The effect of an N-substituent on the recyclization of (2-aminoaryl)bis(5-tert-butyl-2-furyl)methanes: synthesis of 3-furylindoles and triketoindoles

Article abstract of DOI:10.1016/j.tetlet.2007.11.015

The recyclization of (2-aminophenyl)bis(5-tert-butyl-2-furyl)methane derivatives has been studied. It was shown that the acid-catalyzed recyclization of N-tosylamides leads to the formation of 2-(3-oxoalkyl)-3-(2-furyl)indoles. In contrast, under the same reaction conditions, acetamides are transformed into indoles containing three keto groups. The acid-catalyzed removal of the acetyl group from these substrates facilitated protolytic furan ring opening. The same triketones can be directly obtained from (2-aminoaryl)bis(5-tert-butyl-2-furyl)methanes.

Full text of DOI:10.1016/j.tetlet.2007.11.015

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 20–24
The effect of an N-substituent on the recyclization
of (2-aminoaryl)bis(5-tert-butyl-2-furyl)methanes:
synthesis of 3-furylindoles and triketoindoles
Alexander V. Butin,a,* Sergey K. Smirnova and Igor V. Trushkovb
aResearch Institute of Heterocyclic Compounds Chemistry, Kuban State University of Technology,
Moskovskaya St. 2, Krasnodar 350072, Russian Federation
bDepartment of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1/3,
Moscow 119992, Russian Federation
Received 2 October 2007; revised 24 October 2007; accepted 2 November 2007
Available online 7 November 2007
Abstract—The recyclization of (2-aminophenyl)bis(5-tert-butyl-2-furyl)methane derivatives has been studied. It was shown that the
acid-catalyzed recyclization of N-tosylamides leads to the formation of 2-(3-oxoalkyl)-3-(2-furyl)indoles. In contrast, under the same
reaction conditions, acetamides are transformed into indoles containing three keto groups. The acid-catalyzed removal of the acetyl
group from these substrates facilitated protolytic furan ring opening. The same triketones can be directly obtained from (2-amino-
aryl)bis(5-tert-butyl-2-furyl)methanes.
ꢀ 2007 Elsevier Ltd. All rights reserved.
3-Furylindoles are poorly explored heterocyclic com-
XH
R'
XH
R'
H
H+
pounds. Only fragmentary publications dealing with
their synthesis are known to date.1 At the same time,
some of these compounds display different types of
physiological activity and, therefore, are of interest
for biological screening.2 For this screening, the possibil-
ity of modification of the lead molecule is very desir-
able. The introduction of reactive functional groups
into the pharmacophore-containing scaffold is the sim-
plest way for such modification. Earlier, we developed
a general approach to benzannelated heterocycles based
on the recyclization of ortho-substituted benzylfurans
(Scheme 1).3–6 As a continuation of these studies, we
decided to elaborate the synthesis of 3-furylindoles pos-
sessing a keto group, which is appropriate for further
modifications.
+
O
O
R
R
1
X = O, NTs, COO, CONAlk, CH2O
- H+
X
X
H+
- H3O+
O
R
R
O
R'
2
3
For R' = 5-methyl-2-furyl
Scheme 1.
During our previous studies we showed that the direc-
tion of the recyclization depends on the nature of substi-
tuent R0 at the benzyl carbon atom (Scheme 1). When
R0 = alkyl or aryl, the recyclization affords ketones 2
in good yields.3 However, for benzylfurans 1 with
R0 = 2-furyl, this rearrangement was usually accompa-
nied by secondary cyclization leading to tetracyclic
products 3.4 For example, treatment of (2-acetylamino-
aryl)difurylmethanes 4 with ethanolic hydrogen chloride
gave rise to tetracyclic salts 5 (Scheme 2).5 Variation of
the hydrogen chloride concentration, replacement of
the acetyl protecting group by benzoyl or sulfonyl, the
use of other Bronsted and Lewis acids and variation
of the reaction conditions did not prevent the secondary
Keywords: Furan; Recyclization; Indole; 1,4-Diketone.
*
Corresponding author. Tel.: +7 861 2559556; fax: +7 861 2596592;
e-mail addresses: alexander_butin@mail.ru; av_butin@yahoo.com
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.015

A. V. Butin et al. / Tetrahedron Letters 49 (2008) 20–24
Table 1. Synthesis of starting compounds 8–11
21
O
H
Entry
R1
R2
Yield (%)
N
Cl -
NH
8
9
10
11
+
HCl
EtOH
R'
R
O
a
b
c
H
H
OMe
92
94
90
88
86
83
89
81
58
61
65
68
53
57
58
62
R
R'
OMe
OCH2O
OCH2CH2O
O
O
d
R'
4
5
R'
R' = Me, Et
Scheme 2.
HCl, the corresponding triketones were not observed
in the reaction mixture. All these data together allow
us to conclude that triketones 13 are formed as a result
of a reaction sequence including acetamide deacetyl-
ation,3c recyclization, and protolytic furan ring opening
of the 3-furyl-1H-indole intermediates. Indeed, we
showed that amines 9 were also converted under the
same reaction conditions into the corresponding tri-
ketones (Scheme 6).14
cyclization. At the same time, in some cases, careful
optimization of the reaction conditions resulted in the
target furyl-containing ketones 2 from aryldifuryl-
methanes.4d,e Moreover, our investigation of the (2-
carboxyaryl)difurylmethane to isochromone recycliza-
tion showed that the presence of a tert-butyl group at
C5 atom of the furan ring prevented the secondary cycli-
zation due to significant steric hindrance.4d,6
Thus, protolytic opening of the furan ring appeared to
be impossible for the deactivated NTs-indoles but pro-
ceeded readily with NH-indoles. To prove this, we syn-
thesized indole 14b15 and showed that its treatment
with ethanolic hydrogen chloride gave triketone 13b
(Scheme 7).16
Therefore, for the synthesis of ketone-containing 3-
furylindoles we used the derivatives of (2-aminophenyl)-
bis(5-tert-butyl-2-furyl)methane as starting compounds
which were synthesized by the reaction sequence shown
in Scheme 3. The perchloric acid-catalyzed condensation
of 2-nitrobenzaldehydes 6 with 5-tert-butylfuran 7
yielded (2-nitroaryl)difurylmethanes 8a–d,7 reduction
of which with hydrazine hydrate/Raney nickel in reflux-
ing ethanol led to amines 9a–d8 (Scheme 3, Table 1).
These amines were transformed into the corresponding
amides 10a–d9 and 11a–d10 by tosylation or acetylation
of 9, respectively (Scheme 4, Table 1).
The crucial difference in the reactivity of compounds 12
and 14 in the acid-catalyzed furan ring opening is deter-
mined by the nature of the substituents at C2 of the
furan. Indole 12b is a typical example of a 2-aryl-5-alkyl-
furan, which are known to be much more resistant to
hydrolytic ring opening than 2,5-dialkylfurans due to
conjugation between the two aromatic rings. The ready
acid-catalyzed furan opening in 14b can be explained
by reversible protonation at C3 of the indole moiety
with the formation of tautomeric 3-furyl-3H-indole
(A). In this tautomer, conjugation between the indole
and furan counterparts does not exist, so, formally it
can be considered as an acid-labile 2,5-dialkylfuran
(Scheme 8).
The behavior of compounds 9–11 in the recyclization
experiments differed significantly. When tosylamides 10
were heated at reflux in ethanol saturated with hydrogen
chloride, 3-furylindoles 12a–d11 were isolated as single
reaction products (Scheme 5, Table 2). The secondary
cyclization was not observed for these substrates even
after prolonged heating. This result is in full accordance
with the effect of the tert-butyl group found earlier for
the recyclization of (2-carboxyaryl)difurylmethanes.4b,6
However, acetamides 11 were transformed into tri-
ketones 13a–d12 by keeping them either in ethanolic
hydrogen chloride for 1 week or in acetic acid in the
presence of hydrochloric acid for 24 h at room tempera-
ture13 (Scheme 6, Table 2). In contrast, even in the case
of prolonged heating of tosylamides 10 in ethanolic
In summary, the direction of the recyclization of (2-ami-
nophenyl)bis(5-tert-butyl-2-furyl)methane
derivatives
depends on the nature of the substituents on the nitro-
gen atom. The use of tosylamides allows the synthesis
of ketone-containing 3-furylindoles as potential physio-
logically active agents. In contrast, N-unsubstituted
derivatives and acetamides form the corresponding
triketones as a result of protolytic opening of the furan
R1
R2
R1
R2
R1
NO2
NO2
NH2
HClO4
NH2NH2
Ni/Ra
+
R2
O
1,4-dioxane
O
O
CHO
O
O
6a-d
7
9a-d
8a-d
Scheme 3.

22
A. V. Butin et al. / Tetrahedron Letters 49 (2008) 20–24
Ac
NH
Ts
NH
R1
R2
R1
R2
R1
R2
NH2
TsCl
Py
Ac2O
O
O
O
O
O
O
11a-d
9a-d
10a-d
Scheme 4.
Table 2. Synthesis of 3-furylindoles 12 and triketones 13
Ts
NH
Ts
N
R1
R2
R1
R2
Entry
R1
R2
Yield (%)
HCl
O
12
13
EtOH
O
a
b
c
H
OMe
OCH2O
OCH2CH2O
H
OMe
59
62
61
65
42
51
56
49
O
O
d
12a-d
10a-d
Scheme 5.
for preparative chemistry of indoles due to possible
transformations of the 1,4-dioxoalkyl substituent at
C3 into a variety of 3-hetaryl- and other 3-substituted
indoles.
ring in the 3-furyl-3H-indole tautomeric form of inter-
mediates. The last transformation can be valuable
Ac
NH
R1
R1
R1
H
N
NH2
HCl
HCl
O
R2
R2
O
EtOH
AcOH
O
R2
O
O
O
O
13a-d
9b
11a-d
Scheme 6.
Ts
N
Ts
N
MeO
MeO
MeO
O
O
MeO
O
O
O
12b
KOH
MeOH
H
H
N
MeO
MeO
MeO
MeO
N
HCl
EtOH
O
O
O
O
O
(56%)
(61%)
13b
14b
Scheme 7.

A. V. Butin et al. / Tetrahedron Letters 49 (2008) 20–24
23
H
N
R1
R2
R1
R2
H
N
H+
+
- H+
+ H+
O
O
H
O
O
14
R1
R2
H
N
R1
R2
N
O
O
H+
O
O
O
A
13
Scheme 8.
V.; Smirnov, S. K.; Stroganova, T. A.; Bender, W.;
Krapivin, G. D. Tetrahedron 2007, 63, 474–491.
Acknowledgments
4. (a) Butin, A. V.; Krapivin, G. D.; Zavodnik, V. E.;
Kul’nevich, V. G. Chem. Heterocycl. Compd. (Engl.
Transl.) 1993, 29, 524–533; Khim. Geterotsikl. Soedin.
1993, 616–626; (b) Butin, A. V.; Gutnov, A. V.; Abaev, V.
T.; Krapivin, G. D. Chem. Heterocycl. Compd. (Engl.
Transl.) 1998, 34, 762–770; Khim. Geterotsikl. Soedin.
1998, 883–892; (c) Butin, A. V.; Abaev, V. T.; Mel’chin, V.
V.; Dmitriev, A. S. Tetrahedron Lett. 2005, 46, 8439–8441;
(d) Abaev, V. T.; Dmitriev, A. S.; Gutnov, A. V.;
Podelyakin, S. A.; Butin, A. V. J. Heterocycl. Chem.
2006, 43, 1195–1204; (e) Dmitriev, A. S.; Abaev, V. T.;
Bender, W.; Butin, A. V. Tetrahedron 2007, 63, 9437–9447.
5. (a) Smirnov, S. K.; Butin, A. V.; Stroganova, T. A.;
Didenko, A. V. Chem. Heterocycl. Compd. (Engl. Transl.)
2005, 41, 929–931; Khim. Geterotsikl. Soedin. 2005, 1098–
1100; (b) Butin, A. V.; Smirnov, S. K.; Stroganova, T. A.
J. Heterocycl. Chem. 2006, 43, 623–628.
6. Dmitriev, A. S.; Podelyakin, S. A.; Abaev, V. T.; Butin, A.
V. Chem. Heterocycl. Compd. (Engl. Transl.) 2005, 41,
1194–1196; Khim. Geterotsikl. Soedin. 2005, 1400–1402.
7. A typical procedure is as follows: To a solution of 2-
nitrobenzaldehde 6b (6.33 g, 30 mmol) and 2-tert-butylfu-
ran 7 (9.3 g, 75 mmol) in 1,4-dioxane (25 mL), 70% HClO4
(1 mL) was added. The reaction mixture was stirred at 65–
70 ꢁC until all the starting compound had been consumed
(TLC monitoring), then poured into water, neutralized
with NaHCO3, and left overnight at room temperature.
The product was extracted with CH2Cl2 (2 · 100 mL). The
organic layer was separated, washed with water
(2 · 50 mL), dried over anhydrous Na2SO4, and evapo-
rated under reduced pressure. The residue was dissolved in
hexane, and the resultant solution was filtered through a
pad of silica gel (5–40 lm), and evaporated under reduced
pressure to dryness. The resulting yellow oil, 8b (12.44 g,
94%) was used as such in the next step.
Financial support was provided by Bayer HealthCare
AG and the Russian Foundation of Basic Research
(grant 03-03-32759 and 07-03-00352).
References and notes
1. (a) Gabrielyan, G. E.; Papayan, G. L. Arm. Khim. Zh.
1973, 26, 768–774; Chem. Abstr. 1974, 80, 70638; (b)
Holla, B. S.; Ambekar, S. Y. J. Chem. Soc., Chem.
Commun. 1979, 221; (c) Holla, B. S.; Ambekar, S. Y.
Indian J. Chem. 1982, 21B, 638–641; (d) Campbell, M. M.;
Cosford, N.; Li, Z.; Sainsbury, M. Tetrahedron 1987, 43,
1117–1122; (e) Couture, A.; Deniau, E.; Gimbert, Y.;
Grandclaudon, P. J. Chem. Soc., Perkin Trans. 1 1993,
2463–2466; (f) Katritzky, A. R.; Wang, J.; Karodia, N.;
Li, J. Synth. Commun. 1997, 27, 3963–3976; (g) Butin, A.
V.; Stroganova, T. A.; Abaev, V. T.; Zavodnik, V. E.
Chem. Heterocycl. Compd. (Engl. Transl.) 1997, 33, 1393–
1399; Khim. Geterotsikl. Soedin. 1997, 1614–1621; (h)
Nishida, A.; Miyashita, N.; Fuwa, M.; Nakagawa, M.
Heterocycles 2003, 59, 473–476; (i) Miyagi, T.; Hari, Y.;
Aoyama, T. Tetrahedron Lett. 2004, 45, 6303–6305.
2. (a) Bottcher, H.; Marz, J.; Greiner, H.; Harting, J.;
Bartoszyk, G.; Seyfried, C.; Van Amsterdam, C. Patent
WO 2,001,007,434, 2001; Chem. Abstr. 2001, 134, 131549;
(b) Stolle, A.; Dumas, J. P.; Carley, W.; Coish, P. D. G.;
Magnuson, S. R.; Wang, Y.; Nagarathnam, D.; Lowe, D.
B.; Su, N.; Bullock, W. H.; Campbell, A.-M.; Qi, N.;
Baryza, J. L.; Cook, J. H. Patent WO 2,002,030,895, 2002;
Chem. Abstr. 2002, 136, 309846; (c) Townsend, L. B.;
Drach, J. C. Patent WO 2,005,034,943, 2005; Chem. Abstr.
2005; 142, 411589; (d) Allen, J. R.; Amegadzie, A. K.;
Gardinier, K. M.; Gregory, G. S.; Hitchcock, S. A.;
Hoogestraat, P. J.; Jones, W. D., Jr.; Smith, D. L. Patent
WO 2,005,066,126, 2005. Chem. Abstr. 2005, 143, 133274;
(e) Williams, J. D.; Ptak, R. G.; Drach, J. C.; Townsend,
L. B. J. Med. Chem. 2004, 47, 5773–5782.
8. A typical procedure is as follows: To an ethanolic solution
(60 mL) of compound 8b (6.17 g, 14 mmol), active Raney
nickel (4 g) was added along with 5 mL of hydrazine
hydrate and the reaction mixture refluxed for 1 h. After
completion of the reaction (TLC monitoring) the nickel
was filtered off and the filtrate was evaporated under
reduced pressure. The residue was dissolved in CH2Cl2/
hexane mixture and filtered through a pad of silica gel
3. (a) Gutnov, A. V.; Butin, A. V.; Abaev, V. T.; Krapivin,
G. D.; Zavodnik, V. E. Molecules 1999, 4, 204–218; (b)
Butin, A. V.; Stroganova, T. A.; Lodina, I. V.; Krapivin,
G. D. Tetrahedron Lett. 2001, 42, 2031–2033; (c) Butin, A.

24
A. V. Butin et al. / Tetrahedron Letters 49 (2008) 20–24
(5–40 lm) and evaporated under reduced pressure to
(50 mL) prepared by saturation of 200 g of EtOH with
100 g gaseous HCl was left at room temperature until all
the starting compound had been consumed (TLC moni-
toring). The reaction mixture was poured into water,
neutralized with NaHCO3; the precipitate was filtered off,
washed with water, and dried. Compound 13b was
isolated by column chromatography (silica gel, 50–
160 lm; eluent: hexane–acetone–CH2Cl2, 15:5:3) as a
white solid. Yield of 13b (0.98 g, 51%). Mp = 138–
139 ꢁC. Anal. Calcd for C25H35NO5: C, 69.90; H, 8.21;
N, 3.26. Found: C, 69.96; H, 8.05; N, 3.11; mmax (KBr):
3344, 2969, 1702, 1693, 1625, 1480, 1462, 1127, 1015, 856,
dryness. The obtained residue, 9b (4.78 g, 83%) was used
as such in the next step.
9. A typical procedure is as follows: p-Toluenesulfonyl
chloride (1.06 g, 5.6 mmol) was added to a solution of
compound 9b (1.64 g, 4 mmol) in pyridine (7 mL) at room
temperature and the mixture was left for 40 min. Then, it
was poured into an excess of water and the precipitate was
filtered off, washed with water, and dried. Recrystalliz-
ation from CH2Cl2–hexane (1:6) afforded product 10b as a
white solid (1.38 g, 61%). Mp = 117–119 ꢁC. Anal. Calcd
for C32H39NO6S: C, 67.94; H, 6.95; N, 2.48. Found: C,
68.05; H, 7.01; N, 2.45; mmax (KBr): 3282, 2959, 1600,
1513, 1462, 1387, 1342, 1207, 1161, 1091, 1008, 904, 784,
1
817, 756 cmꢀ1; H NMR (250 MHz, CDCl3): d 1.09 (9H,
s, t-Bu), 1.23 (9H, s, t-Bu), 2.97–3.06 (m, 4H, CH2), 3.21–
3.26 (m, 2H, CH2), 3.33–3.38 (m, 2H, CH2), 3.91 (s, 3H,
OMe), 3.96 (s, 3H, OMe), 6.86 (s, 1H, HInd), 7.46 (s, 1H,
HInd), 9.07 (br s, 1H, NH); 13C NMR (50 MHz, CDCl3): d
22.3, 26.4 (3C), 26.7 (3C), 30.8, 36.2, 36.6, 44.1 (2C), 56.1,
56.5, 94.6, 103.5, 113.5, 119.1, 128.9, 145.5, 146.2, 146.9,
195.3, 215.2, 217.8; MS (EI) m/z: 429 (36), 344 (14), 288
(13), 272 (10), 244 (12), 204 (16), 190 (15), 141 (85), 113
(48), 58 (100), 57 (54).
678 cmꢀ1 1H NMR (200 MHz, CDCl3): d 1.25 (18H, s,
;
t-Bu), 2.42 (3H, s, Me), 3.68 (3H, s, OMe), 3.85 (3H, s,
OMe), 4.79 (1H, s, CH), 5.67 (2H, d, J 3.1 Hz, HFur), 5.83
(2H, d, J 3.1 Hz, HFur), 6.42 (s, 1H, HAr), 6.58 (1H, br s,
NH), 7.02 (s, 1H, HAr), 7.27 (2H, d, J 8.2 Hz, HTs), 7.63
(2H, d, J 8.2 Hz, HTs).
10. A typical procedure is as follows: A mixture of compound
9b (5.34 g, 13 mmol) in acetic anhydride (2.5 mL) was left
at 55–60 ꢁC for 15 min. Then, it was poured into an excess
of water; the precipitate was filtered off, washed with
water, and dried. Recrystallization from CH2Cl2–hexane
(1:8) afforded compound 11b as a white solid (3.36 g,
57%). Mp = 122 ꢁC. Anal. Calcd for C27H35NO5: C,
71.50; H, 7.78; N, 3.09. Found: C, 71.70; H, 7.69; N,
3.02; mmax (KBr): 3294, 2968, 1658, 1533, 1257, 1208, 1103,
13. Refluxing of 11 in ethanolic HCl led to significant
decomposition and, as a result, to lower yields of the
reaction products.
14. Thirty-five percent of hydrochloric acid (7 mL) was added
to a cooled solution (10–12 ꢁC) of compound 9b (1.0 g,
2.4 mmol) in AcOH (25 mL). The reaction mixture was
left at room temperature for 24 h. After completion of the
reaction (TLC monitoring), the mixture was poured into
water, neutralized with NaHCO3, and extracted with
CH2Cl2 (3 · 50 mL). The extract was dried over anhy-
drous Na2SO4 and evaporated to dryness. Compound 13b
was isolated as described in Ref. 12. Yield of 13b (0.44 g,
43%).
15. Compound 12b (1.13 g, 2 mmol) was added to solution of
KOH (5.6 g, 100 mmol) in MeOH (23 mL) and the
mixture was refluxed for 4 h. After completion of the
reaction (TLC monitoring), the mixture was poured into
200 mL of water and the product was extracted with
CH2Cl2 (4 · 50 mL). The organic layer was washed with
water (3 · 100 mL) and dried over anhydrous Na2SO4.
The solvent was evaporated under reduced pressure, and
the residue was recrystallized from CH2Cl2–hexane (1:10).
Yield of 14b (0.50 g, 61%) as a white solid. Mp = 140–
141 ꢁC. Anal. Calcd for C25H33NO4: C, 72.96; H, 8.08; N,
3.40. Found: C, 73.01; H, 8.09; N, 3.42; mmax (KBr): 3356,
2964, 1704, 1488, 1456, 1336, 1220, 1200, 1188, 1132, 1008;
1H NMR (300 MHz, CDCl3): d 1.12 (9H, s, t-Bu), 1.39
(9H, s, t-Bu), 2.96–3.00 (m, 2H, CH2), 3.19–3.23 (m, 2H,
CH2), 3.90 (s, 3H, OMe), 3,95 (s, 3H, OMe), 6.08 (1H, d, J
3.1 Hz, HFur), 6.27 (1H, d, J 3.1 Hz, HFur), 6,83 (s, 1H,
HInd), 7,36 (s, 1H, HInd), 8,53 (br s, 1H, NH); 13C NMR
(50 MHz, CDCl3): d 21.3, 26.5 (3C), 29.2 (3C), 32.7, 36.9,
44.2, 56.2, 56.3, 94.4, 101.9, 103.2, 104.1, 104.9, 118.8,
129.4, 134.2, 145.1, 146.7, 149.1, 161.8, 217.4; MS (EI)
m/z: 411 (100, M+), 396 (42), 57 (70).
1014, 785 cmꢀ1 1H NMR (200 MHz, CDCl3): d 1.26
;
(18H, s, t-Bu), 2.03 (3H, s, Me), 3.76 (3H, s, OMe), 3.88
(3H, s, OMe), 5.38 (1H, s, CH), 5.89 (1H, br s, NH), 5.90–
5.92 (4H, m, HFur), 6.58 (1H, s, HAr), 7.41 (1H, s, HAr).
11. A typical procedure is as follows: Ethanolic HCl (25 mL)
prepared by saturation of 200 g of EtOH with 100 g
gaseous HCl was added to a solution of compound 10b
(2.26 g, 4 mmol) in EtOH (20 mL). The reaction mixture
was refluxed until all the starting compound had been
consumed (TLC monitoring). The reaction mixture was
poured into water and the precipitate obtained was filtered
off, washed with water, and dried. Recrystallization from
CH2Cl2–hexane (1:3) afforded compound 12b as a white
solid (1.40 g, 62%). Mp = 138–139 ꢁC. Anal. Calcd for
C32H39NO6S: C, 67.94; H, 6.95; N, 2.48. Found: C, 68.16;
H, 7.11; N, 2.51; mmax (KBr): 2961, 1701, 1489, 1365, 1307,
1157, 1059, 1013, 848, 783 cmꢀ1 1H NMR (200 MHz,
;
CDCl3): d 1.20 (9H, s, t-Bu), 1.34 (9H, s, t-Bu), 2.35 (3H, s,
Me), 2.99–3.07 (2H, m, CH2), 3.33–3.41 (2H, m, CH2),
3.93 (3H, s, OMe), 4.00 (3H, s, OMe), 6.09 (1H, d, J
3.2 Hz, HFur), 6.39 (1H, d, J 3.2 Hz, HFur), 7.19 (2H, d, J
8.2 Hz, HTs), 7.35 (1H, s, HInd), 7.60 (2H, d, J 8.2 Hz,
HTs), 7.88 (1H, s, HInd); 13C NMR (50 MHz, CDCl3): d
21.6, 22.4, 26.5 (3C), 29.1 (3C), 32.7, 37.6, 44.1, 56.0, 56.4,
99.0, 102.1, 103.7, 108.2, 113.7, 121.2, 126.2 (2C), 130.0
(2C), 130.9, 135.0, 135.9, 144.9, 146.1, 147.4, 147.8, 163.5,
214.9; MS (EI) m/z: 565 (3, M+), 412 (29), 411 (100), 397
(23), 396 (81), 326 (12), 313 (15), 312 (70), 297 (14), 296
(33), 92 (18), 91 (34), 57 (53).
16. Transformation of 14b into 13b was performed
analogously to the preparation of 13b from 11b (see Ref.
12).
12. A typical procedure is as follows: A suspension of
compound 11b (2.04 g, 4.5 mmol) in ethanolic HCl