Ketosulfonyl indoles in the regiodefined synthesis of tryptophols and related indole derivatives

Article abstract of DOI:10.1039/c2ob25056j

Reduction of ketosulfonyl indoles with sodium borohydride provides a ready entry to tryptophols in a regiocomplementary fashion with respect to the traditional oxirane ring-opening by indoles under Friedel-Crafts conditions. Compared to traditional β-ketosulfones, ketosulfonyl indoles show a peculiar behavior since they undergo a Lewis acid promoted elimination of the arylsulfonyl group allowing the preparation of indolyl-substituted 1,4-dicarbonyl derivatives.

Full text of DOI:10.1039/c2ob25056j

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PAPER
Ketosulfonyl indoles in the regiodefined synthesis of tryptophols and related
indole derivatives†
Alessandro Palmieri and Marino Petrini*
Received 9th January 2012, Accepted 29th February 2012
DOI: 10.1039/c2ob25056j
Reduction of ketosulfonyl indoles with sodium borohydride provides a ready entry to tryptophols in a
regiocomplementary fashion with respect to the traditional oxirane ring-opening by indoles under
Friedel–Crafts conditions. Compared to traditional β-ketosulfones, ketosulfonyl indoles show a peculiar
behavior since they undergo a Lewis acid promoted elimination of the arylsulfonyl group allowing the
preparation of indolyl-substituted 1,4-dicarbonyl derivatives.
Introduction
A considerable number of compounds containing the indole
nucleus, both of synthetic and natural origin, are known for their
outstanding pharmacological profile.1 Tryptophol is a trypto-
phane metabolite featuring a C-3 hydroxyethyl side chain on the
indole nucleus which is involved in some neuronal disorders
such as sleeping sickness.2 Tryptophol has been also recognized
as one of the many components in extracts of marine origin and
terrestrial Streptomyces.3 Additionally, tryptophol derivatives are
widely employed as pivotal intermediates for the synthesis of
non-steroidal anti-inflammatory drugs (Etodolac, Pemedolac)4
Scheme 1 General synthetic strategy for tryptophols.
and 5-lipoxygenase inhibitors.5 The whole body of approaches
for the preparation of tryptophol derivatives generally enjoys the
entry to regiocomplementary tryptophols 4 using a two-step pro-
viable and fully exploited chemistry related to the indole syn-
cedure involving a preliminary installation of a C-3 side chain in
thesis. The Fischer indole reaction provides an exceptionally
the indole ring bearing a carbonyl function in a proper position
powerful method to access differently substituted systems,
as in ketosulfonyl indoles 3, followed by its reduction to the
including those bearing a 3-(2-hydroxyethyl) moiety.6 A differ-
hydroxy group. Besides, other applications of the newly prepared
ent approach consists in the functionalization of indoles at C-3
ketosulfonyl indoles 3 in the regiocomplementary synthesis of
through the Friedel–Crafts process involving a regioselective
1,4-dicarbonyl derivatives embedding the indole ring are
epoxide ring opening. The utilization of 2-aryloxiranes in such
reported.
acid promoted reactions with indoles 1 invariably leads to the
preferential formation of 2-(3-indolyl)-2-aryl-1-ethanols 2,
reflecting the higher stabilization pertaining to the incipient
Results and discussion
benzylic carbocations involved in the transition state
(Scheme 1).7 Chiral Lewis acids have been successfully used in
such processes thus providing high level of enantioselection in
the obtained tryptophols.8 Interestingly, the observed regioselec-
tion is inverted when 2-alkyloxiranes are used for the same
purpose.9 The aim of the present work is to provide an efficient
The three-component coupling of indoles with aldehydes and
arylsulfinic acids represents a straightforward way to access sul-
fonyl indoles which can be fruitfully employed as gramine
equivalents in the preparation of functionalized indole deriva-
tives.10 The utilization of 2-oxoaldehyes 5 in the same reaction
readily provides similar adducts that can be also considered as
β-ketosulfonyl derivatives (Scheme 2).11
School of Science and Technology, Chemistry Division, Università di
Camerino, via S. Agostino, 1 I-62032 Camerino, Italy. E-mail: marino.
petrini@unicam.it; Fax: +39 0737 402297; Tel: +39 0737 402253
†This paper is dedicated to Prof. Giuseppe Bartoli on the occasion of
his retirement.
However, the presence of the indole nucleus brings about a
significant change in the chemical properties of these ketosulfo-
nyl indoles enabling different reaction pathways when they are
treated with nucleophilic reagents. Ordinary β-ketosulfones
3486 | Org. Biomol. Chem., 2012, 10, 3486–3493
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Scheme 2 Synthesis of ketosulfonyl indoles.
Scheme 4 Reduction of N-methylketosulfonyl indoles.
Table 1 Reduction of ketosulfonyl indoles
Entry
Substrate
Product
Yielda (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
82
81
95
92
87
96
88
75
3g
3h
4g
4h
a Yield of pure isolated product.
Scheme 5 Reductive removal of the arylsulfonyl group using Na–Hg
amalgam.
synthesis of compound 4e (Table 1, entry 5). As reducing agent,
NaBH4 has been selected because of its mildness and chemo-
selectivity that allows survival of other reducible functional
groups present in the molecule (Table 1, entries 6, 8). It is worth
noting that protection of the indole nitrogen atom by methylation
as in compounds 3i,j prevents formation of the indolenine 6
allowing reduction of the sole carbonyl moiety leading to
hydroxy derivatives 4i,j (Scheme 4).
Scheme 3 Reductive pathway to tryptophols.
undergo to a simple reduction of the carbonyl moiety when
made to react with complex hydride reagents leading to the cor-
responding β-hydroxysulfones.12 Ketosulfonyl indoles 3 behave
differently in the presence of NaBH4 since reduction of the car-
bonyl group is coupled with removal of the arylsulfonyl group
leading to the corresponding tryptophols 4 in excellent yields
(Table 1).
Reductive removal of the arylsulfonyl group from 1-phenyl-
β-ketosulfones can be easily carried out exploiting the synergis-
tic activating properties of the carbonyl and aromatic rings
toward radical processes. When classical reaction conditions
involving Na–Hg amalgam are used, the only notable process
observed is formation of sulfonylmethylindole 8 from the parent
functionalized indole 3i (Scheme 5).13
Formation of tryptophols 4 is the result of three distinct pro-
cesses involving a base assisted elimination of p-toluenesulfinic
acid with consequent formation of the alkylideneindolenine 6
that is reduced to ketoindole 7 and finally converted to trypto-
phol 4 by further reduction of the carbonyl group (Scheme 3).
The overall sequence may be obviously reverted since it is
possible that reduction of the carbonyl group precedes the alkyli-
deneindolenine formation and its reaction with excess of NaBH4
even though the final result is unchanged. Although this strategy
is particularly valuable to prepare 1-aryl derivatives 4, it can be
adopted also for straight chain analogues as demonstrated for the
Compound 8 is probably the result of a reductive process
involving the carbonyl group followed by a retro-sulfonylaldol
reaction. As a matter of fact, acylation of the hydroxy group in
compound 3i gives acetate 9 which cannot undergo to a retro
condensation reaction and under classical Julia olefination con-
ditions leads stereoselectively to the formation of (E)-alkenylin-
dole 10.14
Ketosulfonyl indoles 3 are rather insensitive also to other
desulfonylation procedures involving radical intermediates such
as reduction with Bu3SnH which is on the contrary effective
with other sulfonyl indoles.10a,15 Under different radical
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conditions proved to be adequate for particularly sensitive
β-ketosulfones, compound 3k is totally reduced to alcohol 4k
albeit in modest yield (Scheme 6).16
Alkylative displacement of the arylsulfonyl group represents a
viable opportunity to implement the molecular carbon skeleton
but with few notable exceptions, is effective only on selected
substrates such as acetylenic, allylic and vinylic sulfones.17 The
carbocationic stabilizing effect pertaining to the indole ring has
been already evidenced on simple sulfonyl indole and indazole
derivatives.18 However, to the best of our knowledge, no report
on the behavior of a vicinal carbonyl group in such stabilization
has been reported.19 Interestingly, the same reaction conditions
which are operative on sulfonyl indoles are also effective in the
reaction of N-protected ketosulfonyl indoles 3i–m with various
nucleophilic reagents (Table 2). Utilization of silyl enol ethers
and ketene acetals leads to the formation of regiodefined 1,4-
dicarbonyl compounds and γ-ketoesters not accessible through a
direct Friedel–Crafts process between indoles and 4-oxoalkeno-
ates such as adducts 12a,b. The regioselectivity displayed in the
reaction of indoles with 4-oxoalkenoates is usually in favor of
compound 13 which is the result of attack to the more electrophi-
lic carbon atom (Scheme 7).20
This result is regiocomplementary to that obtained in the reac-
tion of ketosulfonyl indoles 3 with silyl ketene acetal 11b
leading to γ-ketoester 12c (Table 2). It becomes even more
difficult to make a distinction between electrophilic carbon
atoms in unsymmetrical 1,4-enediones which roughly possess
the same reactivity. Thus selective preparation of compound 12d
would be impossible using the Friedel–Crafts reaction of indoles
with enediones. The synthetic value of the proposed approach, is
further witnessed by the possibility of introducing butenolide
Scheme 6 Reductive removal of the arylsulfonyl group under radical
conditions.
Table 2 Reaction of ketosulfonyl indoles with enol ethers and electron-rich aromaticsa
a Yield of pure isolated product.
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Synthesis of ketosulfonyl indoles 3
Ketosulfonyl indoles 3 were prepared following a previously
reported procedure using CHCl3 as solvent at 60 °C as reported
in Scheme 2.11
3a. Yield 61%. Pale brown solid, m.p. 92–94 °C. IR (Nujol)
νmax/cm−1: 666, 743, 802, 845, 1287, 1605, 1674, 3364. 1H
NMR (400 MHz, CDCl3) δ: 2.34 (s, 6H), 6.48 (s, 1H),
7.03–7.24 (m, 7H), 7.33 (d, 1H, J = 7.8 Hz), 7.50 (d, 2H, J =
8.1 Hz), 7.63 (d, 1H, J = 7.8 Hz), 7.82 (d, 2H, J = 8.1 Hz), 8.53
(bs, 1H). 13C NMR (100 MHz, CDCl3) δ: 21.8, 21.9, 68.9,
104.0, 111.8, 118.8, 120.9, 123.0, 127.0, 129.1, 129.2, 129.4,
129.7, 130.4, 133.8, 134.2, 136.0, 144.9, 145.2, 191.1. Anal.
Calcd for C24H21NO3S (403.49): C, 71.44; H, 5.25; N, 3.47.
Found: C, 71.50; H, 5.34; N, 3.61.
Scheme 7 Regioselective Friedel–Crafts reaction of indoles with
enediones.
3b. Yield 65%. White solid, m.p. 136–138 °C. IR (Nujol)
νmax/cm−1: 671, 684, 704, 752, 811, 827, 988, 1277, 1596, 1683,
1
3337. H NMR (400 MHz, CDCl3) δ: 1.30 (t, 3H, J = 7.7 Hz),
2.34 (s, 3H), 2.82 (q, 2H, J = 7.7 Hz), 6.47 (s, 1H), 6.98–7.17
(m, 5H), 7.36 (t, 2H, J = 7.7 Hz), 7.43–7.53 (m, 4H), 7.89
(d, 2H, J = 8.1 Hz), 9.04 (bs, 1H). 13C NMR (100 MHz, CDCl3)
δ: 14.0, 21.9, 24.0, 69.1, 103.9, 116.4, 121.1, 121.4, 126.5,
126.8, 127.3, 128.9, 129.0, 129.1, 130.4, 134.0, 134.3, 135.1,
136.3, 144.9, 191.6. Anal. Calcd for C25H23NO3S (417.52): C,
71.92; H, 5.55; N, 3.35. Found: C, 72.09; H, 5.59; N, 3.29.
3c. Yield 62%. Yellow solid, m.p. 173–175 °C. IR (Nujol)
νmax/cm−1: 648, 688, 702, 753, 1250, 1593, 1670, 3328. 1H
NMR (400 MHz, CDCl3) δ: 2.40 (s, 3H), 6.36 (s, 1H), 6.94 (t,
1H, J = 7.7 Hz), 7.07–7.15 (m, 3H), 7.20 (d, 2H, J = 8.1 Hz),
7.27 (d, 1H, J = 8.1 Hz), 7.34 (t, 1H, J = 7.7 Hz), 7.38–7.45 (m,
3H), 7.50–7.58 (m, 3H), 7.64–7.70 (m, 2H), 7.79 (d, 2H, J = 8.1
Hz), 8.48 (bs, 1H). 13C NMR (100 MHz, CDCl3) δ: 21.9, 71.1,
100.7, 110.9, 121.0, 122.4, 123.0, 126.9, 128.6, 128.7, 129.3,
129.4, 129.5, 129.6, 130.6, 131.6, 133.6, 135.6, 135.9, 136.0,
140.4, 145.1, 190.3. Anal. Calcd for C29H23NO3S (465.56): C,
74.81; H, 4.98; N, 3.01. Found: C, 74.63; H, 5.07; N, 3.11.
3d. Yield 64%. White solid, m.p. 195–197 °C. IR (Nujol)
Scheme 8 Attempt to use a β-ketosulfone bearing a simple phenyl
group in the Lewis acid promoted substitution reaction.
frameworks and electron-rich aromatic systems (compounds 12e,
f) and the allyl moiety by reaction with allyltributyltin (com-
pound 12g). The peculiar behavior of the indole ring in deter-
mining the special reactivity of ketosulfonyl indoles 3 is further
highlighted by a test experiment carried out on the parent β-keto-
sulfone 14 in which the indole nucleus is substituted by a phenyl
ring (Scheme 8). Under the same reaction conditions which give
valuable results for compounds 3i–m the phenyl analogue 14 is
totally unreactive.
Conclusions
Ketosulfonyl indoles 3 are structural analogs of β-ketosulfones
but the presence of the indole ring introduces a peculiar reactiv-
ity, since it makes the arylsulfonyl group easily removable under
basic and acidic conditions. Reduction of ketosulfonyl indoles
with sodium borohydride allows the preparation of tryptophols
in a regiocomplementary way compared to those obtained by
oxirane ring-opening by indoles under Friedel–Crafts conditions.
Furthermore, elimination of the arylsulfonyl group in N-alkyl-
ketosulfonyl indoles promoted by AlEtCl2 allows the introduc-
tion in the molecular framework of weak nucleophilic reagents
resulting in the synthesis of functionalized 1,4-dicarbonyl
derivatives and other interesting compounds.
1
νmax/cm−1: 685, 738, 994, 1267, 1596, 1683, 3319. H NMR
(400 MHz, CDCl3) δ: 2.28 (s, 3H), 2.36 (s, 3H), 6.23 (s, 1H),
6.96 (t, 1H, J = 7.7 Hz), 7.07 (t, 1H, J = 7.7 Hz), 7.13 (d, 2H,
J = 8.1 Hz), 7.20–7.33 (m, 4H), 7.41–7.48 (m, 1H), 7.63 (d, 2H,
J = 7.7 Hz), 7.79 (d, 2H, J = 8.1 Hz), 8.10 (bs, 1H). 13C NMR
(100 MHz, CDCl3) δ: 12.4, 21.8, 70.5, 99.9, 110.5, 118.8, 120.8,
122.1, 128.6, 128.9, 129.2, 130.5, 133.9, 135.0, 135.3, 135.9,
136.8, 144.8, 190.9. Anal. Calcd for C24H21NO3S (403.49): C,
71.44; H, 5.25; N, 3.47. Found: C, 71.56; H, 5.17; N, 3.39.
3e. Yield 67%. Red sticky oil. IR (neat) νmax/cm−1: 651, 698,
739, 817, 1596, 1715, 3315. 1H NMR (400 MHz, CDCl3) δ: 2.09
(s, 3H), 2.35 (s, 3H), 2.64–2.96 (m, 4H), 5.27 (s, 1H), 6.90–6.96
(m, 1H), 7.00 (d, 2H, J = 7.7 Hz), 7.04–7.25 (m, 8H), 7.51
(d, 2H, J = 7.7 Hz), 8.24 (bs, 1H). 13C NMR (100 MHz, CDCl3)
δ: 12.0, 21.8, 29.8, 44.3, 73.7, 99.0, 110.6, 120.7, 122.1, 126.4,
128.5, 128.7, 129.3, 129.4, 129.9, 135.1, 135.3, 137.36, 140.4,
144.8, 200.4. Anal. Calcd for C26H25NO3S (431.55): C, 72.36;
H, 5.84; N, 3.25. Found: C, 72.43; H, 5.92; N, 3.19.
Experimental
General experimental
1H NMR were recorded at 400 MHz on a Varian Mercury Plus
400.13C NMR were recorded at 100 MHz. Microanalyses were
performed with a CHNS-O analyzer Model EA 1108 from
Fisons Instruments. Mass spectra were performed with a GC/MS
system Agilent Technologies 6850 II/5973 Inert by means of the
EI technique (70 eV). IR spectra were recorded with a Perkin-
Elmer Paragon 500 FT-IR. All chemicals used were commercial.
3f. Yield 63%. Yellow solid, m.p. 183–185 °C. IR (Nujol)
νmax/cm−1: 694, 706, 746, 759, 852, 1287, 1309, 1356, 1536,
1
1596, 1605, 1702, 3396. H NMR (400 MHz, CD3COCD3) δ:
2.42 (s, 3H), 6.61 (s, 1H), 7.01 (t, 1H, J = 7.7 Hz), 7.13 (t, 1H,
Org. Biomol. Chem., 2012, 10, 3486–3493 | 3489
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J = 7.7 Hz), 7.35 (d, 2H, J = 8.5 Hz), 7.39 (d, 1H, J = 8.1 Hz),
7.55–7.74 (m, 8H), 7.83 (d, 2H, J = 8.1 Hz), 8.02 (d, 2H, J =
8.5 Hz), 10.92 (bs, 1H). 13C NMR (100 MHz, CD3COCD3) δ:
20.9, 70.9, 99.0, 111.5, 120.3, 122.0, 122.7, 123.6, 127.3, 129.3,
129.4, 129.5, 129.6, 129.7, 130.0, 131.5, 136.6, 136.7, 140.6,
141.1, 145.2, 150.5, 189.6. Anal. Calcd for C29H22N2O5S
(510.56): C, 68.22; H, 4.34; N, 5.49. Found: C, 68.31; H, 4.43;
N, 5.56.
3g. Yield 62%. White solid, m.p. 151–153 °C. IR (nujol)
νmax/cm−1: 742, 752, 768, 863, 1267, 1608, 1676, 3419. 1H
NMR (400 MHz, CDCl3) δ: 2.33 (s, 3H), 6.50 (d, 1H, J = 2.5
Hz), 6.97–7.21 (m, 7H), 7.32 (d, 1H, J = 8.1 Hz), 7.42–7.54
(m, 4H), 7.84 (dt, 1H, J = 1.7, 7.7 Hz), 9.20 (bs, 1H). 13C NMR
(100 MHz, CDCl3) δ: 21.8, 72.5, 72.6, 102.8, 111.8, 116.9,
117.2, 118.9, 120.7, 122.7, 124.9, 125.0, 125.3, 127.1, 127.3,
129.2, 130.2, 131.5, 131.6, 134.5, 135.7, 135.8, 136.1, 144.9,
160.4, 163.0, 189.4, 189.5. Anal. Calcd for C23H18FNO3S
(407.06): C, 67.80; H, 4.45; N, 3.44. Found: C, 67.97; H, 4.38;
N, 3.32.
136.5, 136.6, 137.0, 144.8, 191.8. Anal. Calcd for C30H25NO3S
(479.59): C, 75.13; H, 5.25; N, 2.92. Found: C, 75.01; H, 5.18;
N, 2.87.
3l. Yield 65%. Red solid, m.p. 72–74 °C. IR (Nujol) νmax
/
cm−1: 666, 741, 1604, 1679. H NMR (400 MHz, CDCl3) δ:
2.35 (s, 3H), 2.37 (s, 3H), 3.69 (s, 3H), 6.46 (s, 1H), 7.05 (s,
1H), 7.11–7.20 (m, 5H), 7.21–7.32 (m, 2H), 7.52 (d, 2H, J = 8.1
Hz), 7.59 (d, 1H, J = 8.1 Hz), 7.82 (d, 2H, J = 8.1 Hz). 13C
NMR (100 MHz, CDCl3) δ: 21.8, 21.9, 33.3, 68.7, 102.3, 109.8,
118.9, 120.6, 122.5, 127.4, 129.0, 129.1, 129.7, 130.4, 131.3,
133.8, 134.4, 137.0, 144.9, 145.1, 191.1. Anal. Calcd for
C25H23NO3S (417.52): C, 71.92; H, 5.55; N, 3.35. Found: C,
72.11; H, 5.63; N, 3.44.
1
3m. Yield 63%. White solid, m.p. 73–75 °C. IR (cm−1
,
Nujol) νmax/cm−1: 666, 740, 813, 976, 1215, 1262, 1597, 1673.
1H NMR (400 MHz, CDCl3) δ: 2.33 (s, 3H), 3.84 (s, 3H), 5.09
(d, 1H, J = 16.2 Hz), 5.24 (d, 1H, J = 16.2 Hz), 6.50 (s, 1H),
6.89 (d, 2H, J = 9.0 Hz), 6.98–7.07 (m, 5H), 7.15–7.32 (m, 6H),
7.45 (d, 2H, J = 7.7 Hz), 7.74–7.80 (m, 1H), 7.96 (d, 2H, J =
8.5 Hz). 13C NMR (100 MHz, CDCl3) δ: 21.9, 50.5, 55.8, 68.5,
103.6, 110.3, 114.3, 119.3, 120.9, 122.9, 127.0, 127.6, 128.0,
128.9, 129.0, 129.3, 130.6, 130.7, 131.5, 133.7, 136.5, 137.1,
144.8, 164.4, 190.1. Anal. Calcd for C31H27NO4S (509.62): C,
73.06; H, 5.34; N, 2.75. Found: C, 73.18; H, 5.42; N, 2.83.
3h. Yield 65%. Pale brown solid, m.p. 128–131 °C. IR (nujol)
νmax/cm−1: 666, 756, 786, 821, 874, 803, 982, 1582, 1616,
1
1681, 1704, 3321. H NMR (400 MHz, CDCl3) δ: 2.33 (s, 3H),
3.93 (s, 3H), 6.54 (d, 1H, J = 2.1 Hz), 7.02–7.09 (m, 1H), 7.12
(d, 2H, J = 8.1 Hz), 7.21 (t, 1H, J = 7.7 Hz), 7.33–7.38 (m, 2H),
7.46–7.55 (m, 3H), 7.83–7.91 (m, 2H), 8.10 (s, 1H), 8.90 (bs,
1H). 13C NMR (100 MHz, CDCl3) δ: 21.8, 52.2, 72.0, 72.1,
104.6, 111.5, 117.0, 117.2, 121.5, 122.9, 124.2, 125.0, 125.1,
126.8, 128.6, 129.4, 130.0, 131.5, 131.6, 134.3, 135.9, 136.0,
138.4, 145.3, 160.4, 163.0, 168.0, 189.2, 189.3. Anal. Calcd for
C25H20FNO5S (465.49): C, 64.51; H, 4.33; N, 3.01. Found: C,
64.39; H, 4.39; N, 3.12.
3i. Yield 67%. White solid, m.p. 162–164 °C. IR (Nujol)
νmax/cm−1: 643, 681, 710, 747, 988, 1269, 1594, 1682. 1H
NMR (400 MHz, CDCl3) δ: 2.38 (s, 3H), 3.70 (s, 3H), 6.48 (s,
1H), 7.06 (s, 1H), 7.11–7.18 (m, 3H), 7.21–7.32 (m, 2H), 7.39
(t, 2H, J = 7.7 Hz), 7.49–7.55 (m, 3H), 7.58 (dd, 1H, J = 0.9,
8.1 Hz), 7.92 (d, 2H, J = 8.1 Hz). 13C NMR (100 MHz, CDCl3)
δ: 21.9, 33.3, 68.9, 102.1, 109.9, 118.9, 120.7, 122.6, 127.3,
128.9, 129.0, 129.1, 130.4, 131.3, 134.0, 134.4, 136.4, 137.0,
144.9, 191.6. Anal. Calcd for C24H21NO3S (403.49): C, 71.44;
H, 5.25; N, 3.47. Found: C, 71.60; H, 5.36; N, 3.55.
General procedure for the reduction of ketosulfonyl indoles 3
To a stirred solution of the appropriate ketosulfonyl indole 3
(1 mmol) in EtOH (10 mL) kept under nitrogen atmosphere at
0 °C, NaBH4 (4 mmol) was added portionwise under stirring.
After 1.5 h at room temperature, the reaction mixture was
quenched by addition of a saturated solution of NH4Cl (5 mL)
and the aqueous phase extracted with CH2Cl2 (4 × 10 mL). The
organic phase was dried over MgSO4 and after evaporation of
the solvent under reduced pressure the crude product thus
obtained was purified by flash chromatography (hexanes–ethyl
acetate 75 : 25).
4a. Yield 82%. Green viscous oil. IR (neat) νmax/cm−1: 819,
1
1041, 1515, 1620, 3054, 3417. H NMR (400 MHz, CDCl3) δ:
2.33 (bs, 1H), 2.43 (s, 3H), 3.15 (dd, 1H, J = 9.0, 14.5 Hz), 3.26
(dd, 1H, J = 4.3, 14.5 Hz), 5.00 (dd, 1H, J = 4.3, 9.0 Hz), 6.93
(s, 1H), 7.17–7.31 (m, 4H), 7.32–7.40 (m, 3H), 7.69 (d, 1H, J =
8.1 Hz), 8.13 (bs, 1H). 13C NMR (100 MHz, CDCl3) δ: 13C
NMR (100 MHz, CDCl3) δ: 21.5, 36.1, 74.1, 111.6, 112.2,
119.1, 119.7, 122.4, 123.5, 126.2, 127.8, 129.4, 136.6, 137.4,
141.5. MS (EI) m/z: 251[M+, (5)], 130(100), 131(57), 121(8),
103(10), 91(15), 77(26). Anal. Calcd for C17H17NO (251.32): C,
81.24; H, 6.82; N, 5.57. Found: C, 80.99; H, 6.92; N, 5.70.
3j. Yield 65%. Pale grey solid, m.p. 170–172 °C. IR (Nujol)
νmax/cm−1: 639, 682, 709, 738, 760, 790, 814, 844, 982, 1272,
1
1594, 1682. H NMR (400 MHz, CDCl3) δ: 2.41 (s, 3H), 3.56
(s, 3H), 6.12 (s, 1H), 6.99 (t, 1H, J = 7.7 Hz), 7.11–7.30 (m,
8H), 7.33–7.44 (m, 3H), 7.47–7.62 (m, 4H), 7.75 (d, 2H, J = 7.7
Hz). 13C NMR (100 MHz, CDCl3) δ: 21.9, 31.5, 71.2, 100.4,
109.5, 120.8, 122.5, 122.6, 126.1, 128.5, 128.7, 129.5, 129.7,
130.3, 130.6, 130.8, 131.7, 133.6, 135.8, 136.2, 137.4, 143.1,
144.9, 190.5. Anal. Calcd for C30H25NO3S (479.59): C, 75.13;
H, 5.25; N, 2.92. Found: C, 75.18; H, 5.31; N, 2.99.
4b. Yield 81%. Pink solid, m.p. 89–91 °C. IR (Nujol) νmax
/
cm−1: 698, 730, 751, 792, 818, 870, 910, 990, 1048, 1612,
3395, 3507. 1H NMR (400 MHz, CDCl3) δ: 1.39 (t, 3H, J = 7.7
Hz), 2.19 (bs, 1H), 2.87 (q, 2H, J = 7.7 Hz), 3.11 (dd, 1H, J =
9.0, 14.5 Hz), 3.27 (dd, 1H, J = 3.8, 14.5 Hz), 5.02 (dd, 1H, J =
3.8, 9.0 Hz), 7.02 (s, 1H), 7.07–7.17 (m, 2H), 7.29–7.35 (m,
1H), 7.40 (t, 2H, J = 7.7 Hz), 7.44–7.50 (m, 2H), 7.52 (d, 1H, J
= 7.7 Hz), 8.04 (bs, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.1,
24.2, 36.4, 74.1, 112.7, 116.9, 120.1, 121.0, 123.0, 126.1, 126.9,
127.5, 127.7, 128.6, 135.5, 144.4. EI-MS: m/z 265[M+, (11)],
3k. Yield 64%. Red solid, m.p. 46–48 °C. IR (Nujol) νmax
/
cm−1: 666, 686, 740, 999, 1595, 1682. 1H NMR (400 MHz,
CDCl3) δ: 2.34 (s, 3H), 5.11 (d, 1H, J = 15.8 Hz), 5.24 (d, 1H, J
= 15.8 Hz), 6.54 (s, 1H), 6.99–7.02 (m, 3H), 7.05 (d, 2H, J =
8.1 Hz), 7.18–7.30 (m, 6H), 7.40–7.48 (m, 4H), 7.55 (t, 1H, J =
7.3 Hz), 7.74–7.78 (m, 1H), 7.96 (d, 2H, J = 8.1 Hz). 13C NMR
(100 MHz, CDCl3) δ: 21.8, 50.5, 68.9, 103.3, 110.3, 119.2,
120.9, 122.9, 127.0, 127.6, 128.0, 129.0, 130.6, 133.7, 134.0,
3490 | Org. Biomol. Chem., 2012, 10, 3486–3493
This journal is © The Royal Society of Chemistry 2012

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247(7), 158(100), 143(20), 115(7), 77(9). Anal. Calcd for
C18H19NO (265.35): C, 81.47; H, 7.22; N, 5.28. Found: C,
81.60; H, 7.12; N, 5.33.
3.26 (dd, 1H, J = 5.1, 14.5 Hz), 3.88 (s, 3H), 4.45 (bs, 1H),
5.30–5.38 (m, 1H), 7.01–7.08 (m, 1H), 7.16 (t, 1H, J = 7.7 Hz),
7.21–7.30 (m, 2H), 7.43 (d, 1H, J = 8.5 Hz), 7.60–7.65 (m, 1H),
7.79 (d, 1H, J = 8.5 Hz), 8.36 (s, 1H), 10.36 (bs, 1H). 13C NMR
(100 MHz, CDCl3) δ: 35.4, 51.9, 68.3, 111.8, 111.9, 114.3,
115.5, 115.7, 121.7, 122.5, 123.3, 125.0, 125.1, 126.0, 126.2,
128.5, 128.6, 129.3, 129.4, 133.5, 133.6, 140.1, 159.4, 161.8,
168.4. EI-MS: m/z 313[M+, (5)], 295(5), 188(100), 174(21), 129
(36), 102(9), 77(12). Anal. Calcd for C18H16FNO3 (313.32): C,
69.00; H, 5.15; N, 4.47. Found: C, 69.22; H, 5.23; N, 4.34.
4i. Diastereomeric mixture d.r. 7 : 3. Yield 60%. White solid,
m.p. 133–135 °C. IR (Nujol) νmax/cm−1: 741, 816, 1129, 1280,
1594, 3403. 1H NMR (400 MHz, CDCl3) δ: 2.29 (s, 2.1H), 2.36
(s, 0.9H), 2.99 (bs, 1H), 3.60 (s, 0.9H), 3.80 (s, 2.1H), 4.67 (s,
0.7H), 4.82 (d, 0.3H, J = 9.4 Hz), 5.77 (d, 0.3H, J = 9.4 Hz),
5.96 (s, 0.7H), 6.75–6.91 (m, 2H), 6.98–7.30 (m, 10H), 7.41 (d,
0.6H, J = 8.1 Hz), 7.56 (d, 1.4H, J = 8.1 Hz). 13C NMR
(100 MHz, CDCl3) δ: 21.7, 21.8, 33.1, 33.4, 68.8, 70.3, 70.8,
74.1, 100.4, 104.1, 109.3, 117.9, 118.9, 119.6, 119.8, 121.6,
121.9, 125.5, 126.2, 127.3, 127.8, 128.1, 128.2, 128.3, 128.5,
129.0, 129.1, 129.3, 129.4, 129.6, 130.1, 131.4, 134.9, 135.1,
136.0, 136.3, 140.1, 144.8, 144.9. EI-MS: m/z 249(12), 144
(100), 77(16). Anal. Calcd for C24H23NO3S (405.51): C, 71.09;
H, 5.72; N, 3.45. Found: C, 71.27; H, 5.81; N, 3.59.
4c. Yield 95%. White solid, m.p. 48–50 °C. IR (Nujol) νmax
/
cm−1: 699, 737, 823, 912, 1019, 1607, 3391, 3499. H NMR
(400 MHz, CDCl3) δ: 2.04 (bs, 1H), 3.25–3.36 (m, 2H), 5.13
(dd, 1H, J = 5.6, 8.1 Hz), 7.15–7.21 (m, 1H), 7.22–7.41 (m,
8H), 7.45 (t, 2H, J = 7.7 Hz), 7.56 (d, 2H, J = 7.7 Hz), 7.70 (d,
1H, J = 7.7 Hz), 8.27 (bs, 1H). 13C NMR (100 MHz, CDCl3) δ:
35.6, 74.6, 109.0, 111.2, 119.5, 120.1, 122.7, 126.0, 127.7,
128.1, 128.6, 129.1, 129.4, 133.0, 136.2, 136.7, 144.4. EI-MS:
m/z 313[M+, (9)], 295(9), 207(34), 206(100), 204(33), 178(19),
77(10). Anal. Calcd for C22H19NO (313.39): C, 84.31; H, 6.11;
N, 4.47. Found: C, 84.10; H, 6.22; N, 4.15.
1
4d. Yield 92%. Pale yellow oil. IR (neat) νmax/cm−1: 705,
743, 811, 1031, 1597, 3401, 3497. 1H NMR (400 MHz, CDCl3)
δ: 2.17 (s, 3H), 2.19 (bs, 1H), 3.06–3.19 (m, 2H), 4.99 (dd, 1H,
J = 6.0, 7.3 Hz), 7.10–7.21 (m, 2H), 7.24–7.42 (m, 6H), 7.58 (d,
1H, J = 7.7 Hz), 7.84 (bs, 1H). 13C NMR (100 MHz, CDCl3) δ:
11.7, 35.4, 74.5, 107.4, 110.6, 118.3, 119.7, 121.5, 126.1, 127.6,
128.6, 129.1, 133.4, 135.5, 144.5. EI-MS: m/z 251[M+, (6)], 144
(100), 115(6), 77(12). Anal. Calcd for C17H17NO (251.32): C,
81.24; H, 6.82; N, 5.57. Found: C, 81.41; H, 7.73; N, 5.70.
4e. Yield 87%. Brown oil. IR (neat) νmax/cm−1: 742, 909,
1
943, 1052, 1602, 3026, 3058, 3301, 3402. H NMR (400 MHz,
4j. Diastereomeric mixture d.r. 1 : 1. Yield 91%. White waxy
CDCl3) δ: 1.85–1.98 (m, 3H), 2.38 (s, 3H), 2.69–2.84 (m, 2H),
2.86–3.00 (m, 2H), 3.87–3.99 (m, 1H), 7.07–7.35 (m, 8H), 7.50
(d, 1H, J = 7.7 Hz), 7.89 (bs, 1H). 13C NMR (100 MHz, CDCl3)
δ: 12.2, 32.6, 33.0, 38.8, 71.6, 107.9, 110.5, 118.4, 119.7, 121.5,
126.0, 128.6, 128.7, 129.1, 132.9, 135.6, 142.5. EI-MS: m/z 279
[M+, (13)], 144(100), 130(6), 91(13), 77(7). Anal. Calcd for
C19H21NO (279.38): C, 81.68; H, 7.58; N, 5.01. Found: C,
81.79; H, 7.61; N, 4.92.
solid. IR (Nujol) νmax/cm−1: 700, 739, 814, 925, 1134, 1594,
1
3478. H NMR (400 MHz, CDCl3) δ: 2.37 (s, 1.5H), 2.41 (s,
1.5H), 3.19 (s, 1.5H), 3.29 (s, 1.5H), 4.20 (dd, 0.5H, J = 1.3, 3.4
Hz), 4.37 (dd, 0.5H, J = 1.3, 10.3 Hz), 5.72 (d, 0.5H, J = 7.7
Hz), 5.98–6.04 (m, 1.5H), 6.14–6.23 (m, 1H), 6.93–7.39 (m,
16H), 8.09–8.15 (m, 0.5H), 8.41–8.47 (m, 0.5H). 13C NMR
(100 MHz, CDCl3) δ: 21.8, 21.9, 30.9, 31.0, 72.0, 72.4, 72.7,
100.8, 102.9, 109.4, 109.6, 120.5, 120.8, 122.2, 122.4, 122.8,
124.3, 126.1, 126.8, 127.1, 127.9, 128.0, 128.1, 128.3, 128.5,
128.6, 128.9, 129.0, 129.3, 129.4, 129.8, 129.9, 130.1, 130.2,
130.6, 130.9, 135.8, 136.1, 137.2, 137.5, 140.6, 140.8, 142.4,
144.0, 144.4, 144.7. EI-MS: m/z 325(8), 220(100), 204(19), 77
(14). Anal. Calcd for C30H27NO3S (481.61): C, 74.82; H, 5.65;
N, 2.91. Found: C, 74.70; H, 5.55; N, 2.99.
4f. Yield 96%. Yellow waxy solid. IR (Nujol) νmax/cm−1
:
1
698, 740, 853, 1011, 1344, 1377, 1515, 1601, 3391. H NMR
(400 MHz, CDCl3) δ: 2.06 (bs, 1H), 3.27–3.38 (m, 2H), 5.15 (t,
1H, J = 6.8 Hz), 7.15–7.21 (m, 1H), 7.25 (t, 1H, J = 8.1 Hz),
7.33–7.46 (m, 8H), 7.66 (d, 1H, J = 8.1 Hz), 8.04 (d, 2H, J =
8.1 Hz), 8.27 (bs, 1H). 13C NMR (100 MHz, CDCl3) δ: 35.3,
73.7, 107.6, 111.4, 119.1, 120.4, 122.9, 123.6, 126.7, 128.3,
128.4, 129.1, 129.2, 132.7, 136.1, 136.9, 147.4, 151.5. API-ES:
m/z 359[M + H]+, 381[M + Na]+, 397[M + K]+. Anal. Calcd for
C22H18N2O3 (358.39): C, 73.73; H, 5.06; N, 7.82. Found: C,
73.90; H, 5.18; N, 7.70.
Reduction of ketosulfonyl indole 3i with Na–Hg amalgam
5% Na–Hg amalgam (0.9 g) and Na2HPO4 (2 mmol) were
added at room temperature to a stirred solution of ketosulfonyl
indole 3i (0.5 mmol, 0.20 g) in dry EtOH (5 mL). After stirring
for 6 h at 60 °C, the mixture was filtered through a short pad of
florisil, that was subsequently washed with CH2Cl2 (3 × 3 mL).
The crude product obtained after removal of the solvent was
purified by column chromatography (hexanes–ethyl acetate
80 : 20) giving 0.12 g (80%) of sulfonyl indole 8 as a white
solid, m.p. 118–120 °C. IR (cm−1, Nujol) νmax/cm−1: 692, 732,
4g. Yield 88%. White solid, m.p. 108–110 °C. IR (Nujol)
νmax/cm−1: 739, 756, 810, 829, 1005, 1071, 1616, 3402. 1H
NMR (400 MHz, CDCl3) δ: 2.94 (bs, 1H), 3.01 (dd, 1H, J =
9.0, 14.5 Hz), 3.27 (dd, 1H, J = 3.8, 14.5 Hz), 5.28 (dd, 1H, J =
3.4, 9.0 Hz), 6.98–7.26 (m, 6H), 7.34 (d, 1H, J = 7.7 Hz), 7.52
(dt, 1H, J = 1.3, 7.7 Hz), 7.61 (d, 1H, J = 7.7 Hz), 8.79 (bs, 1H).
13C NMR (100 MHz, CDCl3) δ: 35.0, 67.9, 111.5, 111.8, 115.2,
115.4, 119.1, 119.5, 122.2, 123.6, 124.4, 127.4, 127.5, 127.8,
128.7, 128.8, 131.7, 131.8, 136.7, 158.8, 161.2. EI-MS: m/z 255
[M+, (6)], 130(100), 103(7), 77(12). Anal. Calcd for
C16H14FNO (255.29): C, 75.28; H, 5.53; N, 5.49. Found: C,
75.23; H, 5.66; N, 5.50.
1
808, 1137, 1286, 1614. H NMR (400 MHz, CDCl3) δ: 2.38 (s,
3H), 3.74 (s, 3H), 4.49 (s, 2H), 6.95–7.03 (m, 2H), 7.14–7.23
(m, 4H), 7.25–7.28 (m, 1H), 7.57 (d, 2H, J = 8.1 Hz). 13C NMR
(100 MHz, CDCl3) δ: 21.8, 33.2, 54.7, 101.3, 109.6, 118.9,
120.0, 122.2, 127.8, 128.8, 129.7, 130.6, 135.8, 136.9, 144.6.
EI-MS: m/z 299[M+, (1)], 144(100), 128(5), 115(6), 91(9), 77
(7). Anal. Calcd for C17H17NO2S (299.39): C, 68.20; H, 5.72;
N, 4.68. Found: C, 68.41; H, 5.83; N, 4.77.
4h. Yield 75%. White solid, m.p. 142–144 °C. IR (Nujol)
νmax/cm−1: 747, 759, 816, 979, 1377, 1616, 1682, 3395. 1H
NMR (400 MHz, CDCl3) δ: 3.15 (dd, 1H, J = 7.7, 14.5 Hz),
This journal is © The Royal Society of Chemistry 2012
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Synthesis of 3-phenylethenylindole 10
General procedure for the reaction of ketosulfonyl indoles 3 with
nucleophiles in the presence of Lewis acid
Ac2O (1.5 mmol, 0.15 g) and Et3N (1.75 mmol, 0.17 g) were
sequentially added to a stirred solution of alcohol 4i (0.75 mmol,
0.30 g) in dry CH2Cl2 (10 mL) at 0 °C. The reaction mixture
was stirred at room temperature for 3 h and then diluted with
CH2Cl2 (10 mL). After washing with 1 N HCl (3 × 10 mL) and
brine (10 mL), the organic phase was dried over MgSO4 and
after evaporation of the solvent under reduced pressure the crude
product thus obtained was purified by flash chromatography
(hexanes–ethyl acetate 85 : 15) giving 0.27 g (80%) of pure
To a stirred solution of ketosulfonyl indole 3 (1 mmol) in dry
CH2Cl2 (14 mL) kept under nitrogen atmosphere at −15 °C, the
nucleophile (1.5 mmol) and AlEtCl2 (2 mmol) were sub-
sequently added under stirring. After 0.75 h 2 N HCl (12 mL)
was added to the reaction mixture and the aqueous phase
extracted with CH2Cl2 (3 × 10 mL). The organic phase was
dried over Na2SO4 and after evaporation of the solvent under
reduced pressure, the crude product that was purified by flash
chromatography (hexanes–ethyl acetate 95 : 5).
acetate 9 as a white solid, m.p. 65–75 °C. IR (Nujol) νmax/cm−1
:
1
12a. Yield 58%. White waxy solid. IR (Nujol) νmax/cm−1
:
740, 816, 1227, 1596, 1740. H NMR (400 MHz, CDCl3) dia-
stereomeric mixture d.r. 1 : 1 δ: 1.94 (s, 1.5H), 2.17 (s, 1.5H),
2.29 (s, 1.5H), 2.34 (s, 1.5H), 3.61 (s, 1.5H), 3.83 (s, 1.5H),
4.69 (d, 0.5H, J = 1.2 Hz), 5.13 (d, 0.5H, J = 9.8 Hz), 6.69–7.71
(m, 15H). 13C NMR (100 MHz, CDCl3) δ: 21.4, 21.5, 21.7,
21.8, 33.2, 33.5, 67.8, 67.9, 71.8, 74.0, 101.4, 103.1, 109.4,
109.5, 119.9, 120.0, 121.9, 122.0, 125.3, 125.8, 126.6, 127.9,
128.2, 128.4, 128.5, 128.6, 128.7, 128.8, 129.1, 129.2, 129.5,
130.5, 131.4, 135.4, 136.7, 137.7, 138.0, 144.2, 144.7, 169.6,
169.7. EI-MS: m/z 291(20), 249(19), 220(13), 186(100), 144
(47), 77(28). Anal. Calcd for C26H25NO4S (447.55): C, 69.78;
H, 5.63; N, 3.13. Found: C, 69.61; H, 5.75; N, 3.19.
694, 725, 1151, 1601, 1678, 1731. 1H NMR (400 MHz, CDCl3)
δ: 1.29 (s, 3H), 1.48 (s, 3H), 3.63 (s, 3H), 3.69 (s, 3H) 5.39 (s,
1H), 6.87 (s, 1H), 7.17–7.31 (m, 5H), 7.33–7.41 (m, 1H), 7.78
(d, 1H, J = 8.1 Hz), 7.88 (d, 2H, J = 8.1 Hz). 13C NMR
(100 MHz, CDCl3) δ: 21.6, 27.3, 33.1, 46.1, 50.5, 52.2, 107.9,
109.7, 119.2, 119.9, 122.0, 128.5, 128.6, 130.0, 132.5, 137.2,
137.5, 178.8, 199.9. EI-MS: m/z 349[M+, (20)], 248(100), 244
(97), 220(51), 184(49) 144(34), 105(38), 77(44), 42(16). Anal.
Calcd for C22H23NO3 (349.42): C, 75.62; H, 6.63; N, 4.01.
Found: C, 75.51; H, 6.68; N, 3.93.
12b. Yield 76%. White solid, m.p. 44–47 °C. IR (Nujol) νmax
/
cm−1: 691, 722, 1148, 1595, 1677, 1731. H NMR (400 MHz,
CDCl3) δ: 1.28 (s, 3H), 1.43 (s, 3H), 3.62(s, 3H), 5.22 (s, 2H),
5.36 (s, 1H), 6.80–6.86 (m, 2H), 6.92 (s, 1H), 7.11–7.28 (m,
8H), 7.33–7.40 (m, 1H), 7.73–7.79 (m, 1H), 7.83 (d, 2H, J = 8.1
Hz). 13C NMR (100 MHz, CDCl3) δ: 21.5, 27.4, 45.8, 50.2,
51.0, 52.2, 109.0, 110.3, 119.4, 120.2, 122.2, 126.5, 127.7,
128.4, 128.5, 128.7, 128.9, 129.7, 132.5, 136.8, 137.4, 178.7,
199.9. EI-MS: m/z 425[M+, (4)], 324(28), 320(25), 105(16), 91
(100) 77(15). Anal. Calcd for C28H27NO3 (425.52): C, 79.03; H,
6.40; N, 3.29. Found: C, 79.19; H, 6.55; N, 3.38.
1
To a stirred solution of acetate 9 (0.56 mmol, 0.25 g) in 1 : 1
v/v THF–MeOH (10 mL), NaH2PO4 (2.25 mmol, 0.27 g) and
5% Na–Hg amalgam (0.95 g) were added at room temperature.
After stirring for 1 h at room temperature, the mixture was
filtered through a short pad of florisil, that was subsequently
washed with CH2Cl2 (20 mL). The crude product obtained after
removal of the solvent was purified by column chromatography
(hexanes–ethyl acetate 95 : 5) giving 0.085 g (65%) of alkenyl
indole 10 as a white solid, m.p. 97–99 °C. IR (neat) νmax/cm−1
:
1
729, 811, 849, 954, 1071. H NMR (400 MHz, CDCl3) δ: 3.80
(s, 3H), 7.12 (d, 1H, J = 16.7 Hz), 7.19–7.42 (m, 8H), 7.54 (d,
2H, J = 7.7 Hz), 8.02 (d, 1H, J = 7.7 Hz). 13C NMR (100 MHz,
CDCl3) δ: 33.2, 109.9, 114.2, 120.3, 120.5, 121.8, 122.5, 125.0,
125.9, 126.4, 126.7, 128.8, 128.9, 137.9, 138.9. EI-MS: m/z 233
[M+, (100)], 217(38), 189(11), 115(10). Anal. Calcd for
C17H15N (233.31): C, 87.52; H, 6.48; N, 6.00. Found: C, 87.71;
H, 6.35; N, 5.89.
12c. Yield 53%. Yellow viscous oil. IR (neat) νmax/cm−1: 690,
1
725, 1146, 1597, 1681, 1730. H NMR (400 MHz, CDCl3) δ:
2.86 (dd, 1H, J = 4.7, 17.1 Hz), 3.44 (dd, 1H, J = 9.9, 17.1 Hz),
3.65 (s, 3H), 5.20 (d, 2H, J = 3.4 Hz), 5.38 (dd, 1H, J = 4.7, 9.9
Hz), 6.90–6.97 (m, 3H), 7.12–7.25 (m, 6H), 7.34 (d, 2H, J = 7.7
Hz), 7.42–7.49 (m, 1H), 7.72–7.78 (m, 1H), 7.99 (d, 2H, J = 8.5
Hz). 13C NMR (100 MHz, CDCl3) δ: 37.9, 41.0, 50.2, 52.0,
110.3, 112.2, 119.1, 120.1, 122.5, 126.8, 126.9, 127.3, 127.8,
128.6, 128.9, 129.0, 133.0, 136.5, 137.0, 137.3, 173.1, 199.0.
EI-MS: m/z 397[M+, (4)], 292(41), 105(6), 91(100) 77(12).
Anal. Calcd for C26H23NO3 (397.47): C, 78.57; H, 5.83; N,
3.52. Found: C, 78.40; H, 5.97; N, 3.60.
Desulfonylation–reduction of ketosulfonyl indole 3k
Reaction was carried out as previously reported16 on compound
3k (0.5 mmol, 0.24 g) leading to 0.052 g (32%) of alcohol 4k as
a yellow sticky oil. IR (neat) νmax/cm−1: 700, 740, 1048, 1182,
12d. Yield 92%. White waxy solid. IR (Nujol) νmax/cm−1
:
688, 702, 722, 740, 942, 972, 1156, 1596, 1682, 1704.
1H NMR (400 MHz, CDCl3) δ: 1.23(s, 9H), 2.80 (dd, 1H,
J = 3.0, 18.0 Hz), 3.52 (s, 3H), 4.24 (dd, 1H, J = 11.1, 18.0 Hz),
5.22 (dd, 1H, J = 3.0, 11.1 Hz), 7.12–7.19 (m, 3H), 7.20–7.37
(m, 5H), 7.53–7.61 (m, 5H), 7.81 (d, 1H, J = 8.1 Hz).
13C NMR (100 MHz, CDCl3) δ: 26.8, 31.1, 40.0, 40.4, 44.2,
109.0, 109.7, 120.2, 120.6, 122.2, 126.5, 128.2, 128.9, 129.1,
129.2, 130.9, 131.6, 132.5, 136.7, 137.5, 139.0, 198.8,
214.9. EI-MS: m/z 423[M+, (5)], 318(38), 234(20), 217(8), 105
(10), 77(13), 57(100), 41(13). Anal. Calcd for C29H29NO2
(423.55): C, 82.24; H, 6.90; N, 3.31. Found: C, 82.30; H, 6.88;
N, 3.39.
1
1357, 1613, 3030, 3391. H NMR (400 MHz, CDCl3) δ: 2.48
(bs, 1H), 3.14 (dd, 1H, J = 8.5, 14.5 Hz), 3.23 (dd, 1H, J = 4.7,
14.5 Hz), 4.97–5.03 (m, 1H), 5.25 (s, 2H), 6.93 (s, 1H),
7.05–7.16 (m, 3H), 7.20 (t, 1H, J = 7.3 Hz), 7.23–7.38 (m, 6H),
7.39–7.43 (m, 2H), 7.65 (d, 2H, J = 7.7 Hz). 13C NMR
(100 MHz, CDCl3) δ: 36.2, 50.2, 74.2, 110.0, 111.4, 119.4,
119.5, 122.2, 126.2, 127.1, 127.5, 127.6, 127.8, 128.5, 128.6,
129.0, 136.9, 137.8, 144.6. EI-MS: m/z 327[M+, (8)], 221
(18), 220(87), 129(9), 91(100). Anal. Calcd for C23H21NO
(327.42): C, 84.37; H, 6.46; N, 4.28. Found: C, 84.55; H, 6.51;
N, 4.38.
3492 | Org. Biomol. Chem., 2012, 10, 3486–3493
This journal is © The Royal Society of Chemistry 2012

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12e. Diastereomer A. Yield 63%. White solid, m.p. 70–73 °C.
IR (Nujol) νmax/cm−1: 741, 810, 830, 843, 807, 1022, 1082,
1170, 1211, 1574, 1601, 1671, 1755, 3052. 1H NMR (400 MHz,
CDCl3) δ: 3.80 (s, 3H), 4.97 (d, 1H, J = 8.1 Hz), 5.20 (d, 1H, J
= 15.8 Hz), 5.27 (d, 1H, J = 15.8 Hz), 5.90 (d, 1H, J = 8.1 Hz),
6.02 (d, 1H, J = 6.0 Hz), 6.82 (d, 2H, J = 8.5 Hz), 6.93–6.99
(m, 2H), 7.05 (s, 1H), 7.15–7.29 (m, 6H), 7.38 (d, 1H, J = 6.0
Hz), 7.60–7.65 (m, 1H), 7.91 (d, 2H, J = 8.5 Hz). 13C NMR
(100 MHz, CDCl3) δ: 48.2, 50.4, 55.7, 84.1, 107.3, 110.6,
114.0, 118.9, 120.7, 122.3, 122.9, 126.8, 127.0, 128.0, 128.2,
128.7, 129.0, 131.3, 137.0, 137.1, 156.7, 163.9, 173.0, 194.9.
API-ES: m/z 438 [M + H]+, 460 [M + Na]+, 476[M + K]+, 897
[2M + Na]+. Anal. Calcd for C28H23NO4 (437.49): C, 76.87; H,
5.30; N, 3.20. Found: C, 76.95; H, 5.23; N, 3.31. Diastereomer
B. Yield 22%. Yellow sticky oil. IR (Nujol) νmax/cm−1: 741,
810, 830, 843, 807, 1022, 1082, 1170, 1211, 1574, 1601, 1671,
organiche eco-sostenibili mediate da nuovi sistemi catalitici) for
financial support.
Notes and references
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1
1755, 3052. H NMR (400 MHz, CDCl3) δ: 3.79 (s, 3H), 5.00
(d, 1H, J = 7.7 Hz), 5.21 (d, 1H, J = 16.2 Hz), 5.27 (d, 1H, J =
16.2 Hz), 5.74 (d, 1H, J = 7.3 Hz), 6.10 (dd, 1H, J = 1.2, 5.6
Hz), 6.81 (d, 2H, J = 8.9 Hz), 6.93–7.00 (m, 2H), 7.10 (s, 1H),
7.15–7.28 (m, 6H), 7.68 (d, 1H, J = 5.6 Hz), 7.70–7.74 (m, 1H),
7.90 (d, 2H, J = 8.9 Hz). 13C NMR (100 MHz, CDCl3) δ: 48.4,
50.4, 55.7, 84.7, 108.6, 110.5, 114.0, 118.9, 120.5, 122.2, 122.6,
126.8, 127.2, 127.9, 128.4, 128.8, 129.0, 131.3, 137.0, 137.2,
156.0, 163.9, 173.1, 195.5. API-ES: m/z 438 [M + H]+, 460[M
+ Na]+, 476[M + K]+, 897[2M + Na]+. Anal. Calcd for
C28H23NO4 (437.49): C, 76.87; H, 5.30; N, 3.20. Found: C,
77.01; H, 5.40; N, 3.15.
12f. Yield 80%. Yellow sticky oil. IR (neat) νmax/cm−1: 741,
960, 1154, 1189, 1606, 1682, 3054. 1H NMR (400 MHz,
CDCl3) δ: 2.26 (s, 3H), 2.37 (s, 3H), 3.73 (s, 3H), 5.87 (d, 1H, J
= 3.0 Hz), 5.98 (d, 1H, J = 3.0 Hz), 6.23 (s, 1H), 7.00 (s, 1H),
7.13 (t, 1H, J = 7.7 Hz), 7.17–7.32 (m, 4H), 7.63 (d, 1H, J = 8.1
Hz), 7.96 (d, 2H, J = 8.1 Hz). 13C NMR (100 MHz, CDCl3) δ:
13.9, 21.9, 33.1, 44.6, 106.6, 109.4, 109.6, 110.1, 119.2, 119.6,
122.1, 127.1, 128.6, 129.2, 129.5, 134.0, 137.3, 144.0, 151.4,
151.8, 196.0. EI-MS: m/z 343[M+, (2)], 224(100), 180(11), 119
(5), 91(7). Anal. Calcd for C23H21NO2 (343.42): C, 80.44; H,
6.16; N, 4.08. Found: C, 80.59; H, 6.12; N, 4.20.
11 A. Palmieri and M. Petrini, J. Org. Chem., 2007, 72, 1863–1866.
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13 E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 1965, 87, 1345–
1353.
14 C. Aïssa, Eur. J. Org. Chem., 2009, 1831–1844.
15 A. B. Smith III, K. J. Hale and J. P. McCauley Jr, Tetrahedron Lett.,
1989, 30, 5579–5582.
12g. Yield 75%. Yellow oil. IR (neat) νmax/cm−1: 742, 914,
1014, 1181, 1332, 1473, 1606, 1677, 3056. 1H NMR (400 MHz,
CDCl3) δ: 2.34 (s, 3H), 2.62–2.73 (m, 1H), 2.92–3.04 (m, 1H),
3.69 (s, 3H), 4.88–5.00 (m, 2H), 5.09 (d, 1H, J = 17.1 Hz),
5.78–5.91 (m, 1H), 6.89 (s, 1H), 7.13–7.20 (m, 3H), 7.21–7.30
(m, 2H), 7.75 (dd, 1H, J = 0.9, 8.1 Hz), 7.90 (d, 2H, J = 8.1
Hz). 13C NMR (100 MHz, CDCl3) δ: 21.8, 33.0, 38.1, 44.3,
109.7, 112.9, 116.4, 119.0, 119.5, 122.0, 127.0, 127.5, 128.9,
129.4, 134.5, 137.0, 137.3, 143.7, 199.4. EI-MS: m/z 303[M+,
(11)], 262(16), 234(13), 184(100) 168(20), 91(9). Anal. Calcd
for C21H21NO (303.40): C, 83.13; H, 6.98; N, 4.62. Found: C,
83.01; H, 7.10; N, 4.77.
16 R. Giovannini and M. Petrini, Synlett, 1995, 973–974.
17 (a) A. El-Awa, M. N. Noshi, X. Mollat du Jourdin and P. L. Fuchs,
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Synlett, 1996, 1001–1003.
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706–712.
19 The carbocationic nature of the intermediate obtained upon treatment of
compounds 3 with Lewis acids is probably due to the retaining of the aro-
matic character of the pyrrole ring in structure C
Acknowledgements
.
The authors thank the University of Camerino and MIUR-Italy
(FIRB National Project “Metodologie di nuova generazione
nella formazione di legami carbonio-carbonio e carbonio-
eteroatomo in condizioni eco-sostenibili” and PRIN “Sintesi
20 (a) G. Bartoli, M. Bosco, A. Carlone, F. Pesciaioli, L. Sambri and
P. Melchiorre, Org. Lett., 2007, 9, 1403–1405; (b) S. Adachi, F. Tanaka,
K. Watanabe and T. Harada, Org. Lett., 2009, 11, 5206–5209.
This journal is © The Royal Society of Chemistry 2012
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