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doi.org/10.1002/ejoc.202100464
Methyl 4-(4-cyanophenyl)butanoate (4c)
4-(4-Morpholino-4-oxobutyl)benzonitrile (4g)
A solution of sodium methoxide (1.5 mL, 1.5 mmol, 1 M in MeOH)
was added to a solution of 2-(4-cyanophenyl)cyclobut-1-en-1-yl
diethyl phosphate (2b) (146 mg, 0.5 mmol) in dry THF (6 mL/
GP4 starting from phosphate 2b (95 mg, 0.3 mmol), CF3CH2ONa
(113 mg, 0.93 mmol), CF3CH2OH (0.9 mL), morpholine (81 mg,
0.93 mmol) and THF (1 mL) gave (Hexane/AcOEt 2:1, Rf =0.17)
°
1 mmol) and the resultant mixture was stirred for 1 h at 23 C. Then
48 mg (60%) of the title compound as a white solid, mp=55.0–
1
°
the reaction mixture was diluted with ether (30 mL), washed with
water (20 mL) and brine (20 mL) and the organic layer was dried
over MgSO4. The solvents were evaporated under reduce pressure
and column chromatography (Hexane/AcOEt 9:1, Rf =0.23) gave
56.0 C. H NMR (400 MHz, CDCl3) δ 7.55–7.53 (m, 2H), 7.29–7.27 (m,
2H), 3.65–3.57 (mm, 6H), 3.40–3.37 (m, 2H), 2.73–2.70 (m, 2H), 2.32–
2.28 (m, 2H), 2.00–1.91 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ
170.9, 147.5, 132.3, 129.3, 119.1, 109.9, 66.9, 66.6, 45.9, 42.0, 35.4,
31.9, 26.0. HRMS (APCI) [M+H]+ Calcd for C15H18N2O2: 259.1441;
found: 259.1444.
1
71 mg (79%) of the title compound as a colorless liquid. H NMR
(300 MHz, CDCl3) δ 7.59–7.56 (m, 2H), 7.30–7.27 (m, 2H), 3.67 (s, 3H),
2.74–2.69 (m, 2H), 2.36–2.31 (m, 2H), 2.01–1.91 (m, 2H), in
accordance with literature.[39]
N-Benzyl-4-(4-cyanophenyl)butanamide (4h)
GP4 starting from phosphate 2b (140 mg, 0.5 mmol), CF3CH2ONa
(183 mg, 1.5 mmol), CF3CH2OH (1.5 mL), benzylamine (161 mg,
1.5 mmol) and THF (2.0 mL) gave (Hexane/AcOEt 2:1!1:2, Rf =
2,2,2-Trifluoroethyl
1-(4-cyanobenzyl)-2,3-dihydro-1H-indene-2-carboxylate (4d)
0.12) 99 mg (78%) of the title compound as a white solid, mp=
GP3 starting from 1b (157 mg, 0.5 mmol), 4-cyanophenylboronic
acid (96 mg, 0.65 mmol), Pd(OAc)2 (1.2 mg, 1 mol%), RuPhos
(4.7 mg, 2 mol%), K3PO4 (0.75 mL), toluene (2 mL), CF3CH2ONa
(183 mg, 1.5 mmol), CF3CH2OH (1.5 mL), THF (1 mL) gave (Hexane/
AcOEt 9:1, Rf =0.40) 130 mg (76%) of the title compound as a
1
°
103.0–103.5 C. H NMR (400 MHz, CDCl3) δ 7.55–7.53 (m, 2H), 7.35–
7.25 (m, 7H), 5.82 (brs, 1H), 4.42 (d, J=5.7 Hz, 1H), 2.71 (t, J=7.7 Hz,
1H), 2.21 (t, J=7.4 Hz, 1H), 2.03–1.96 (m, 2H). 13C{1H} NMR (101 MHz,
CDCl3) δ 172.0, 147.4, 138.3, 132.3, 129.4, 128.9, 128.0, 127.7, 119.1,
110.0, 43.7, 35.6, 35.4, 26.6. HRMS (APCI) [M - H]À Calcd for
C18H18N2O: 277.1346; found: 277.1347.
white solid, mp=90.5–91.5 C. 1H NMR (400 MHz, CDCl3) δ 7.56–
°
7.53 (m, 2H), 7.26–7.16 (m, 2H), 7.11–7.08 (m, 2H), 7.02–6.98 (m, 1H),
6.40–6.38 (m, 1H), 4.59–4.42 (m, 2H), 3.77–3.71 (m, 1H), 3.64–3.57
(m, 1H), 3.43–3.36 (m, 1H), 3.11–3.05 (m, 1H), 3.00–2.95 (m, 1H),
2.68–2.63 (m, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.6, 144.9,
143.1, 140.6, 132.1, 130.5, 127.7, 126.3, 124.9, 124.8, 123.1 (d, J=
277.1 Hz), 119.0, 110.4, 60.4 (q, J=36.5 Hz), 48.5, 48.1, 37.2, 33.1. 19F
NMR (282 MHz, CDCl3) δ À 73.99 (t, J=8.6 Hz). HRMS (APCI) [M+
H]+ Calcd for C20H16F3NO2: 360.1206; found: 360.1213.
4-(2-(Butylthio)cyclobut-1-en-1-yl)benzonitrile (5a)
GP5 starting from 1a (141 mg, 0.5 mmol), 4-cyanophenylboronic
acid (96 mg, 0.65 mmol), Pd(OAc)2 (1.2 mg, 1 mol%), RuPhos
(4.7 mg, 2 mol%), K3PO4 (0.75 mL), toluene (2 mL), NaH (60 mg,
1.5 mmol), 1-butanethiol (270 mg, 3.0 mmol), THF (2 mL) gave
(Hexane/AcOEt 20:1, Rf =0.43) 108 mg (90%) of the title compound
as a yellow solid, mp=50.5–51.0 C. 1H NMR (400 MHz, CDCl3) δ
°
2,2,2-Trifluoroethyl 4-(pyren-1-yl)butanoate (4e)
7.60–7.57 (m, 2H), 7.39–7.36 (m, 2H), 2.88–2.72 (m, 6H), 1.70–1.62
(m, 2H), 1.50–1.41 (m, 2H), 0.96–0.92 (m, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 139.2, 138.8, 135.4, 132.3, 125.5, 119.6, 108.9, 33.0, 31.4,
29.9, 26.1, 21.9, 13.8. HRMS (APCI) [M+H]+ Calcd for C15H17NS:
244.1155; found: 244.1160.
GP3 starting from 1a (145 mg, 0.5 mmol), 1-pyrenylboronic acid
(150 mg, 0.65 mmol), Pd(OAc)2 (1.2 mg, 1 mol%), RuPhos (4.7 mg,
2 mol%), K3PO4 (0.75 mL), toluene (2 mL), CF3CH2ONa (183 mg,
1.5 mmol), CF3CH2OH (1.5 mL), THF (1 mL) gave (Hexane/AcOEt
20:1, Rf =0.18) 133 mg (71%) of the title compound as a yellow
1
°
solid, mp=98.3–99.1 C. H NMR (400 MHz, CDCl3) δ 8.29–8.27 (m,
Butyl(2-(pyren-1-yl)cyclobut-1-en-1-yl)sulfane (5b)
1H), 8.20–8.11 (m, 4H), 8.04–7.99 (m, 3H), 7.86–7.84 (m, 1H), 4.51 (q,
J=8.5 Hz, 1H), 3.42–3.38 (m, 2H), 2.56 (t, J=7.2 Hz, 1H), 2.27–2.20
(m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 172.0, 135.3, 131.5, 131.0,
130.2, 128.9, 127.6, 127.6, 127.5, 126.9, 126.0, 125.2, 125.1, 125.1,
125.0, 125.0, 123.3, 120.4 (q, J=277.6 Hz), 119.0, 60.4 (q, J=
36.5 Hz), 33.3, 32.7, 26.6. 19F NMR (282 MHz, CDCl3) δ À 74.24 (t, J=
8.5 Hz). HRMS (APCI) [M+H]+ Calcd for C22H17F3O2: 371.1253; found:
371.1256.
GP5 starting from 1a (145 mg, 0.5 mmol), 1-pyrenylboronic acid
(160 mg, 0.65 mmol), Pd(OAc)2 (1.2 mg, 1 mol%), RuPhos (4.7 mg,
2 mol%), K3PO4 (0.75 mL), toluene (2 mL), NaH (60 mg, 1.5 mmol),
1-butanethiol (270 mg, 3.0 mmol), THF (2 mL) gave (Hexane!
hexane/DCM 15:1, Rf =0.18) 98 mg (57%) of the title compound as
a yellow solid, mp=113.8–114.5 C. 1H NMR (400 MHz, CDCl3) δ
°
8.56–8.53 (m, 1H), 8.17–7.97 (m, 8H), 3.32–3.30 (m, 2H), 2.94–2.92
(m, 2H), 2.85 (t, J=7.3 Hz, 1H), 1.70–1.67 (m, 2H), 1.47–1.42 (m, 2H),
0.93 (t, J=7.3 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 138.4, 135.2,
131.6, 131.1, 130.6, 130.2, 127.8, 127.5, 127.2, 127.1, 126.0, 125.6,
125.2, 125.12, 125.05, 124.82, 124.80, 32.9, 31.2, 31.2, 30.7, 22.0,
13.8. HRMS (APCI) [M+H]+ Calcd for C24H22S: 343.1515; found:
343.1519.
2,2,2-Trifluoroethyl 4-(benzo[b]thiophen-2-yl)butanoate (4f)
GP3 starting from 1a (143 mg, 0.5 mmol), Pd(OAc)2 (4.5 mg,
1 mol%, 0.02 mmol), XPhos (19 mg, 8 mol%, 0.04 mmol), benzo-
thiophen-2-ylzinc(II) chloride (1.67 mL, 0.65 mmol, 0.39 M), THF
(3 mL), CF3CH2ONa (183 mg, 1.5 mmol), CF3CH2OH (1.5 mL), THF
(1 mL) gave (Hexane/AcOEt 20:1, Rf =0.28) 74 mg (49%) of the title
1
1-(4-(2-(Butylthio)cyclobut-1-en-1-yl)phenyl)ethan-1-one (5c)
compound as a yellow oil. H NMR (400 MHz, CDCl3) δ 7.77 (d, J=
7.8 Hz, 1H), 7.68 (d, J=7.2 Hz, 1H), 7.34–7.25 (m, 2H), 7.03 (s, 1H),
4.47 (q, J=8.4 Hz, 2H), 2.98 (t, J=7.4 Hz, 2H), 2.51 (t, J=7.4 Hz, 2H),
2.15–2.08 (m, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 171.7, 144.67,
140.2, 139.5, 124.3, 123.8, 123.0, 122.3, 121.5, 60.4 (q, J=36.5 Hz),
32.7, 29.9, 26.0. 19F NMR (282 MHz, CDCl3) δ À 74.30 (t, J=8.4 Hz).
HRMS (APCI) [M+H]+ Calcd for C14H13F3O3S: 319.0610; found:
319.0614.
GP5 starting from 1a (143 mg, 0.5 mmol), 4-acetylphenylboronic
acid (107 mg, 0.65 mmol), Pd(OAc)2 (1.2 mg, 1 mol%), RuPhos
(4.7 mg, 2 mol%), K3PO4 (0.75 mL), toluene (2 mL), NaH (60 mg,
1.5 mmol), 1-butanethiol (270 mg, 3.0 mmol), THF (2 mL) gave
(Hexane/AcOEt 20:1, Rf =0.39) 109 mg (83%) of the title compound
as a yellow solid, mp=34.2–35.0 C. 1H NMR (400 MHz, CDCl3) δ
°
7.92 (d, J=8.4 Hz, 2H), 7.39 (d, J=8.4 Hz, 2H), 2.87–2.83 (m, 2H),
Eur. J. Org. Chem. 2021, 3260–3269
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