Efficient synthesis of dihydrobenzofurans via a multicomponent coupling of salicylaldehydes, amines, and alkynes

Article abstract of DOI:10.1055/s-2008-1078573

A simple and efficient synthesis of dihydrobenzofurans was developed using a multicomponent coupling of various salicylaldehydes, amines, and alkynes. The use of aliphatic alkynes containing a heteroatom is critical to the success of the reaction. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1078573

LETTER
1897
Efficient Synthesis of Dihydrobenzofurans via a Multicomponent Coupling of
Salicylaldehydes, Amines, and Alkynes
Synthesisof
D
ihy
e
drobenzof
n
Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC, H3A 2K6, Canada
Fax +1(514)3983797; E-mail: cj.li@mcgill.ca
Received 7 April 2008
als affording a wide variety of complex molecules. The
Abstract: A simple and efficient synthesis of dihydrobenzofurans
was developed using a multicomponent coupling of various sali-
cylaldehydes, amines, and alkynes. The use of aliphatic alkynes
containing a heteroatom is critical to the success of the reaction.
key step to these syntheses is often the intramolecular
Heck reaction.6 Asymmetric variations of this reaction
have also been reported.7 Recently, we reported an annu-
lation of phenol with dienes leading to dihydrobenzo-
furans.8 To further our interest in such compounds, we
wish to report another approach to dihydrobenzofurans
via a three-component coupling using readily available
components (Scheme 1).
Key words: multicomponent coupling, C–H bond reactions, tan-
dem reactions, heterocycles, catalysis
The dihydrobenzofuran core is an important subunit of
many naturally occurring heterocycles, many of which are
biologically active.1 Therefore, chemists have developed
many efficient methodologies for the synthesis of 2,3-di-
hydrobenzofurans derivatives, such as the radical cycliza-
tion,2 the Bartoli reaction3 or the dehydration method.4 On
the other hand, transition-metal-catalyzed cascade reac-
tions have emerged as the method of choice to access het-
erocycles.5 These cyclizations are often carried out under
mild conditions with readily synthesized starting materi-
We started our investigation using salicylaldehyde, pi-
peridine, and 3,3-dimethylbut-1-yne in acetonitrile with
30 mol% CuI as catalyst (Scheme 2). However, only the
aldehyde–amine–alkyne coupling (A3-coupling) occurred
and no cyclized product was obtained after stirring at
80 °C for 16 hours.9
We then hypothesized that using a propargyl alcohol as
the alkyne would help the cyclization. The Cu(I) species
O
N
cat. [Cu]
or cat. [Ag]
R
H
+
+
H
N
H
O
R
OH
Scheme 1 Multicomponent coupling of salicyldehyde, amine, and alkyne to generate dihydrobenzofurans
O
N
CuI (30 mol%)
MeCN, 80 °C
H
+
H
+
N
H
OH
OH
1a
Scheme 2 Multicomponent coupling of salicylaldehyde, amine, and 3,3-dimethylbut-1-yne
N
– H+
N
N
O
+ H+
M
H
M
OH
OH
OH
O
OH
Scheme 3 Proposed mechanism for the intramolecular cyclization
SYNLETT 2008, No. 12, pp 1897–1901
x
x
.x
x
.2
0
0
8
Advanced online publication: 02.07.2008
DOI: 10.1055/s-2008-1078573; Art ID: U03008ST
© Georg Thieme Verlag Stuttgart · New York

1898
R.-V. Nguyen, C.-J. Li
LETTER
O
OH
CuI (30 mol%)
N
H
H
+
+
N
H
MeCN, 80 °C, 16 h
OH
OH
O
95% (NMR yield)
Scheme 4 Multicomponent coupling of salicylaldehyde, amine, and propargyl alcohol
would coordinate to both the p-bond of the alkyne and the 5 mol% CuI as catalyst in the absence of solvent provided
oxygen (Scheme 3).
optimal conditions in terms of yield and reaction time.
Further attempts to shorten reaction time resulted in in-
complete conversion (Table 1, entries 8 and 9).
Recently, Yamamoto et al. proposed a similar activation
of alkynes in which a Cu(I) species coordinated to a car-
bonyl oxygen and a p-bond of the alkyne.10 To much of Subsequently, various salicylaldehydes, amines, and pro-
our delight, the desired cyclized product was obtained ex- pargyl alcohols were tested under our optimized reaction
clusively with an excellent yield (Scheme 4). Although a conditions (Table 2). We were pleased to find that the re-
similar reaction is known,11 a stoichiometric amount of action was not limited to propargyl alcohols. Indeed, a
copper is required and the scope is limited.
protected propargyl amine can be used, as well as ho-
mopropargyl alcohols (Table 2, entries 3 and 4). The use
of 1-hexynol also affords the cyclized product, albeit in a
lower yield due to competing dimerization (Table 2, entry
5). Unfortunately, primary amines were not effective for
this transformation. It should be noted that under the stan-
dard conditions (oil bath at 80 °C for 16 h), the reaction is
equally effective with 5% CuI. On the other hand, the use
of AgCl as a catalyst under our optimized microwave con-
ditions led to low conversions. Hence, the reaction had to
be run in an oil bath.
Optimization of the reaction conditions was then carried
out (Table 1). When AuI was used as a catalyst, only the
A3-addition product was obtained under the same reaction
conditions (Table 1, entry 2).12 Both AgCl and AgBr were
are also effective for the cascade reaction (Table 1, entries
3 and 4).13 Since CuI is much more economical than AgX
and AuI, further investigations were carried out with CuI.
Under microwave irradiation, we were able to shorten the
reaction time, reduce the amount of catalyst, and eliminate
the use of solvent (Table 1, entries 6 and 7).14 We found
that microwave irradiation at 130 °C for 30 minutes with
Table 1 Multicomponent Coupling of Salicylaldehyde, Piperidine and 2-Methyl-3-butyn-2-ol
O
OH
catalyst
N
O
H
+
+
H
N
H
OH
OH
1a
2a
3a
4
Entrya
Catalyst (mol%)
CuI (30)
AuI (30)
AgBr (20)
AgCl (20)
CuI (30)
CuI (30)
CuI (5)
Conditions
Yield (%)b
1
2
3
4
5
6
7
8
9
MeCN, 80 °C, 16 h
MeCN, 80 °C, 16 h
MeCN, 80 °C, 16 h
MeCN, 80 °C, 16 h
94
0
88
94
74
80
90
54
28
MW, 130 °C, 35 min, MeCN
MW, 130 °C, 35 min, neat
MW, 130 °C, 35 min, neat
MW, 130 °C, 15 min, neat
MW, 130 °C, 5 min, neat
CuI (5)
CuI (5)
a The reactions were performed with 1 equiv of 1a, 2 equiv of 2a, and equiv of 3a.
b NMR yield using nitromethane as an internal standard.
Synlett 2008, No. 12, 1897–1901 © Thieme Stuttgart · New York

LETTER
Synthesis of Dihydrobenzofurans
1899
Table 2 Copper- and Silver-Catalyzed Multicomponent Coupling of Salicylaldehyde, Amine, and Alkyne
O
N
cat. [Cu]
or cat. [Ag]
H
+
+
H
R
N
H
O
OH
R
R
R
1a: R = H
1b: R = naphthyl
1c: R = 5-Cl
1d: R = 3-OMe
Entrya
Aldehyde
Amine
2a
Alkyne
Isolated yield (%)c
85 (77)
1
2
1a
1a
3a
2a
81 (76)
OH
3
4
1a
1a
2a
53 (42)
88 (71)
NHTs
2a
2a
HO
5
6
1a
1a
58 (44)
44 (40)
OH
3a
3a
O
N
7
1a
88 (75)
N
8b
9b
1b
1c
1d
2a
3a
3a
3a
80 (72)
71 (66)
82 (75)
2a
2a
10b
a Reactions were run at 130 °C for 30 min in a microwave reactor using 1 equiv of aldehyde, 2 equiv of amine, and 2 equiv of alkyne under neat
conditions with 5% CuI.
b Acetonitrile was used as a solvent.
c Value in parentheses correspond to reactions run in MeCN using 1 equiv of aldehyde, 2 equiv of amine, and 2 equiv of alkyne with 5% AgCl
for 16 h in a oil bath at 80 °C.
The Z-isomer was obtained exclusively for all compounds multicomponent couplings under conventional heating as
(Figure 1).15 This is consistent with a 5-exo-dig mecha- well as under microwave irradiations. The use of aliphatic
nism as proposed in Scheme 3. The metal coordinates to alkynes bearing a heteroatom is crucial to the cyclization
the p-bond of the alkyne and the oxygen. Intramolecular step. The scope, synthetic application, and mechanism of
attack then occurs, followed by protonolysis to afford the the method are under investigation in our laboratory.16–18
product.
In conclusion, we have developed an expedient route to
dihydrobenzofurans using copper- and silver-catalyzed
Acknowledgment
We are grateful to the Canada Research Chair (Tier I) foundation (to
CJL), NSERC, and McGill University for support of this research.
NOE
N
H
References and Notes
H
(1) For recent publications, see: (a) Van Miert, S.; Van Dyck,
S.; Schmidt, T. J.; Brun, R.; Vlietinck, A.; Lemiere, G.;
Pieters, L. Bioorg. Med. Chem. 2005, 13, 661. (b) Chu, G.-
H.; Gu, M.; Cassel, J. A.; Belanger, S.; Graczyk, T. M.;
OH
O
Figure 1 Determination of stereochemistry by NOE experiment
Synlett 2008, No. 12, 1897–1901 © Thieme Stuttgart · New York

1900
R.-V. Nguyen, C.-J. Li
LETTER
DeHaven, R. N.; Conway-James, N.; Koblish, M.; Little, P.
J.; DeHaven-Hudkins, D. L.; Dolle, R. E. Bioorg. Med.
Chem. 2005, 15, 5114. (c) Shi, G. Q.; Drpinski, J. F.; Zhang,
Y.; Santini, C.; Sahoo, S. P.; Berger, J. P.; MacNaul, K. L.;
Zhou, G.; Agrawal, A.; Alvaro, R.; Cai, T.; Hernandez, M.;
Wright, S. D.; Moller, D. E.; Heck, J. V.; Meinke, P. T.
J. Med. Chem. 2005, 48, 5589.
SiO2 (gradient eluent: hexane–EtOAc = 10:1 to 1:1) to give
241 mg (44% yield) of product (Table 2, entry 6).
(17) Typical Experimental Procedure for the Ag-Catalyzed
Coupling of Aldehyde, Amine, and Alkyne under
Normal Heating Conditions
Salicylaldehyde (209 mL, 2 mmol), morpholine (348 mL, 4
mmol), 2-methyl-3-butyn-2-ol (387 mL, 4 mmol), and AgCl
(14.3 mg, 0.10 mmol) were mixed in a reaction flask at 80 °C
in a oil bath in MeCN overnight. The solvent was removed
under reduced pressure, and the crude mixture was isolated
via column chromatography on SiO2 (gradient eluent:
hexane–EtOAc = 10:1 to 1:1) to give 220 mg (44% yield) of
product (Table 2, entry 6).
(2) Jimenez, M. C.; Miranda, M. A.; Tormos, R. J. Org. Chem.
1998, 63, 1323.
(3) Bartoli, G.; Bosco, M.; Caretti, D.; Dalpozzo, R.; Todesco,
P. E. J. Org. Chem. 1987, 52, 4381.
(4) (a) Bertolini, F.; Crotti, P.; Di Bussolo, V.; Macchia, F.;
Pineschi, M. J. Org. Chem. 2007, 72, 7761. (b) Kuethe, J.
T.; Wang, A.; Journet, M.; Davies, I. W. J. Org. Chem. 2005,
70, 3727.
(18) 2-Methyl-1-(3-piperidin-1-yl-3H-benzofuran-2-
ylidene)propan-2-ol (Table 2, Entry 1)
(5) Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104, 2127.
(6) For a recent example, see: Szlosek-Pinaud, M.; Diaz, P.;
Martinez, J.; Lamaty, F. Tetrahedron 2007, 63, 3340.
(7) (a) Tietze, L. F.; Ila, H.; Bell, H. P. Chem. Rev. 2004, 104,
3453. (b) Shibasaki, M.; Vogl, E. M.; Ohshima, T. Adv.
Synth. Catal. 2004, 346, 1533.
(8) Nguyen, R. V.; Yao, X.; Li, C. J. Org. Lett. 2006, 8, 2397.
(9) For recent examples of A3-coupling, see: (a) Sreedhar, B.;
Reddy, P. S.; Krishna, C. S. V.; Babu, P. V. Tetrahedron
Lett. 2007, 48, 7882. (b) Kidwai, M.; Bansal, V.; Mishra, N.
K.; Kumar, A.; Mozumdar, S. Synlett 2007, 1581. (c) Li, P.;
Wang, L. Tetrahedron 2007, 63, 5455. (d) Gommermann,
N.; Knochel, P. Chem. Eur. J. 2006, 12, 4380. (e) Wei, C.;
Mague, J. T.; Li, C. J. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5749. For a review of the A3-coupling see: (f) Wei,
C.; Li, Z.; Li, C. J. Synlett 2004, 1472.
IR (neat): 3419 (br), 2933, 1696, 1463, 1158 cm–1. 1H NMR
(400 MHz, CDCl3): d = 7.36 (m, 1 H), 7.24 (m, 1 H), 6.99
(m, 1 H) 5.13 (s, 1 H), 4.79 (s, 1 H), 2.58 (m, 2 H), 2.40 (m,
2 H), 1.53–1.39 (m, 12 H) ppm. 13C NMR (75 MHz, CDCl3):
d = 157.7, 152.2, 129.5, 126.3, 125.4, 122.2, 113.8, 109.9,
70.6, 67.8, 49.6, 30.9, 30.8, 26.5, 24.6 ppm. MS (EI): m/z
(%) = 223 [M+], 214, 189. HRMS: m/z calcd for C17H23O2N:
273.1729; found: 273.17.
1-(3-Piperidin-1-yl-3H-benzofuran-2-ylidenemethyl)-
cyclohexanol (Table 2, Entry 2)
IR (neat): 3419 (br), 2948, 1698, 1612, 1464, 1289 cm–1. 1H
NMR (400 MHz, CDCl3): d = 7.33 (m, 1 H), 7.17 (m, 1 H),
6.91 (m, 1 H), 6.85 (m, 1 H), 5.08 (s, 1 H), 4.74 (s, 1 H), 2.53
(m, 2 H), 2.32 (m, 2 H), 1.85–1.36 (m, 16 H) ppm. 13C NMR
(100 MHz, CDCl3): d = 157.6, 152.9, 129.4, 126.2, 125.2,
122.1, 112.4, 109.9, 71.7, 67.8, 49.6, 30.0, 26.5, 25.8, 24.6,
23.0 ppm. MS (EI): m/z (%) = 313 [M+], 229, 214. HRMS:
m/z calcd for C20H27O2N: 313.2036; found: 313.2042.
N-[1-Ethyl-1-(3-piperidin-1-yl-3H-benzofuran-2-
ylidenemethyl)propyl]-4-methylbenzenesulfonamide
(Table 2, Entry 3)
(10) Patil, N. T.; Wu, H.; Yamamoto, Y. J. Org. Chem. 2005, 70,
4531.
(11) Ukhin, L. Y.; Komissarov, V. N.; Lendeman, S. V.;
Khrustalyov, V. N.; Struchkov, Y. T. Chem. Heterocycl.
Compd. 2002, 38, 1174.
(12) (a) Yan, B.; Liu, Y. Org. Lett. 2007, 9, 4323. (b) Kidwai,
M.; Bansal, V.; Kumar, A.; Mozumdar, S. Green Chem.
2007, 9, 742. (c) Lo, V. K. Y.; Liu, Y.; Wong, M. K.; Che,
C. M. Org. Lett. 2006, 8, 1529. (d) Wei, C.; Li, C. J. J. Am.
Chem. Soc. 2003, 125, 9584.
(13) (a) Reddy, K. M.; Babu, N. S.; Suryanarayana, I.; Sai Prasad,
P. S.; Lingaiah, N. Tetrahedron Lett. 2006, 47, 7563.
(b) Yan, W.; Wang, R.; Xu, Z.; Xu, J.; Lin, L.; Shen, Z.;
Zhou, Y. J. Mol. Catal. A: Chem. 2006, 255, 81. (c) Li, Z.;
Wei, C.; Chen, L.; Varma, R. S.; Li, C. J. Tetrahedron Lett.
2004, 45, 2443. (d) Wei, C.; Li, Z.; Li, C. J. Org. Lett. 2003,
5, 4473.
IR (neat): 2970, 2802, 1696, 1612, 1594, 1461, 1157, 1094
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.64 (m, 2 H), 7.25
(m, 2 H), 6.92 (m, 2 H), 6.92 (m, 4 H), 5.26 (s, 1 H), 4.53 (s,
1 H), 4.19 (s, 1 H), 2.39 (m, 1 H), 2.27 (m, 1 H), 2.19 (s, 3
H), 2.03 (m, 3 H), 1.74 (m, 3 H), 1.34 (m, 6 H), 0.84 (m, 6
H) ppm. 13C NMR (75 MHz, CDCl3): d = 157.5, 153.6,
142.5, 139.9, 129.6, 129.0, 127.4, 126.0, 125.3, 122.2,
110.0, 108.0, 67.8, 62.7, 49.6, 30.3, 26.3, 24.5, 21.6, 8.4
ppm. MS (EI): m/z (%) = 454 [M+], 283, 214, 155. HRMS:
m/z calcd for C26H34O3N2S: 454.2290; found: 454.2282.
4-(3-Piperidin-1-yl-3H-benzofuran-2-ylidene)butan-2-ol
(Table 2, Entry 4)
(14) For microwave-promoted A3-coupling, see: (a) Ju, Y.; Li,
C. J.; Varma, R. S. QSAR Comb. Sci. 2004, 23, 891.
(b) Shi, L.; Tu, Y. Q.; Wang, M.; Zhang, F. M.; Fan, C. A.
Org. Lett. 2004, 6, 1001.
(15) (a) Harkat, H.; Blanc, A.; Weibel, J. M.; Pale, P. J. Org.
Chem. 2008, 73, 1620. (b) Liu, Y.; Song, F.; Song, Z.; Liu,
M.; Yan, B. Org. Lett. 2005, 7, 5409. (c) Chaudhuri, G.;
Kundu, N. G. J. Chem. Soc., Perkin Trans. 1 2000, 775.
(d) Gabriele, B.; Salerno, G.; Lauria, E. J. Org. Chem. 1999,
64, 7687.
IR (neat): 3382 (br), 2931, 1701, 1612, 1475, 1218, 1151
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.36 (m, 1 H), 7.20
(m, 1 H), 6.94 (m, 1 H), 6.80 (m, 1 H), 4.96 (m, 1 H), 4.78
(s, 1 H), 3.93 (sept, 1 H, J = 6.0 Hz), 2.39 (m, 6 H), 1.53–
1.38 (m, 9 H) ppm. 13C NMR (75 MHz, CDCl3): d = 158.1,
154.9, 129.5, 126.4, 125.9, 121.7, 109.8, 101.7, 68.1, 67.2,
49.6, 35.4, 26.4, 24.6, 23.1 ppm. MS (EI): m/z (%) = 273
[M+], 214, 188. HRMS: m/z calcd for C17H23O2N: 273.1729;
found: 273.1723.
5-(3-Diethylamino-3H-benzofuran-2-ylidene)pentan-1-
(16) Typical Experimental Procedure for the Cu-Catalyzed
Coupling of Aldehyde, Amine, and Alkyne under
Microwave Irradiation
ol (Table 2, Entry 5)
IR (neat): 3412 (br), 2935, 1711, 1611, 1463, 1234 cm–1. 1H
NMR (400 MHz, CDCl3): d = 7.27 (m, 1 H), 7.11 (m, 1 H),
6.84 (m, 1 H), 6.74 (m, 1 H), 4.78 (t, 1 H, J = 6.4 Hz), 4.62
(s, 1 H), 3.46 (m, 2 H), 2.45–2.17 (m, 4 H), 1.56–1.26 (m, 12
H) ppm. 13C NMR (75 MHz, CDCl3): d = 158.2, 152.6,
129.4, 126.4, 125.7, 121.5, 109.5, 66.8, 61.9, 49.2, 35.3,
32.0, 29.8, 25.3, 20.1 ppm. MS (EI): m/z (%) = 287 [M+],
214, 202. HRMS: m/z calcd for C18H25O2N: 287.1872;
In a 5 mL Biotage microwave vial, salicylaldehyde (209 mL,
2 mmol), morpholine (348 mL, 4 mmol), 2-methyl-3-butyn-
2-ol (387 mL, 4 mmol), and CuI (19 mg, 0.10 mmol) were
mixed. The vial was then capped and was subjected to
microwave irradiation for 30 min at 130 °C. The crude
mixture was directly isolated via column chromatography on
Synlett 2008, No. 12, 1897–1901 © Thieme Stuttgart · New York

LETTER
found: 287.1875.
Synthesis of Dihydrobenzofurans
1901
m/z calcd for C21H25O2N: 323.1885; found: 323.1879.
1-(5-Chloro-3-piperidin-1-yl-3H-benzofuran-2-ylidene)-
2-methylpropan-2-ol (Table 2, Entry 9)
2-Methyl-1-(3-morpholin-4-yl-3H-benzofuran-2-
ylidene)propan-2-ol (Table 2, Entry 6)
IR (neat): 3419 (br), 2967, 1612, 1462, 1374, 1232, 1115
cm–1. 1H NMR (400 MHz; CDCl3): d = 7.41 (m, 1 H), 7.26
(m, 1 H), 7.01 (m, 1 H), 6.94 (m, 1 H), 5.15 (s, 1 H), 4.79 (s,
1 H), 3.66 (m, 4 H), 2.63 (m, 2 H), 2.41 (m, 2 H), 1.50 (s, 3
H), 1.48 (s, 3 H) ppm. 13C NMR (75 MHz CDCl3):
d = 157.7, 151.4, 136.1, 129.9, 126.3, 122.4, 114.5, 110.1,
70.6, 67.4, 48.6, 30.8, 30.8 ppm. MS (EI): m/z (%) = 275
[M+], 216, 189, 131, 86. HRMS: m/z calcd for C16H21O3N:
275.1521; found: 275.1519.
IR (neat): 3401 (br), 2936, 1702, 1608, 1469, 1234, 1154
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.34 (s, 1 H), 7.20
(m, 1 H), 6.86 (m, 1 H), 5.14 (m, 1 H), 4.76 (s, 1 H), 2.58 (m,
2 H), 2.39 (m, 2 H), 1.54–1.46 (m, 12 H) ppm. 13C NMR (75
MHz, CDCl3): d = 156.2, 152.1, 129.5, 127.4, 126.3, 114.2,
110.9, 70.6, 69.8, 67.8, 49.6, 30.9, 26.5, 24.5 ppm. MS (EI):
m/z (%) = 307 [M+], 248, 223. HRMS: m/z calcd for
C17H22O2N35Cl: 307.1339; found: 307.1344. HRMS: m/z
calcd for C17H22O2N37Cl: 309.1312; found: 309.1312.
1-(6-Methoxy-3-piperidin-1-yl-3H-benzofuran-2-
ylidene)-2-methylpropan-2-ol (Table 2, Entry 10)
IR (neat): 3580 (br), 2938, 1736, 1699, 1620, 1444, 1280
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.22 (m, 1 H), 6.50
(m, 1 H), 5.09 (m, 1 H), 4.67 (s, 1 H), 3.75 (s, 3 H), 2.53 (m,
2 H), 2.31 (m, 2 H), 1.49–1.36 (m, 12 H) ppm. 13C NMR (75
MHz, CDCl3): d = 161.2, 158.9, 153.0, 126.5, 117.2, 113.8,
108.1, 96.1, 70.6, 67.4, 55.7, 49.4, 30.9, 30.8, 26.4, 24.6
ppm. MS (EI): m/z (%) = 303 [M+], 244, 219. HRMS: m/z
calcd for C18H25O3N: 303.1834; found: 303.1831.
2-Methyl-1-(3-pyrrolidin-1-yl-3H-benzofuran-2-
ylidene)propan-2-ol (Table 2, Entry 7)
IR (neat): 3430 (br), 2911, 1672, 1561, 1341, 1160 cm–1. 1H
NMR (400 MHz, CDCl3): d = 7.35 (m, 1 H), 7.19 (m, 1 H),
6.93 (m, 1 H), 6.87 (m, 1 H), 5.12 (s, 1 H), 4.74 (s, 1 H), 2.57
(m, 2 H), 2.36 (m, 2 H), 1.54–1.24 (m, 10 H) ppm. 13C NMR
(75 MHz, CDCl3): d = 157.6, 152.2, 129.5, 125.4, 122.2,
113.7, 109.9, 70.6, 67.8, 49.6, 30.9, 26.5, 24.6 ppm. MS
(EI): m/z (%) = 258 [M+], 189, 131. HRMS: m/z calcd for
C16H21O2N: 258.1494; found: 258.1491.
2-Methyl-1-{3-piperidin-1-yl-3H-naphtho[2,3-b]furan-
2-ylidene}propan-2-ol (Table 2, Entry 8)
2-(4,4-Dimethyl-1-piperidin-1-yl-pent-2-ynyl)phenol (1b)
IR (neat): 2936, 2233, 1644, 1465, 1458, 1362, 1244, 1153
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.51 (m, 1 H), 7.22
(m, 1 H), 6.87 (m, 2 H), 4.88 (s, 1 H), 2.64 (m, 4 H), 1.68 (m,
6 H), 1.39 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): d =
158.0, 129.3, 128.6, 122.1, 110.0, 116.4, 99.1, 95.41, 71.3,
60.7, 31.6, 28.0, 26.2, 24.4 ppm. MS (EI): m/z (%) = 271
[M+], 186, 84. HRMS: m/z calcd for C18H25ON: 271.1936;
found: 271.1933.
IR (neat): 3581 (br), 2934, 1688, 1522, 1249, 1161 cm–1. 1H
NMR (400 MHz CDCl3): d = 8.18 (m, 1 H), 7.83 (m, 1 H),
7.75 (m, 1 H), 7.52 (m, 1 H), 7.38 (m, 1 H), 2.53 (m, 4 H),
1.64–1.32 (m, 12 H) ppm. 13C NMR (75 MHz, CDCl3):
d = 155.2, 151.2, 131.2, 130.8, 130.5, 128.8, 127.9, 124.0,
124.0, 117.9, 115.1, 111.4, 70.9, 68.2, 49.3, 31.2, 31.1, 26.8,
25.0 ppm. MS (EI): m/z (%) = 323 [M+], 264, 181. HRMS:
Synlett 2008, No. 12, 1897–1901 © Thieme Stuttgart · New York

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