F
A. Basante-Avendaño et al.
Paper
Synthesis
Diastereoisomer I
13C NMR (75 MHz, CDCl3): δ = 207.4, 147.8, 146.8, 131.4, 121.8, 118.6,
1H NMR (300 MHz, CDCl3): δ = 9.77 (t, J = 0.97 Hz, 1 H), 6.80 (d, J = 8.0
Hz, 1 H), 6.76 (m, 1 H), 6.70 (ddd, J = 1.0, 1.8, 8.0 Hz, 1 H), 5.95 (s, 2 H),
3.77–3.70 (m, 1 H), 3.15–3.03 (m, 1 H), 2.92 (ddd, J = 1.1, 7.6, 17.6 Hz,
1 H), 2.58–2.47 (m, 1 H), 2.30 (ddd, J = 0.9, 5.2, 17.7 Hz, 1 H), 2.11–
1.88 (m, 4 H), 1.81–1.71 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 209.40, 200.77, 147.66, 146.63, 132.16,
121.78, 109.22, 108.23, 101.04, 57.26, 46.03, 43.82, 36.44, 34.88,
25.67.
109.1, 108.3, 101.1, 57.2, 47.4, 36.3, 34.3, 25.2, 18.1.
HRMS (DART): m/z [M + H]+ calcd for C15H15NO3: 258.11302; found:
258.11413.
trans-Diastereoisomer 23b
Yellowish solid; mp 110–113 °C.
1H NMR (300 MHz, CDCl3): δ = 6.79 (d, J = 8.0 Hz, 1 H), 6.73–6.70 (m, 1
H), 6.69–6.64 (m, 1 H), 5.97–5.94 (m, 2 H), 3.80–3.75 (m, 1 H), 2.79
(ddt, J = 5.3, 7.9, 10.6 Hz, 1 H), 2.64 (dd, J = 17.0, 5.1 Hz, 1 H), 2.60–
2.52 (m, 1 H), 2.39 (dd, J = 8.1, 17.0 Hz, 1 H), 2.34–2.23 (m, 1 H), 2.11–
1.91 (m, 2 H), 1.89–1.80 (m, 1 H), 1.67–1.52 (m, 1 H).
HRMS (DART): m/z [M + H]+ calcd for C15H16O4: 261.11268; found:
261.11368.
Diastereoisomer II
13C NMR (75 MHz, CDCl3): δ = 209.4, 148.5, 146.8, 130.4, 120.2, 118.5,
108.9, 107.5, 101.3, 53.4, 43.7, 33.3, 30.1, 20.8, 18.1.
1H NMR (300 MHz, CDCl3): δ = 9.79 (t, J = 1.0 Hz, 1 H), 6.76 (d, J = 7.9
Hz, 1 H), 6.63 (d, J = 1.7 Hz, 1 H), 6.56 (ddd, J = 0.3, 1.7, 7.9 Hz, 1 H),
5.92 (s, 2 H), 3.68–3.58 (m, 1 H), 3.19–3.07 (m, 1 H), 2.99 (dd, J = 1.1,
7.6 Hz, 1 H), 2.30 (ddd, J = 0.8, 4.9, 17.6 Hz, 1 H), 2.35–2.17 (m, 2 H),
2.06–1.87 (m, 4 H).
(3aR*,7S*,7aS*)-7-(Benzo[d][1,3]dioxol-5-yl)octahydro-1H-indole
(24)
A mixture of nitrile 23a (66 mg, 0.26 mmol, 1 equiv) and PtO2 (19.8
mg, 30% w/w) in glacial acetic acid (3 mL) in a Fisher–Porter appara-
tus was stirred under hydrogen atmosphere (250 psi) at r.t. for 24 h. A
solution of 2 M NaOH (20 mL) was added and the reaction mixture
was extracted with DCM (3 × 20 mL). The organic layer was washed
with brine, dried over Na2SO4, filtered, and concentrated. The crude
residue was purified by column chromatography (silica gel, CHCl3/
MeOH/NEt3, 9:1:0.1) to afford compound 24 as a yellow oil; yield:
56.6 mg (90%).
1H NMR (300 MHz, CDCl3): δ = 6.82 (s, 1 H), 6.74 (brs, 2 H), 5.91 (s, 2
H), 3.23 (t, J = 3.8 Hz, 1 H), 3.17–3.08 (m, 1 H), 2.93–2.86 (m, 2 H),
2.12–2.05 (m, 1 H), 1.98–1.85 (m, 3 H), 1.65–1.50 (m, 3 H), 1.34–1.25
(m, 3 H).
7-(Benzo[d][1,3]dioxol-5-yl)-4,5,6,7-tetrahydro-1H-indole (22)
To a solution of 21 (50 mg, 0.19 mmol) in MeOH (4 mL) at 0 °C were
added ammonium acetate (30 mg, 0.38 mmol) and 4 Å molecular
sieves (50 mg). After stirring for 2 h at 0 °C, MeOH was evaporated off
from the reaction flask and the residue was partitioned between H2O
and EtOAc. The mixture was extracted with EtOAc (3 × 10 mL), dried
(Na2SO4), filtered, and concentrated in vacuo. After column chroma-
tography (silica gel, hexane/EtOAc, 15:1), 22 was obtained as a red-
dish oil; yield: 37 mg (80%).
1H NMR (300 MHz, CDCl3): δ = 7.51 (br s, 1 H), 6.74 (d, J = 8.5 Hz, 1 H),
6.65–6.60 (m, 3 H), 6.01 (t, J = 2.6 Hz, 1 H), 5.92 (s, 2 H), 3.91 (t, J = 6.7
Hz, 1 H), 2.63–2.59 (m, 2 H), 2.18–2.10 (m, 1 H), 1.95–1.85 (m, 1 H),
1.78–1.67 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 147.7, 146.0, 138.4, 120.4, 108.3, 108.2,
100.9, 63.6, 44.3, 43.3, 38.9, 31.3, 27.4, 25.8, 24.9.
HRMS (DART): m/z [M + H]+ calcd for C15H19NO2: 246.14940; found:
246.14854.
13C NMR (75 MHz, CDCl3): δ = 147.9, 146.3, 139.2, 129.0, 121.2, 118.4,
116.5, 108.6, 108.5, 107.2, 101.0, 41.5, 34.5, 23.1, 22.7.
HRMS (DART): m/z [M + H]+ calcd for C15H15NO2: 242.11810; found:
242.11773.
Funding Information
2-(3-(Benzo[d][1,3]dioxol-5-yl)-2-oxocyclohexyl)acetonitrile (23)
Dirección General de Asuntos del Personal Académico, Universidad
Nacional Autónoma de México (DGAPA-UNAM) for project number
IN205318 and for a postdoctoral fellowship for A.S.-E. Consejo Nacio-
nal de Ciencia y Tecnología (CONACYT) for grants numbers 767928
A solution of enol acetate 10 (150 mg, 0.58 mmol) and iodoacetoni-
trile (83 μL, 1.15 mmol) in 1,2-DCE (5.8 mL) was refluxed under nitro-
gen for 10 min. Then, DLP was added portionwise (69.4 mg, 0.174
mmol) every hour until the complete consumption of starting materi-
al (monitored by TLC). The reaction mixture was concentrated under
reduced pressure and the residue purified by column chromatogra-
phy (silica gel, hexane/EtOAc/NEt3, 20:1:0.1) to afford compound 23
as a mixture of diastereoisomers (24:1); combined yield: 124 mg
(84%).
(A.B.-A.) and 620665 (V.E.G.-A.).
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Acknowledgment
The authors thank Angeles Peña-González, Elizabeth Huerta-Salazar,
Beatriz Quiroz, and Carmen García-González for technical support
(NMR and MS). We also thank Prof. Fernando Sartillo-Piscil (BUAP)
and Prof. Marcos Hernández-Rodríguez (UNAM) for helpful sugges-
tions during the preparation of the manuscript.
cis-Diastereoisomer 23a
White solid; mp 106–109 °C.
1H NMR (300 MHz, CDCl3): δ = 6.77 (d, J = 7.9 Hz, 1 H), 6.62 (d, J = 1.7
Hz, 1 H), 6.56 (dd, J = 1.7, 7.9 Hz, 1 H), 5.93 (s, 2 H), 3.58 (dd, J = 5.4,
12.3 Hz, 1 H), 2.88–2.80 (m, 1 H), 2.71 (dd, J = 5.0, 17.1 Hz, 1 H), 2.49
(ddd, J = 2.4, 4.2, 9.9 Hz, 1 H), 2.43 (dd, J = 8.2, 17.1 Hz, 1 H), 2.34–2.29
(m, 1 H), 2.10–2.04 (m, 1 H), 1.97–1.91 (m, 2 H), 1.68–1.58 (m, 1 H).
Supporting Information
Supporting information for this article is available online at
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G