4-iminocyclobutenones: Synthesis and building-blocks of aminohydroquinones and annulated quinolines

Article abstract of DOI:10.1055/s-0029-1218767

Two methods are presented for the synthesis of the title compounds starting from cyclobutenediones: an alkoxide substitution approach and a Staudinger reaction. Unsaturated lithiumorganyls may be added to the remaining carbonyl group and on heating lead to ring enlargement in a cascading process. 4-Alkenyl or 4-aryl derivatives yield aminophenols or -naphthols; 4-alkynyl compounds give cyclopenta-annulated quinolines. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218767

PAPER
2027
4-Iminocyclobutenones: Synthesis and Building-Blocks of Aminohydroquinones
and Annulated Quinolines
S
ynthesis and Tran
e
sformation
r
Reactio
r
ns of 4-I
i
minoc
y
t
clobutenonesOppermann,a Michael Stranberg,b Harold W. Moore,b Ernst Schaumann,*a Gunadi Adiwidjajac
a
Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstr. 6, 38678 Clausthal-Zellerfeld, Germany
Fax +49(5323)722858; E-mail: ernst.schaumann@tu-clausthal.de
b
c
Department of Chemistry, University of California, Irvine, CA 92717, USA
Mineralogisch-Petrographisches Institut der Universität Hamburg, Grindelallee 46, 20146 Hamburg, Germany
Received 14 January 2010; revised 22 March 2010
The final step in the conversion of 1 into 3 involves the
displacement of trifluoroacetate in 2 by water in an SN2¢
reaction; analogously, alcohols can be used to supply cy-
clobutenone acetals.6–8 We now find that amines can be
Abstract: Two methods are presented for the synthesis of the title
compounds starting from cyclobutenediones: an alkoxide substitu-
tion approach and a Staudinger reaction. Unsaturated lithiumorga-
nyls may be added to the remaining carbonyl group and on heating
lead to ring enlargement in a cascading process. 4-Alkenyl or 4-aryl employed to give iminocyclobutenones. Thus, treatment
of 1 (R1 = i-Pr) with anilines or 3-aminopyridine yields
iminocyclobutenones 7, the title compounds of the present
study (Scheme 2). For the given examples, yields are
good to excellent (Table 1); however, imines formed with
alkylamines, with the exception of N-tert-butylamine,
were found to be too sensitive to hydrolysis during work-
derivatives yield aminophenols or -naphthols; 4-alkynyl com-
pounds give cyclopenta-annulated quinolines.
Key words: alkenes, Schiff bases, electrocyclic reactions, ring ex-
pansion, ring opening
Cyclobutenones have attracted wide attention as synthetic up, thus giving cyclobutenediones 3 as the final product.
building-blocks primarily due to their facile electrocyclic
R2
ring opening to reactive conjugated ketenes, intermediates
that lead to a variety of useful stable products. This chem-
istry has been studied by a number of research groups.1–5
R1N
H2O
OH
Ph
i-PrO
1. PhLi
2. TFAA
3. R1NH2
An important feature of the methodology rests on the sim-
ple substitution of an alkoxy group in the readily available
dialkyl squarates 1 by a variety of other substituents upon
treatment with carbanions to give 3 in a one-pot reaction
sequence.6–8 Subsequent 1,2-addition of unsaturated orga-
nometallics yields 4 which sets the stage for an electrocy-
clic cascade to, for example, hydroquinones 6 via the
corresponding dienylketene 5 (Scheme 1).
8a–j
R1N
O
O
O
R2Li
i-PrO
Oi-Pr
i-PrO
Ph
R2
1
7a–e
R1N
CF3SO3Me
(R1 = i-Pr)
OMe
Ph
i-PrO
9a–c
Compared to cyclobutene(di)ones, the corresponding het-
eroanalogues have received relatively little attention.
Thione derivatives have been prepared as such9 or as
thioacetals10,11 and there are scattered reports on cy-
clobutenimines although no general synthesis is avail-
able.12–14 The present study fills this gap and opens the
door for a comparison of the cyclobutenone chemistry
outlined in Scheme 1 with that of the nitrogen congeners.
Ph
PhN
TMSCl
34%
OTMS
8e
i-PrO
Ph
10
Scheme 2 Synthesis of iminocyclobutenones 7 and reaction with
organometallics
M
R3
1.
R3
R3
1. R2M
2. TFAA
R1O
R1O
O
R3
R1O
R1O
O
O
O
O
O
O
H2O
Δ
2. H2O
HO
HO
R1O
OH
HO
R1O
OCOF3
R1O
R2
R1O
R2
R2
R2
R2
1
2
3
4
5
6
Scheme 1 Modification of squarates 1 and electrocyclic ring opening to hydroquinones 6
SYNTHESIS 2010, No. 12, pp 2027–2038
x
x.
x
x
.
2
0
1
0
Advanced online publication: 05.05.2010
DOI: 10.1055/s-0029-1218767; Art ID: T01110SS
© Georg Thieme Verlag Stuttgart · New York

2028
G. Oppermann et al.
PAPER
Another limitation of the method described in Scheme 2 be silylated to silyl ether 10 (Scheme 2). Products 8, 9 can
was found in attempts to use 4-aminopyridine. Here, no be isolated without competing hydrolysis of the imino
reaction was observed apparently due to the reduced nu- unit. However, hydrolysis can be achieved by stirring with
cleophilicity of the conjugated amino group. However, we dilute hydrochloric acid to give the corresponding oxo
found that the Staudinger reaction15 of cyclobutenediones compound as shown for the conversion of imine 8b into
3 (R1 = i-Pr, R2 = Ph) with iminophosphoranes offers an cyclobutenone 11 (Scheme 4).
alternative (Scheme 3). This method gave an even better
yield of iminocyclobutenone 7a and, furthermore allowed
Table 2 Addition of Organometallics to Iminocyclobutenones 7
the synthesis of imine 7f bearing the 4-pyridyl substituent
(Table 1).
Starting material Reagent R2Li
Product Yield (%) of 8 or 9
7a
7a
7a
7a
7a
7b
7c
7d
7e
7f
H2C=CHLi
H2C=CMeLi
PhLi
8a
8b
8c
8d
8e
8f
46
82
96
59
89
67
Ph3P=NR1
O
O
R1N
O
benzene, heat
i-PrO
Ph
i-PrO
Ph
7a R1 = Ph
3
TMSCH2C≡CLi
PhC≡CLi
PhC≡CLi
PhC≡CLi
PhC≡CLi
PhC≡CLi
PhC≡CLi
PhLi
7f R1 = 4-pyridyl
Scheme 3 Staudinger reaction of cyclobutenedione 3
Table 1 Synthesis of Cyclobutenimines 7 from Diisopropyl
Squarate (1) According to Scheme 2 or from Cyclobutenedione 3
(Scheme 3)
a
8g
8h
8i
–
86
80
36
60
70
87
Compound R1
Method of scheme Yield (%)
7a
Ph
2
3
83
69
8j
7a
7a
7a
9a
9b
9c
7b
7c
7d
7e
7f
4-MeOC6H4
4-F3CC6H4
2
2
2
2
3
85
71
52
50
68
3-MeC6H4Li
3-MeOC6H4Li
2,4,6-Me3C6H2
3-H2NC6H4N
4-H2NC5H4N
a The compound was generated and used in situ for the synthesis of
25d (Table 4).
O
In general, iminocyclobutenones 7 are characterized by IR
absorptions at approximately 1690 cm–1 (imino stretch)
and 1750 cm–1 (carbonyl stretch); the 13C NMR spectra
show resonances for the imino and carbonyl carbons at
approximately 165 and 188 ppm, respectively. Interest-
ingly, only one set of NMR data is observed though inver-
sion at the imino nitrogen should be slow on the NMR
time scale (vide infra for 16, 22, 27). This indicates that
only one isomer is formed, but there is no clue as to struc-
ture assignment.
dil. HCl, THF
89%
OH
Ph
8b
i-PrO
11
Scheme 4 Hydrolysis of iminocyclobutenone 8b
It should be noted that product 11 is regioisomeric with 4
(R1 = i-Pr, R2 = Ph, R3 = Me), formed directly from dione
3. Thus, the imino group in 7 functions as a protective
group for one oxo unit directing the addition of the lithi-
As noted above, additions of sp2-hybridized carbon-based umorganyl to the otherwise less reactive vinylogous ester
nucleophiles to cyclobutenediones provide 1,2-adducts unit in 7. In fact, the imino group appears to be a general
and they can function as precursors to a variety of ring ex-
panded products via an electrocyclic cascade (Scheme 1).
It was of interest to study analogous reactions of iminocy-
clobutenones 8 and 9 where it is an open question as to
whether a dienylketenimine intermediate 12 will allow
ring-closure reactions similar to those observed for the
more electrophilic16 dienylketenes 5 (Scheme 1).
and efficient protective group in cyclobutenone chemistry.
Thermolysis of cyclobutenimines 8a,b in refluxing p-xy-
lene followed by rapid workup to avoid oxidation gave
aminophenols 14a,b as the sole product (Scheme 5). This
result is consistent with the paradigm that the ring expan-
sion of iminocyclobutenes proceeds via a mechanism
analogous to that described for the corresponding cy-
clobutenones (Scheme 1), that is, the switch from an inter-
Lithiumorganyls give a smooth 1,2-addition to the carbo-
nyl group in iminocyclobutenones 7 (Scheme 2). The re- mediate dienylketene to a dienylketenimine does not
action mixture may be quenched with water to give change the reaction route. It may be noted that heat is re-
tertiary alcohols 8 or the alkoxide intermediate may be quired; the ring expansion is obviously not sufficiently
methylated to provide ethers 9 (Table 2); alcohol 8e can supported by the oxy-anion, formed as an intermediate on
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

PAPER
Synthesis and Transformation Reactions of 4-Iminocyclobutenones
2029
of 9a gave aminonaphthalene 18 (X = H) in 81% yield.
For the 3-tolyl and 3-methoxy derivatives 9b,c there are
two possible options for ring closure, p- (‘attack a’) or o-
substitution (‘attack b’) relative to substituent X. Not un-
expectedly, mixtures of 18/19 were formed with a clear
preference for the ‘p-product’ 18 (Table 3). This is in line
with the smaller steric shielding of position ‘a’ and with a
polarized transition state of the electrocyclic process. The
same competition of two substitution pathways was ob-
served earlier for the cyclization of the ketene congeners
of ketenimines 17.18 In that case, the cyclization was
found to be less selective, demonstrating the higher elec-
trophilicity and thus lower selectivity for the ketene attack
as compared to the ketenimine. In addition, the smaller
carbonyl group in ketenes relative to the imino unit in 17
would be expected to further reduce selectivity.
R2
Ph
R2
Ph
p-xylene
heat
PhN
8a,b
OH
PhN
i-PrO
OH
i-PrO
12
13
R2
PhNH
i-PrO
OH
Ph
14a R2 = H 42%
14b R2 = Me 88%
Scheme 5 Thermolysis of 4-alkenylcyclobutenimines 8a,b
addition of lithiumorganyls to cyclobutenones
(Scheme 2).
7
Table 3 Products of the Ring Expansion of 4-Aryl-4-methoxycy-
clobutenimines 9
To emphasize once again the regiocontrol available with
iminocyclobutenones as compared to the related cy-
clobutenones, note that aminophenol 14b (arising from
8b, Scheme 5) bears a substitution pattern different from
that of the hydroquinone that would arise form the corre-
sponding cyclobutenone 4 (Scheme 1).
Starting
material
Substituent Product
Yield
(%)
Product
19
Yield
(%)
X
18
9a
9b
9c
H
18a
18b
18c
81
40
57
–
–
Me
OMe
19a
19b
11
18
The thermolysis studies were extended to include the ring
expansion of 4-aryl analogues. This resulted in a viable
route to aminonaphthols as shown for the ring expansion
of 8c (Scheme 6). However, the initially formed air-sensi-
tive aminonaphthol 15 was not isolated, but oxidized
(Ag2O)17 directly to iminonaphthoquinone 16, isolated in
59% yield (Scheme 6). The NMR spectra of 16 are quite
complex obviously due to slow inversion at the imino ni-
trogen and formation of E/Z isomers.
While there is no reason to doubt the concerted nature of
the electrocyclizations of dienylketenes such as 5 or dien-
ylketenimines such as 12, ring closure of the correspond-
ing enynylketene intermediates arising from 8d–j and 10
is likely proceed via a diradical intermediate as was ob-
served for the corresponding 4-alkynylcyclobuten-
ones.19,20
The ring expansion studies were further expanded to in-
clude the ethers 9 (Scheme 7). For example, thermolysis
Interestingly, the phenyl group on the imino nitrogen al-
lows additional delocalization of an unpaired electron and
apparently this opens additional avenues for cyclization.
For example, thermolysis of 4-alkynylcyclobutenimines
8d–g results in a novel cyclization mode, yielding cyclo-
penta-annulated quinolines 25 (Scheme 8, Table 4). This
unusual structure was unambiguously established by an
X-ray structural analysis of 25a (Figure 1).21
NPh
NHPh
p-xylene
heat
i-PrO
Ph
i-PrO
Ph
Ag2O
8c
O
16
OH
15
(59%)
Scheme 6 Thermolysis of 4-phenylcyclobutenimine 8c
NHPh
i-PrO
attack a
Ph
X
NPh
OMe
i-PrO
Ph
•
PhCl, heat
18
9a–c
a
X
PhHN
X
OMe
b
i-PrO
Ph
17
attack b
OMe
19
Scheme 7 Aminonaphthyl ethers from ethers 9
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

2030
G. Oppermann et al.
PAPER
R1
OMe
N
from 8f
i-PrO
Ph
R2
N
i-PrO
Ph
Ph
R1
OR3
N
O
i-PrO
21
R2
22 (16%)
Δ
8d–g,i,j
Ph
R1
R1
OR3
N
N
20
i-PrO
i-PrO
R2
R2
OR3
Ph
OR3
Ph
23B
23A
R3 = H
R1
R1
N
HN
i-PrO
i-PrO
R2
– 2 H
R2
Ph
O
Ph
OH
25
24
N
9
N
N
N
i-PrO
i-PrO
Ph
Ph
Ph
25eB
O
Ph
25eA
O
Scheme 8 Ring enlargement of 4-alkynylcyclobutenimines
Table 4 Cyclopenta[b]quinolin-1-ones 25a–d, Cyclopenta [b][1,n]-
naphthyridin-4-ones 25e,f (n = 5–7) and Cyclopentenes 26,27
Starting Product R1
material
R2
R3
Yield (%)
8d
8e
8f
25a
25b
25c
25d
27
H
CH2TMS
H
H
H
H
H
H
12
49
49
36
53
H
Ph
Ph
Ph
4-OMe
4-CF3
8g
8h
8i
2,4,6-Me3 Ph
25eA
25eB
3-aza
Ph
12
7
8j
25f
26
4-aza
H
Ph
Ph
H
22
19
Figure 1 X-ray crystal structure of compound 25a
10
TMS
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

PAPER
Synthesis and Transformation Reactions of 4-Iminocyclobutenones
2031
Formation of 25 arises from diradical ring closure on the
o-position in the N-phenyl substituent. Moreover, the pri-
mary cyclization product 24 apparently undergoes dehy-
drogenation. Possible hydrogen acceptors might be
iminoquinones as formed from diradical 21. In fact, an
iminoquinone 22 could be isolated from 8f; other dehy-
drogenation partners are conceivable and may also ac-
count for the relatively low yield of 25 in the complex
product mixture.
Interestingly, 4-pyridyl derivatives 8i,j follow the same
pathway as 4-aryl derivatives 8d–g (Table 4). However,
starting from the unsymmetrical 4-(3-pyridyl) compound
8i, two cyclization modes are possible and both were con-
firmed by the isolation of 25eA and 25eB (Scheme 8,
Table 4). A characteristic spectroscopic feature of 25eA is
a broad singlet in the 1H NMR spectrum at d = 9.44 for
H-9 (Scheme 8).
Figure 2 X-ray crystal structure of compound 27
The dehydrogenation of intermediate 24 was suppressed
by starting with the silyl ether 10 (R3 = TMS). Here, 26, a
silylated tautomer of alcohol 24, was isolated (Scheme 9).
Evidence for the suggested structure comes from the H
NMR spectrum showing the cyclopentyl methine hydro-
gen at 5.53 ppm and from NOE experiments.
All air- or water-sensitive reactions were carried out in oven dried
glassware under a slight positive pressure of N2 or argon (as indicat-
ed), which was dried by passage through a column of KOH/Drierite.
Air and moisture-sensitive liquids were transferred via syringe
through a rubber septum. THF was degassed with N2 and then
passed through two 4 × 36 inch columns of anhyd neutral A-2 alu-
mina (8 × 14 mesh; LaRoche Chemicals; activated under a flow of
argon at 350 °C for 3 h) to remove H2O. Xylenes, toluene, benzene,
Et3N, and CH2Cl2 were distilled from CaH2 at atmospheric pressure.
Unless specified as anhyd, all solvents were unpurified reagent
grade. Petroleum ether (PE) used refers to the fraction boiling in the
range 60–70 °C. Flash or column chromatography was performed
using Merck silica gel (230–400 mesh). Radial chromatography
was performed on glass plates coated with Merck silica gel, TLC
grade 7749, with gypsum binder and fluorescent indicator. Subli-
mation was performed using a Büchi oven model GHR-51 equipped
with a sublimation assembly. Analytical TLC analyses were per-
formed on E. Merck silica gel 60 F254 coated on plastic or glass.
Melting points were taken on a Büchi 510 or Dr. Totolli melting
point apparatus and are not corrected.
1
N
H
10
23 (R3 = TMS)
Ph
OTMS
i-PrO
Ph
26
N
8h
i-PrO
Ph
Ph
O
IR spectra were recorded on a Perkin-Elmer 1620 single beam or a
Bruker Vektor 22 FT spectrophotometer. IR recordings were taken
in CDCl3 unless otherwise specified. 1H and 13C NMR spectra were
recorded on Bruker ARX 400 (100 MHz), GN 500 MHz or Omega
500 MHz NMR instruments in CDCl3. All NMR recording were
referenced to CHCl3 resonances (7.26 and 77.0 ppm), unless other-
wise specified. Mass spectra were recorded on a Hewlett Packard
instrument HP 5989B. High-resolution mass spectra (HRMS) were
obtained on a VG Analytic 7070E spectrometer. Elemental analyses
were performed by Robertson Laboratories, Inc., Madison, NJ. Re-
crystallization of compounds were carried out at r.t., unless other-
wise indicated.
27
Scheme 9 Ring enlargement of 4-silyl ether 10 and of N-mesityl de-
rivative 8h
In accord with the suggested mechanism, N-mesityl deriv-
ative 8h where methyl substitution prevents the cycliza-
tion to a 25-type product gives cyclopentene 27. This is
assumed to arise via a H-atom abstraction from the proxi-
mal hydroxy group in a diradical intermediate analogous
to 23A (R3 = H).
3-Isopropoxy-4-N-(phenyl)imino-2-phenylcyclobut-2-en-1-ones
7a-e; General Procedure
The structure of 27 was established by a single-crystal X-
ray investigation (Figure 2).22 Interestingly, the observed
E-configuration of the exocyclic C=C unit in 27 speaks
against an intramolecular hydrogen transfer from the hy-
droxy group in 23A (R3 = H). Although the yields of prod-
ucts 22 (16%), 25 (7–49%), 26 (19%), 27 (53%) have yet
to be optimized, these unusual structures give new evi-
dence of the versatility of iminocyclobutenone chemistry.
Under N2, a 100 mL one-necked round-bottomed flask equipped
with a magnetic stirring bar and rubber septum was charged with
THF (30 mL) and PhBr (2.0 mL, 19 mmol) and cooled to ca. –78 °C
for 15 min. Then n-BuLi (11.3 mL of a 1.6 M solution in hexane,
18.1 mmol) was added in a dropwise manner. The reaction mixture
was stirred for 30 min at ca. –78 °C, then transferred via cannula un-
der positive pressure of N2 to a 250 mL one-necked round-bottomed
flask equipped with a magnetic stirring bar and rubber septum,
charged with THF (40 mL) and 18,23 (R1 = i-Pr; 3.0 g, 15.1 mmol)
and also kept at –78 °C. The resulting solution was treated with
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

2032
G. Oppermann et al.
PAPER
TFAA (2.7 mL, 19.4 mmol) followed by the addition of a freshly
distilled arylamine (for 7a–d; 20 mmol or the quantity given below)
or pyridylamine (for 7e; 20 mmol or the quantity given below) in a
dropwise manner and subsequently warmed to r.t. This solution was
stirred for ca. 2 h when TLC analysis indicated no change in the
product pattern. This was followed by a brine quench (15 mL) and
the aqueous phase was extracted with Et2O (2 × 50 mL). The com-
bined organic layers were washed with brine (2 × 50 mL), dried
(MgSO4), filtered, and concentrated to a viscous dark yellow oil.
Column chromatography of the oil (elution with 20:1 mixture of
hexanes–EtOAc) furnished the product. Note that occasionally after
chromatography there was an impurity that had a similar Rf value as
7, which could be removed by sublimation in a Büchi microsubli-
mation oven attachment at 100 °C (0.1–0.2 mm Hg) or the desired
product was obtained by recrystallization from CH2Cl2–pentane.
HRMS (CI): m/z calcd for C20H16F3NO2: 359.1133; found:
359.1132.
3-Isopropoxy-2-phenyl-4-N-(2,4,6-trimethylphenyl)iminocy-
clobut-2-en-1-one (7d)
Prepared from PhLi (11 mL, 2 M in Bu2O, 22 mmol) and 1 (R1 = i-
Pr; 3.96 g, 20 mmol), then TFAA (3.7 mL, 5.56 g, 26.6 mmol) and
2,4,6-trimethylaniline (5.6 mL, 5.4 g, 40 mmol); yellow solid; yield:
3.47 g (52%); mp 101 °C.
IR (KBr): 2981, 1772, 1693, 1582, 1407, 1338, 1089, 1049, 788,
759, 693 cm–1.
1H NMR (200 MHz): d = 7.95–7.85 (m, 2 H), 7.50–7.30 (m, 4 H),
6.84 (d, J = 0.5 Hz, 2 H), 6.06 (sept, J = 6.2 Hz, 1 H), 2.26 (s, 3 H),
2.13 (s, 6 H), 1.62 (d, J = 6.2 Hz, 6 H).
13C NMR (50 MHz): d = 186.4, 185.8, 168.3, 154.5, 143.3, 133.1,
130.3, 128.8, 128.7, 128.5, 126.9, 126.5, 79.2, 23.2, 20.8, 18.3.
3-Isopropoxy-2-phenyl-4-N-phenyliminocyclobut-2-en-1-one
(7a)
Prepared using aniline (2.8 mL, 29 mmol); yellow solid; yield: 3.65
g (83%); mp 91–93 °C.
MS (70 eV): m/z (%) = 333 (75, [M]+), 290 (20), 262 (40), 234 (23),
204 (5), 145 (100), 117 (20), 89 (30), 77 (6).
IR (KBr): 3061, 2984, 2341, 2252, 1756, 1666, 1566, 1494, 1410,
3-Isopropoxy-2-phenyl-4-N-(3-pyridyl)iminocyclobut-2-en-1-
one (7e)
762, 692 cm–1
.
Prepared from PhLi (3 mL, 2 M in Bu2O, 6 mmol) and 1 (R1 = i-Pr;
1.2 g, 6.1 mmol), then TFAA (1.1 mL, 1.66 g, 7.9 mmol) and 3-py-
ridylamine (1.13 g, 12 mmol); yellow solid; yield: 0.88 g (50%);
mp 109 °C.
1H NMR (200 MHz): d = 7.90–8.00 (m, 2 H), 7.15–7.50 (m, 8 H),
7.22–7.20 (m, 1 H), 6.16 (sept, J = 6.2 Hz, 1 H), 1.59 (d, J = 6.2 Hz,
6 H).
13C NMR (50 MHz): d = 187.3, 185.8, 167.9, 153.8, 145.8, 130.3,
128.8, 128.7, 128.6, 126.9, 126.2, 123.6, 78.8, 23.2.
IR (KBr): 1758, 1668, 1556, 1420, 1088, 1025, 798, 704, 688 cm–1.
1H NMR (200 MHz): d = 8.62 (d, J = 2.1 Hz, 1 H), 8.43 (dd, J = 1.5,
4.7 Hz, 1 H), 8.0–7.80 (m, 3 H), 7.55–7.35 (m, 3 H), 7.35–7.28 (m,
1 H), 6.13 (sept, J = 6.2 Hz, 1 H), 1.61 (d, J = 6.2 Hz, 6 H).
13C NMR (50 MHz): d = 186.2, 185.4, 170.1, 155.3, 147.0, 146.2,
142.0, 130.7, 129.7, 128.9, 128.6, 127.1, 123.3, 79.2, 23.2.
HRMS (EI): m/z calcd for C19H17NO2: 291.1259; found: 291.1253.
Anal. Calcd for C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C,
78.12; H, 5.85; N, 4.66.
3-Isopropoxy-2-phenyl-4-N-(4-methoxyphenyl)iminocyclobut-
2-en-1-one (7b)
MS (70 eV): m/z (%) = 292 (87, [M]+), 250 (53 ), 221 (47 ), 194
Prepared using PhBr (290 mL, 2.75 mmol), n-BuLi (1.6 mL of a 1.6
M solution in hexane, 2.6 mmol), 1 (R1 = i-Pr; 400 mg, 20.2 mmol),
followed by TFAA (390 mL, 2.8 mmol) and a solution of THF (100
mL) containing p-anisidine (340 mg, 276 mmol); yellow solid;
yield: 0.55 g (85%); mp 94–96 °C.
(23), 145 (100), 78 (11).
3-Alkoxy-4-N-(het)arylimino-2-phenylcyclobut-2-en-1-ones via
the Aza-Wittig Reaction; 3-Isopropoxy-2-phenyl-4-N-phenyl-
iminocyclobut-2-en-1-one (7a); Typical Procedure
Under N2, a 100 mL one-necked round-bottomed flask equipped
with a magnetic stirring bar and reflux condenser was charged with
benzene (50 mL), 38 (690 mg, 3.2 mmol), and N-(triphenylphospho-
ranylidene)aniline (1.3 g, 3.7 mmol), and the mixture was refluxed
until TLC analysis indicated consumption of starting material (ca.
18 h). Concentration of the reaction solution in vacuo followed by
column chromatography (elution with a 10:1 mixture of hexanes–
EtOAc) gave 644 mg (69%) of 7a; yellow solid with identical prop-
erties to the material prepared as given above.
IR: 3060, 2982, 2835, 1759, 1672, 1603, 1566, 1506, 1495, 1465,
1448, 1408, 1337, 1295, 1248, 1174, 1089, 1033 cm–1.
1H NMR (500 MHz): d = 7.95–7.93 (m, 2 H), 7.52–7.51 (m, 2 H),
7.44–7.37 (m, 3 H), 6.90–6.89 (m, 2 H), 6.18 (sept, J = 6.2 Hz, 1
H), 3.82 (s, 3 H), 1.57 (d, J = 6.2 Hz, 6 H).
13C NMR (125 Hz): d = 187.3, 186.9, 165.6, 158.3, 151.8, 139.3,
129.9, 129.0, 128.7, 126.6, 125.9, 113.9, 78.5, 55.4, 23.3.
HRMS (CI): m/z calcd for C20H19NO3 [M + H]+: 322.1445; found:
322.1408.
3-Isopropoxy-2-phenyl-4-N-(4-pyridylimino)cyclobut-2-en-1-
one (7f)
Prepared analogously from 3 (1.2 g, 5.6 mmol) and (4-pyridylimi-
no)phosphorane24 (5.5 g, 15.7 mmol) in toluene (80 mL) at 85–
90 °C; yellow solid; yield: 1.11 g (68%); mp 118 °C (dec.).
3-Isoproxy-2-phenyl-4-N-(4-trifluoromethyl)phenyliminocy-
clobut-2-ene-1-one (7c)
Prepared using PhBr (580 mL, 5.5 mmol), n-BuLi (11.3 mL of a 1.6
M solution in hexane, 18.1 mmol), 1 (R1 = i-Pr; 1.0 g, 5.1 mmol),
then TFAA (800 mL, 5.8 mmol) and 4-(trifluoromethyl)aniline [pre-
pared from the hydrochloride (1.2 g, 6.1 mmol) and Et3N (874 mL,
6.3 mmol) in THF (10 mL)]; yellow solid; yield: 1.3 g (71%); mp
97–98 °C.
IR (KBr): 3055, 2984, 1764, 1666, 1568, 1413, 1342, 1088, 1037,
834, 798, 760, 696 cm–1.
1H NMR (200 MHz): d = 8.56 (dd, J = 1.5, 4.5 Hz, 2 H), 8.00–7.90
(m, 2 H), 7.50–7.40 (m, 3 H), 7.15 (dd, J = 1.5, 4.5 Hz, 2 H), 6.03
(sept, J = 6.2 Hz, 1 H), 1.60 (d, J = 6.2 Hz, 6 H).
13C NMR (50 MHz): d = 185.5, 184.5, 171.0, 157.2, 152.8, 150.4,
131.1, 128.9, 128.4, 127.2, 117.4, 79.4, 23.2.
IR: 3021, 1767, 1681, 1571, 1496, 1413, 1324, 1210, 1168, 1126,
1066, 1041 cm–1.
1H NMR (500 MHz): d = 7.98–7.60 (m, 2 H), 7.62 (d, J = 10 Hz, 2
H), 7.48–7.42 (m, 5 H), 6.10 (sept, J = 6.2 Hz, 1 H), 1.62 (d, J = 6.2
Hz, 6 H).
13C NMR (125 MHz): d = 186.1, 185.2, 169.7, 155.7, 148.9, 130.7,
128.8, 127.1, 125.8, 125.80, 123.3, 79.2, 23.3.
MS (70 eV): m/z (%) = 292 (48, [M]+), 250 (42), 221 (50), 194 (27),
145 (96), 89 (100).
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

PAPER
Synthesis and Transformation Reactions of 4-Iminocyclobutenones
2033
4-Substituted Cyclobutenimines 8a–f,h,j, 9a–c; General Proce-
dure
13C NMR (125 MHz): d = 164.7, 152.5, 147.2, 140.1, 139.0, 130.1,
128.6, 128.4, 128.3, 128.1, 127.7, 127.1, 125.6, 124.0, 122.0, 74.4,
55.2, 23.2, 23.2.
A 250 mL one-necked round-bottomed flask equipped with a mag-
netic stirring bar and rubber septum was charged with THF (200
mL) and 7 (1.9 mmol or the amount given below). After 15 min at
ca. –78 °C, the corresponding organyllithium compound (2.1
mmol) was added in a dropwise manner. Upon consumption of
starting material as confirmed by TLC analysis, at –20 °C brine (20
mL) (for 8a–f,h–j) or methyl triflate (for 9a–c) was added and the
reaction was allowed to warm to r.t. The aqueous phase was extract-
ed with Et2O (2 × 100 mL), dried (MgSO4), filtered, and concentrat-
ed to a viscous yellow oil. Column chromatography (elution with a
10:1 mixture of hexanes–EtOAc) gave the pure product 8 or 9.
HRMS (EI): m/z calcd for C25H23NO2: 369.1729; found: 369.1717.
Anal. Calcd for C25H23NO2: C, 81.27; H, 6.27; N, 3.79. Found: C,
81.08; H, 6.18; N, 3.75.
3-Isoproxy-2-phenyl-4-phenylimino-1-(3-trimethylsilylprop-1-
ynyl)cyclobut-2-en-1-ol (8d)
Prepared from 7a (400 mg, 1.37 mmol), trimethyl(propargyl)silane
(0.8 mL, 5.5 mmol), and n-BuLi (3.9 mL of a 1.6 M solution in hex-
ane, 6.2 mmol) and using gradient elution with 20:1 → 15:1 mix-
tures of hexanes–EtOAc for chromatography; dark yellow oil;
yield: 328 mg (59%).
3-Isopropoxy-2-phenyl-4-phenylimino-1-vinylcyclobut-2-en-1-
ol (8a)
Prepared from 7a (496 mg, 1.77 mmol) and vinyllithium (900 mL,
2.3 M in Et2O, 2.1 mmol); yellow oil; yield: 260 mg (46%).
IR: 3519, 3404, 3060, 2978, 2884, 2225, 1943, 1695, 1587, 1489,
1449, 1387, 1346, 1250, 1132, 1104, 1074, 1006 cm–1.
1H NMR (500 MHz): d = 7.83 (d, J = 6.9 Hz, 2 H), 7.44–7.39 (m, 4
H), 7.38–7.35 (m, 2 H), 7.33–730 (m, 1 H), 7.15 (m, 1 H), 5.61
(sept, J = 6.1 Hz, 1 H), 2.44 (s, 1 H), 1.49 (d, J = 6.1 Hz, 3 H), 1.48
(s, 2 H), 1.46 (d, J = 6.1 Hz, 3 H), 0.01 (s, 9 H).
13C NMR (125 MHz): d = 161.8, 151.4, 147.1, 139.0, 130.1, 128.6,
128.4, 128.37, 127.5, 124.5, 122.9, 87.0, 74.9, 74.3, 23.1, 23.0, 7.3,
–2.2.
IR: 3586, 3083, 2982, 2935, 1697, 1606, 1590, 1104 cm–1.
1H NMR (500 MHz): d = 7.69–7.67 (m, 2 H), 7.38–7.35 (m, 2 H),
7.32–7.28 (m, 3 H), 7.21–7.20 (m, 2 H), 7.13–7.09 (m, 1 H), 6.00
(dd, J = 10.8, 17.2 Hz, 1 H), 5.61 (sept, J = 6.4 Hz, 1 H), 5.39 (dd,
J = 1.4, 17.2 Hz, 1 H), 5.15 (dd, J = 1.4, 10.8 Hz, 1 H), 2.41 (s, 1 H),
1.49–1.46 (m, 6 H).
13C NMR (125 MHz): d = 164.5, 151.1, 147.4, 138.4, 137.8, 130.6,
128.5, 128.4, 128.39, 127.4, 124.5, 122.5, 116.2, 84.4, 74.2, 23.2,
23.1.
HRMS (EI): m/z calcd for C25H29NO2Si: 403.1968; found:
403.1971.
3-Isopropoxy-2-phenyl-1-phenylethynyl-4-phenyliminocyclo-
but-2-en-1-ol (8e)
Prepared from 7a (400 mg, 1.37 mmol), phenylacetylene (1.6 mL,
14.6 mmol), and n-BuLi (9.2 mL of a 1.6 M solution in hexane, 15.8
mmol) and using radial chromatography with gradient elution of
10:1 → 5:1 mixtures of hexanes–EtOAc; dark yellow oil; yield: 479
mg (89%).
HRMS (EI): m/z calcd for C21H21NO2: 319.1572; found: 319.1562.
Anal. Calcd for C21H21NO2: C, 78.97, H; 6.63; N, 4.39. Found: C,
78.82; H, 6.69; N, 4.28.
3-Isopropoxy-2-phenyl-4-phenylimino-2-propenylcyclobut-2-
en-1-ol (8b)
Prepared from 7a (516 mg, 1.77 mmol), 2-bromopropene (210 mL,
2.4 mmol), and t-BuLi (2.5 mL, 1.6 M in pentane, 4.0 mmol) using
a 5:1 mixture of hexanes–EtOAc for chromatography; yellow solid;
yield: 482 mg (82%); mp 104–106 °C.
IR: 3519, 3393, 3061, 2980, 2933, 2227, 1696, 1589, 1489, 1448,
1389, 1346, 1245, 1141, 1102, 1068 cm–1.
1H NMR (500 MHz): d = 7.82 (m, 2 H), 7.40–7.29 (m, 6 H), 7.28–
7.22 (m, 6 H), 7.14–7.11 (m, 1 H), 5.56 (sept, J = 6.1 Hz, 1 H), 5.53
(s, 1 H), 1.47 (d, J = 6.1 Hz, 3 H), 1.44 (d, J = 6.1 Hz, 3 H).
IR: 3588, 3065, 2981, 2937, 1698, 1590, 1488, 1448, 1386, 1104
cm–1.
13C NMR (125 MHz): d = 161.1, 151.7, 147.4, 137.9, 131.6, 130.0,
128.7, 128.6, 128.5, 128.1, 127.5, 124.6, 122.4, 122.2, 87.7, 87.0,
74.8, 74.7, 23.2, 23.1.
HRMS (CI): m/z calcd for C27H23NO2 [M + H]+: 394.1737; found:
394.1759.
1H NMR (500 MHz): d = 7.65 (dd, J = 8.4, 1.5 Hz, 2 H), 7.35 (t,
J = 7.3 Hz, 2 H), 7.29–7.26 (m, 3 H), 7.15 (t, J = 8.4 Hz, 2 H), 7.09
(t, J = 7.3 Hz, 1 H), 5.60 (sept, J = 6.2 Hz, 1 H), 5.30 (s, 1 H), 4.98
(s, 1 H), 2.26 (s, 1 H), 1.64 (s, 3 H), 1.47 (d, J = 6.2 Hz, 3 H), 1.45
(d, J = 6.2 Hz, 3 H).
13C NMR (125 MHz): d = 164.5, 151.7, 147.2, 143.4, 138.0, 128.6,
3-Isopropoxy-4-(4-methoxy)phenylimino-2-phenyl-1-(phenyl-
ethynyl)cyclobut-2-en-1-ol (8f)
Prepared from 7b (400 mg, 1.24 mmol), phenylacetylene (1.4 mL,
12.8 mmol), and n-BuLi (8.6 mL of a 1.6 M solution in hexane, 13.8
mmol) and using radial chromatography with gradient elution of
10:1 → 5:1 mixtures of hexanes–EtOAc; dark red oil; yield: 354 mg
(67%).
128.5, 127.0, 124.5, 122.3, 113.6, 86.4, 74.1, 23.2, 23.1, 19.6.
HRMS (EI): m/z calcd for C22H23NO2: 333.1729; found: 333.1732.
Anal. Calcd for C22H23NO2: C, 79.25; H, 6.95; N, 4.20. Found: C,
79.29; H, 6.80; N, 4.11.
3-Isopropoxy-1,2-diphenyl-4-phenyliminocyclobut-2-en-1-ol
(8c)
Prepared from 7a (800 mg, 2.75 mmol), PhBr (345 mL, 3.28 mmol),
and n-BuLi (2.1 mL of a 1.6 M solution in hexane, 3.4 mmol); yel-
low solid; yield: 970 mg (96%); mp 149–150 °C.
IR: 3368, 3060, 2978, 2933, 2191, 1762 (overtone), 1688, 1607,
1551, 1505, 1445, 1386, 1349, 1295, 1247, 1176, 1102, 1066, 1033
cm–1.
1H NMR (500 MHz): d = 7.83 (d, J = 7.3 Hz, 2 H), 7.44 (d, J = 8.8
Hz, 2 H), 7.41 (t, J = 7.6 Hz, 2 H), 7.32–7.24 (m, 8 H), 5.61 (sept,
J = 6.0 Hz, 1 H), 3.80 (s, 3 H), 2.49 (s, 1 H), 1.48, 1.44 (d each,
J = 6.0 Hz, 3 H).
13C NMR (125 MHz): d = 159.4, 157.2, 152.2, 140.0, 137.5, 131.7,
130.1, 128.7, 128.5, 128.5, 128.2, 127.3, 124.7, 122.3, 113.9, 87.8,
87.2, 75.1, 74.8, 55.4, 23.2, 23.1.
IR: 3436, 3061, 2978, 1692, 1588, 1489, 1448, 1384, 1341, 1170,
1103, 1014 cm–1.
1H NMR (500 MHz): d = 7.52–750 (m, 2 H), 7.35–7.33 (m, 2 H),
7.28–7.25 (m, 3 H), 7.22–7.15 (m, 3 H), 7.10–7.07 (m, 2 H), 6.97–
6.94 (m, 1 H), 6.79–6.77 (m, 2 H), 5.65 (sept, J = 6.2 Hz, 1 H), 2.41
(s, 1 H), 1.51 (d, J = 6.2 Hz, 3 H), 1.509 (d, J = 6.2 Hz, 3 H).
HRMS (CI): m/z calcd for C28H25NO3: 423.1834; found: 423.1678.
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

2034
G. Oppermann et al.
PAPER
3-Isopropoxy-4-(2,4,6-trimethylphenyl)imino-2-phenyl-1-phe-
nylethynylcyclobut-2-en-1-ol (8h)
Prepared from 7d (740 mg, 2.2 mmol), phenylacetylene (2.9 mL,
26.4 mmol), and n-BuLi (14.0 mL of a 1.6 M solution in hexane,
22.4 mmol); red oil; yield: 652 mg (68%).
13C NMR (125 MHz): d = 163.2, 152.5, 146.9, 140.3, 137.2, 130.9,
128.5, 128.4, 128.1, 127.9, 127.2, 127.1, 125.9, 124.3, 122.0, 90.6,
74.0, 51.5, 23.2, 23.1.
HRMS (EI): m/z calcd for C26H25NO2: 383.1885; found: 383.1890.
IR (film): 3407, 2997, 2916, 1707, 1616, 1387, 1347, 1102, 982,
757, 690 cm–1.
2-Isopropoxy-4-methoxy-3,N-diphenyl-4-(3-methylphenyl)cy-
clobut-2-en-1-imine (9b)
Prepared from 7a (400 mg, 1.37 mmol), 3-bromotoluene (206 mL,
1.7 mmol), n-BuLi (1.2 mL of a 1.6 M solution in hexane, 1.92
mmol), and methyl triflate (180 mL, 1.6 mmol) using radial chroma-
tography (elution with 50:1 mixture of hexanes–EtOAc); yellow
solid; yield: 380 mg (70%); mp 108–110 °C.
1H NMR (200 MHz): d = 7.95–7.85 (m, 2 H), 7.45–7.20 (m, 8 H),
6.85 (s, 2 H), 5.57 (sept, J = 6.1 Hz, 1 H), 2.28 (s, 3 H), 2.22 (s, 6
H), 1.50 (m, 6 H).
13C NMR (50 MHz): d = 160.1, 151.0, 143.6, 137.2, 132.5, 132.1,
131.6, 130.0, 128.7, 128.6, 128.6, 128.5, 128.2, 127.5, 122.2, 86.3,
77.2, 75.1, 74.4, 23.2, 23.1, 20.8, 18.5.
IR: 3060, 3028, 2979, 2932, 2825, 1692, 1608, 1587, 1488, 1383,
1345, 1170, 1144, 1102, 1086, 1011 cm–1.
1H NMR (400 MHz): d = 7.53 (d, J = 7.2 Hz, 2 H), 7.25 (m, 2 H),
7.19–7.17 (m, 3 H), 7.11–7.04 (m, 3 H), 7.00–6.93 (m, 2 H), 6.93
(sept, J = 6.0 Hz, 1 H), 6.76 (d, J = 7.6 Hz, 2 H), 3.36 (s, 3 H), 2.20
(s, 3 H), 1.50 (d, J = 6.0 Hz, 3 H), 1.49 (d, J = 6.0 Hz, 3 H).
13C NMR (125 MHz): d = 163.3, 152.3, 147.0, 140.2, 137.3, 137.1,
131.0, 128.5, 128.4, 128.0, 127.9, 127.7, 127.3, 126.8, 124.2, 122.9,
122.0, 90.6, 74.0, 51.5, 23.3, 23.1, 21.5.
MS (70 eV): m/z (%) = 436 (5, [M + H]+), 392 (8), 378 (90), 316 (3),
202 (100).
3-Isopropoxy-2-phenyl-1-phenylethynyl-4-(3-pyridyl)iminocy-
clobut-2-en-1-ol (8i)
Prepared from 7e (238mg, 0.82 mmol), phenylacetylene (0.82 g, 8.0
mmol), and n-BuLi (5.0 mL of a 1.6 M solution in hexane, 8.0
mmol) and using consecutive flash and radial chromatography with
1:2 → 2:1 mixtures of hexanes–EtOAc; red oil; yield: 258 mg
(80%).
HRMS (EI): m/z calcd for C27H27NO2: 397.2042; found: 397.2038.
IR (film): 3059, 2980, 1696, 1601, 1571, 1491, 1387, 1102, 989,
756, 691 cm–1.
2-Isopropxy-4-methoxy-3,N-diphenyl-4-(3-methoxyphenyl)cy-
clobut-2-en-1-imine (9c)
Prepared from 7a (411 mg, 1.41 mmol), 3-bromoanisole (211 mL,
1.7 mmol), n-BuLi (1.2 mL of a 1.6 M solution in hexane, 1.92
mmol), and methyl triflate (180 mL, 1.6 mmol) using column chro-
matography (elution with 20:1 mixture of hexanes–EtOAc) and re-
crystallization from pentane–CH2Cl2; yellow solid; yield: 504 mg
(87%); mp 109–110 °C.
1H NMR (200 MHz): d = 8.55 (d, J = 2.0 Hz, 1 H), 8.00 (dd,
J = 1.5, 4.8 Hz, 1 H), 7.90 (dd, J = 1.5, 8.1 Hz, 2 H), 7.65–7.55 (m,
1 H), 7.05–7.25 (m, 8 H), 7.14 (dd, J = 4.8, 8.1 Hz, 1 H), 5.47 (sept,
J = 6.2 Hz, 1 H), 1.45 (dd, J = 2.4, 6.2 Hz, 6 H).
13C NMR (50 MHz): d = 164.5, 150.8, 144.3, 144.1, 142.8, 140.0,
131.7, 130.0, 130.0, 128.9, 128.7, 128.7, 128.3, 127.8, 127.1, 123.1,
122.2, 88.3, 79.2, 73.8, 23.3, 23.1.
IR: 3060, 2979, 2934, 2829, 1692, 1589, 1486, 1449, 1383, 1343,
1283, 1164, 1081, 1048 cm–1.
1H NMR (500 MHz): d = 7.53 (m, 2 H), 7.27–7.19 (m, 3 H), 7.13–
7.01 (m, 3 H), 7.00–6.96 (m, 2 H), 6.76 (m, 2 H), 6.70 (dd, J = 1.2,
8.0 Hz, 1 H), 5.70 (sept, J = 6.0 Hz, 1 H), 3.67 (s, 3 H), 3.36 (s, 3
H), 1.5 (d, J = 6.0 Hz, 6 H).
13C NMR (125 MHz): d = 163.0, 159.3, 152.4, 147.0, 142.1, 137.0,
130.9, 128.8, 128.5, 128.4, 128.2, 127.3, 124.3, 122.0, 118.3, 113.0,
111.5, 90.4, 74.1, 55.1, 51.6, 23.2, 23.1.
MS (70 eV): m/z (%) = 395 (100, [M + H]+), 251 (68), 275 (53).
3-Isopropoxy-2-phenyl-1-phenylethynyl-4-(4-pyridyl)iminocy-
clobut-2-en-1-ol (8j)
Prepared from 7f (650 mg, 2.2 mmol), phenylacetylene (2.83 g,
27.7 mmol), and n-BuLi (13.8 mL of a 1.6 M solution in hexane, 22
mmol) and using flash chromatography with a 1:1 mixture of hex-
anes–EtOAc; red oil; yield: 310 mg (36%).
IR (film): 3407, 3083, 2978, 1709, 1589, 1394, 1105, 988, 758, 691
cm–1.
HRMS (EI): m/z calcd for C27H27NO3: 413.1991; found: 413.1981.
2-Isopropoxy-3,N-diphenyl-4-phenylethynyl-4-trimethylsilyl-
oxycyclobut-2-en-1-imine (10)
1H NMR (200 MHz): d = 8.09 (dd, J = 1.5 Hz, 4.7 Hz, 2 H), 7.94 (d,
J = 1.5 Hz, 1 H), 7.90 (d, J = 1.3 Hz, 1 H), 7.50–7.20 (m, 8 H), 7.01
(dd, J = 1.5, 4.8 Hz, 2 H), 5.41 (sept, J = 6.2 Hz, 1 H), 1.46 (dd,
J = 6.2, 8.8 Hz, 6 H).
13C NMR (50 MHz): d = 164.6, 156.4, 149.8, 148.5, 140.8, 131.3,
129.9, 129.0, 128.7, 128.6, 128.6, 128.0, 122.4, 117.0, 89.7, 86.1,
79.7, 73.2, 23.3, 23.1.
A 50 mL one-necked round-bottomed flask equipped with a mag-
netic stirring bar and rubber septum was charged with CH2Cl2 (25
mL), 8a (212 mg, 0.66 mmol), TMSCl (98 mL, 0.77 mmol) and Et3N
(233 mL, 1.67 mmol) and stirred overnight. The crude reaction mix-
ture was concentrated followed by column chromatography (gradi-
ent elution with 10:1 → 5:1 hexanes–EtOAc); yellow oil; yield: 103
mg (34%).
2-Isopropoxy-4-methoxy-3,4,N-triphenylcyclobut-2-en-
1-imine (9a)
Prepared from 7a (500 mg, 1.72 mmol), PhBr (216 mL, 2.1 mmol),
n-BuLi (1.4 mL of a 1.6 M solution in hexane, 2.2 mmol), and
methyl triflate (225 mL, 2.0 mmol); yellow solid; yield: 341 mg
(60%); mp 149–150 °C.
IR: 3061, 2978, 2225, 1758 (overtone), 1690, 1606, 1581, 1491,
1448, 1386, 1350, 1252, 1176, 1102, 1008 cm–1.
1H NMR (500 MHz): d = 7.85 (d, J = 7.7 Hz, 2 H), 7.48 (d, J = 8.0
Hz, 2 H), 7.39–7.26 (m, 9 H), 7.17–7.15 (m, 2 H), 5.65 (sept, J = 6.1
Hz, 1 H), 1.52, 1.46 (d each, J = 6.1 Hz, 3 H), –0.06 (s, 9 H).
IR: 3061, 2979, 2932, 2826, 1694, 1682, 1607, 1590, 1487, 1447,
1384, 1347, 1313, 1242, 1193, 1145, 1102, 1086, 1032, 1011 cm–1.
1H NMR (500 MHz): d = 7.52 (d, J = 7.3 Hz, 2 H), 7.41 (d, J = 7.1
Hz, 2 H), 7.23 (t, J = 7.2 Hz, 2 H), 7.18–7.13 (m, 4 H), 7.11–7.06
(m, 3 H), 6.95 (t, J = 7.4 Hz, 1 H), 6.77 (d, J = 7.5 Hz, 2 H), 5.73
(sept, J = 6.2 Hz, 1 H), 3.36 (s, 3 H), 1.48 (d, J = 6.2 Hz, 6 H).
13C NMR (125 MHz): d = 161.1, 151.9, 146.9, 139.6, 131.6, 130.5,
128.5, 128.4, 128.3, 128.2, 127.6, 124.8, 123.6, 122.7, 88.9, 86.5,
74.6, 23.5, 23.2, 1.3.
HRMS (EI): m/z calcd for C30H31NO2Si: 465.2124; found:
465.2123.
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

PAPER
Synthesis and Transformation Reactions of 4-Iminocyclobutenones
2035
Hydrolysis of 8b; 4-Hydroxy-2-isopropoxy-3-phenyl-4-(prop-2-
enyl)cyclobut-2-en-1-one (11)
EtOAc); red-wine colored oil; yield: 150 mg (59%); complex E/Z
mixture.
A 25 mL one-necked round-bottomed flask equipped with a mag-
netic stirring bar was charged with THF (5 mL), 8b (35 mg, 0.1
mmol), and 10% aq HCl (2.0 mL) and the mixture was stirred. After
complete conversion into the ketone via TLC analysis, 5% NaHCO3
(10 mL) was added to the reaction mixture. The aqueous layer was
extracted with Et2O (2 × 20 mL), and the combined organic layers
washed with brine (2 × 20 mL), dried (MgSO4), filtered, concentrat-
ed, and purified by radial chromatography (elution with 20:1 hex-
anes–EtOAc); yellow oil; yield: 23 mg (89%).
IR: 3060, 2978, 2932, 1648, 1591, 1484, 1446, 1361, 1298, 1274,
1231, 1181, 1097 cm–1.
1H NMR (500 MHz): d = 8.39 (d, J = 7.5 Hz, 2 H), 8.20 (d, J = 7.7
Hz, 2 H), 7.69 (t, J = 6.9 Hz, 2 H), 7.64 (t, J = 7.2 Hz, 2 H), 7.50–
7.36 (m, 12 H), 7.16 (m, 2 H), 7.10 ( t, J = 7.1 Hz, 2 H), 6.93 (d,
J = 7.4 Hz, 2 H), 6.85 (br, 2 H), 4.92 (br, 1 H), 3.62 (br, 1 H), 1.20
(br, 6 H), 0.57–0.47 (br, 6 H).
13C NMR (125 MHz): d = 185.1, 155.2, 151.6, 150.9, 134.8, 132.6,
132.4, 131.2, 131.1, 131.0, 129.5, 128.2, 128.1, 128.0, 127.8, 127.7,
127.6, 127.3, 127.2, 126.1, 125.6, 124.2, 123.5, 118.3, 117.7, 76.4,
74.7, 22.6, 20.9.
IR: 3597, 3457, 2981, 1754, 1377 cm–1.
1H NMR (500 MHz): d = 7.75 (d, J = 1.8 Hz, 2 H), 7.74–7.38 (m, 3
H), 5.41 (s, 1 H), 5.20 (s, 1 H), 5.16 (sept, J = 6.1 Hz, 1 H), 2.53 (s,
1 H), 1.76 (s, 3 H), 1.42, 1.40 (d each, J = 6.1 Hz, 3 H).
HRMS (EI): m/z calcd for C25H21NO2: 367.1572; found: 367.1572.
13C NMR (125 MHz): d = 188.2, 152.3, 150.3, 141.8, 130.4, 129.8,
128.8, 128.3, 114.2, 90.6, 75.0, 23.0, 22.96, 19.9.
Anal Calcd for C25H21NO2: C, 81.72; H, 5.76; N, 3.81. Found: C,
81.42; H, 5.51; N, 3.58.
HRMS (EI): m/z calcd for C16H18O3 [M + H]+: 259.1334; found:
259.1334.
Thermolysis of 4-Aryl-4-methoxycyclobutenimines; General
Procedure
A 100 mL round-bottomed flask equipped with a stirring bar and re-
flux condenser was charged with 9 (0.6 mmol) in PhCl (40 mL) and
refluxed for 9.5 days. Upon consumption of starting material, the
solvent was removed in vacuo to a viscous yellow oil and product
18,19 isolated by column chromatography (gradient elution with
30:1 → 20:1 hexanes–EtOAc).
4-(N-Phenylamino)-3-isopropoxy-2-phenylphenol (14a)
A 100 mL round-bottomed flask equipped with a stirring bar and re-
flux condenser was charged with a solution of 8a (223 mg, 0.7
mmol) in p-xylene (50 mL) and refluxed for 1.5 h. When TLC anal-
ysis had confirmed consumption of starting material, the solvent
was evaporated followed by column chromatography (elution with
10:1 hexanes–EtOAc); yellow oil; yield: 93.8 mg (42%).
2-Isopropoxy-4-methoxy-1-(N-phenylamino)-3-phenylnaph-
IR: 3552, 3422, 3061, 2976, 2931, 1601, 1506, 1470, 1441, 1340,
1273, 1171, 1106, 1014 cm–1.
thalene (18a)
Prepared from 9a (211 mg, 5.5 mmol); amorphous solid; yield: 171
mg (81%).
1H NMR (500 MHz): d = 7.53–7.45 (m, 2 H), 7.43–7.40 (m, 3 H),
7.37–7.23 (m, 2 H), 7.04 (d, J = 8.1 Hz, 2 H), 6.86 (t, J = 7.3 Hz, 1
H), 6.73 (d, J = 8.7 Hz, 1 H), 5.90 (s, 1 H), 4.78 (s, 1 H), 3.66 (sept,
J = 6.1 Hz, 1 H), 0.88 ( d, J = 6.2 Hz, 6 H).
13C NMR (125 MHz): d = 147.7, 146.2, 144.5, 133.3, 130.6, 130.2,
129.3, 129.2, 129.1, 128.0, 123.0, 119.8, 119.3, 116.3, 110.6, 75.5,
22.2.
IR: 3390, 3054, 2975, 2931, 2842, 1600, 1498, 1455, 1364, 1301,
1238, 1212, 1180, 1152, 1104, 1079, 1038, 1005 cm–1.
1H NMR (500 MHz): d = 8.17 (d, J = 8.4 Hz, 1 H), 7.85 (d, J = 8.3
Hz, 1 H), 7.58–7.57 (m, 2 H), 7.44 (t, J = 7.2 Hz, 3 H), 7.40–7.34
(m, 2 H), 7.13 (t, J = 7.5 Hz, 2 H), 6.78 (t, J = 7.3 Hz, 1 H), 6.68–
6.67 (m, 2 H), 6.14 (s, 1 H), 3.67 (sept, J = 6.1 Hz, 1 H), 3.47 (s, 3
H), 0.79 (d, J = 6.1 Hz, 6 H).
13C NMR (125 MHz): d = 151.1, 147.2, 146.9, 134.6, 130.9, 129.9,
128.9, 127.8, 127.6, 127.1, 126.9, 126.2, 125.8, 125.0, 124.8, 122.7,
119.1, 115.1, 75.5, 61.1, 22.2.
HRMS (EI): m/z calcd for C21H21NO2: 319.1572; found: 319.1572.
4-(N-Phenylamino)-3-isopropoxy-5-methyl-2-phenylphenol
(14b)
Prepared analogous to 14a from 8b (165 mg, 0.5 mmol) by reflux-
ing in p-xylene (20 mL) for 1 h; yellow oil; yield: 146 mg (88%).
HRMS (EI): m/z calcd for C26H25NO2: 383.1885; found: 383.1880.
IR: 3553, 3421, 2976, 1598, 1466 cm–1.
2-Isopropoxy-4-methoxy-6-methyl-3-phenyl-1-(N-phenylami-
no)naphthalene (18b) and 3-Isopropoxy-1-methoxy-5-methyl-
2-phenyl-4-(N-phenylamino)naphthalene (19a)
Prepared from 9b (298 mg, 0.75 mmol); oil; yield: 151 mg (51%) as
a mixture in a 3.8:1 ratio.
1H NMR (500 MHz): d = 7.62 (t, J = 7.6 Hz, 2 H), 7.56–7.51 (m, 3
H), 7.36 (t, J = 7.51 Hz, 3 H), 7.26–7.15 (m, 2 H), 6.97 (t, J = 7.3
Hz, 1 H), 6.01 (s, 1 H), 5.97 (s, 1 H), 3.73 ( sept, J = 6.2 Hz, 1 H),
2.35 (s, 3 H), 0.98 (d, J = 6.2 Hz, 6 H).
IR: 3390, 3054, 2975, 2931, 1600, 1497, 1449, 1412, 1365, 1301,
1192, 1104, 1077, 1031 cm–1.
13C NMR (125 MHz): d = 145.6, 144.7, 144.1, 133.5, 130.7, 129.4,
129.3, 128.1, 122.4, 120.8, 119.7, 119.6, 116.1, 75.6, 22.3, 16.2.
1H NMR (500 MHz): d = 8.0 (d, J = 8.3 Hz, 1 H), 7.93 (s, 1 H), 7.75
(d, J = 8.6 Hz, 1 H), 7.59–7.56 (m, 3 H), 7.44 (t, J = 7.4 Hz, 3 H),
7.37–7.33 (m, 2 H), 7.25–7.21 (m, 2 H), 7.15–7.08 (t, 3 H), 6.78 (t,
J = 7.3 Hz, 1 H), 6.75 (t, J = 7.3 Hz, 1 H), 6.67 (d, J = 7.6 Hz, 2 H),
6.52 ( d, J = 7.7 Hz, 2 H), 3.62 (sept, J = 5.8 Hz, 2 H), 3.45 (s, 3 H),
2.71 (s, 3 H), 2.52 (s, 3 H), 0.78 (d, J = 5.8 Hz, 6 H), 0.74 ( d, J = 5.8
Hz, 6 H).
13C NMR (100 MHz): d = 151.6, 150.6, 148.8, 148.7, 147.0, 146.4,
134.9, 134.7, 134.6, 131.3, 130.9, 130.8, 130.3, 129.1, 128.9, 128.4,
128.1, 128.0, 127.8, 127.6, 127.1, 127.07, 126.9, 126.86, 125.9,
124.8, 121.6, 121.0, 119.0, 118.8, 115.5, 114.2, 75.5, 75.0, 61.1,
60.9, 23.3, 21.8.
HRMS (EI): m/z calcd for C22H23NO2: 333.1729; found: 333.1732.
3-Isopropoxy-2,N-diphenyl-p-naphthaquinonimine (16)
A 100 mL round-bottomed flask equipped with a stirring bar, reflux
condenser, and gas inlet/outlet (argon) was charged with a solution
of 8c (253 mg, 0.7 mmol) in p-xylene (60 mL) and refluxed for 15
h. Upon consumption of starting material, the solvent was removed
in vacuo to give an oil, which was dissolved in a mixture of freshly
distilled benzene (70 mL), KHCO3 (392 mg, 2.8 mmol), and Ag2O
(381 mg, 2.8 mmol) under a blanket of N2 and stirred for 2 h. The
reaction mixture was filtered through a bed of Celite, concentrated,
and the product isolated as a viscous red oil. Column chromatogra-
phy (gradient elution with 10:1 → 5:1 mixtures of hexanes–
HRMS (EI): m/z calcd for C27H27NO2: 397.2042; found: 397.2040.
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

2036
G. Oppermann et al.
PAPER
3-Isopropoxy-2-phenyl-9-(trimethylsilylmethyl)cycopen-
2-Isopropoxy-4,6-dimethoxy-3-phenyl-1-(N-phenylami-
no)naphthalene (18c) and 3-Isopropoxy-1,5-dimethoxy-2-phe-
nyl-4-(N-phenylamino)naphthalene (19b)
Prepared from 9c (148 mg, 0.36 mmol) by refluxing for 35 days; oil;
yield: 151 mg (48%) as a mixture in a 3.8:1 ratio. Crude 1H NMR
showed a 3.1:1 mixture of isomers. Radial chromatography (elution
with 20:1 hexanes–EtOAc) gave one major fraction containing both
isomers 18c and 19b; oil; yield: 111 mg (75%).
ta[b]quinolin-1-one (25a)
Prepared from 8d (100 mg, 0.25 mmol), reflux time 90 min, fol-
lowed by radial chromatography (gradient elution with 200:1 →
100:1 → 100:10 pentane–EtOAc) to give one major fraction, which
contained a mixture of three compounds; recrystallized from
CH2Cl2–pentane; yellow solid; yield: 12 mg (17%); mp 135–
136 °C.
IR: 3406, 3055, 2972, 2930, 2840, 1600, 1496, 1446, 1401, 1371,
1303, 1227, 1176, 1105, 1060, 1011 cm–1.
IR: 3076, 2957, 1688, 1602, 1577, 1525, 1493, 1464, 1392, 1336,
1249, 1189, 1141, 1096, 1006 cm–1.
1H NMR (500 MHz): d = 7.81–7.79 (d, J = 8.4 Hz, 1 H), 7.58–7.57
(m, 2 H), 7.47–7.42 (m, 3 H), 7.38–7.30 (m, 1 H), 7.20 (t, J = 7.2
Hz, 2 H), 7.07 (dd, J = 2.6, 9.2 Hz, 1 H), 6.83–6.78 (m, 1 H), 6.67
(d, J = 8.2 Hz, 2 H) and further overlapping signals.
13C NMR (125 MHz): d = 156.6, 149.1, 145.8, 145.5, 134.7, 131.3,
128.3, 127.5, 124.7, 123.6, 120.6, 118.8, 115.9, 115.8, 106.4, 73.7,
60.9, 56.2, 22.2.
1H NMR (500 MHz): d = 8.01 (dd, J = 1.2, 8.4 Hz, 1 H), 7.94 (dd,
J = 1.2, 8.4 Hz, 1 H), 7.89 (dd, J = 1.2, 8.4 Hz, 2 H), 7.68–7.65 (m,
1 H), 7.52–7.49 (m, 1 H), 7.44–741 (m, 2 H), 7.33–7.29 (m, 1 H),
6.38 (sept, J = 6.0 Hz, 1 H), 3.22 (br s, 2 H), 1.49 (d, J = 6.2 Hz, 6
H), 0.03 (s, 9 H).
13C NMR (125 MHz): d = 192.2, 168.2, 159.6, 148.4, 145.7, 130.8,
130.3, 129.1, 128.0, 127.9, 127.4, 126.6, 125.6, 121.3, 120.0, 75.6,
23.3, 18.8, –0.7.
HRMS (EI): m/z calcd C27H27NO3: 413.1991; found: 413.1994.
HRMS (EI): m/z calcd for C25H27NO2Si: 401.1811; found:
401.1817.
A minute amount of 18c crystallized out of solution upon standing;
mp 174–176 °C.
3-Isopropoxy-2,9-diphenylcyclopenta[b]quinolin-1-one (25b)
Prepared from of 8e (139 mg, 0.35 mmol) and isolated by column
chromatography (gradient elution 7:1 → 5:1 hexanes–EtOAc) plus
recrystallization from CH2Cl2–pentane; yellow solid; yield: 67 mg
(49%); mp 204–206 °C.
18c
IR: 3390, 3051, 2973, 2932, 2837, 1598, 1497, 1420, 1372, 1300,
1224, 1176, 1106, 1073, 1014 cm–1.
1H NMR (500 MHz): d = 7.75 (d, J = 4.2 Hz, 1 H), 7.58–7.57 (m, 2
H), 7.47–7.44 (m, 3 H), 7.38–7.35 (m, 1 H), 7.16–7.13 (m, 2 H) 7.08
(dd, J = 2.6, 9.2 Hz, 1 H), 6.81–6.78 (m, 1 H), 6.69–6.67 (m, 2 H),
6.12 (s, 1 H), 3.94 (s, 3 H), 3.61 (sept, J = 6.0 Hz, 1 H), 3.45 (s, 3
H), 0.78 (d, J = 6.0 Hz, 6 H).
13C NMR (125 MHz): d = 157.4, 149.9, 147.0, 145.2, 134.7, 130.9,
128.9, 128.1, 127.9, 127.1, 126.8, 126.6, 125.1, 119.2, 118.7, 115.5,
100.9, 75.5, 60.7, 55.4, 22.2.
IR: 3057, 2982, 2927, 1693, 1620, 1551, 1491, 1459, 1388, 1337,
1298, 1124, 1056 cm–1.
1H NMR (500 MHz): d = 8.10 (d, J = 8.2 Hz, 1 H), 7.89–7.87 (m, 2
H), 7.70–7.67 (m, 1 H), 7.64 (d, J = 7.8 Hz, 1 H), 7.52–7.51 (m, 3
H), 7.45–7.34 (m, 5 H), 7.27 (t, J = 7.3 Hz, 1 H), 6.47 (sept, J = 6.1
Hz, 1 H), 1.53 (d, J = 6.1 Hz, 6 H).
13C NMR (125 MHz): d = 189.5, 169.0, 159.5, 148.9, 143.1, 133.0,
130.6, 130.5, 130.4, 129.5, 129.1, 128.7, 128.0, 127.9, 127.6, 127.4,
122.0, 121.9, 75.9, 23.3.
HRMS (EI): m/z calcd for C27H27NO3: 413.1991; found: 413.1992.
Iminoquinone 22 and 3-Isopropoxy-2-phenylcyclopen-
ta[b]quinolin-1-ones 25; General Procedure
HRMS (EI): m/z calcd for C27H21NO2: 391.1572; found: 391.1565.
A 100 mL round-bottomed flask equipped with a stirring bar, re-
fluxing condenser, and gas inlet/outlet (argon) was charged with
8d–g,i,j or 10 (0.34 mmol) and refluxed for 60 min followed by col-
umn chromatography (gradient elution 20:1 → 10:1 hexanes–
EtOAc) to give a complex mixture of at least three compounds on
TLC. The least polar fraction contained 25.
3-Isopropoxy-2,9-diphenyl-7-methoxycyclopenta[b]quinolin-1-
one (25c)
Prepared from of 8f (100 mg, 0.24 mmol) along with 22 (vide supra)
and isolated by column chromatography (gradient elution 10:1 →
5:1 hexanes–EtOAc) plus recrystallization from CH2Cl2–pentane;
yellow solid; yield: 52 mg (49%); mp 204–206 °C.
2-Isopropoxy-N-(4-methoxyphenyl)-3,6-diphenyl-p-benzo-
quinonemonoimine (22)
Prepared from 8f (100 mg, 0.24 mmol) by chromatography along
with 25c (vide infra); yellow oil; yield: 16 mg (16%); mixture of
E/Z diastereomers.
IR: 1684, 1651, 1618, 1559, 1523, 1457, 1394, 1338, 1294, 1258,
1136, 1088, 1030 cm–1.
1H NMR (500 MHz): d = 8.00 (d, J = 9.1 Hz, 1 H), 7.86 (dd, J = 1.2,
8.8 Hz, 2 H), 7.52–7.51 (m, 2 H), 7.40–7.38 (m, 2 H), 7.36–7.32 (m,
2 H), 7.31 (m, 1 H), 7.27–7.25 (m, 2 H), 6.96 (m, 1 H), 6.44 (sept,
J = 6.0 Hz, 1 H), 3.74 (s, 3 H), 1.52 (d, J = 6.0 Hz, 6 H).
13C NMR (125 MHz): d = 189.7, 169.5, 158.7, 157.1, 144.3, 142.0,
133.2, 131.6, 130.6, 129.3, 129.1, 129.07, 128.6, 128.1, 127.8,
127.4, 122.3, 121.1, 120.8, 107.8, 75.8, 55.5, 23.3.
IR: 2978, 1692, 1624, 1585, 1498, 1446, 1378, 1307, 1245, 1161,
1092, 1061, 1034 cm–1.
1H NMR (500 MHz): d = 8.43–8.41 (m, 2 H), 8.02 (d, J = 7.9 Hz, 2
H), 7.69 (s, 1 H), 7.60 (s, 1 H), 7.47–7.35 (m, 8 H), 7.09 (t, J = 7.2
Hz, 2 H), 6.92 (t, J = 7.6 Hz, 2 H), 6.88–6.86 (m, 6 H), 6.70 (d,
J = 8.7 Hz, 2 H), 6.37 (d, J = 8.7 Hz, 2 H), 6.10 (sept, J = 5.9 Hz, 1
H), 4.24 (sept, J = 6.0 Hz, 1 H), 3.83 (s, 3 H), 3.62 (s, 3 H), 1.49 (d,
J = 6.0 Hz, 6 H), 0.71 (d, J = 5.9 Hz, 6 H).
HRMS (EI): m/z calcd for C28H23NO3: 421.1678; found: 421.1673.
Anal. Calcd for C28H23NO3: C, 79.79; H, 5.55; N, 3.32. Found: C,
79.50; H, 5.77; N, 3.18.
13C NMR (125 MHz): d = 172.3, 158.0, 156.3, 154.8, 144.4, 142.0,
136.6, 135.1, 133.5, 133.5, 130.8, 130.2, 129.8, 129.7, 129.3, 129.2,
128.7, 128.2, 128.1, 127.3, 126.0, 123.2, 119.8, 113.4, 75.9, 74.9,
55.7, 55.4, 23.8, 21.5.
3-Isopropoxy-2-phenyl-9-propyl-7-(trifluoromethyl)cyclopen-
ta[b]quinolin-1-one (25d)
Starting from 7c (360 mg, 1.0 mmol), crude 8g (269 mg, 0.58
mmol) was prepared and refluxed for 1.5 h following the General
Procedure. After chromatography (gradient elution 10:1 → 7:1
hexanes–EtOAc), the product was obtained by recrystallization
HRMS (EI): m/z calcd for C28H25NO3: 423.1834; found: 423.1832.
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

PAPER
Synthesis and Transformation Reactions of 4-Iminocyclobutenones
2037
from CH2Cl2–pentane; yellow solid; yield: 96 mg (36%); mp 215–
218 °C.
MS (70 eV): m/z (%) = 393 (42, [M + H]+), 249 (56), 221 (47), 193
(21), 145 (100), 89 (89), 78 (56).
IR: 2985, 2361, 1696, 1615, 1560, 1424, 1394, 1311, 1282, 1179,
1152, 1121, 1089 cm–1.
1H NMR (500 MHz): d = 8.2 (d, J = 10 Hz, 1 H), 7.91–7.87 (m, 4
H), 7.56–7.54 (m, 3 H), 7.40–7.36 (m, 4 H), 7.31–7.28 (m, 1 H),
6.42 (sept, J = 5.0 Hz, 1 H), 1.54 (d, J = 5.0 Hz, 6 H).
13C NMR (100 MHz): d = 188.8, 168.5, 161.5, 150.3, 143.3, 131.9,
131.2, 130.1, 129.5, 129.2, 128.3, 128.0, 127.95, 127.6, 126.5,
126.47, 125.4, 123.1, 122.7, 76.3, 23.2.
2-Isopropoxy-3,5-diphenyl-4-(trimethylsilyloxy)-2H-cyclopen-
ta[b]quinoline (26)
Prepared from 10 (100 mg, 0.22 mmol) following the General Pro-
cedure, but refluxing for 1.5 h and using p-xylene (100 mL) as sol-
vent. Isolation by radial chromatography (eluent: hexanes–EtOAc,
10:1); oil; yield: 20 mg (19%).
IR: 3059, 2970, 1592, 1492, 1444, 1388, 1308, 1253, 1176, 1119,
1076, 1043 cm–1.
1H NMR (500 MHz): d = 8.17–8.15 (m, 1 H), 7.74–7.73 (m, 2 H),
7.64–7.61 (m, 2 H), 7.53–7.45 (m, 3 H), 7.42–7.36 (m, 4 H), 7.25–
7.23 (m, 2 H), 5.53 (s, 1 H), 4.29 (sept, J = 6.1 Hz, 1 H), 1.15, 1.12
(d each, J = 6.1 Hz, 3 H), –0.49 (s, 9 H).
13C NMR (125 MHz): d = 164.7, 150.9, 146.7, 137.5, 134.9, 134.4,
131.6, 131.3, 129.7, 129.2, 128.9, 128.2, 128.1, 128.05, 127.99,
127.93, 127.5, 127.1, 126.8, 126.3, 125.9, 78.4, 70.2, 23.8, 22.8,
–0.24.
HRMS (EI): m/z calcd for C28H20F3NO2: 459.1446; found:
459.1535.
2-Isopropoxy-3,5-diphenylcyclopenta[b][1,5]naphthyridin-4-
one (25eB) and 2-Isopropoxy-3,5-diphenylcyclopen-
ta[b][1,7]naphthyridin-4-one (25eA)
Prepared from 8i (420 mg, 1.06 mmol) following the General Pro-
cedure, but using p-xylene (100 mL) as solvent. Isolation from the
crude red oil by radial chromatography (eluent: PE–EtOAc, 25:1)
and recrystallization from EtOAc–PE.
HRMS (EI): m/z calcd for C30H31NO2Si: 465.2124; found:
465.2121.
25eA
Sticky orange colored mass; yield: 51 mg (12%).
(E/Z)-5-Benzylidene-3-isopropoxy-2-phenyl-4-(2,4,6-trimeth-
ylphenylimino)cyclopent-2-en-1-one (27)
IR (KBr): 3441, 2987, 2961, 2927, 1696, 1619, 1547, 1393, 1341,
Obtained from 8h (550 mg, 1.26 mmol) following the General Pro-
cedure, but using p-xylene (100 mL) as solvent and refluxing for 30
min. Isolation from the crude red oil by radial chromatography (elu-
ent: PE–EtOAc, 25:1) and recrystallization from EtOAc–PE; red
crystals; two diastereomers in a 1:0.6 ratio (as far as possible, iso-
mer signals are indicated by subscripts 1 or 2 in the 1H NMR spec-
trum); yield: 290 mg (53%); mp 147 °C.
1301, 904, 776, 692 cm–1
.
1H NMR (200 MHz): d = 9.44 (br s, 1 H), 8.56 (br d, 1 H, J = 5.0
Hz), 7.30–7.60 (m, 9 H), 7.89 (m, 2 H), 6.49 (sept, 1 H, J = 6.2 Hz),
1.56 (d, 6 H, J = 6.2 Hz).
13C NMR (50 MHz): d = 188.4, 168.9, 160.6, 153.6, 145.9, 141.6,
132.4, 131.4, 129.9, 129.5, 129.3, 129.2, 128.2, 128.0, 127.9, 127.5,
125.0, 123.3, 120.0, 76.6, 23.4.
IR (KBr): 3069, 2972, 2910, 1693, 1644, 1626, 1589, 1488, 1381,
1308, 1248, 1127, 1095, 1076, 1036, 770, 753, 697 cm–1
MS (70 eV): m/z (%) = 392 (2, [M]+), 350 (100), 321 (25).
.
1H NMR (400 MHz): d = 8.43 (br s, 2 H2), 8.03 (s, J = 7.3 Hz, 2 H2),
7.87 (s, 1 H1), 7.67 (d, J = 7.1 Hz, 2 H2), 7.55–7.30 (m, H1 and H2),
6.99 (s, 2 H2), 6.86 (s, 2 H1), 6.78 (s, 1 H2), 6.28 (sept, J = 6.1 Hz),
4.30 (sept, J = 6.0 Hz, 1 H1), 2.86 (s, 3 H1), 2.31 (s, 3 H2), 2.27 (s,
3 H1), 2.13 (s, 6 H2), 2.10 (s, 3 H1), 1.49 (d, J = 6.1 Hz, 6 H2), 0.68
(d, J = 6.0 Hz, 6 H1).
25eB
Sticky orange colored mass; yield: 28 mg (7%).
IR (KBr): 3443, 3056, 3020, 2988, 1698, 1620, 1552, 1498, 1399,
1383, 1296, 1088, 785, 696, 689 cm–1
.
1H NMR (200 MHz): d = 1.52 (d, J = 6.1 Hz, 6 H), 6.32 (sept,
J = 6.1 Hz, 1 H), 7.27–7.50 (m, 8 H), 7.60 (dd, J = 4.3, 8.3 Hz, 1 H),
7.80–7.90 (m, 2 H), 8.38 (dd, J = 1.8, 8.3 Hz, 1 H), 8.88 (dd, J = 1.8,
4.3 Hz, 1 H).
MS (70 eV): m/z (%) = 435 (100, [M]+), 392 (48), 378 (90), 348
(34), 346 (13), 314 (19), 234 (16), 191 (16), 179 (19).
13C NMR (50 MHz): d = 188.8, 168.3, 160.2, 150.6, 144.8, 143.8,
137.7, 131.5, 130.5, 130.1, 129.3, 129.2, 129.1, 128.0, 127.9, 127.5,
127.1, 124.8, 122.9, 76.2, 23.3.
Acknowledgment
We thank the Fonds der Chemischen Industrie, Frankfurt, Germany
as well as the National Institutes of Health for generous financial
support.
MS (70 eV): m/z (%) = 393 (3, [M + H]+), 350 (100).
2-Isopropoxy-3,5-diphenylcyclopenta[b][1,6]naphthyridin-4-
one (25f)
Prepared from 8j (280 mg, 0.71 mmol) following the General Pro-
cedure, but using p-xylene (40 mL) as solvent and refluxing for 30
min. Isolation by column chromatography (eluent: PE–EtOAc,
1:1); semi-solid yellow material; yield: 62 mg (22%).
References
(1) (a) Moore, H. W.; Yerxa, B. R. Chemtracts 1992, 5, 273.
(b) Moore, H. W.; Yerxa, B. R. Adv. Strain Org. Chem.
1995, 4, 81.
(2) Liebeskind, L. S. Tetrahedron 1989, 45, 3053.
(3) (a) Paquette, L. A.; Morwick, T. M. J. Am. Chem. Soc. 1997,
119, 1230. (b) Paquette, L. A.; Hamme, A. T.; Kuo, L. H.;
Doyon, J.; Krezholz, R. J. Am. Chem. Soc. 1997, 119, 1242.
(4) Yamamoto, Y.; Nunokawa, K.; Okamoto, K.; Ohno, M.;
Eguchi, S. Synthesis 1995, 571.
IR (KBr): 3445, 3060, 2972, 1701, 1611, 1563, 1425, 1393, 1302,
1091, 836, 790, 702 cm–1
.
1H NMR (200 MHz): d = 9.00 (s, 1 H), 8.77 (d, J = 5.7 Hz, 1 H),
7.80–7.95 (m, 3 H), 7.30–7.60 (m, 8 H), 6.35 (sept, J = 6.2 Hz, 1 H),
1.53 (d, J = 6.2 Hz, 6 H).
13C NMR (100 MHz): d = 188.5, 168.0, 163.6, 152.2, 152.2, 148.9,
143.0, 131.0, 129.9, 129.6, 129.3, 129.3, 128.2, 128.1, 128.0, 123.9,
123.0, 122.8, 122.7, 76.3, 23.3.
(5) Zora, M.; Herndon, J. W.; Li, Y.; Rossi, J. Tetrahedron
2001, 57, 5097.
(6) Gayo, L. M.; Winters, M. P.; Moore, H. W. J. Org. Chem.
1992, 57, 6896.
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York

2038
G. Oppermann et al.
PAPER
(7) Reed, M. W.; Pollart, D.; Perri, S. T.; Foland, L.; Moore, H.
W. J. Org. Chem. 1988, 53, 2477.
(8) Liebeskind, L. S.; Fengl, R. W.; Wirtz, K. R.; Shawe, T. T.
J. Org. Chem. 1988, 53, 2482.
(9) Müller, M.; Heileman, M. J.; Moore, H. W.; Schaumann, E.;
Adiwidjaja, G. Synthesis 1997, 50.
(10) Regenhardt, W.; Schaumann, E.; Moore, H. W. Synthesis
2001, 1076.
(18) Foland, L.; Karlsson, J. O.; Perri, S. T.; Schwabe, R.; Xu, S.
L.; Patil, S.; Moore, H. W. J. Am Chem. Soc. 1989, 111, 975.
(19) Moore, H. W.; Perri, S. T. J. Org. Chem. 1988, 53, 996.
(20) Karlsson, J. O.; Nguyen, N. V.; Foland, L. D.; Moore, H. W.
J. Am. Chem. Soc. 1985, 107, 3392.
(21) Unit cell parameters: a = 10.4030(13) Å, b = 13.3488(11) Å,
c = 25.005(2) Å, a = 84.276(7)°, b = 87.124(9)°,
g = 70.792(9)°, V = 3262.2(6) Å3, Z = 6; triclinic, space
group P1, R = 0.0452, Rw = 0.0761. CCDC 758016 contains
the supplementary cyrstallographic data for this compound.
These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via
(11) Benda, K.; Regenhardt, W.; Schaumann, E.; Adiwidjaja, G.
Eur. J. Org. Chem. 2009, 1016.
(12) Ried, W.; Kunstmann, W. Angew. Int., Ed. Engl. 1968, 7,
135; Angew. Chem. 1968, 80, 121.
(13) (a) Obata, N.; Takizawa, T. Bull. Chem. Soc. Jpn. 1977, 50,
2017. (b) Obata, N.; Takizawa, T. Tetrahedron Lett. 1970,
2231.
(14) Chickos, J. S. J. Org. Chem. 1973, 38, 3642.
(15) Palacios, F.; Alonso, C.; Aparicio, D.; Rubiales, G.;
de los Santos, J. M. Tetrahedron 2006, 63, 523.
(16) Tidwell, T. T. Ketenes; Wiley-VCH: Weinheim, 2006.
(17) Carreño, M. C.; Ribagorda, M. In Science of Synthesis, Vol.
28; Griesbeck, A. G., Ed.; Thieme: Stuttgart, 2006, 629.
www.ccdc.cam.ac.uk/data_request/cif.
(22) Unit cell parameters: a = 9.4990(10) Å, b = 17.7990(10) Å,
c = 14.7910(10) Å, a = b = g = 90°, V = 2500.8(3) Å3,
Z = 4; orthorhombic, space group Pna2(1), R = 0.0542,
Rw = 0.1274. CCDC 75 80 17. To obtain the data, see ref. 21.
(23) Lui, H.; Tomooka, C. S.; Moore, H. W. Synth. Commun.
1997, 27, 2177.
(24) Boedeker, J.; Koeckritz, A.; Koeckritz, P.; Radeglia, R.
J. Prakt. Chem. 1985, 327, 723.
Synthesis 2010, No. 12, 2027–2038 © Thieme Stuttgart · New York