowing the tarry material to settle down to
the bottomof the test tube, supernatant was taken by sy-
ringe and filtered by PTFE membrane filter (0.45 mm).
Amount of Pd in the filtrate was estimated by X-ray fluores-
cent analysis.
1
yield: 814 mg (95%). IR (ATR): nmax =1712 cmÀ1; H NMR
(CDCl3): d=7.10 (d, J=8.7 Hz, 2H), 6.82 (d, J=8.7 Hz,
2H), 3.78 (s, 3H), 2.87–2.82 (m, 2H), 2.72–2.67 (m, 2H),
2.39 (q, J=7.3 Hz, 2H), 1.04 (t, J=7.3 Hz, 3H); EI-MS:
m/z=192 (M+); APCI m/z=193 (M+1).
1
Characterization of Zinc Species using H NMR
1,4-Dioxo-1-phenylhexane (3c):[16] Yield: 95%; IR (ATR):
1
nmax =1713, 1683 cmÀ1; H NMR (CDCl3): d=8:00–7.97 (m,
Et2Zn (1.1M toluene solution, Aldrich) was added to a mix-
ture of toluene-d8, THF-d8 and DMF-d7 (1.4:1:0.7) (v/v/v)
and 1H NMR of the mixture was measured (d=0.33 ppm,
EtZnCH2CH3). To a suspension of Zn dust in a mixture of
toluene-d8, THF-d8 and DMF-d7 (1.4:1:0.7) (v/v/v) was
added Br2 followed by Et2Zn (1.1M toluene solution, Al-
2H), 7.59–7.54 (m, 1H), 7.49–7.43 (m, 2H), 3.32–3.27 (m,
2H), 2.89–2.84 (m, 2H), 2.57 (q, J=7.3 Hz, 2H), 1.10 (t, J=
7.3 Hz, 3H); APCI: m/z=191 (M+1).
Methyl 6-oxooctanoate (3d):[17] Yield: quantitative; IR
(ATR): nmax =1735, 1713 cmÀ1 1H NMR (CDCl3): d=3.67
;
2036
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2027 – 2038