Tandem reactions via barton esters with intermolecular addition and vinyl radical substitution onto indole

Article abstract of DOI:10.1021/jo5008543

A one-pot initiator-free Barton ester decomposition with tandem radical addition onto alkyl propiolates or phenylacetylene with aromatic substitution of the resultant vinyl radical allows convenient access to new 9-substituted 6,7-dihydropyrido[1,2-a]indoles. Propyl radical cyclizations compete when forming the expanded 7,8-dihydro-6H-azepino[1,2-a]indole system. 2-Thiopyridinyl S-radical is incorporated into aromatic adducts when using unsubstituted indole-1-alkanoic acid precursors. X-ray crystallography on substitution products allows selectivity of the radical addition onto less reactive internal alkynes to be determined.

Full text of DOI:10.1021/jo5008543

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Note
Tandem Reactions via Barton Esters with Intermolecular
Addition and Vinyl Radical Substitution onto Indole
Robert Coyle, Patrick McArdle, and Fawaz Aldabbagh
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo5008543 • Publication Date (Web): 16 May 2014
Downloaded from http://pubs.acs.org on May 26, 2014
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Tandem Reactions via Barton Esters with Intermolecular Addition and Vinyl
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Radical Substitution onto Indole
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Robert Coyle, Patrick McArdle and Fawaz Aldabbagh*
School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland
∗ Corresponding author. Tel.: +353 (0) 91 493120; fax: +353 (0) 91 49557
eꢀmail: fawaz.aldabbagh@nuigalway.ie (F. Aldabbagh)
ABSTRACT: A oneꢀpot initiatorꢀfree Barton ester decomposition, tandem radical addition onto
alkyl propiolates or phenylacetylene with aromatic substitution of the resultant vinyl radical allows
convenient access to new 9ꢀsubstituted 6,7ꢀdihydropyrido[1,2ꢀa]indoles. Propyl radical cyclizations
compete when forming the expanded 7,8ꢀdihydroꢀ6Hꢀazepino[1,2ꢀa]indole system. 2ꢀThiopyridinyl
Sꢀradical is incorporated into aromatic adducts when using unsubstituted indoleꢀ1ꢀalkanoic acid
precursors. Xꢀray crystallography on substitution products allows selectivity of the radical addition
onto less reactive internal alkynes to be determined.
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Stork and Baine first demonstrated the synthetic utility of vinyl radicals by carrying out reductive
cyclizations to form five and sixꢀmembered rings.1 Bu3SnH and azobisisobutyronitrile (AIBN)
were used to carry out vinyl radical cyclizations onto indole yielding mainly reduced adducts.2
Later vinyl radical cyclization with aromatic substitution was achieved using a tinꢀfree chain
reaction, where displacement of indoleꢀ2ꢀsulfonyl substitutent occurs.3 Effective five and sixꢀ
membered intramolecular aromatic substitutions of vinyl radicals using Bu3SnH and AIBN were
reported by Padwa et al.4 Although, usually the use of the “reductant” Bu3SnH is not conducive
with efficient aromatic substitution, where netꢀloss of H● or “oxidation” occurs.5,6 Where prior to
the substitution the vinyl radical is generated via an intermolecular addition onto alkynes,7 yields of
aromatic product are traditionally modest.8 The first synthetically viable tandem process containing
an intermolecular addition onto alkynes was reported by Santi et al. using Mn(III)ꢀmediated
oxidation of benzylmalonates with the subsequent vinyl radical aromatic substitution giving
naphthalene derivatives in moderate to good yields.9 Most recently, Zhou and coworkers used a
photoꢀredox catalytic system to synthesize 2ꢀtrifluoromethyl quinolines with imidoyl radical
addition onto alkyne followed by aromatic substitution,10 and Li and coworkers reported
benzothiophenes under oxidative catalytic conditions with an initial sulfanyl radical addition onto
butꢀ2ꢀynedioates.11
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The decomposition of Barton esters {Oꢀacyl thiohydroxamate ester or pyridineꢀ2ꢀthioneꢀNꢀ
oxycarbonyl (PTOC)}12 provides a means of achieving aromatic substitution under mild initiatorꢀ
free conditions,13ꢀ15 as demonstrated by Barton et al. for intermolecular substitution of nucleophilic
alkyl radicals onto heteroaromatic salts.13 Most recently we used Barton esters in radical
cyclizations resulting in some high yielding five to sevenꢀmembered alkyl and cyclopropyl
annulations of indoles and benzimidazoles.14,15 In the present article we report a new use of Barton
esters, as precursors for oneꢀpot initiatorꢀfree cascade/tandem reactions (Scheme 1). The tandem
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reaction involves intermolecular addition of alkyl radicals onto alkyl propiolates or phenylacetylene
followed by intramolecular substitution of vinyl radicals onto indoles. Investigations into the use of
disubstituted (internal) alkynes with two different substituents are also presented with substitution
products demonstrating the selectivity of the radical addition onto the alkyne.
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Scheme 1. One-pot initiator-free tandem reactions with 3-substituted indoles
Conditions: (i) Barton ester formation; HOTT (1.5 equiv.), Et3N (3 equiv.), THFꢀMeCN, rt, dark,
40 min; (ii) radical generation and tandem reactions; alkyl propiolate (8 equiv.), CSA (4 equiv.),
MeCN, reflux, 6 h.
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The twoꢀstep oneꢀpot protocol involves initial transformation of indole carboxylic acids (e.g. 1a
and 1b) into Barton esters using Garner’s HOTT (Sꢀ(1ꢀoxidoꢀ2ꢀpyridinyl)ꢀ1,1,3,3ꢀtetramethyl
thiouronium hexafluorophosphate)16 in the absence of light (Scheme 1). HOTT is a useful coupling
reagent for forming labile Barton esters from hindered or difficult carboxylic acids. The alkyne is
present in excess (8 equivalents) in order to favor the intermolecular addition with reactions using
terminal alkynes only proceeding efficiently by carrying out the radical generation and tandem
reactions step under acidic conditions {4 equivalents of camphorsulfonic acid (CSA)}. CSA
neutralizes remaining triethylamine from the Barton ester formation step, which would otherwise
cause inadvertent dimerization of the alkyne. The oneꢀpot reaction sequence begins with Barton
ester thermal dissociation to give a nucleophilic ethyl radical that undergoes addition onto the
unsubstituted carbon of the terminal alkyne resulting in a vinyl radical for aromatic substitution.
The yields for reactions with indoleꢀ3ꢀcarbonitrile 1a and indoleꢀ3ꢀcarbaldehyde 1b with methyl
and ethyl propiolate to give 6,7ꢀdihydropyrido[1,2ꢀa]indoles 2a, 2b and 2d are 72ꢀ79%, with a
smaller isolated yield obtained of adduct 2c (68%) from the reaction of 1a with tertꢀbutyl
propiolate. The tandem protocol is insensitive to substituents at the indoleꢀ3ꢀposition with 3ꢀ
methylindoleꢀ1ꢀpropanoic acid (1c) giving 10ꢀmethylꢀ6,7ꢀdihydropyrido[1,2ꢀa]indoleꢀ9ꢀ
carboxylate 2e in 76% yield inferring a nonꢀpolar cyclizing radical. An efficient chain for vinyl
radical aromatic substitution is indicated since no other indoleꢀadducts were observed.
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Scheme 2. One-pot initiator-free tandem reactions with 3-unsubstituted indole
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Though ESR data has suggested αꢀcarboxy and αꢀphenyl vinylic radicals adopt close to linear πꢀ
type resonance stabilized structures,17,18 a bent σꢀtype structure has been reported.19 The
conjugation of the vinyl radical with the adjacent substituent gives an electrophilic radical, while a
nucleophilic or neutral radical would be expected if the σꢀtype structure is adopted. The isolation of
only aromatic substitution product 3a in 72% yield from the reaction of 3ꢀunsubstituted 1ꢀ
indolepropanoic acid 1d with methyl propiolate (Scheme 2) confirmed that the intermediate vinyl
radical is not influenced by polar effects. In agreement with the Barton et al. chain proposal,13 it
can be inferred that the 2ꢀthiopyridinyl Sꢀradical traps the intermediate cyclized radical (the indolꢀ
3ꢀyl radical in Scheme 1) prior to elimination of 2ꢀpyridinethiol on rearomatization. In contrast to
3ꢀsubstituted indoles, aromatic Sꢀradical adduct 3a is formed by oxidation during the reaction
(presumably by the presence of adventitious oxygen), as confirmed by analysis of the reaction
mixture. A mechanism similar to that proposed by Curran and Keller may be involved where
● 20
hydrogen atom transfer to oxygen would give HO2 , which is used to explain the formation of
“oxidized” aromatic substitution products from metal hydrideꢀmediated reactions.20,21
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A sevenꢀmembered vinyl radical cyclization would allow access to the 7,8ꢀdihydroꢀ6Hꢀ
azepino[1,2ꢀa]indole system. Use of 3ꢀformylindoleꢀ1ꢀbutanoic acid 1f and methyl propiolate
allowed isolation of sevenꢀmembered adduct 7,8ꢀdihydroꢀ6Hꢀazepino[1,2ꢀa]indoleꢀ10ꢀcarboxylate
5 albeit in 23% yield with 2,3ꢀdihydroꢀ1Hꢀpyrrolo[1,2ꢀa]indole 6 predominating in 51% yield
(Scheme 3). The higher yield for the propyl radical adduct 6 is in accordance with a more
favourable fiveꢀmembered cyclization, where there is also compatible polar effects between the
nucleophilic radical and the activated 2ꢀposition of indoleꢀ3ꢀcarbaldehyde. We previously reported
a fiveꢀmembered alkyl radical cyclization occurring in 78% yield via the decomposition of the
Barton ester of 3ꢀcyanoindoleꢀ1ꢀbutanoic acid.14 Thus, it seemed that the tandem reaction via a
cyclizing sevenꢀmembered vinyl radical would be more favorable using nonꢀactivated indole 1e
(Scheme 2), however unexpectedly this gave 2,3ꢀdihydroꢀ1Hꢀpyrrolo[1,2ꢀa]indole 4 as the major
product in 53% yield with the desired 7,8ꢀdihydroꢀ6Hꢀazepino[1,2ꢀa]indoleꢀ10ꢀcarboxylate 3b
isolated in 21% yield. Therefore, it seems that cyclizations of alkyl like vinyl radicals onto indoles
are not significantly influenced by polar effects.
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Scheme 3. 7,8-Dihydro-6H-azepino[1-2-a]indole via one-pot initiator-free tandem reactions
The addition of nucleophilic radicals (tꢀBu●) onto electronꢀdeficient alkyl propiolates is reported to
be about ten times faster than onto phenylacetylene (~ k = 2 x 105 Mꢀ1 sꢀ1 for alkyl propiolates in
1,2ꢀepoxypropane in comparison to k = 2.1 x 104 Mꢀ1 sꢀ1 for phenylacetylene in isopropanol at 300
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K),7,17 which may explain the higher yield for reaction of indoleꢀ3ꢀcarbaldehyde 1b with alkyl
propiolates (Scheme 1) in comparison with phenylacetylene to give the phenyl analogue 7a in 61%
yield with 14% isolated of 2-thiopyridine 8a (Scheme 4). Nevertheless this convenient tandem
radical approach represents the first synthesis of 9ꢀsubstituted 6,7ꢀdihydropyrido[1,2ꢀa]indoles.
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Scheme 4. One-pot initiator-free tandem reactions with less reactive alkynes
Yields of 8,9ꢀdisubstituted 6,7ꢀdihydropyrido[1,2ꢀa]indoles 7b and 7c (5ꢀ23% in Scheme 4) were
low from reactions of 3ꢀcyanoindoleꢀ1ꢀpropanoic acid (1a) with internal alkynes under analogous
Barton ester conditions to those used for terminal alkynes. The major product was 1ꢀ[2ꢀ(pyridinꢀ2ꢀ
ylthio)ethyl]ꢀ1Hꢀindoleꢀ3ꢀcarbonitrile (8b) (in 59ꢀ81% yield) indicative of a less competitive chain
for the aromatic substitution. The addition of the intermediate ethyl radical onto disubstituted
alkynes is expected to be slow, as indicated by literature radical addition rates of nucleophilic
radicals (tꢀBu●) onto ethyl 3ꢀphenylpropꢀ2ꢀynoate and methyl butꢀ2ꢀynoate, which are k = 4.2 x 104
Mꢀ1 sꢀ1 and k = 5.2 x 102 Mꢀ1 sꢀ1 respectively in 1,2ꢀepoxypropane at 300 K;7,17 factors of 10ꢀ1000
times slower than onto alkyl propiolates. The selectivity of the ethyl radical addition onto ethyl 3ꢀ
phenylpropꢀ2ꢀynoate to give an αꢀstyryl vinylic radical and onto methyl hexꢀ2ꢀynoate to give an αꢀ
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propyl vinylic radical respectively was confirmed by the Xꢀray crystal structures of the substitution
products (Figures S1 and S2); ethyl 10ꢀcyanoꢀ9ꢀphenylꢀ6,7ꢀdihydropyrido[1,2ꢀa]indoleꢀ8ꢀ
carboxylate (7b) and methyl 10ꢀcyanoꢀ9ꢀpropylꢀ6,7ꢀdihydropyrido[1,2ꢀa]indoleꢀ8ꢀcarboxylate (7c).
The addition is thus dictated by steric factors in agreement with the ESR observation of αꢀphenyl
vinyl radical formation from the addition of Me3C● onto alkyl 3ꢀphenylpropꢀ2ꢀynoates.17 The
lowest yielding tandem reaction to give adduct 7c emphasizes the steric congestion about methyl
hexꢀ2ꢀynoate. The formation of sulfides 8a and 8b is only observed where the alkyne is less
reactive, and can occur by alternative ethyl radical reactions such as combination with the 2ꢀ
thiopyridinyl Sꢀradical or from addition onto the Barton ester13,22 to establish a chain.
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In summary a radical initiatorꢀfree (and metal catalystꢀfree) tandem approach has allowed access to
novel alicyclic [1,2ꢀa] ringꢀfused indoles from commercially available reactants. The aromatic
substitutions revealed that the vinylꢀradical is nonꢀpolar, as well as, allowing the assessment of
alkyl radical reactivity towards alkynes.
EXPERIMENTAL SECTION
Materials. Carboxylic acids 1b-1f used are commercially available, although 1a and 1e were
readily prepared on gramꢀscale from indoleꢀ3ꢀcarbonitrile14 and indole23 respectively by basic
alkylation and hydrolysis of methyl esters. HOTT though commercially available, was accessed
using the literature procedure,16 which in our hands yielded almost 10 g of HOTT in 65% yield.
Solvents were distilled over appropriate drying agents prior to use and all reactions were carried out
under a nitrogen atmosphere. Et3N was distilled over CaH2 before use. Monitoring of reactions by
Thin Layer Chromatography (TLC) was carried out on aluminumꢀbacked plates coated with silica
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gel (60 F254). Column chromatography was carried out using silica gel 60 (particle size 0.040ꢀ0.063
mm).
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Measurements. IR spectra were obtained using a FTꢀIR spectrophotometer with ATR accessory.
NMR spectra were recorded using a 400 MHz instrument. Chemical shifts are reported relative to
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1
Me4Si as internal standard and NMR assignments were supported by DEPT and Hꢀ13C and 1Hꢀ1H
NMR correlation 2D spectra. Highꢀresolution mass spectra (HRMS) were measured using an ESI
timeꢀofꢀflight mass spectrometer (TOFMS) in positive mode. The precision of all accurate mass
measurements is better than 5 ppm.
General procedure for one-pot Barton ester formation and tandem radical reactions. Et3N
(0.32 mL, 2.30 mmol) in THF (5.7 mL) was added to a mixture of carboxylic acid 1a-1f (0.76
mmol) and HOTT (0.424 g, 1.14 mmol) in MeCN (1.9 mL). The solution was stirred at room
temperature in the absence of light for 40 min. Alkyne (6.08 mmol) in MeCN (40 mL) and
containing CSA (0.711 g, 3.06 mmol) for alkyl propiolates was added, and heated under reflux for
6 h. The solution was evaporated, dissolved in CH2Cl2 (10 mL) and washed with H2O (2 x 10 mL).
The organic extract evaporated and purified by column chromatography using silica gel as
absorbent with a gradient elution of hexanes and Et2O or CH2Cl2.
Methyl 10-cyano-6,7-dihydropyrido[1,2-a]indole-9-carboxylate (2a) (0.151 g, 79%) offꢀwhite
solid; mp 125ꢀ126 ˚C; Rf 0.62 (Et2O); IR vmax (neat, cmꢀ1) 2952, 2215 (CN), 1724 (C=O), 1623,
1
1473, 1457, 1439, 1337, 1276, 1198, 1082, 1017; H NMR (400 MHz, CDCl3) δ 7.77 (d, J 8.2 Hz,
1H, 1ꢀH), 7.32ꢀ7.25 (m, 4H), 4.17 (t, J 7.1 Hz, 2H, 6ꢀCH2), 3.98 (s, 3H, OCH3), 2.83ꢀ2.77 (m, 2H,
13
7ꢀCH2); C NMR (100 MHz, CDCl3) δ 164.4 (C=O), 138.7 (8ꢀCH), 135.2, 128.9, 125.7 (all C),
124.8, 122.4 (2,3ꢀCH), 120.2 (1ꢀCH), 115.8 (C), 109.6 (4ꢀCH), 85.1 (CN), 52.2 (OCH3), 39.0 (6ꢀ
CH2), 24.3 (7ꢀCH2); HRMS (ESI) m/z: (M+H)+ Calcd for C15H13N2O2 253.0977; Found 253.0973.
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Methyl 10-formyl-6,7-dihydropyrido[1,2-a]indole-9-carboxylate (2b) (0.140 g, 72%) yellow solid;
mp 119ꢀ120 ˚C; Rf 0.32 (Et2O); IR vmax (neat, cmꢀ1) 2952, 1724 (C=O), 1623 (C=O), 1473, 1457,
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1439, 1337, 1276, 1198, 1082, 1017; H NMR (400 MHz, CDCl3) δ 10.13 (s, 1H, CHO), 8.36 (d, J
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7.7 Hz, 1H, 1ꢀH), 7.33ꢀ7.24 (m, 4H), 4.14 (t, J 7.0 Hz, 2H, 6ꢀCH2), 3.88 (s, 3H, OCH3), 2.76 (q, J
13
7.0 Hz, 2H, 7ꢀCH2); C NMR (100 MHz, CDCl3) δ 186.0 (CHO), 166.3, (COOMe), 138.6 (8ꢀ
CH), 136.7, 136.0, 127.1, 126.2 (all C), 124.5, 123.2 (2,3ꢀCH), 122.5 (1ꢀCH), 113.5 (C), 109.2 (4ꢀ
CH), 52.8 (OCH3), 38.6 (6ꢀCH2), 24.2 (7ꢀCH2); HRMS (ESI) m/z: (M+H)+ Calcd for C15H14NO3
256.0974; Found 256.0971.
tert-Butyl 10-cyano-6,7-dihydropyrido[1,2-a]indole-9-carboxylate (2c) (0.152 g, 68%) yellow oil;
Rf 0.76 (Et2O); IR vmax (neat, cmꢀ1) 2978, 2217 (CN), 1715 (C=O), 1533, 1457, 1428, 1393, 1368,
1
1287, 1254, 1163, 1080, 1016; H NMR (400 MHz, CDCl3) δ 7.79 (d, J 7.8 Hz, 1H, 1ꢀH), 7.34ꢀ
7.24 (m, 3H), 7.17 (t, J 4.8 Hz, 1H, 8ꢀH), 4.16 (t, J 7.1 Hz, 2H, 6ꢀCH2), 2.78ꢀ2.73 (m, 2H, 7ꢀ
13
CH2), 1.65 (s, 9H, tBu); C NMR (100 MHz, CDCl3) δ 163.1 (C=O), 137.3 (8ꢀCH), 135.7, 135.0,
128.7, 127.5 (all C), 124.5, 122.1 (2,3ꢀCH), 120.1 (1ꢀCH), 115.9 (C), 109.5 (4ꢀCH), 83.4 (CN),
38.8 (6ꢀCH2), 28.0 ((CH3)C), 24.1 (7ꢀCH2); HRMS (ESI) m/z: (M+H)+ Calcd for C18H19N2O2
295.1447; Found 295.1439.
Ethyl 10-formyl-6,7-dihydropyrido[1,2-a]indole-9-carboxylate (2d) (0.160 g, 78%) brown solid;
mp 105ꢀ107 ˚C; Rf 0.49 (Et2O); IR vmax (neat, cmꢀ1) 1719 (C=O), 1649 (C=O), 1456, 1436, 1400,
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1333, 1271, 1185, 1130, 1085; H NMR (400 MHz, CDCl3) δ 10.15 (s, 1H, CHO), 8.39ꢀ8.36 (m,
1H, 1ꢀH), 7.33ꢀ7.22 (m, 4H), 4.36 (q, J 7.1 Hz, 2H), 4.14 (t, J 7.1 Hz, 2H, 6ꢀCH2), 2.78ꢀ2.73 (m,
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2H, 7ꢀCH2), 1.35 (t, J 7.1 Hz, 3H, CH3); C NMR (100 MHz, CDCl3) δ 186.1 (CHO), 165.9
(COOEt), 138.4 (8ꢀCH), 136.9, 136.0, 127.4, 126.2 (all C), 124.5, 123.2 (2,3ꢀCH), 122.6 (1ꢀCH),
113.5 (C), 109.2 (4ꢀCH), 62.0 (OCH2), 38.6 (6ꢀCH2), 24.2 (7ꢀCH2), 14.2 (CH3); HRMS (ESI) m/z
(M+H)+ C16H16NO3 calcd 270.1130, Found 270.1132.
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Methyl 10-methyl-6,7-dihydropyrido[1,2-a]indole-9-carboxylate (2e) (0.139 g, 76%) yellow oil;
Rf 0.43 (CH2Cl2); IR vmax (neat, cmꢀ1) 2949, 1726 (C=O), 1464, 1438, 1385, 1334, 1271, 1195,
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1179, 1077, 1016; H NMR (400 MHz, CDCl3) δ 7.57 (d, J 7.8 Hz, 1H, 1ꢀH), 7.22ꢀ7.21 (m, 2H),
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7.10ꢀ7.05 (m, 1H), 6.79 (t, J 5.0 Hz, 1H, 8ꢀH), 4.07 (t, J 6.6 Hz, 2H, 6ꢀCH2), 3.90 (s, 3H, OCH3),
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2.68ꢀ2.63 (m, 2H, 7ꢀCH2), 2.30 (s, 3H, CH3); C NMR (100 MHz, CDCl3) δ 167.1 (C=O), 135.8
(C), 131.8 (8ꢀCH), 129.0, 127.9, 127.2 (all C), 122.7 (CH), 119.3 (1ꢀCH), 119.0 (CH), 109.1 (C),
108.4 (4ꢀCH), 52.1 (OCH3), 38.7 (6ꢀCH2), 24.8 (7ꢀCH2), 10.0 (CH3); HRMS (ESI) m/z: (M+H)+
Calcd for C15H16NO2 242.1181; Found 242.1178.
Methyl 10-(pyridine-2-ylthio)-6,7-dihydropyrido[1,2-a]indole-9-carboxylate (3a) (0.183 g, 72%)
yellow oil; Rf 0.45 (Et2O); IR vmax (neat, cmꢀ1) 3052, 2947,2983, 1726 (C=O), 1574, 1559, 1448,
1
1435, 1417, 1341, 1272, 1194, 1170, 1127, 1070; H NMR (400 MHz, CDCl3) δ 8.41ꢀ8.39 (m, 1H,
pyrꢀ6ꢀH), 7.56 (d, J 8.0 Hz, 1H, 1ꢀH), 7.37ꢀ7.28 (m, 3H), 7.15ꢀ7.11 (m, 1H), 6.95ꢀ6.92 (m, 1H, pyrꢀ
5ꢀH), 6.79 (t, J 4.9 Hz, 1H, 8ꢀH), 6.75 (d, J 8.0 Hz, 1H, pyrꢀ3ꢀH), 4.22 (t, J 6.8 Hz, 2H, 6ꢀCH2),
13
3.50 (s, 3H, OCH3), 2.77ꢀ2.72 (m, 2H, 7ꢀCH2); C NMR (100 MHz, CDCl3) δ 167.3, (C=O),
162.6 (pyrꢀ2ꢀC), 149.2 (pyrꢀ6ꢀCH), 136.5 (pyrꢀ4ꢀCH), 135.1 (C), 133.1 (8ꢀCH), 130.0, 128.0 (both
C), 123.9, 121.1 (both CH), 120.2 (X 2 CH), 119.2 (pyrꢀ5ꢀCH), 109.2 (4ꢀCH), 98.3 (C), 52.1
(OCH3), 39.3 (6ꢀCH2), 24.4 (7ꢀCH2); HRMS (ESI) m/z (M+H)+ C19H17N2O2S calcd 337.1011,
Found 337.1003.
Methyl 11-(pyridin-2-ylthio)-7,8-dihydro-6H-azepino[1,2-a]indole-10-carboxylate (3b) (56 mg,
21%) yellow oil; Rf 0.55 (Et2O); IR vmax (neat, cmꢀ1) 2949, 1719 (C=O), 1577, 1559, 1449, 1417,
1
1265, 1126, 1045; H NMR (400 MHz, CDCl3) δ 8.39ꢀ8.37 (m, 1H, pyrꢀ6ꢀH), 7.57 (d, J 8.0 Hz,
1H, 1ꢀH), 7.41 (d, J 8.5 Hz, 1H, 4ꢀH), 7.36 (t, J 7.0 Hz, 1H, 9ꢀH) 7.33ꢀ7.28 (m, 2H), 7.17ꢀ7.12 (m,
1H) 6.92ꢀ6.89 (m, 1H, pyrꢀ5ꢀH), 6.69 (d, J 8.3 Hz, 1H, pyrꢀ3ꢀH), 4.28 (t, J 6.3 Hz, 2H, 6ꢀCH2),
13
3.43 (s, 3H, OCH3), 2.35ꢀ2.29 (m, 2H), 2.28ꢀ2.21 (m, 2H); C NMR (100 MHz, CDCl3) δ 166.4
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(C=O), 162.3 (pyrꢀ2ꢀC), 149.1 (pyrꢀ6ꢀCH), 144.0 (9ꢀCH), 139.3, 136.6 (both C), 136.3 (pyrꢀ4ꢀ
CH), 129.1, 128.4 (both C), 123.1, 120.9 (both CH), 119.9 (X 2 CH), 119.0 (pyrꢀ5ꢀCH), 109.3 (4ꢀ
CH), 99.9 (C), 52.0 (OCH3), 41.9 (6ꢀCH2), 29.7, 25.3 (both CH2); HRMS (ESI) m/z: (M+H)+ Calcd
for C20H19N2O2S 351.1167; Found 351.1180.
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9-(Pyridin-2-ylthio)-2,3-dihydro-1H-pyrrolo[1,2-a]indole (4) (107 mg, 53%) offꢀwhite solid; mp
147ꢀ148 ˚C; Rf 0.68 (Et2O); IR vmax (neat, cmꢀ1) 2953, 1574, 1558, 1449, 1417, 1339, 1298, 1229,
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1125, 1010; H NMR (400 MHz, CDCl3) δ 8.41ꢀ8.39 (m, 1H, pyrꢀ6ꢀH), 7.55 (d, J 8.0 Hz, 1H, 8ꢀ
H), 7.33ꢀ7.28 (m, 2H), 7.22ꢀ7.18 (m, 1H), 7.15ꢀ7.11 (m, 1H), 6.92ꢀ6.89 (m, 1H, pyrꢀ5ꢀH), 6.70 (d,
J 8.3 Hz, 1H, pyrꢀ3ꢀH), 4.19 (t, J 7.1 Hz, 2H, 3ꢀCH2), 3.08 (t, J 7.6 Hz, 2H, 1ꢀCH2) 2.70ꢀ2.62 (m,
2H, 2ꢀCH2); 13C NMR (100 MHz, CDCl3) δ 163.3 (pyrꢀ2ꢀC), 151.0 (C), 149.3 (pyrꢀ6ꢀCH), 136.4
(pyrꢀ4ꢀCH), 134.1, 133.3 (both C), 121.5, 120.4, 119.2, 119.1 (all CH), 118.9 (pyrꢀ5ꢀCH), 109.9 (5ꢀ
CH), 90.3 (C), 44.8 (3ꢀCH2), 27.0 (2ꢀCH2), 24.0 (1ꢀCH2); HRMS (ESI) m/z (M+H)+ C16H15N2S
calcd 267.0956, Found 267.0963.
Methyl 11-formyl-7,8-dihydro-6H-azepino[1,2-a]indole-10-carboxylate (5) (47 mg, 23%) yellow
oil; Rf 0.33 (Et2O); IR vmax (neat, cmꢀ1) 2952, 1720 (C=O), 1653 (C=O), 1575, 1518, 1458, 1438,
1
1393, 1376, 1267, 1246, 1210, 1128, 1072, 1051; H NMR (400 MHz, CDCl3) δ 10.03 (s, 1H,
CHO), 8.34ꢀ8.31 (m, 1H, 1ꢀH), 7.69 (t, J 7.3 Hz, 1H, 9ꢀH), 7.40ꢀ7.30 (m, 3H), 4.24 (t, J 6.4 Hz,
13
2H, 6ꢀCH2), 3.82 (s, 3H, OCH3), 2.33ꢀ2.31 (m, 4H); C NMR (100 MHz, CDCl3) δ 184.8 (CHO),
165.5 (COOMe), 147.0 (9ꢀCH), 142.1, 136.2, 127.8, 125.8 (all C), 123.9, 123.0 (2,3ꢀCH), 121.7 (1ꢀ
CH), 114.9 (C), 109.2 (4ꢀCH), 52.6 (OCH3), 41.5 (6ꢀCH2), 30.4, 24.7 (both CH2); HRMS (ESI)
m/z: (M+H)+ calcd for C16H16NO3 270.1130; Found 270.1136.
2,3-Dihydro-1H-pyrrolo[1,2-a]indole-9-carbaldehyde (6) (72 mg, 51%) offꢀwhite solid; mp 134ꢀ
135 °C (mp24 136 °C).
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9-Phenyl-6,7-dihydropyrido[1,2-a]indole-10-carbaldehyde (7a) (0.127 g, 61%) yellow solid; 123ꢀ
124 °C; Rf 0.65 (Et2O); IR vmax (neat, cmꢀ1) 2978, 1643 (C=O), 1576, 1469, 1456, 1428, 1394,
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1368, 1331, 1300, 1175, 1127, 1067; H NMR (400 MHz, CDCl3) δ 9.20 (s, 1H, CHO), 8.41 (d, J
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7.8 Hz, 1H, 1ꢀH), 7.45ꢀ7.30 (m, 7H), 7.29ꢀ7.26 (m, 1H), 6.33 (t, J 5.0 Hz, 1H, 8ꢀH), 4.22 (t, J 7.1
13
Hz, 2H, 6ꢀCH2), 2.80ꢀ2.74 (m 2H, 7ꢀCH2); C NMR (100 MHz, CDCl3) δ 186.9, (CHO), 142.2,
139.9, 136.2, 134.5 (all C), 129.0 (8ꢀCH, PhꢀCH), 128.6, 128.3 (PhꢀCH), 126.2 (C), 124.4, 123.2,
123.1 (1,2,3ꢀCH), 113.8 (C), 109.0 (4ꢀCH), 39.4 (6ꢀCH2), 24.0 (7ꢀCH2); HRMS (ESI) m/z: (M+H)+
Calcd for C19H16NO 274.1232; Found 274.1229.
1-[2-(Pyridin-2-ylthio)ethyl]-1H-indole-3-carbaldehyde (8a) (30 mg, 14%) pale yellow oil; Rf
0.35 (Et2O); IR vmax(neat, cmꢀ1) 3046, 2809, 1655 (C=O), 1558, 1577, 1531, 1467, 1454, 1415,
1
1400, 1388, 1164, 1151, 1125, 1043; H NMR (400 MHz, CDCl3) δ 9.95 (s, 1H, CHO), 8.43ꢀ8.41
(m, 1H, pyrꢀ6ꢀH), 8.28 (d, J 7.8 Hz, 1H, 4ꢀH), 7.72 (s, 1H, 2ꢀH), 7.56 (d, J 8.3 Hz, 1H, 7ꢀH), 7.48ꢀ
7.43 (m, 1H, pyrꢀ4ꢀH), 7.36ꢀ7.27 (m, 2H, 5,6ꢀH), 7.14 (d, J 8.2 Hz, 1H, pyrꢀ3ꢀH), 7.02ꢀ6.98 (m,
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1H, pyrꢀ5ꢀH), 4.48 (t, J 7.1 Hz, 2H, NCH2), 3.55 (t, J 7.1 Hz, 2H, CH2); C NMR (100 MHz,
CDCl3) δ 184.7 (CHO), 156.9 (pyrꢀ2ꢀC), 149.6 (pyrꢀ6ꢀCH) 139.0 (2ꢀCH), 137.2 (C), 136.3 (pyrꢀ4ꢀ
CH), 125.5 (C), 124.1, (pyrꢀ3ꢀCH), 123.0, 122.7 (5,6ꢀCH) 122.2 (4ꢀCH), 120.1 (pyrꢀ5ꢀCH), 118.3
(C), 110.4 (7ꢀCH), 47.1 (NCH2), 29.3 (CH2); HRMS (ESI) m/z: (M+H)+ Calcd for C16H15N2OS
283.0905; Found 283.0911.
Ethyl 10-cyano-9-phenyl-6,7-dihydropyrido[1,2-a]indole-8-carboxylate (7b) (60 mg, 23%) offꢀ
white solid; mp 119ꢀ120 ˚C; Rf 0.31 (CH2Cl2); IR vmax(neat, cmꢀ1) 2980, 2213 (CN), 1696 (C=O),
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1475, 1426, 1378, 1296, 1247, 1216, 1130, 1110, 1017; H NMR (400 MHz, CDCl3) δ 7.68 (d, J
8.0 Hz, 1H, 1ꢀH), 7.53ꢀ7.43 (m, 3H), 7.40ꢀ7.35 (m, 2H), 7.30ꢀ7.21 (m, 3H), 4.31 (t, J 7.2 Hz, 2H,
6ꢀCH2), 3.98 (q, J 7.2 Hz, 2H, OCH2), 3.11 (t, J 7.2 Hz, 2H, 7ꢀCH2), 0.90 (t, J 7.2 Hz, 3H, CH3);
13C NMR (100 MHz, CDCl3) δ 167.3 (C=O), 140.1, 137.5, 135.9, 135.8, 129.2 (all C), 129.1,
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129.0, 128.5 (PhꢀCH), 126.6 (C), 125.5, 122.5 (2,3ꢀCH), 120.3 (1ꢀCH), 113.6 (CN), 109.9 (4ꢀCH),
88.3 (C), 61.0 (OCH2), 40.0 (6ꢀCH2), 25.7 (7ꢀCH2), 13.6 (CH3); HRMS (ESI) m/z: (M+H)+ Calcd
for C22H19N2O2 343.1447; Found 343.1444.
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1-[2-(Pyridin-2-ylthio)ethyl]-1H-indole-3-carbonitrile (8b) (0.125 g, 59%) yellow oil; Rf 0.28
(CH2Cl2); IR vmax (neat, cmꢀ1) 2927, 2217 (CN), 1578, 1558, 1533, 1467, 1455, 1415, 1392, 1349,
1283, 1250, 1167, 1125, 1015; 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J 5.0 Hz, 1H, pyrꢀ6ꢀH), 7.73
(d, J 8.3 Hz, 1H, pyrꢀ4ꢀH), 7.64 (s, 1H, 2ꢀH), 7.61 (d, J 8.2 Hz, 1H, 4ꢀH), 7.52ꢀ7.46 (m, 1H, 7ꢀH),
7.37ꢀ7.26 (m, 2H, 5,6ꢀH), 7.15 (d, J 7.8 Hz, 1H, pyrꢀ3ꢀH), 7.04ꢀ7.00 (m, 1H, pyrꢀ5ꢀH), 4.50 (t, J
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7.1 Hz, 2H, NCH2), 3.55 (t, J 7.1 Hz, 2H); C NMR (100 MHz, CDCl3) δ 156.8 (pyrꢀ2ꢀC), 149.6
(pyrꢀ6ꢀCH), 136.4 (pyrꢀ4ꢀCH), 135.4 (C), 135.3 (2ꢀCH), 128.0 (C), 124.0 (pyrꢀ3ꢀCH) 122.8, 122.3
(5,6ꢀCH), 120.1 (pyrꢀ5ꢀCH), 120.0 (4ꢀCH), 116.0 (CN), 110.9 (7ꢀCH), 85.9 (C), 47.1 (NCH2),
29.4 (CH2); HRMS (ESI) m/z: (M+H)+ Calcd for C16H14N3S 280.0908; Found 280.0905.
Methyl 10-cyano-9-propyl-6,7-dihydropyrido[1,2-a]indole-8-carboxylate(7c) (11 mg, 5%) pale
yellow solid; mp 120ꢀ122 ˚C; Rf 0.63 (Et2O); IR vmax (neat, cmꢀ1) 2925, 2215 (CN), 1715 (C=O),
1
1596, 1457, 1423, 1292, 1272, 1245, 1213, 1086; H NMR (400 MHz, CDCl3) δ 7.77 (d, J 8.0 Hz,
1H, 1ꢀH), 7.39ꢀ7.33 (m, 2H), 7.29ꢀ7.25 (m, 1H), 4.15 (t, J 7.1 Hz, 2H, 6ꢀCH2), 3.85 (s, 3H, OCH3),
3.18 (t, J 8.0 Hz, 2H), 2.93 (t, J 7.1 Hz, 2H, 7ꢀCH2), 1.76ꢀ1.66 (m, 2H), 1.08 (t, J 7.3 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.5 (C=O), 149.9, 139.9, 135.4, 128.9 (all C), 125.3, 122.6 (2,3ꢀCH),
122.3 (C), 120.1 (1ꢀCH), 116.3 (CN), 109.9 (4ꢀCH), 85.4 (C), 52.1 (OCH3), 39.9 (6ꢀCH2), 31.2
(CH2), 25.6 (7ꢀCH2), 23.8 (CH2), 13.9 (CH3); HRMS (ESI) m/z: (M+H)+ Calcd for C18H19N2O2
295.1447; Found 295.1445.
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ASSOCIATED INFORMATION
Supporting Information
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Xꢀray crystal structures of 7b and 7c (with CIF files) and H NMR and C NMR of all products.
Crystallographic data (excluding structure factors) has been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication CCDCꢀ996100 for (7b) and CCDCꢀ
996099 for (7c). This material is available free of charge via the Internet at http://pubs.acs.org.
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ACKNOWLEDGEMENTS
The authors thank the College of Science, National University of Ireland Galway for a Postgraduate
Scholarship for Robert Coyle.
REFERENCES
1. Stork, G.; Baine, N. H. J. Am. Chem. Soc. 1982, 104, 2321.
2. Ziegler, F. E.; Jeroncic, L. O. J. Org. Chem. 1991, 56, 3479.
3. Caddick, S.; Shering, C. L.; Wadman, S. N. Tetrahedron 2000, 56, 465.
4. Padwa, A.; Rashatasakhon, P.; Ozdemir, A. D.; Willis, J. J. Org. Chem. 2005, 70, 519.
5. Minisci, F.; Fontana, F.; Pianese, G.; Yan, Y. M. J. Org. Chem. 1993, 58, 4207.
6. Bowman, W. R.; Storey, J. M. D. Chem. Soc. Rev. 2007, 36, 1803.
7. Wille, U. Chem. Rev. 2012, 113, 813.
8. (a) Leardini, R.; Nanni, D.; Pedulli, G. F.; Tundo, A.; Zanardi, G. J. Chem. Soc., Perkin Trans.
1 1986, 1591. (b) Back, T. G.; Krishna, M. V. J. Org. Chem. 1988, 53, 2533. (c) Leardini, R.;
Nanni, D.; Tundo, A.; Zanardi, G. Tetrahedron Lett. 1998, 39, 2441. (d) Montevecchi, P. C.;
Navacchia, M. L. J. Org. Chem. 1998, 63, 537. (e) Leardini, R.; Nanni, D.; Zanardi, G. J. Org.
Chem. 2000, 65, 2763.
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9
9. Santi, R.; Bergamini, F.; Citterio, A.; Sebastiano, R.; Nicolini, M. J. Org. Chem. 1992, 57,
4250. (b) Citterio, A.; Sebastiano, R.; Maronati, A.; Santi, R.; Bergamini, F. J. Chem. Soc.,
Chem. Commun. 1994, 1517.
10
11
12
13
14
15
16
17
18
19
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21
22
23
24
25
26
27
28
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41
42
43
44
45
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53
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55
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60
10. Dong, X.; Xu, Y.; Liu, J. J.; Hu, Y.; Xiao, T.; Zhou, L. Chem. –Eur. J. 2013, 19, 16928.
11. Liu, K.; Jia, F.; Xi, H.; Li, Y.; Zheng, X.; Guo, Q.; Shen, B.; Li, Z. Org. Lett. 2013, 15, 2026.
12. (a) Barton, D. H. R.; Crich, D.; Motherwell, W. B. J. Chem. Soc., Chem. Commun. 1983, 939.
(b) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron 1985, 41, 3901.
13. Barton, D. H. R.; Garcia, B.; Togo, H.; Zard, S. Z. Tetrahedron Lett. 1986, 27, 1327.
14. Coyle, R.; Fahey, K.; Aldabbagh, F. Org. Biomol. Chem. 2013, 11, 1672.
15. Fahey, K.; Coyle, R.; McArdle, P.; Aldabbagh, F. Arkivoc 2013, (iii), 401.
16. Garner, P.; Anderson, J. T.; Dey, S.; Youngs, W. J.; Galat, K. J. Org. Chem. 1998, 63, 5732.
17. Rubin, H.; Fischer, H. Helv. Chim. Acta. 1996, 79, 1670.
18. Neilson, G. W.; Symons, M. C. R. J. Chem. Soc., Perkin Trans. 2 1973, 1405.
19. (a) Ito, O.; Omori, R.; Matsuda, M. J. Am. Chem. Soc. 1982, 104, 3934. (b) Korth, H.ꢀG.;
Lusztyk, J.; Ingold, K. U. J. Chem. Soc., Perkin Trans. 2 1990, 1997. (c) Goumans, T. P. M.;
van Alem, K.; Lodder, G. Eur. J. Org. Chem. 2008, 2008, 435.
20. Curran, D. P.; Keller, A. I. J. Am. Chem. Soc. 2006, 128, 13706.
21. Fagan, V.; Bonham, S.; Carty, M. P.; Aldabbagh, F. Org. Biomol. Chem. 2010, 8, 3149.
22. Newcomb, M.; Park, S. U. J. Am. Chem. Soc. 1986, 108, 4132.
23. Guida, W. C.; Mathre, D. J. J. Org. Chem. 1980, 45, 3172.
24. Moody, C. J.; Norton, C. L. J. Chem. Soc., Perkin Trans. 1 1997, 2639.
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