Synthesis of DibenzoACHTUNGTRENNUNG[a,g]quinolizin-8-one Derivatives
FULL PAPER
Table 1. Ruthenium-catalyzed oxidative coupling of isoquinolones with alkynes.[a]
corded with Bruker AV300 and AV400
NMR spectrometers with CDCl3 as
solvent. Chemical shifts of 1H, 19F, and
13C NMR spectra are reported in parts
per million (ppm). The residual sol-
vent signals were used as references
and the chemical shifts were converted
into the TMS scale (CDCl3: dH =
7.26 ppm). All coupling constants (J
values) are reported in Hertz (Hz).
Multiplicities are reported as follows:
singlet (s), doublet (d), doublet of
doublets (dd), doublet of doublet of
doublets (ddd), doublet of triplets (dt),
triplet (t), triplet of doublets (td),
quartet (q), and multiplet (m).
Column chromatography was per-
formed on silica gel 200–300 mesh. IR
spectra were recorded as KBr disks
with a Nicolet 380 FTIR spectrometer.
MS (EI) and HRMS were recorded
with Thermo Finnigan TRACE DSQ
and Varian 7.0 T FTICR-mass spec-
trometers, respectively.
General procedure A: Preparation of
alkyne insertion ruthenium complex 4:
A
mixture of isoquinolone (1)
(0.20 mmol, 1.0 equiv), alkyne (2)
(0.4 mmol,
cymene)]2
2.0 equiv),
(122.0 mg,
[RuCl
0.20 mmol,
2ACHTUNGTRENNUNG(p-
1.0 equiv), and NaOAc (49.2 mg,
0.60 mmol, 2.0 equiv) were weighed in
a Schlenk tube equipped with a stir
bar. Anhydrous MeOH (10.0 mL) was
added and the mixture was stirred at
408C for 48 h under an Ar atmos-
phere. The mixture was then diluted
with CH2Cl2 and transferred to
a
[a] Isolated product yield.
round-bottom flask. Silica was added
to the flask and volatiles were evapo-
rated under reduced pressure. Purifica-
tion was performed by flash column
chromatography on silica gel.
lones with alkynes. All of the key intermediates involved in
Typical procedure for the preparation of cyclometalated complex 5: Pyri-
dine (28.4 mg, 0.36 mmol) was added to a solution of [RuCl2ACTHUNTRGNEU(GN p-cymene)]2
À
acetate-assisted C H bond activation (5), alkyne insertion
À
À
of the Ru C bond (4), and oxidative coupling of the C N
bond (6) were isolated and determined by X-ray crystallo-
graphic analysis of their single crystals. The study clearly
showed a RuII–Ru0–RuII catalytic cycle. These mechanism
(111.2 mg, 0.18 mmol) in CH2Cl2 (20 mL) at RT. After vigorous stirring
for 3 h, NaOAc (36.9 mg, 0.45 mmol) and 1 (0.3 mmol) were added to the
solution with Et3N (1.0 mL), and vigorous stirring was continued for 20 h.
When the reaction was complete, the solution was transferred to a
round-bottom flask. Silica was added to the flask and volatiles were
evaporated under reduced pressure. The crude product was purified by
column chromatography on silica gel.
insights should be helpful for the development of more effi-
II
À
cient Ru -catalyzed C H bond functionalization reactions
with alkyne systems. We also developed an efficient and
Transformation of complex 5 into 4 through alkyne insertion: A mixture
of 5 (0.05 mmol, 1.0 equiv) and 1,2-diphenylethyne (0.1 mmol, 2.0 equiv)
was weighed in a Schlenk tube equipped with a stir bar. Anhydrous
MeOH (5.0 mL) was added and the mixture was stirred at 408C for 24 h
under an Ar atmosphere. The mixture was diluted with CH2Cl2 and trans-
ferred to a round-bottom flask. Silica was added to the flask and volatiles
were evaporated under reduced pressure. Purification was performed by
flash column chromatography on silica gel.
highly regioselective [{RuCl
tive annulation of isoquinolones with alkynes to synthesize
dibenzo[a,g]quinolizin-8-one derivatives with a broad sub-
2ACHTUNGERTN(NUNG p-cymene)}2]-catalyzed oxida-
ACHTUNGTRENNUNG
strate scope. Further studies to explore ruthenium-catalyzed
À
oxidative C H bond transformations are under investiga-
tion.
Preparation of ruthenium(0) complex 6ja: Compound 4ja (76.0 mg,
0.1 mmol) was weighed in a Schlenk tube equipped with a stir bar. Anhy-
drous PhCl (2.0 mL) was added and the mixture was stirred at 1208C for
24 h under an Ar atmosphere. The mixture was diluted with CH2Cl2 and
transferred to a round-bottom flask. Silica was added to the flask and
volatiles were evaporated under reduced pressure. The title compound
6ja was isolated by column chromatography (EtOAc/petroleum ether=
1:15) as a tan-yellow solid (43 mg, 57%). M.p. 2158C (decomposed);
Experimental Section
General procedures: All the reactions were carried out under an argon
atmosphere by using standard Schlenk techniques. 1H (300 MHz or
400 MHz), 19F (376 MHz), and 13C NMR (75 MHz or 100 MHz) were re-
Chem. Eur. J. 2012, 00, 0 – 0
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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