3-Cyclopropyl- and 3-tert-butyl-substituted propyne iminium salts as dienophiles in Diels-Alder reactions

Article abstract of DOI:10.1055/s-2006-942423

Starting from cyclopropylacetylene and 3,3-dimethyl-but-1-yne, and an imidoyl chloride 5, the alkynyl imines 6 were prepared and then converted into propyne iminium triflates 7 by N-methylation. These electron-deficient acetylenes were found to be reactiv

Full text of DOI:10.1055/s-2006-942423

PAPER
2251
3-Cyclopropyl- and 3-tert-Butyl-Substituted Propyne Iminium Salts as
Dienophiles in Diels–Alder Reactions
3
-Cyclopropylprop
o
yne Iminium
l
Salts
g
in
D
iels–Ald
e
er Reaction
r
s
Gerster, Sigrid Espenlaub, Gerhard Maas*
Division of Organic Chemistry I, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany
Fax +49(731)5022803; E-mail: gerhard.maas@uni-ulm.de
Received 7 May 2006
Dedicated to Professor Dieter Hoppe on the occasion of his 65th birthday
R1
1a: R1 = Ph, NR22 = morpholino
Abstract: Starting from cyclopropylacetylene and 3,3-dimethyl-
but-1-yne, and an imidoyl chloride 5, the alkynyl imines 6 were pre-
pared and then converted into propyne iminium triflates 7 by N-
methylation. These electron-deficient acetylenes were found to be
reactive dienophiles in Diels–Alder reactions with cyclopentadiene,
furan, 2,3-dimethylbuta-1,3-diene, and anthracene. Reduction of
the iminium function, which is present in the cycloaddition prod-
ucts, generates tertiary amines. In this manner, norbornadiene (8, 9),
7-oxanorbornadiene (10, 11), cyclohexa-1,4-diene (12), benzene
(13, 14), and dibenzobarrelene (15, 16) derivatives with a novel vic-
inal substitution pattern were obtained.
Ph
1b: R1 = Me, NR22 = morpholinom
1c: R1 = H, NR22 = NMe2
N+R2
2
TfO
X
Ph
2a: R1 = Me, R2 = Me, X = TfO
2b: R1 = Et, R2 = Et, X = BF4
2c: R1 = Ph, R2 = Bn, X = TfO
Me3Si
N+R1R2
OEt
3: R1, R2 = H, alkyl, R3 = H, Ph, t-Bum
R3
N+R1R2
X
Key words: alkynes, imines, iminium salts, cycloadditions, Diels–
Alder reactions
Figure 1
now, both types of propyne iminium salts do react quite
well, giving rise to carbo- and heterocyclic systems with a
novel vicinal substitution pattern.
Cycloaddition reactions of acetylenic iminium salts pro-
vide a convenient approach to carbo- and heterocyclic
ring systems bearing a reactive iminium substituent,
which offers different opportunities for further transfor-
mation. In fact, we have observed earlier that propyne
iminium salts 1a–c1,2 and 2a–c2 (Figure 1) can serve as di-
enophiles in Diels–Alder reactions with common acyclic
and cyclic 1,3-dienes. However, in spite of the activation
of the acetylenic bond by the electron-withdrawing imin-
ium function, these reactions proceed rather slowly (e.g.,
with cyclopentadiene in toluene: 20–72 h at 20 °C; with
anthracene: 7–12 h at 120 °C for 2a–c, 26–69 h at 110 °C
for 1a,c). Although no quantitative kinetic comparison
was made, it appeared that the trimethylsilyl-substituted
propyne iminium salts 2 reacted more smoothly, and also
in better yield, than their phenyl-substituted relatives 1
with the less reactive diene moiety of anthracene. On the
other hand, it was reported that propyne amidinium salts
The novel propyne iminium triflates 7 were obtained by
an approach via alkynyl imines which we had developed
earlier.5 Starting from cyclopropylacetylene (4a) and 3,3-
dimethylbut-1-yne (4b), and arene imidoyl chlorides 5,
the alkynyl imines 6 were synthesized (Scheme 1). In or-
der to optimize the yields of the coupling reaction, several
variations were first tested for the combination of 4a with
5a (R1 = Ph, R3 = Me). By far the best yield was obtained
from the Cu(I)-catalyzed coupling reaction using the alky-
nyl Grignard derivative of 4a (Table 1). In the absence of
the copper salt, the yield was rather low, in contrast to the
analogous reaction of trimethylsilylacetylene or 1-hexyne
with 5a.5,6 Notably, the direct palladium-catalyzed cou-
pling of 4a under Sonogashira-type conditions produced
rather disappointing results, in contrast to literature re-
ports where analogous reactions of other 1-alkynes and
imidoyl chlorides were described.5,7 Effective Sonoga-
shira coupling of terminal alkynes with some cyclic imi-
doyl halide functionalities has also been reported, e.g., the
coupling between 4a and 2-bromo-1,3-thiazole8 or be-
tween phenylacetylene and 5-chloro-1,3-dihydro-1,4-
benzodiazepin-2(2H)ones.9 Using the organocopper
route, alkynyl imines 6a–p could be prepared in yields of
41–81%, while the preparation of 2-furyl-substituted de-
rivative 6q suffered from significant loss of material dur-
ing work up (Table 2).
3
undergo
a
smooth [4+2] cycloaddition with
cyclopentadiene3 and buta-1,3-diene4 when R3 = H, but
the reaction rate is strongly decreased when R3 = Ph or
t-Bu.3
These observations suggest that the dienophilic character
of acetylenic iminium salts very much depends on both
electronic and steric effects. Under both aspects, branched
alkyl groups, such as cyclopropyl and tert-butyl, as sub-
stituents at the C≡C bond did not appear to be a good
choice for successful Diels–Alder reactions. As we report
Selected N-methyl alkynyl imines 6 were then converted
into N,N-dimethyl alkynyl iminium triflates 7 with methyl
triflate (Scheme 1 and Tables 3 and 4). The crystalline
solids obtained after recrystallization can be stored with-
out problems provided that moisture is excluded.
SYNTHESIS 2006, No. 13, pp 2251–2259
Advanced online publication: 23.06.2006
DOI: 10.1055/s-2006-942423; Art ID: C02606SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
6

2252
H. Gerster et al.
PAPER
1. EtMgBr, THF, 0 °C, 30 min,
then CuBr⋅Me2S
Table 1 Conditions and Yields for the Coupling Reaction 4a + 5a
→ 6a
R1
2. R1C(Cl)=NR3 (5)
R2
R2
Conditions
Yield (%)
25–81%
NR3
4a: R2 = c-Pr
4b: R2 = t-Bu
6
4aa + BuLi (1.5 equiv), Et2O, 0 °C, then 5a, 0 °C
4aa + MeMgBr (1 equiv), THF, 0 °C, then 5a, 0 °C
18
20
R1
MeOTf
R2
Et2O, –20 °C
4aa + MeMgBr (1 equiv), CuBr·Me2S (0.05 equiv), THF, 67
0 °C, then 5a, 0 °C
N
47–95%
TfO
R3
7
4aa + 5a, Pd(PPh3)2Cl2 (3 mol%), CuI (10 mol%), Et3N 20b
Scheme 1 Synthesis of alkynyl imines 6 and propyne iminium trif-
lates 7; for R1–R3, see Tables 2 and 3
(solvent), 70 °C, 7 h
4aa + 5a, Pd(dba)2 (3 mol%), P(t-Bu)3 (6 mol%), Et3N
5
(1.2 equiv), dioxane, 70 °C, 7 h
[4+2]-Cycloaddition reactions of several 1,3-dienes with
the alkynyl iminium salts 7a,b,l,n,p were investigated
next (Scheme 2 and Table 5). The reactions with cyclo-
a A 70% solution in toluene was used.
b Similar or even lower yields were obtained using several variations
pentadiene and furan proceeded at moderate temperatures of this method [e.g., dioxane as solvent, Et3N (1.2 equiv), Cs2CO3 (1.2
equiv), or K3PO4 (1.0 equiv) as bases].
and gave the bicyclo[2.2.1]hepta-2,5-diene systems 8 and
10, respectively. Reactions with furan were carried out in
rotation. NOE experiments suggest that the dominating
isomer has the iminium group in an endo orientation with
respect to the norbornadiene framework, while an exo ori-
entation (endo-phenyl orientation) is found in the minor
isomer.
the temperature range 40–46 °C in order to avoid the for-
mation of unspecific side or decomposition products
which was observed at higher temperatures. Oxanorbor-
nadiene derivatives 10a,l,n were observed to decompose
at their melting points; a closer inspection for 10a showed
that the retro-Diels–Alder reaction took place to furnish
7a and furan.
The cycloaddition products 8, 10, 12, 13 and 15 still con-
tain a reactive iminium function, which offers opportuni-
ties for several different transformations. We show here
exemplarily the conversion into tertiary amines using lith-
ium aluminium hydride as the reducing agent. Amines 9a,
14a and 16a were so obtained in yields of 69–98%, while
the oxanorbornadiene-substituted iminium salt 10a did
not react selectively and furnished amine 11a only in
~20% yield besides several other products. Efforts to op-
timize this transformation are underway. Both 9a and 11a
were obtained as a mixture of diastereomers in 61:39 and
60:40 ratios, respectively. However, reduction of 8a with
L-Selectride changed the diasteromeric ratio for 9a to
91:9.
Cycloaddition reactions with 2,3-dimethylbuta-1,3-diene
gave the 1,4-cyclohexadien-1-yl iminium salts 12 which
could be isolated in mostly good yields. Under the given
conditions, including the exclusion of air, partial dehydro-
genating aromatization, leading to arene iminium salts 13,
was not a problem, although 12l,n showed a tendency to
aromatize on heating when oxygen was not rigorously ex-
cluded. This enhanced reactivity was exploited for the di-
rect synthesis of 13l from 7l, carrying out the [4+2]
cycloaddition in the presence of air. The conversion 12a
→ 13a was achieved using established procedures. The
Diels–Alder reaction of 7a and anthracene required the
most forcing conditions, which were similar to those for
3-phenyl-substituted propyne iminium salt 1a (see intro-
duction), yielding dibenzobarrelene derivative 15a almost
quantitatively.
In conclusion, we have shown that both 3-cyclopropyl-
and 3-tert-butyl-substituted propyne iminium salts are
suitable dienophiles for the Diels–Alder reaction of more
(cyclopentadiene, furan, 2,3-dimethylbuta-1,3-diene) or
less (anthracene) reactive 1,3-diene moieties. The imini-
um group in the resulting cycloaddition products provides
a handle for various further transformations, as shown
here exemplarily for the hydride reduction providing a ter-
tiary amine function. The vicinal cyclopropyl/dialkylami-
nomethyl substitution pattern obtained after reduction of
the cycloadducts is a novel one. The synthetic transforma-
tions presented in this paper have outlined a novel appli-
cation of cyclopropylacetylene as a building block which,
with the [4+2] cycloaddition of 3-cyclopropylpropyne
iminium salts as the key step, allows a convenient intro-
duction of the cyclopropyl substituent at six-membered
carbo- and heterocyclic ring systems. Similar cycloaddi-
tion chemistry has been described for methyl 3-(1-chloro-
cyclopropyl)propynoate, which, however, undergoes the
Diels–Alder reaction more reluctantly than propyne imin-
ium triflates 7. Methyl 3-cyclopropylpropyonate, on the oth-
er hand, does not react with cyclopentadiene up to 180 °C.10
As expected, the presence of a tert-butyl substituent in-
stead of cyclopropyl considerably slowed down the reac-
tion rate for steric reasons. The decreased reaction rates,
which are observed when the iminium carbon atom carries
a 4-methoxyphenyl or 4-tolyl rather than a phenyl substit-
uent, can be attributed to a better charge stabilization
which raises the LUMO energy of the dienophile.
1H and 13C NMR data of cycloaddition products 8, 10, 12,
13, 15 are presented in Table 6. The spectra of 8b show
two sets of signals, the ratio of which is slightly tempera-
ture-dependent (in DMSO-d6, 300 K: 59.5:40.5; 375 K:
57:43). It is reasonable to assume the presence of two at-
ropisomers, caused by hindered rotation about the C(sp2,
norbornadiene)–C(=N+Me2) single bond. We have ob-
served this before in a structurally similar case, where
steric interaction of the iminium moiety with a SiMe3
rather than a tert-butyl group was the reason for hindered
Synthesis 2006, No. 13, 2251–2259 © Thieme Stuttgart · New York

PAPER
3-Cyclopropylpropyne Iminium Salts in Diels–Alder Reactions
2253
Table 2 Alkynyl Imines 6 Prepared (Scheme 1) and Selected IR Data
Product R1
R2
R3
Molecular formula
Yielda Mp (°C) or
IRc (cm–1)
(%)
66
77
73
80
81
67
76
69
46
55
44
45
bp (°C/mbar)b
nC≡C
other signals
6a
6b
6c
6d
6e
6f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
c-C3H5 Me
t-Bu Me
c-C3H5 Et
t-Bu Et
c-C3H5 Bn
t-Bu Bn
c-C3H5 Cy
t-Bu Cy
C13H13N (183.25)
C14H17N (199.29)
C14H15N (197.28)
C15H19N (213.32)
C19H17N (259.35)
C20H21N (275.39)
C18H21N (251.37)
C19H25N (267.41)
C16H19N (225.33)
C15H17N (211.31)
C16H21N (227.35)
C14H15NO (213.28)
135/0.03
2210
2216
2216
2217
2214
2214
2211
2217
2215
2214
2217
2211
1593, 1572, 1282, 921, 692
1595, 1574, 1292, 774, 693
1591, 1567, 1281, 931, 692
1592, 1571, 1287, 773, 692
1593, 1568, 1280, 919, 691
1594, 1569, 1288, 921, 693
1591, 1567, 1256, 776, 695
1592, 1567, 1285, 773, 692
1592, 1569, 1280, 773, 692
1592, 1569, 1281,773, 692
1593, 1571, 1287, 773, 692
100/0.001
115/0.001d
110/0.001
Oild
Oild
6g
6h
6i
40-41; 180/0.001
140/0.001
150/0.001
160/0.001
120/0.001
135/0.001
c-C3H5 Bu
c-C3H5 Pr
6j
6k
6l
t-Bu
Pr
C6H4-4-OMe c-C3H5 Me
1605, 1591, 1569, 1509, 1247,
1167, 1030, 921
6m
C6H4-4-OMe t-Bu
Me
C15H19NO (229.32)
41
37-38; 120/0.001
2218
1607, 1590, 1571, 1509, 1310,
1249, 1167, 1029
6n
6o
6p
6q
4-Tol
c-C3H5 Me
t-Bu Me
C14H15N (197.28)
C15H19N (213.32)
C11H11NS (189.28)
C11H11NO (173.21)
70
55
69
25e
130/0.001
140/0.001
120/0.001
120/0.001f
2211
2216
2214
2215
1591, 1566, 1285, 922, 825
1593, 1567, 1292, 889, 825
1580, 1430, 1293, 706
4-Tol
2-Thienyl
2-Furyl
c-C3H5 Me
c-C3H5 Me
1657, 1595, 1560, 941, 744
a All compounds except 6c,e,f gave satisfactory elemental analyses.
b Kugelrohr distillation.
c Film or KBr pellet.
d A small amount of the benzamide, derived from unreacted imidoyl chloride during hydrolytic work-up, could not be removed.
e Purification by reversed-phase column chromatography [RP-18, elution with a cyclohexane–Et2O–Et3N (9:1:0.05) mixture].
f Partial decomposition of the imine during distillation was observed.
Table 3 Proypne Iminium Triflates 7 Prepared (Scheme 1) and Selected IR Data
Product R1
R2
R3
Molecular formula Yielda Mp (°C) (solvent)
(%)
IRb (cm–1)
nC≡C
other signals
7a
7b
7l
Ph
Ph
c-C3H5
t-Bu
Me
Me
Me
Me
Me
Me
C15H16F3NO3S
(347.36)
95
47
88
81
84
64
76-78 (EtOAc)
2202
1620, 1264, 1146, 1032, 638
1640, 1264, 1152, 1034, 639
1587, 1256, 1148, 1028, 634
1600, 1259, 1145, 1028, 634
1586, 1259, 1144, 1023, 634
1614, 1263, 1143, 1027, 635
C16H20F3NO3S
(363.40)
116-117 (CH2Cl2–Et2O) 2219
C6H4-4-OMe c-C3H5
C16H18F3NO4S
(377.38)
99-100 (EtOAc)
95-96 (EtOAc)
64-65 (EtOAc)
109-111 (EtOAc)
2191
2191
2207
2213
7n
7p
7q
4-Tol
c-C3H5
c-C3H5
c-C3H5
C16H18F3NSO3
(361.38)
2-Thienyl
2-Furyl
C13H14F3 NS2O3
(353.37)
C13H14F3NO4S
(337.31)
a All salts gave satisfactory elemental analyses.
b KBr pellet or neat (ATR measurement).
Synthesis 2006, No. 13, 2251–2259 © Thieme Stuttgart · New York

2254
H. Gerster et al.
PAPER
R2
R1
R2
R1
a)
X
X
X
N
N
X = CH2: CH2Cl2, 20–43 °C
X = O: furan, 40–46 °C
TfO
X = CH2: 8a,b
X = O: 10a,l,n
X = CH2: 9a
X = O: 11a
R2
R2
R2
R1
R1
N
MeCN, 70 °C, 24 h
b)
a)
R2
N
N
N
R3
TfO
7a,b,l,n,p
R1
R1
TfO
TfO
12a,b,l,n,p
13a,l
14a
R1
R1
N
N
a)
toluene, 120 °C, 18 h
R2
R2
TfO
15a
16a
Scheme 2 Reagents and conditions: a) LiAlH4, THF, –20 °C → r.t., 24 h; b) o-chloranil, CH2Cl2, 20 °C, 72 h; or nitrobenzene, 150 °C, 32 h.
See Table 5 for R1, R2, further reaction conditions, and yields.
Table 4 1H and 13C NMR Data of Compounds 6 and 7
Product 1H NMR (400.13 MHz, CDCl3/TMS)
13C{1H} NMR (100.61 MHz, CDCl3)
d, J (Hz)
d, J (Hz)
6a
6b
6c
0.89-0.94 (m, 2 H, CH2, c-C3H5), 0.96-0.99 (m, 2 H, CH2, c-C3H5), 0.04 (CH, c-C3H5), 9.43 (CH2, c-C3H5), 43.16 (NCH3), 68.92
1.49-1.58 (m, 1 H, CH, c-C3H5), 3.57 (s, 3 H, NCH3), 7.35-7.39 (m, (NCC≡C), 105.46 (NCC≡C), 127.15, 128.02, 130.00, 137.75
3 H, CHPh), 7.94-7.98 (m, 2 H, CHPh)
(CPh), 152.52 (C=N)
1.38 (s, 9 H, t-Bu), 3.57 (s, 3 H, NCH3), 7.37-7.40 (m, 3 H), 7.97-
7.99 (m, 2 H)
28.32 [C(CH3)3], 30.70 [C(CH3)3], 43.24 (NCH3), 72.06
(NCC≡C), 109.23 (NCC≡C), 127.21, 128.10, 130.10, 137.78
(CPh), 152.75 (C=N)
0.86-0.90 (m, 2 H), 0.92-0.98 (m, 2 H), 1.31 (t, J = 7.3 Hz, 3 H), 1.51 0.04, 9.34, 15.47, 50.39, 69.03, 104.31, 127.26, 127.99,
(tt, J = 5.0, 8.2 Hz, 1 H), 3.79 (q, J = 7.3 Hz, 2 H), 7.34-7.38 (m, 3
H), 7.96-7.98 (m, 2 H)
129.93, 137.95, 150.47
6d
6e
1.31 (t, J = 7.3 Hz, 3 H), 1.37 (s, 9 H), 3.81 (q, J = 7.2 Hz, 2 H), 7.36- 15.38, 28.29, 30.68, 50.39, 72.22, 108.79, 127.34, 128.07,
7.39 (m, 3 H), 7.98-8.00 (m, 2 H)
130.00, 138.01, 150.78
0.85-0.94 (m, 2 H), 0.95-1.04 (m, 2 H), 1.52 (tt, J = 4.6, 8.5 Hz, 1
0.15, 9.49, 59.75, 69.46, 105.06, 126.61, 127.57, 127.92,
H), 4.98 (s, 2 H), 7.24-7.26 (m, 1 H), 7.31-7.45 (m, 7 H), 8.04-8.05 128.07, 128.32, 130.26, 137.77, 140.17, 151.58
(m, 2 H)
6f
1.39 (s, 9 H), 5.00 (s, 2 H), 7.22-7.26 (m, 1 H), 7.31-7.36 (m, 2 H),
7.37-7.44 (m, 5 H), 8.04-8.09 (m, 2 H)
6g
0.86-0.90 (m, 2 H), 0.95-1.00 (m, 2 H), 1.23-1.44 (m, 3 H), 1.48- –0.09, 9.14, 24.61, 25.65, 33.25, 63.91, 69.02, 102.88,
1.58 (m, 3 H), 1.65-1.69 (m, 1 H), 1.74-1.77 (m, 2 H), 1.81-1.86 (m, 127.18, 127.73, 129.60, 138.02, 148.14
2 H), 3.80 (tt, J = 4.1, 10.2 Hz, 1 H, CH), 7.34-7.39 (m, 3 H), 7.95-
7.97 (m, 2 H)
6h
6i
1.35-1.52 (m, 3 H), 1.42 (s, 9 H), 1.58-1.67 (m, 2 H), 1.73-1.76 (m, 24.83, 25.78, 28.15, 30.56, 33.28, 64.12, 72.48, 107.42,
1 H), 1.86-1.94 (m, 4 H), 3.88-3.95 (m, 1 H), 7.41-7.42 (m, 3 H),
8.06-8.08 (m, 2 H)
127.36, 127.91, 129.77, 138.11, 148.71
0.86-1.00 (m, 4 H), 0.96 (t, J = 7.3 Hz, 3 H), 1.44 (sext, J = 7.5 Hz, 2 0.09, 9.36, 13.97, 20.74, 32.72, 55.89, 69.29, 104.13, 127.32,
H), 1.48-1.56 (m, 1 H), 1.71 (quint, J = 7.3 Hz, 2 H), 3.77 (t, J = 7.1 128.03, 129.92, 138.06, 150.55
Hz, 2 H), 7.35-7.38 (m, 3 H), 7.95-7.98 (m, 2 H)
6j
0.86-0.90 (m, 2 H), 0.94-1.02 (m, 2 H), 1.00 (t, J = 7.2 Hz, 3 H),
1.49-1.56 (m, 1 H), 1.75 (sext, J = 7.3 Hz, 2 H), 3.73 (t, J = 7.0 Hz, 2 128.03, 129.94, 138.06, 150.65
H), 7.35-7.38 (m, 3 H), 7.96-7.98 (m, 2 H)
0.09, 9.38, 12.15, 23.89, 57.94, 69.32, 104.19, 127.32,
Synthesis 2006, No. 13, 2251–2259 © Thieme Stuttgart · New York

PAPER
3-Cyclopropylpropyne Iminium Salts in Diels–Alder Reactions
2255
Table 4 1H and 13C NMR Data of Compounds 6 and 7 (continued)
Product 1H NMR (400.13 MHz, CDCl3/TMS)
13C{1H} NMR (100.61 MHz, CDCl3)
d, J (Hz)
d, J (Hz)
6k
6l
1.00 (t, J = 7.3 Hz, 3 H), 1.37 (s, 9 H), 1.76 (sext, J = 7.2 Hz, 2 H),
3.76 (t, J = 7.1 Hz, 2 H), 7.36-7.39 (m, 3 H), 7.97-8.02 (m, 2 H)
12.15, 23.79, 28.28, 30.68, 57.91, 72.47, 108.58, 127.36,
128.05, 129.96, 138.04, 150.90
0.88-0.94 (m, 2 H), 0.95-1.01 (m, 2 H), 1.54 (tt, 1 H, J = 5.0, 8.2 Hz, 0.08, 9.44, 43.01, 55.28, 68.98, 105.10, 113.40, 128.71,
1 H), 3.57 (s, 3 H), 3.82 (s, 3 H), 6.88 (d, J = 8.8 Hz, 2 H), 7.90 (d,
J = 8.8 Hz, 2 H)
130.81, 151.91, 161.25
6m
6n
6o
1.38 (s, 9 H), 3.53 (s, 3 H), 3.83 (s, 3 H), 6.90 (d, J = 9.1 Hz, 2 H), 7.93 28.32, 30.76, 43.02, 55.28, 72.12, 109.57, 113.43, 128.75,
(d, J = 8.8 Hz, 2 H)
130.84, 152.07, 161.27
0.88-0.92 (m, 2 H), 0.93-1.00 (m, 2 H), 1.53 (tt, J = 5.1, 8.3 Hz, 1
0.09, 9.45, 21.29, 43.10, 69.05, 105.19, 127.15, 128.02,
H), 2.36 (s, 3 H), 3.57 (s, 3 H), 7.17, 7.84 (AA¢BB¢, 2J = 7.9 Hz, 4 H) 130.00, 137.75, 152.48
1.37 (s, 9 H), 2.37 (s, 3 H), 3.55 (s, 3 H), 7.18, 7.86 (AA¢BB¢, 2J = 7.9 21.30, 28.32, 30.74, 43.12, 72.18, 109.66, 127.20, 128.83,
Hz, 4 H)
135.29, 140.20, 152.67
6p
0.88-0.92 (m, 2 H), 0.95-1.02 (m, 2 H), 1.52 (tt, J = 5.1, 8.3 Hz, 1
H), 3.49 (s, 3 H), 7.02 (dd, J = 3.7, 4.9 Hz, 1 H), 7.31 (d, J = 5.1 Hz, 144.85, 147.12
1 H), 7.48 (d, J = 3.7 Hz, 1 H)
–0.01, 9.43, 42.72, 68.06, 103.83, 127.04, 128.27, 128.87,
6q
7a
0.87-0.93 (m, 2 H), 0.95-1.01 (m, 2 H), 1.52 (tt, J = 5.0, 8.3 Hz, 1
H), 3.51 (s, 3 H), 6.43 (dd, J = 1.8, 3.3 Hz, 1 H), 6.81 (d, J = 3.5 Hz, 144.26, 152.53
1 H), 7.46 (d, J = 1.0 Hz, 1 H)
–0.08, 9.34, 42.63, 67.51, 103.21, 111.27, 112.92, 142.89,
1.07-1.11 (m, 2 H, CH2), 1.21-1.26 (m, 2 H, CH2), 1.65-1.71 (m, 1 1.78 (CH, c-C3H5), 12.35 (CH2, c-C3H5), 45.22 (NCH3),
H, CH), 3.63 (s, 3 H, NCH3), 3.90 (s, 3 H, NCH3), 7.46-7.51 (m, 2 H, 47.49 (NCH3), 73.05 (NCC≡C), 120.75 (q, 1JCF = 318.8 Hz,
CHPh), 7.54-7.58 (m, 1 H, CHPh), 7.62-7.65 (m, 2 H, CHPh)
CF3), 128.73, 129.15 (CPh), 130.66 (NCC≡C), 131.1, 133.17
(CPh), 163.19 (C=N)
7b
1.37 (s, 9 H, t-Bu), 3.74 (s, 3 H, NCH3), 4.01 (s, 3 H, NCH3), 7.53-
7.57 (m, 2 H, CHPh), 7.61-7.66 (m, 1 H, CHPh), 7.72-7.74 (m, 2 H,
CHPh)
29.17 [C(CH3)3], 29.45 [C(CH3)3], 45.48 (NCH3), 47.67
(NCH3), 75.48 (NCC≡C), 120.84 (q, 1JCF = 320.8 Hz, CF3),
128.88, 129.07, 130.91 (NCC≡C), 131.15, 133.30, 163.49
(C=N)
7l
1.07 (dt, J = 7.5, 4.5 Hz, 2 H), 1.21 (td, J = 7.8, 4.6 Hz, 2 H), 1.66 (tt, 1.67, 12.15, 45.50, 47.53, 55.78, 72.82, 114.72, 120.81 (q,
J = 8.3, 4.9 Hz, 1 H), 3.67 (s, 3 H), 3.82, 3.83 (2 × s, 3 H each), 6.95- JCF = 320.8 Hz), 122.94, 128.55, 132.51, 162.21, 164.17
6.98 (m, 2 H), 7.64-7.66 (m, 2 H)
1
7n
7p
7q
1.13 (dt, J = 7.7, 4.7 Hz, 2 H), 1.26 (td, J = 7.7, 4.6 Hz, 2 H), 1.66 (tt, 1.85, 12.37, 21.68, 45.42, 47.64, 73.09, 120.85 (q, 1JCF
J = 4.9, 8.3 Hz, 1 H), 2.42 (s, 3 H), 3.70 (s, 3 H), 3.93 (s, 3 H), 7.33, 319.1 Hz), 128.31, 129.33, 129.95, 144.93, 163.29
7.57 (AA¢BB¢, 3J = 8.1 Hz, 4 H)
=
1.15-1.19 (m, 2 H), 1.26-1.31 (m, 2 H), 1.76 (tt, J = 4.8, 8.4 Hz, 1
1.49, 11.87, 45.82, 48.78, 71.58, 123.96 (q, 1JCF = 320.3 Hz),
H), 3.91 (s, 3 H), 3.93 (s, 3 H), 7.34-7.36 (m, 1 H), 8.08-8.12 (m, 2 124.94, 130.12, 133.19, 140.12, 140.38, 152.53
H)
1.15-1.21 (m, 2 H), 1.22-1.29 (m, 2 H), 1.72-1.79 (m, 1 H), 3.89 (s, 1.35, 11.63, 45.64, 48.61, 68.91, 115.17, 122.64, 131.21,
3 H), 3.97 (s, 3 H), 6.83 (dd, J = 1.5, 3.8 Hz, 1 H), 7.71 (d, J = 3.8 Hz, 145.16, 145.64, 152.36
1 H), 7.99-8.00 (m, 1 H)
Table 5 [4+2] Cycloaddition Products 8, 10, 12, 13, 15 Prepared (Scheme 2)a
Product R1
R2
Molecular formula
Reaction conditions
CH2Cl2, 20 °C, 48 h
CH2Cl2, 43 °C, 48 h
Furan, 46 °C, 39 h
Furan, 40 °C, 10 d
Furan, 40 °C, 10 d
MeCN, 70 °C, 24 h
MeCN, 85 °C, 64 h
Yield (%) Mp (°C) (Solvent)
8a
8b
Ph
Ph
Ph
c-C3H5
t-Bu
C20H22F3NO3S (413.46)
C21H26F3NO3S (429.50)
C19H20F3NO4S (415.43)
C20H22F3NO5S (445.45)
C20H22F3NO4S (429.45)
C21H26F3NO3S (429.50)
C22H30F3NO3S (445.54)
92
51
60
68
67
77
82
110 (EtOAc–Et2O)
95 (EtOAc–Et2O)
10a
10l
c-C3H5
113 (dec.) (CH2Cl2–Et2O)
117 (dec.) (EtOAc–Et2O)
114 (dec.) (EtOAc–Et2O)
157 (EtOAc–Et2O)
C6H4-4-OMe c-C3H5
10n
12a
12b
4-Tol
Ph
c-C3H5
c-C3H5
t-Bu
Ph
94 (EtOAc–Et2O)
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PAPER
Table 5 [4+2] Cycloaddition Products 8, 10, 12, 13, 15 Prepared (Scheme 2)a (continued)
Product R1
R2
Molecular formula
Reaction conditions
MeCN, 75 °C, 94 h
MeCN, 75 °C, 94 h
Yield (%) Mp (°C) (Solvent)
12l
C6H4-4-OMe c-C3H5
C22H28F3NO4S (459.52)
C22H28F3NO3S (443.52)
98
80
65
124 (EtOAc–Et2O)
12n
12p
13a
4-Tol
2-Thienyl
Ph
c-C3H5
c-C3H5
c-C3H5
94 (EtOAc–Et2O)
93 (EtOAc)
C19H24F3NO3S2 (435.52) MeCN, 80 °C, 72 h
C21H24F3NO3S (427.48)
C22H26F3NO4S (457.51)
C29H26F3NO3S (525.59)
12a in CH2Cl2, chloranil, 20 °C, 72 h 89
12a in nitrobenzene, 150 °C, 32 h
160 (CH2Cl2–Et2O)
90
13l
C6H4-4-OMe c-C3H5
From 7l and 1,3-diene in MeCN,
98
126 (EtOAc)
75 °C, 94 h, airb
15a
Ph
c-C3H5
Toluene, 120 °C, 18 h
97
237 (toluene)
a All reactions were carried out under an argon atmosphere (except for the preparation of 13l) in closed thick-walled Schlenk tubes.
b Cyclohexadiene 12l was not isolated under these conditions.
Table 6 1H and 13C NMR Data and Selected IR Data for Compounds 8, 10, 12, 13, 15
Product 1H NMR (400.13 MHz, CDCl3/TMS)a
13C{1H} NMR (100.6 MHz, CDCl3)a
d, J (Hz)
IRb
d, J (Hz)
n (cm–1)
8a
0.84-0.94 (m, 3 H, CH2 cp), 1.02-1.08 (m, 1 H, CH2 cp), 1.27- 7.63, 8.21 (CH2 cp), 14.81 (CH cp), 45.91, 1601 (C=N), 1263,
1.33 (m, 1 H, CH cp), 2.02, 2.06 (AB system, 2J = 7.3 Hz, 2 H, 46.49 (NCH3), 51.60 (C-4), 54.31 (C-1),
1158, 1035 (TfO–),
7-H2), 3.23 (s, 1 H, 4-H), 3.53 (s, 3 H, NCH3), 3.70 (s, 4 H, 1-H, 67.9 (C-7), 122.40 (q, 1JCF = 319.3 Hz, CF3), 638
NCH3), 6.59-6.61 (m, 1 H, 5-H), 6.70-6.72 (m, 1 H, 6-H), 7.38- 129.28, 129.37, 131.32, 132.89, 140.03 (C-
7.41 (m, 2 H), 7.48-7.52 (m, 2 H), 7.54-7.59 (m, 1 H)
5), 140.56 (C-2), 143.75 (C-6), 178.27
(C=N), 183.75 (C-3)
8bc
A: 1.16 (s, 9 H, t-Bu), 1.92 (dt, 2J = 7.3 Hz, 3J < 1 Hz, 1 H, 7-HA), A: 27.31 (CMe3), 35.11 (CMe3), 45.81,
1611, 1595 (C=N),
2.04-2.10 (m, 7-HB, overlap with B), 3.70 (br s, 1 H, CH), 3.78 47.93 (NCH3), 55.28, 55.80, 67.65, 140.84, 1264, 1141, 1031
(s, 3 H, NCH3), 3.90 (br s, 1 H, CH), 3.91 (s, 3 H, NCH3), 6.27 142.52, 170.32, 185.05.
(TfO–), 634
(dd, J = 2.9, 4.9 Hz, 1 H, =CH), 6.71-6.73 (m, 1 H, =CH), 7.45- B: 27.76 (CMe3), 35.09 (CMe3), 46.33,
7.47 (m, 2 H, CH), 7.54-7.69 (m, 3 H, CH).
47.45 (NCH3); 54.23, 57.80, 71.81, 141.85,
B: 1.09 (s, 9 H, t-Bu), 1.98 (dt 2J = 6.6 Hz, 3J < 1 Hz, 1 H, 7-HA), 143.94, 170.42, 187.99.
2.04-2.10 (m, 7-HB, overlap with A), 3.52 (s, 3 H, NCH3), 3.78 Further signals: 127.96, 129.39 (2 × C),
(s, 4 H, CH, NCH3), 3.84 (br s, 1 H, CH), 6.83 (dd, J = 3.4, 4.4 130.20, 130.34, 131.68, 133.90, 134.09,
Hz, 1 H, =CH), 7.17 (dd, J = 2.9, 4.9 Hz, 1 H, =CH), 7.54-7.69 137.61, 139.32
(m, 3 H), 7.73-7.75 (m, 2 H)
10a
10l
0.88-1.06 (m, 3 H, CH2 cp), 1.17-1.24 (m, 1 H, CH2 cp), 1.47- 7.48, 9.42 (CH2 cp), 14.28 (CH cp), 46.06, 1603, 1573, 1556,
1.53 (m, 1 H, CH cp), 3.55 (s, 3 H, NCH3), 3.72 (s, 3 H, NCH3), 46.22 (NCH3), 83.31, 85.31 (C-1, C-4),
5.00 (br s, 1 H, CHO), 5.53 (br s, 1 H, CHO), 6.93 (dd, J = 2.0, 120.72 (q, 1JCF = 320.5 Hz, CF3), 129.09,
5.3 Hz, 1 H, =CH), 6.98 (dd, J = 1.6, 5.4 Hz, 1 H, =CH), 7.41- 129.55, 130.07, 133.12, 139.49, 140.64,
1253, 1223, 1145,
1028, 634
7.43 (m, 2 H), 7.52-7.56 (m, 2 H), 7.58-7.62 (m, 1 H)
144.44, 176.34 (C=N), 183.04 (C-3)
0.86-0.92 (m, 1 H, CH2 cp), 0.95-1.06 (m, 2 H, CH2 cp), 1.16- 7.26, 9.29 (CH2 cp), 14.18 (CH cp), 46.14, 1595, 1258, 1140,
1.25 (m, 1 H, CH2 cp), 1.40-1.46 (m, 1 H, CH cp), 3.62 (s, 3 H, 46.17 (NCH3), 55.74 (OCH3), 83.26, 85.60, 1031, 636
NCH3), 3.67 (s, 3 H, NCH3), 3.89 (s, 3 H, OCH3), 5.01 (br s, 1 H, 114.99, 120.82 (q, 1JCF = 320.3 Hz, CF3),
CHO), 5.56 (br s, 1 H, CHO), 6.96 (dd, J = 2.0, 5.6 Hz, 1 H,
122.25, 132.56, 139.81, 141.41, 144.78,
=CH), 7.02-7.05 (m, 2 H, CHAr), 7.15 (dd, J = 1.5, 5.3 Hz, 1 H, 163.91, 175.65 (C=N), 182.89 (C-3)
=CH), 7.41-7.45 (m, 2 H, CHAr)
10n
12a
0.89-1.02 (m, 2 H, CH2 cp), 1.04-1.11 (m, 1 H, CH2 cp), 1.22- 7.48, 9.41 (CH2 cp), 14.35 (CH cp), 21.71
1.29 (m, 1 H, CH2 cp), 1.54-1.60 (m, 1 H, CH cp), 2.44 (s, 3 H, (CH3), 46.22, 46.34 (NCH3), 83.41, 85.52,
CH3), 3.60 (s, 3 H, NCH3), 3.75 (s, 3 H, NCH3), 5.02 (br s, 1 H, 127.28, 129.47, 130.32, 139.50, 140.81,
1595, 1573, 1556,
1260, 1149, 1030,
635
CHO), 5.50 (br s, 1 H, CHO), 6.94 (dd, J = 5.3, 2.0 Hz, 1 H,
=CH), 7.05 (dd, J = 1.6, 5.4 Hz, 1 H, =CH), 7.32, 7.36 (AA¢BB¢,
3J = 8.3 Hz, 4 H)
144.62, 144.70, 176.61 (C=N), 182.86 (C-3)
0.64-0.80 (m, 3 H, CH2 cp), 0.97-1.04 (m, 1 H, CH2 cp), 1.45 4.64, 4.84 (CH2), 14.70 (CH), 17.37, 17.82 1647, 1268, 1152,
(s, 3 H, CH3), 1.47-1.52 (m, 1 H, CH cp), 1.52 (s, 3 H, CH3), (CH3), 31.08 (C-3), 34.28 (C-6), 45.79 1032, 637
2.20-2.39 (m, 3 H, CH2), 2.64-2.72 (m, 1 H, CH2), 3.68 (s, 3 H, (NCH3), 46.29 (NCH3), 120.62 (q, 1JCF
NCH3), 3.78 (s, 3 H, NCH3), 7.46-7.60 (m, 5 H) 319.3 Hz, CF3), 121.07 (C-4), 121.81 (C-5),
=
124.75 (C-1), 128.53, 129.16, 130.64,
133.01, 141.27 (C-2), 184.22 (C=N)
Synthesis 2006, No. 13, 2251–2259 © Thieme Stuttgart · New York

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3-Cyclopropylpropyne Iminium Salts in Diels–Alder Reactions
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Table 6 1H and 13C NMR Data and Selected IR Data for Compounds 8, 10, 12, 13, 15 (continued)
Product 1H NMR (400.13 MHz, CDCl3/TMS)a
13C{1H} NMR (100.6 MHz, CDCl3)a
d, J (Hz)
IRb
d, J (Hz)
n (cm–1)
12b
1.15 (s, 9 H, t-Bu), 1.62 (s, 3 H, CH3), 1.69 (s, 3 H, CH3), 2.39- 17.33, 18.15 (CH3), 29.12 [C(CH3)3], 35.13, 1632, 1257, 1153,
2.43 (m, 1 H, CH2), 2.83-2.88 (m, 3 H, CH2), 3.85 (s, 3 H,
37.23, 37.39 [C(CH3)3, C-3, C-6], 45.79,
1027, 636
NCH3), 3.90 (s, 3 H, NCH3), 7.59-7.61 (m, 2 H), 7.63-7.66 (m, 46.29 (NCH3), 122.16, 123.39, 123.62,
1 H), 7.81-7.83 (m, 2 H)
129.52, 130.44, 131.23, 134.56, 146.73,
186.62 (C=N)
12l
0.71-0.80 (m, 3 H, CH2 cp), 0.95-1.01 (m, 1 H, CH2 cp), 1.38- 4.65, 4.96 (CH2 cp), 14.77 (CH cp), 17.62, 1600, 1256, 1156,
1.44 (m, 1 H, CH cp), 1.54 (s, 3 H, CH3), 1.61 (s, 3 H, CH3), 18.08 (CH3), 31.59, 35.19 (C-3, C-6), 46.05, 1025, 633
2.32-2.48 (m, 3 H, CH2), 2.68-2.75 (m, 1 H, CH2), 3.79 (s, 3 H, 46.46 (NCH3), 55.75 (OCH3), 115.00,
NCH3), 3.82 (s, 3 H, NCH3), 3.88 (s, 3 H, OCH3), 7.05 (d, J = 8.8 121.36, 121.98, 122.25, 125.35, 132.72,
Hz, 2 H), 7.67 (d, J = 8.8 Hz, 2 H)
141.23, 164.17, 183.40 (C=N)
12n
12p
0.73-0.85 (m, 3 H, CH2 cp), 1.01-1.07 (m, 1 H, CH2 cp), 1.43- 4.78, 5.08 (CH2 cp), 14.93 (CH cp), 17.65, 1642 (w), 1606,
1.50 (m, 1 H, CH cp), 1.55 (s, 3 H, CH3), 1.62 (s, 3 H, CH3), 18.11, 21.74 (CH3), 31.53, 34.84 (C-3, C-6), 1270, 1256, 1151,
2.25-2.43 (m, 3 H, CHallyl), 2.45 (s, 3 H, CH3), 2.71-2.78 (m, 1 46.09, 46.67 (NCH3), 121.25, 122.26,
1026, 634
H, CHallyl), 3.81 (s, 3 H, NCH3), 3.86 (s, 3 H, NCH3), 7.38, 7.57 125.33, 127.63, 129.47, 130.20, 141.19,
(AA¢BB¢ system, 3J = 8.1 Hz, 4 H)
145.00, 184.51 (C=N)
0.63-0.74 (m, 3 H, CH2 cp), 0.85-0.95 (m, 1 H, CH2 cp), 1.30- 4.69, 4.94 (CH2 cp), 14.71 (CH cp), 17.74, 1647 (w), 1610,
1.37 (m, 1 H, CH cp), 1.64 (s, 3 H, CH3), 1.66 (s, 3 H, CH3),
18.20 (CH3), 31.19, 35.92 (C-3, C-6), 46.15, 1513, 1405, 1255,
2.34-2.47 (m, 2 H, CH2), 2.66, 2.85 (2 × dt, 2J = 21.6 Hz, 3J =
46.81 (NCH3), 120.79 (q, 1JCF = 320.5 Hz,
1165, 1146, 1028,
746, 635
7.1 Hz, 2 H, CH2), 3.82 (s, 3 H, NCH3), 4.05 (s, 3 H, NCH3), 7.41 CF3), 121.76, 122.01, 125.36, 130.48,
(t, J = 4.4 Hz, 1 H, CHThie), 8.11-8.13 (m, 2 H, CHThie
)
132.37, 140.46, 140.52, 140.94, 173.74
(C=N)
13a
13l
0.37-0.44 (m, 1 H, CH2 cp), 0.64-0.74 (m, 2 H, CH2, cp), 0.99- 8.61, 9.31 (CH2 cp), 12.94 (CH cp), 18.95, 1649, 1267, 1152,
1.06 (m, 1 H, CH2 cp), 1.46-1.53 (m, 1 H, CH cp), 2.23 (s, 3 H, 19.99 (CH3), 47.03, 47.73 (NCH3), 120.84 1032, 638
CH3), 2.25 (s, 3 H, CH3), 3.73 (s, 3 H, NCH3), 3.94 (s, 3 H,
(q, 1JCF = 318.6 Hz, CF3), 126.63, 128.57,
NCH3), 6.74 (s, 1 H, CHPh), 7.17 (s, 1 H, CHPh), 7.48-7.52 (m, 2 129.03, 130.4, 131.21, 132.69, 133.69,
H, CHPh), 7.57-7.61 (m, 3 H, CHPh) 135.34, 139.01, 142.30, 184.71 (C=N)
0.42-0.49 (m, 1 H, CH2 cp), 0.65-0.73 (m, 2 H, CH2 cp), 0.96- 8.59, 8.91 (CH2 cp), 12.85 (CH cp), 19.00, 1623 (w), 1593,
1.04 (m, 1 H, CH2 cp), 1.40-1.47 (m, 1 H, CH cp), 2.24 (s, 3 H, 20.00 (CH3), 47.00, 47.53 (NCH3), 55.80
1258, 1181, 1145,
CH3), 2.27 (s, 3 H, CH3), 3.64 (s, 3 H, CH3), 3.88 (s, 3 H, CH3), (OCH3), 114.60, 120.84 (q, 1JCF = 318.6 Hz, 1030, 635
3.98 (s, 3 H, CH3), 6.76 (s, 1 H, CHPh), 6.99 (d, J = 8.8 Hz, 2 H, CF3), 124.43, 126.75, 128.99, 131.48,
CHAr), 7.08 (s, 1 H, CHPh), 7.56 (d, J = 8.8 Hz, 2 H, CHAr)
134.14, 135.28, 139.31, 142.18, 164.47,
184.71 (C=N)
15a
0.89-1.19 (m, 4 H, CH2 cp), 1.44-1.50 (m, 1 H, CH cp), 3.50 (s, 6.25 (2 × CH2 cp), 13.77 (CH cp), 46.17,
3 H, NCH3), 3.70 (s, 3 H, NCH3), 4.63 (s, 1 H, CH), 5.10 (s, 1 H, 47.30 (NCH3), 50.62, 53.35 (C-9, C-10),
CH), 6.90-7.01 (m, 5 H), 7.22-7.25 (m, 3 H), 7.26-7.27 (m, 1 123.21, 124.04 (q, 1JCF = 318.6 Hz, CF3),
1616, 1258, 1222,
1150, 1030, 639
H), 7.38-7.41 (m, 3 H), 7.54-7.58 (m, 1 H)
125.29, 125.43, 126.15, 128.1, 129.17,
130.40, 130.45, 131.64, 133.66, 137.71,
166.84, 181.15 (C=N)
a NMR assignments were confirmed by 2D correlation spectra, if necessary; cp = cyclopropyl.
b KBr pellet (8a,b, 15a) or neat (ATR measurement); w = weak.
c Two atropisomers, A:B = 64:36 (CDCl3, 300 K).
NMR spectroscopic measurements. IR spectra were obtained on a
Bruker Vector 22 FT-IR spectrophotometer. Melting points were
determined on a Büchi Melting Point B-540 apparatus and are un-
corrected. Elemental analyses were carried out with an Elementar
Vario EL instrument at the University of Ulm or on a Heraeus
CHN–O–Rapid analyzer at the University of Kaiserslautern. The re-
quired imidoyl chlorides 5 were prepared according to literature
procedures.14,15
A number of bioactive molecules contain cyclopropyl-
substituted arene moieties. For example, recent patent
claims mention activities such as reverse transcriptase in-
hibition,11 COX-2,12 and bactericidal properties.13 Under
these aspects, the method developed here may be useful
for the construction of more complex targets with poten-
tial biological activity.
All reactions involving moisture-sensitive compounds were carried
out in rigorously dried glassware under an argon atmosphere. Sol-
vents were dried by established procedures and stored over molec-
ular sieves (4 Å; 3 Å for acetonitrile and ethyl acetate). NMR
spectra were recorded on a Bruker DRX 400 spectrometer operating
at 400.13 MHz for 1H and 100.61 MHz for 13C. Tetramethylsilane
N-Methyl-3-cyclopropyl-1-phenylprop-2-yn-1-imine (6a);
Typical Procedure
To a solution of EtMgBr in THF (30 mL), prepared from magne-
sium turnings (0.85 g, 35.0 mmol) and bromoethane (4.50 g, 41
mmol), was slowly added at 0 °C cyclopropylacetylene (4a; 3.15 g,
31.5 mmol, 70% solution in toluene). The solution was stirred for
30 min at 0 °C, then at r.t., until gas evolution ceased. Copper(I) bro-
1
served as internal standard for H and CDCl3 (d = 77.0) for 13C
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H. Gerster et al.
PAPER
Dimethyl-[1-(cyclopropyl-4,5-dimethylcyclohexa-1,4-dien-1-
yl)-1-phenylmethylene]ammonium Trifluoromethanesulfonate
(12a)
The solution of salt 7a (1.00 g, 2.88 mmol) and 2,3-dimethylbuta-
1,3-diene (2.00 g, 24.3 mmol) in MeCN (10 mL) was stirred at 70
°C for 24 h. The solvent and excess diene were removed in vacuo,
the residue was dissolved in EtOAc and precipitated with Et2O. The
solid was washed twice with Et2O, yielding 12a as an off-white
powder (0.95 g, 77%); mp 157 °C.
mide dimethyl sulfide complex (0.324 g, 1.6 mmol, 5 mol%) was
added in one portion at r.t. and the reaction mixture was stirred for
another 5 min. N-Methylchloro(phenyl)methanimine (5a; 5.38 g, 35
mmol) was slowly added at 0 °C from a dropping funnel. The mix-
ture turned dark red and was stirred overnight at r.t. After dilution
with water (100 mL) and extraction with Et2O (3 × 100 mL), the
combined organic layers were washed with sat. aq NaHCO3 solu-
tion, dried over Na2SO4 and concentrated. The residue was purified
by Kugelrohr distillation (135 °C/0.03 mbar) to give 6a as a color-
less oil (3.84 g, 67%).
Spectroscopic data are presented in Table 6.
Spectroscopic data are presented in Tables 2 and 4.
Anal. Calcd for C21H26F3NO3S (429.50): C, 58.73; H, 6.10; N, 3.26.
Found: C, 58.78; H, 6.11; N, 3.26.
Anal. Calcd for C13H13N (183.25): C, 85.21; H, 7.15; N, 7.64.
Found: C, 85.12; H, 7.16; N, 7.69.
Compounds 12b,l,n,p were prepared analogously (Tables 5 and 6).
Dimethyl-(3-cyclopropyl-1-phenylprop-2-yn-1-ylidene)ammo-
nium Trifluoromethanesulfonate (7a); Typical Procedure for
Alkylation of Imines 6 with Methyl Triflate
Dimethyl-[1-(2-cyclopropyl-4,5-dimethylphenyl)-1-phenyl-
methylene]ammonium Trifluoromethanesulfonate (13a)
(a) The solution of salt 12a (0.95 g, 2.21 mmol) and o-chloranil
(0.66 g, 2.44 mmol) in CH2Cl2 (10 mL) was stirred for 72 h at r.t.
The solvent was evaporated, and the residue was dissolved in
CH2Cl2 (5 mL) and precipitated with Et2O. The solvent was pipetted
off and the precipitate was washed twice with Et2O, yielding 13a as
a beige powder (0.84 g, 89%); mp 160 °C.
To a cooled (–20 °C) solution of methyl triflate (3.50 g, 21.3 mmol)
in Et2O (10 mL) was slowly added a solution of 6a (2.45 g, 13.3
mmol) in Et2O (5 mL) from a cooled (–78 °C) dropping funnel. The
reaction mixture was stirred at –20 °C for 2 h, during which time an
off-white precipitate formed. The liquid phase was pipetted off and
the precipitate was triturated twice with Et2O. The light-brown solid
was dried in vacuo and recrystallized several times from EtOAc to
afford salt 7a as white crystals (3.23 g, 9.3 mmol, 70%); mp 76–78
°C.
(b) Salt 12a (0.20 g, 0.46 mmol) was heated in nitrobenzene at 150
°C for 32 h. The solvent was removed in vacuo and the residue was
recrystallized from CH2Cl2–Et2O. Yield of 13a: 0.18 g (90%).
Spectroscopic data are presented in Table 6.
Spectroscopic data are presented in Tables 3 and 4.
Anal. Calcd for C21H24F3NO3S (427.48): C, 59.0; H, 5.66; N, 3.28.
Found: C, 58.90; H, 5.60; N, 3.25.
Anal. Calcd for C15H16F3NO3S (347.36): C, 51.87; H, 4.64; N, 4.03.
Found: C, 51.83; H, 4.61; N, 4.05.
Compound 13l was prepared by heating 7l (0.50 g, 1.32 mmol) and
2,3-dimethylbuta-1,3-diene (0.95 g, 11.56 mmol) in MeCN (4 mL)
under aerobic conditions at 75 °C for 6 d. The solvent and excess
diene were removed in vacuo. Addition of Et2O to the oily residue
and sonication (30 min) furnished a solid which was recrystallized
from EtOAc, yielding 13l (0.59 g, 98%) as a white powder; mp 126
°C.
Compounds 7b,l,n,p,q were prepared analogously, but the methyla-
tions of 6l and 6n were carried out at r.t. (Tables 3 and 4).
Dimethyl-{1-(3-cyclopropylbicyclo[2.2.1]hepta-2,5-dien-2-yl)-
1-phenylmethylene}ammonium Trifluoromethanesulfonate
(8a)
The solution of salt 7a (1.00 g, 2.88 mmol) and freshly distilled cy-
clopentadiene (0.68 g, 10.33 mmol) in CH2Cl2 (10 mL) was stirred
for 48 h at r.t. The solvent and excess cyclopentadiene were re-
moved in vacuo. The residue was recrystallized from EtOAc, dis-
solved in CH2Cl2 and precipitated with Et2O, yielding 8a as a white
powder (1.10 g, 92%); mp 110 °C.
Spectroscopic data are presented in Table 6.
N,N-Dimethyl-1-(16-cyclopropyltetracyclo[6.6.2.0.0]hexadeca-
1,3,5,7,9,11,13,15-octaen-15-yl)-1-phenylmethaniminium
Trifluoromethanesulfonate (15a)
The solution of salt 7a (1.00 g, 2.88 mmol) and anthracene (2.00 g,
11.22 mmol) in toluene (15 mL) was heated in a thick-walled
Schlenk tube at 120 °C and stirred for 18 h. A yellow precipitate was
formed during the reaction. The hot organic layer was decanted and
the solid residue was stirred twice for additional 10 min in toluene
(15 mL) at 120 °C (closed Schlenk tube) in order to extract unreact-
ed anthracene. Filtration of the hot mixture furnished 15a as a beige
powder (1.41 g, 93%); mp 237 °C.
Spectroscopic data are presented in Table 6.
Anal. Calcd for C20H22F3NO3S (413.46): C, 58.10; H, 5.36; N, 3.39.
Found: C, 58.10; H, 5.36; N, 3.36.
Compound 8b was prepared analogously (Tables 5 and 6).
Dimethyl-{1-(3-cyclopropyl-7-oxabicyclo[2.2.1]hepta-2,5-dien-
2-yl)-1-phenylmethylene}ammonium Trifluoromethane-
sulfonate (10a)
The solution of salt 7a (2.00 g, 5.76 mmol) in furan (15 mL) was
stirred for 39 h at 46 °C. The solvent and excess furan were removed
in vacuo. The residue was dissolved in CH2Cl2 and precipitated with
Et2O. The precipitate was washed with Et2O and EtOAc, yielding
10a as a slightly yellow powder (1.44 g, 60%); mp 113 °C (dec.).
Spectroscopic data are presented in Table 6.
Anal. Calcd for C29H26F3NO3S (525.59): C, 66.27; H, 4.99; N, 2.67.
Found: C, 66.16; H, 4.97; N, 2.67.
Dimethyl-{1-(3-cyclopropylbicyclo[2.2.1]hepta-2,5-dien-2-yl)-
1-phenylmethyl}amine (9a); Typical Procedure for Reduction
of Iminium Salts 8, 10, 13, and 15
Spectroscopic data are presented in Table 6.
Anal. Calcd for C19H20F3NO4S (415.43): C, 54.93; H, 4.85; N, 3.37.
Found: C, 54.92; H, 5.09; N, 3.43.
To a stirred solution of LiAlH4 in THF (9 mL, 1 mol/L) was slowly
added a solution of 8a (1.00 g, 2.42 mmol) in THF (25 mL) at –20
°C. The mixture was allowed to warm to r.t. over 24 h. H2O (100
mL) was added and the aqueous phase was extracted with CH2Cl2
(3 × 150 mL). The combined organic layers were washed with sat.
aq NaCl solution (150 mL) and dried (Na2SO4). The solvent was re-
moved in vacuo to yield 9a as a light-yellow oil (0.50 g, 78%),
which decomposed on attempted Kugelrohr distillation; 61:39 mix-
Compounds 10l,n were prepared analogously (Tables 5 and 6).
Synthesis 2006, No. 13, 2251–2259 © Thieme Stuttgart · New York

PAPER
3-Cyclopropylpropyne Iminium Salts in Diels–Alder Reactions
2259
ture of diastereomers.
IR (ATR): 1623, 1594, 1576, 1555, 1255, 720 cm–1.
Anal. Calcd for C20H25N (279.42): C, 85.97; H, 9.02; N, 5.01.
Found: C, 85.92; H, 8.99; N, 5.06.
1H NMR (CDCl3; major/minor isomer): d = 0.48–0.53/0.38–0.45
(m, 1 H, CH2 cp), 0.56–0.68 (m, 2 H, CH2 cp, A + B), 0.76–0.83 (m,
1 H, CH2 cp, A +B), 1.43, 1.67/1.71, 1.82 (AB system, 2J = 5.7 Hz,
2 H, 7-H2), 1.88–1.95/1.83–1.87 (m, 1 H, CH cp), 2.11/2.27 (s, 3 H,
NCH3), 2.91/2.96 (br s, 1 H, 1-H or 4-H), 3.51/3.54 (br s, 1 H, 1-H
or 4-H), 4.10/4.00 (s, 1 H, NCH), 6.52–6.54/6.06–6.08 (m, 1 H, 5-
H or 6-H), 6.82–6.84/6.17–6.19 (m, 1 H, 5-H or 6-H), 7.14–7.32 (m,
6 H, CHPh, B), 7.22 (m, 4 H, CHPh, A), 7.40–7.42 (m, 2 H, CHPh, A).
13C NMR (CDCl3): d = 2.65, 3.17 (CH2 cp, A + B), 4.37, 4.48 (CH2
cp, A + B), 9.85, 9.95 (CH cp, A + B), 44.59, 44.63 (NCH3, A + B),
48.54, 49.25, 50.38, 51.30 (C-1, C-4, A + B), 67.33 (C-7, B), 70.27,
70.47, 70.76 (C-7, A and NCH, A + B), 126.28–128.12 (6 signals),
138.81, 140.27–148.61 (9 signals).
Dimethyl-{1-(16-cyclopropyltetracyclo[6.6.2.0.0]hexadeca-
1,3,5,7,9,11,13,15-octaen-15-yl)1-phenylmethyl}amine (16a)
Prepared from 15a (0.30 g, 0.57 mmol); white solid (0.15 g, 69%);
mp 182–183 °C.
IR (KBr): 1453, 1019, 758, 707 cm–1.
1H NMR (CDCl3): d = 0.71–0.87 (m, 4 H, CH2 cp), 1.97–2.03 (m, 1
H, CH cp), 2.10 (s, 6 H, NCH3), 4.23 (s, 1 H, CH), 4.43 (s, 1 H,
NCH), 5.23 (s, 1 H, CH), 6.62–6.67 (m, 2 H), 6.72–6.78 (m, 1 H),
6.93–6.99 (m, 2 H), 7.02–7.04 (m, 1 H), 7.11–7.18 (m, 1 H), 7.18–
7.22 (m, 3 H), 7.34–7.37 (m, 3 H).
13C NMR (CDCl3): d = 3.77 (CH2 cp), 4.25 (CH2 cp), 10.46 (CH
cp), 44.69 (NCH3), 50.13, 50.74, 70.17 (NCH), 121.75–127.98 (11
signals), 140.84, 144.10, 144.17, 145.11, 146.15, 146.60, 146.86.
Anal. Calcd for C19H23N (265.39): C, 85.99; H, 8.74; N, 5.28.
Found: C, 85.67; H, 8.72; N, 5.29.
Anal. Calcd for C28H27N (377.52): C, 89.08; H, 7.21; N, 3.71.
Found: C, 88.97; H, 7.12; N, 3.68.
Dimethyl-{1-(3-cyclopropyl-7-oxabicyclo[2.2.1]hepta-2,5-dien-
2-yl)-1-phenylmethyl}amine (11a)
Acknowledgment
From salt 10a (1.13 g, 2.72 mmol) in CH2Cl2 (10 mL), analogously
to the preparation of 9a. The product mixture obtained after hydro-
lytic work-up was submitted to column chromatography [silica gel,
elution with cyclohexane–EtOAc–Et3N (2:1:0.03, 1:1:0.02, and
0:1:0.01)], which furnished pure product 11a in the third fraction
and additional product as the major component of the fourth frac-
tion; total yield: ca 130 mg (ca 20%). Light-yellow oil; 60:40 mix-
ture of diastereomers.
We thank BASF AG (Ludwigshafen/Rhein) for a gift of cyclopro-
pylacetylene.
References
(1) Maas, G.; Singer, B.; Wald, P.; Gimmy, M. Chem. Ber.
1988, 121, 1847.
(2) Nikolai, J.; Schlegel, J.; Regitz, M.; Maas, G. Synthesis
IR (ATR): 1452, 992, 872, 701, 649 cm–1.
1H NMR (CDCl3; major/minor isomer): d = 0.48–0.55/0.41–0.46
(m, 1 H, CH2 cp), 0.66–0.76 (m, 2 H, CH2 cp, A + B), 0.87–0.96 (m,
1 H, CH2 cp, A + B), 1.96–2.02/1.80–1.86 (m, 1 H, CH cp), 2.16/
2.31 [s, 6 H, N(CH3)2], 4.08/4.04 (s, 1 H, NCH), 4.83/4.88 (br s, 1
H, CHO), 5.28/5.36 (br s, 1 H, CHO), 6.30 (dd, J = 1.5, 5.3 Hz, 1 H,
=CH, B), 6.52 (dd, J = 1.8, 5.3 Hz, 1 H, =CH, B), 6.86 (dd, J = 1.8,
5.3 Hz, 1 H, =CH, A), 7.00 (dd, J = 1.6, 5.4 Hz, 1 H, =CH, A), 7.19–
7.39 (m, 5 H, A + B).
13C NMR (CDCl3; major/minor isomer): d = 2.57/2.38 (CH2 cp),
4.73/4.79 (CH2 cp), 9.23/8.90 (CH cp), 44.25/44.30 [N(CH3)2],
69.62/66.25 (NCH), 81.79/82.31 (CHO), 84.28/83.16 (CHO),
126.74, 126.89, 127.24, 127.88, 128.21, 128.31, 138.76, 139.32,
140.33, 140.65, 144.04/143.08, 147.88/147.54, 149.83/148.91.
2002, 497.
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(b) Baum, J. S.; Viehe, H. G. J. Org. Chem. 1976, 41, 183.
(4) François, J.-P.; Gittos, M. W. Synth. Commun. 1979, 9, 741.
(5) Schlegel, J.; Maas, G. Synthesis 1999, 100.
(6) We found, however, that the yield of
(Me3Si)C≡CC(Ph)=NMe from (Me3Si)C≡CMgBr (ref. 5)
increased from 73% to 79% in the presence of CuBr·Me2S (5
mol%).
(7) (a) Austin, W. B.; Bilow, N.; Kelleghan, W. J.; Lau, K. S. Y.
J. Org. Chem. 1981, 46, 2280. (b) Lin, S.-Y.; Sheng, H.-Y.;
Huang, Y.-Z. Synthesis 1991, 235.
(8) Siebeneicher, H.; Doye, S. Eur. J. Org. Chem. 2002, 1213.
(9) Nadin, A.; Sanchez Lopez, J. M.; Owens, A. P.; Howells, D.
M.; Talbot, A. C.; Harrison, T. J. Org. Chem. 2003, 68,
2844.
Anal. Calcd for C18H21NO (267.37): C, 80.86; H, 7.92; N, 5.24.
Found: C, 80.65; H, 8.01; N, 5.10.
(10) (a) Liese, T.; Splettstaesser, G.; de Meijere, A. Tetrahedron
Lett. 1982, 33, 3341. (b) Bengtson, G.; Keyaniyan, S.; de
Meijere, A. Chem. Ber. 1986, 119, 3607.
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[a-(2-Cyclopropyl-4,5-dimethylphenyl)benzyl]dimethylamine
(14a)
Prepared from 13a (0.70 g, 1.60 mmol); colorless oil (0.44 g, 98%).
IR (ATR): 1452, 908, 731, 669 cm–1.
1H NMR (CDCl3): d = 0.54–0.60 (m, 1 H, CH2 cp), 0.64–0.70 (m, 1
H, CH2 cp), 0.85–0.91 (m, 1 H, CH2 cp), 0.98–1.05 (m, 1 H, CH2
cp), 1.90–2.01 (m, 1 H, CH cp), 2.17 (s, 3 H, CH3), 2.22 (s, 6 H,
NCH3), 2.25 (s, 3 H, CH3), 4.69 (s, 1 H, NCH), 6.77 (s, 1 H, CHPh),
7.14–7.18 (m, 1 H, CHPh), 7.23–7.27 (m, 2 H, CHPh), 7.45–7.47 (m,
2 H, CHPh), 7.56 (s, 1 H, CHPh).
13C NMR (CDCl3): d = 6.95 (CH2 cp), 7.50 (CH2 cp), 13.07 (CH
cp), 19.34 (CH3), 19.45 (CH3), 45.0 (NCH3), 71.94 (NCH), 126.65,
128.06, 128.26, 128.32, 134.41, 134.46, 137.23, 140.36, 143.27.
(14) Ugi, I.; Beck, F.; Fetzer, U. Chem. Ber. 1962, 95, 126.
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Young, J. H. Tetrahedron 1994, 50, 3139.
Synthesis 2006, No. 13, 2251–2259 © Thieme Stuttgart · New York