Double Palladium Catalyzed Reductive Cyclizations. Synthesis of 2,2′-, 2,3′-, and 3,3′-Bi-1H-indoles, Indolo[3,2-b]indoles, and Indolo[2,3-b]indoles

Article abstract of DOI:10.1021/acs.joc.6b01987

A palladium catalyzed, carbon monoxide mediated, double reductive cyclization of 1,4-, 1,3-, and 2,3-bis(2-nitroaryl)-1,3-butadienes to afford 2,2′-, 2,3′-, and 3,3′-biindoles, respectively, was developed. In contrast, reductive cyclizations of 1,2-bis(2-nitroaryl)ethenes were nonselective, affording mixtures of monocyclized indoles, indolo[3,2-b]indole, indolo[1,2-c]quinazolin-6(5H)-ones, and 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones. Nonselective product formation was also observed from reductive cyclization of 1,1-bis(2-nitroaryl)ethenes, producing indolo[2,3-b]indoles and indolo[2,3-c]quinolin-6-ones. Carbon monoxide insertion to give the carbonyl containing products was the major or sole reaction path starting from 1,1- or 1,2-bis(2-nitroaryl)ethenes.

Full text of DOI:10.1021/acs.joc.6b01987

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Article
Double palladium catalyzed reductive cyclizations. Synthesis of 2,2’-,
2,3’- and 3,3’-bi-1H-indoles, indolo[3,2-b]-, and indolo[2,3-b]-indoles.
Nurul H Ansari, Christopher A Dacko, Novruz G Akhmedov, and Bjorn C. G. Soderberg
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01987 • Publication Date (Web): 17 Sep 2016
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Double palladium catalyzed reductive cyclizations. Synthesis of 2,2’-, 2,3’- and 3,3’-bi-1H-
indoles, indolo[3,2-b]-, and indolo[2,3-b]-indoles.
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Nurul H. Ansari, Christopher A. Dacko, Novruz G. Akhmedov, and Björn C. G. Söderberg*
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C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia
26506-6045, United States
Abstract A palladium catalyzed, carbon monoxide mediated, double reductive cyclization of 1,4-,
1,3-, and 2,3-bis(2-nitroaryl)-1,3-butadienes to afford 2,2’-, 2,3’- and 3,3’-biindoles, respectively,
was developed. In contrast, reductive cyclizations of 1,2-bis(2-nitroaryl)ethenes were
nonselective affording mixtures of monocyclized indoles, indolo[3,2-b]indole, indolo[1,2-
c]quinazolin-6(5H)-ones, and 5,11-dihydro-6H-indolo[3,2-c]quinolin-6-ones. Nonselective
product formation was also observed from reductive cyclization of 1,1-bis(2-nitroaryl)ethenes
producing indolo[2,3-b]indoles and indolo[2,3-c]quinolin-6-ones. Carbon monoxide insertion to
give the carbonyl containing products was the major or sole reaction path starting from 1,1- or
1,2-bis(2-nitroaryl)ethenes.
Introduction Reductive cyclization of 2-nitrostyrenes and 2-nitrobiphenyls to give indoles and
carbazoles, respectively, can be accomplished using a number of reagents. The more commonly
employed reducing agents are trialkyl phosphites or triphenylphosphine, at elevated
temperatures, reactions originally described by Cadogan1 and Sundberg.2 More recently,
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reductive cyclizations using transition metal catalysts in the presence of carbon monoxide, as the
ultimate reducing agent, have been developed. Palladium complexes are the most commonly
used catalysts for this transformation and this very facile cyclization has been used in total
synthesis of a number of indole alkaloids.3 We envisioned this cyclization as an expedient
methodology for the synthesis of a variety of compounds containing two indole units, either
connected via a single bond or fused together. Five different types of substrates, three bis(2-
nitrophenyl)butadienes and two bis(2-nitrophenyl)ethenes were selected as biindole precursors
(Figure 1). The formation of 2,2’-, 3,3’-, and 2,3’-biindoles from 1,4-, 2,3-, and 1,3-bis(2-
nitroaryl)-1,3-butadienes, respectively, was anticipated via a cyclization onto each of the two
double bonds of the butadiene (A-C, Figure 1). In related reactions, successful reductive
cyclizations of 1,2-bis(2-nitroaryl)ethenes and 1,1-bis(2-nitroaryl)ethenes onto a shared alkene
would furnish indolo[3,2-b]indoles and indolo[2,3-b]indoles (D-E, Figure 1).
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Figure 1. Possible cyclizations (A-E) of bis(2-nitrophenyl)-butadienes and -ethenes
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We report herein short and efficient synthetic sequences to a variety of substituted biindoles
using a double reductive cyclization of 1,4-, 2,3-, and 1,3-bis(2-nitroaryl)-1,3-butadienes as the
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ultimate and key step forming both indole rings. Also discussed below are nonselective reactions
of 1,2-bis(2-nitroaryl)ethenes and 1,1-bis(2-nitroaryl)ethenes leading to mixtures of products.
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Result and Discussion The first type of cyclization studied was the reaction of 1,4-bis(2-
nitroaryl)buta-1,3-dienes (cyclization A in Figure 1). The parent compound, 1,4-bis(2-
nitrophenyl)-1,3-butadiene (6), was prepared following the procedure of Lowinger et al4 via a
Wittig reaction of 2-nitrocinnamaldehyde (4) with 2-nitrobenzyl triphenylphosphonium
bromide (45) in the presence of a base (Table 1). To our delight, subjecting compound 6 to a
palladium catalyzed reductive cyclization using a bis(dibenzylideneacetone)palladium - 1,3-
bis(diphenyl)propane - 1,10-phenanthroline catalyst system, in the presence of carbon
monoxide (pCO=6 atm, 120 oC ) in N,N-dimethylformamide, afforded 2-(1H-indol-2-yl)-1H-indole
(11)5 in good isolated yield (Table 1).
2,2’-Indoles not also connected in the 3,3’-position have not to date been isolated from natural
sources. However, a number of synthetic pathways to these biindoles have been reported in the
literature. For example, the parent compound 2,2’-bi-1H-indole (11) has been prepared by
iridium,6 gold,7 and base8 catalyzed cyclization of the diamine corresponding to 6, Cadogan-
Sundberg type cyclizations of 6 using triphenylphosphine,9 or triethylphosphite,10 and a double
Madelung cyclization.11 Pertinent to the current methodology, Cenini et al reported a Pd(TMB)2-
TMphenantroline12 catalyzed carbon monoxide (pCO=40 atm, 140 oC) mediated cyclization of 6
to give 11 (40%) in addition to the monocyclized product 2-(2-nitrophenyl)indole (26%).13 A
related transformation has also been described by Davies et al using a palladium catalyst but
without experimental details or yields.14
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Four additional cyclization substrates (7-10, Table 1) were synthesized by treatment of Wittig
salts 1–3, prepared in 55-75% yield from the corresponding benzyl bromides, with 2-
nitrocinammaldehyde (4) or 5-bromo-2-nitrocinnamaldehyde (5) in the presence of a base. 5-
Bromo-2-nitrocinnamaldehyde (5) was obtained by reaction of 5-bromo-2-nitrobenzaldehyde
with (formylmethyl)triphenylphosphonium chloride in the presence of 4-(N,N-
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dimethylamino)pyridine (DMAP, Scheme 1). A fair amount of dienal 16, derived from two
consecutive Wittig reactions, was also isolated in addition to 5. The dienes (7-10) were smoothly
transformed into the corresponding 2,2’-bi-1H-indoles 12-15 under the same conditions used
for 6 (Table 1). A good to excellent yield of product was observed for all substrates examined.
Table 1. Synthesis of 2,2’-bi-1H-indoles from 1,4-bis(2-nitrophenyl)-1,3-butadienes.
Phosphane
Aldehyde
Dienea,b
2,2’-Bi-1H-indolea
6 (R=R’=H)
11 (R=R’=H, 73%)
1 (R=6-Cl)
2 (R=3-OMe)
3 (R=4-Br)
3 (R=4-Br)
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7 (R=6-Cl, R’=H, 55%)
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9 (R=4-Br, R’=H, 73%)
10 (R=4-Br, R’=5-Br, 75%)
12 (R=6-Cl, R’=H, 94%)
13 (R=7-OMe, R’=H, 93%)
14 (R=6-Br, R’=H, 74%)
15 (R=6-Br, R’=5-Br, 71%)
4 (R=H)
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5 (R’=5-Br)
a) Isolated yield of pure product after chromatography. b) Mixtures of EE/EZ isomers were obtained for 8-10.
Scheme 1. Synthesis of 5-bromo-2-nitrocinnamaldehyde (5).
5 (51%)
16 (21%)
Encouraged by the results shown in Table 1, double cyclizations of 2,3-bis(2-nitrophenyl)-1,3-
butadienes to give 3,3’-biindoles (cyclization B, Figure 1) were examined next and the results are
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summarized in Table 2. The parent cyclization precursor 2,3-bis(2-nitrophenyl)-1,3-butadiene
(27) has previously been prepared using a palladium catalyzed double cross coupling of 2-
nitrophenylboronic acid with 1,4-bis(methoxycarbonyloxy)-2-butyne.15 We have recently
reported the formation of 28 (Table 2), a substituted analog of 27, as side product in a Kosugi-
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Migita-Stille reaction of 23 with an aryl bromide.16 It seemed plausible that homocoupling of 23,
and related alkenyltin reagents, would be the major reaction path in the absence of a cross
coupling partner. In order to examine this idea, tributyl(1-(2-nitrophenyl)ethenyl)tin (22) was
prepared from 1-ethynyl-2-nitrobenzene (17) in excellent isolated yield using the regioselective
palladium catalyzed hydrostannation developed by Alami and co-workers.17 As expected, the β-
isomer was not detected by 1H NMR of the crude reaction mixture. To our delight, palladium
catalyzed homocoupling of 22 proceeded smoothly in DMF to give homocoupling product 27.
With the cyclization precursor in hand, exposure of 27 to the reductive cyclization protocol
resulted in the formation of 3,3’-biindole 3218 as the sole product (Table 2).
3,3’-Biindoles are relatively rare in nature but a few examples of halogenated and/or sulfur
containing alkaloids of this type have been isolated from algea.19,20,21,22 In addition, the
unsubstituted 3,3’-biindole 32 (Table 2) was isolated from a terrestrial fungus.23 Recent
synthesis of 3,3’-biindoles include, for example, a Masuda indole borylation – Suzuki arylation
sequence,24 a tellurium tetrachloride mediated25 and a palladium catalyzed oxidative
dimerizations of indoles.26
To briefly examine the scope of the double cyclization, four additional 1-(2-
nitrophenyl)ethenyl)tin derivatives (23-26) were prepared in a similar fashion to 22. Palladium
catalyzed homocoupling of 23 gave the expected product 28 in good yield. However, the yield of
the chloro-substiuted dimer 29 was low using this type of reaction and a different methodology
was pursued. Homocoupling of organotin reagents have been reported using an excess CuCl in
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DMF,27 an excess of CuNO3 in THF,28 or a catalytic amount of CuCl2 in the presence of 0.5
equivalents of iodine in DMF.29 In our hands, treatment of tin derivatives 24-26 with 2.5
equivalents of CuCl in DMF at ambient temperature furnished 1,3-butadienes 29-31 in excellent
yields (Table 2). Double reductive cyclizations of 28-31 gave the expected 3,3’-biindoles 33-36
in 64-100% isolated yield.
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Table 2. Synthesis of 3,3’-biindoles from 2,3-bis(2-nitrophenyl)-1,3-butadienes.
Alkyne
Vinyltina
Dienea
3,3’-bi-1(H)indolea
17 (R=H)
22 (95%)
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18 (R=5-OBn)
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23 (96%)
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25 (78%)
26 (90%)
28 (78%)b
33 (R=5,5’-diOBn, 87%)
34 (R=6,6’-diCl, 100%)
35 (R=6,6’-diCO2Me, 100%)
36 (R=6,6’-diOMe, 64%)
29 (36%,b 80%c)
30 (92%c)
20 (R=4-CO2Me)
21 (R=4-OMe)
31 (98%c)
a) Isolated yield of pure products after chromatography. b) PdCl2(PPh3)2 was used. c) CuCl was used.
An example of a synthesis of a 3,3’-diazaindole was pursued using the hydrostannation,
dimerization, cyclization sequence discussed above. Thus, 4,4’-diaza-3,3’-bi-1H-indole (40) was
prepared in three steps from the previously reported 2-ethynyl-3-nitropyridine (37) (Scheme 2).
Scheme 2. Synthesis of 4,4’-diaza-3,3’-bi-1H-indole (40).
37
38 (61%)
39 (54%)
40(74%)
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An unsymmetric 2,3-bis(2-nitrophenyl)-1,3-butadiene was also prepared (Scheme 3). Treatment
of 41 with HBr in 3-pentanone as the solvent furnished vinyl bromide 42.30 Kosugi-Migita-Stille
cross coupling of 42 with ethenyltin 22 gave 1,3-butadiene 43. Tin impurities from the cross
coupling were removed by chromatography using a 9:1 SiO2/K2CO3 stationary phase as
described by Harrowven et al.31 Double cyclization smoothly transformed 43 to the expected
3,3’-biindole 44 in quantitative yield.32
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Scheme 3 Synthesis of the unsymmetrically substituted 3,3’-bi-1H-indole 44.
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44 (100%)
The third permutation of the double cyclization of substituted 1,3-butadienes is the synthesis of
2,3’-bi-1H-indoles from 1,3-bis(2-nitrophenyl)-1,3-butadienes (cyclization C, Figure 1). 2,3’-Bi-
1H-indoles have previously been prepared, for example, via the Fischer indole synthesis,33 acid
mediated reaction of 3-bromoindole with indole,34 and Lewis acid mediated dimerization to give
2,3-dihydro-2,3’-bisindole followed by oxidation.35 To date, only four natural products
containing a 2,3’-bisindole have been isolated.36 All four compounds are connected by an
ethylene bridge between the 2 and 3’ carbons of the respective indoles.
The parent cyclization precursor 48 was prepared in moderate yield by a Wittig reaction of 45
with 2-(2-nitrophenyl)-2-propenal (47, Table 3).37 Three additional 1,3-bis(2-nitrophenyl)-1,3-
butadienes (49-51) were prepared in a similar fashion by reaction of Wittig salts 2, 3, and 46
with 47 under basic conditions. Low to moderate yields of products were isolated. Treatment of
48-51 with carbon monoxide, under the palladium catalyzed conditions described above, gave
the anticipated 2,3’-bi-1H-indoles (52-55) in 61-72% yield.
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Table 3. Synthesis of 2,3’-bi-1H-indoles from 1,3-bis(2-nitrophenyl)-1,3-butadienes.
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Phosphane
45 (R=H)
Dienea
2,3’-bi-1(H)indolea
52 (R=H, 61%)
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49 (R=3-OMe, 38%)
50(R=4-Br, 21%)
51 (R=5-Br, 22%)
53 (R=7-OMe, 72%)
54 (R=6-Br, 66%)
55 (R=5-Br, 67%)
a) Isolated yield of pure products after chromatography.
The fourth variation of a double cyclization (cyclization D in Figure 1) is the cyclization of two
adjacent 2-nitroaryl groups onto a single alkene with the anticipated formation of an indolo[3,2-
b]indole. In the event, subjecting the known parent compound 1,2-bis(2-nitrophenyl)ethene
(56)38 to the palladium catalyzed reductive cyclization conditions for 56 h did not furnish the
double cyclization product indolo[3,2-b]indole (57)39 but gave two isomeric tetracyclic
compounds, indolo[1,2-c]quinazolin-6(5H)-one (58) and 5,11-dihydro-6H-indolo[3,2-c]quinolin-
6-one (59) (Scheme 4). The products were identified by 2D NMR experiments and by
comparison of analytical data with reported values. It should be noted that Nishiyama et al has
reported a reductive cyclization, related to the transition metal catalyzed reactions. For example,
treatment of 56 with a catalytic amount of selenium (40 mol-%) under 30 atmospheres of
carbon monoxide at 100 oC gave 58 in 60% yield (Scheme 4).40
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Scheme 4. Reductive cyclization of 1,2-bis(2-nitrophenyl)ethene (56).
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57 (not observed)
58 (76%)
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Carbon monoxide insertion to form an isocyanate (60) was suggested as a possible intermediate
in the selenium catalyzed transformation followed by reaction with the indole N-H (Scheme 4).
Isocyanate 60 has previously been reported as an intermediate in a Curtius rearrangement of the
corresponding acid affording a 1:1 mixture of 58 and 59.41 Compound 59 was not observed in
the selenium-catalyzed reactions. Products derived from insertion of carbon monoxide have
been isolated in a few additional cases from transition metal catalyzed reductive cyclizations of
nitro aromatic compounds.42 For example, rhodium catalyzed reductive cyclization of 61
afforded in addition to indole 62 as the major product, quinolinone 63 and amine 64 (Scheme
5).43
Scheme 5
61
62 (35%)
63 (17%)
64 (5%)
In order to evaluate the palladium catalyzed double reductive cyclization of 1,2-bis(2-
nitrophenyl)alkenes as a general methodology toward indolo[1,2-c]quinazolin-6(5H)-ones, two
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additional substrates 65 and 68 were prepared by Wittig reactions of 1 and 2 with 2-
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nitrobenzaldehyde (Schemes 6-7). Upon reductive cyclization of the chloro-substituted
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compound 65, both an indolo[1,2-c]quinazolin-6(5H)-one (66) and an indolo[3,2-b]indole (67)
were isolated (Scheme 6). The latter compound represents the first case of the formation of an
indolo[3,2-b]indole from a transition metal catalyzed reductive cyclization although, the yield
was very low. In contrast to 65, the methoxy-substituted substrate 68 did not participate in a
double cyclization as readily as 56 and 65. In the event, two mono-cyclized products 69 and 70
were isolated in 10% and 74%, respectively, together with a minor amount of the indolo[3,2-
c]quinolin-6-one 71 (Scheme 7). Indole 70 was presumed to be the immediate precursor to the
tetracyclic compound 71 however, only a miniscule amount of 71 (2%) was isolated from an
attempted cyclization of 70 under identical reaction conditions. Although all of the starting
material was consumed in the reaction, no other product could be identified.
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Scheme 6. Synthesis and reductive cyclization of 65.
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Scheme 7. Synthesis and reductive cyclization of 68.
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70 (74%)
71 (6%)
Finally, a synthesis of indolo[2,3-b]indoles was envisioned starting from 1,1-bis(2-
nitrophenyl)ethenes (cyclization E in Figure 1). Kosugi-Migita-Stille cross coupling of 1-iodo-2-
nitrobenzene with 22 afforded cyclization precursor 72 in good yield.44 As observed in previous
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palladium catalyzed reactions involving stannane 22, dimer 27 was also isolated as a minor
product in 11% yield. Palladium catalyzed reductive cyclization of 72 gave the anticipated
indolo[2,3-b]indole (73) although, in a very low isolated yield together with indolo[2,3-
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c]quinolinone 74 as the major product (Scheme 8). Formation of the latter compound is perhaps
not so surprising in light of the results discussed above using 1,2-bis(2-nitrophenyl)ethenes. It
should be noted that a Cadogan-Sundberg type cyclizations of 3-(2-nitrophenyl)indoles using
PPh345 or P(OEt)346 to afford indolo[3,2-b]indoles have been reported.
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Scheme 8 Formation of indolo[2,3-b]indole (73) and indolo[2,3-c]quinolinone (74).
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72 (62%)
73 (14%)
74(58%)
The reaction sequence seen in Scheme 8 represents a very short route to indolo[2,3-c]quinolin-
6-ones starting from a symmetrical substrate like 72. A number of methodologies have been
developed for the construction of the indoloquinolin-6-one skeleton. This includes cyclizations of
N-arylindole-2-carboxamides utilizing a Heck reaction,47 photochemical cyclizations of indole-2-
carboxylic acid arylamides48 and 3-(2-azidophenyl)-N-phenylacrylamides,49 oxidative
cyclizations of 3-arylindole-2-carboxamides,50 and a platinum catalyzed reduction of ethyl 3-(2-
nitrophenyl)-1H-indole-2-carboxylates.51
The unsymmetrically substituted substrate 76 containing a methoxy group meta to one of the
nitro groups and a benzyloxy group para to the second nitro group was also prepared via a
Kosugi-Migita-Stille reaction of 23 with 2-nitro-4-methoxy-1-iodobenzene (75, Scheme 9).
Compound 76 was subjected to the cyclization conditions and three different products were
obtained after chromatography, an indolo[2,3-b]indole 77 and two isomeric indolo[2,3-
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c]quinolin-6-ones 78 and 79 in an approximately 1:1:1 ratio. The structures of the isomeric
tetracycles 78-79 were elucidated using 2D NMR experiments. Apparently, there is little
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preference for the initial (presumed) cyclization to form the indole skeleton prior to the second
cyclization.
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While the use of unsymmetrical cyclization precursor probably will furnish two isomeric
indolo[2,3-c]quinolin-6-ones, the present methodology may be of synthetic value employing
symmetrical starting materials.
Scheme 9 Formation of indolo[2,3-b]indole 77 and indolo[2,3-c]quinolinones 78-79.
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76 (69%)
77 (30%)
78 (38%)
79 (31%)
Summary Short synthetic routes to 2,2’-, 2,3’-, 3,3’-bi-indoles have been developed clearly
demonstrating the palladium catalyzed reductive cyclization as a potentially useful methodology
toward these ring systems. Based on the results shown in Schemes 4,6-9 and from the selenium
catalyzed reactions reported in the literature, it appears that general syntheses of indolo[3,2-
b]indoles indolo[2,3-b]indoles via a palladium catalyzed carbon monoxide mediated double
reductive cyclization of 1,2-bis(2-nitrophenyl)ethenes or 1,1-bis(2-nitrophenyl)ethenes,
respectively are not feasible. Mono-cyclized products and products derived from carbon
monoxide insertion are the major products seen in these reactions.
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Experimental Section
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General Procedures. All NMR spectra were recorded in CDCl3 at 600 MHz (1H NMR) and 150
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MHz (13C NMR, 1H-broadband decoupled) at ambient temperature unless otherwise stated. The
chemical shifts are expressed in δ values relative to Me4Si (0.0 ppm, 1H and 13C) or CDCl3 (77.0
ppm, 13C) internal standards. HRMS data were obtained via ESI with an ion trap mass analyzer in
positive ion mode unless otherwise stated.
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THF was purified/dried via two consecutive columns composed of activated alumina and Q5
catalyst on a Glass Contours solvent purification system. Dichloromethane and toluene was
purified/dried via two consecutive columns composed of activated alumina on a Glass Contours
solvent purification system.
Chemicals prepared according to literature procedures have been footnoted first time used; all
other reagents were obtained from commercial sources and used as received. All reactions were
performed under a nitrogen atmosphere in oven-dried glassware unless otherwise stated.
Solvents were removed from reaction mixtures and products on a rotary evaporator at water
aspirator pressure unless otherwise stated.
[(6-Chloro-2-nitrophenyl)methyl]triphenylphosphonium bromide (1). To a solution of 2-
chloro-6-nitrobenzylbromide (3.03 g, 12.1 mmol) in toluene (36 mL) was added, in portions,
triphenylphosphine (PPh3, 3.49 g, 13.3 mmol). The resulting solution was stirred under a
nitrogen atmosphere, at 100 oC, for 12 h. A precipitate started to form after 15 min. The mixture
was cooled to ambient temperature, the precipitate was removed by filtration, the solid was
washed with Et2O and the solvents were removed to afford 1 (6.21 g, 12.1 mmol, 100%) as a
white solid. mp=235-243 oC; 1H NMR (600 MHz, DMSO-d6) δ 7.96 (d, J=8.4 Hz, 1H), 7.89-7.85 (m,
4H), 7.73-7.66 (m, 12H), 7.63 (td, J=7.8, 1.8 Hz, 1H), 5.34 (d, J=14.4 Hz, 2H); 13C NMR (150 MHz,
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DMSO-d6) δ 149.7 (d, JCP=4.5 Hz), 136.4 (d, JCP=6.0 Hz), 135.4 (d, JCP=3.0 Hz), 135.1 (d, JCP=3.0 Hz),
133.8 (d, JCP=10.5 Hz), 131.3 (d, JCP=3.0 Hz), 130.0 (d, JCP=13.5 Hz), 124.9 (d, JCP=3.0 Hz), 123.5 (d,
JCP=9.0 Hz), 117.9 (d, JCP=85.5 Hz), 25.9 (d, JCP=51.0 Hz); IR (ATR) 1533, 1434, 1355, 1107, 748
cm-1; HRMS (ESI, negative ion mode) calcd for C25H20BrClNO2P (M-) 511.0104, found 511.0133.
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[(3-Methoxy-2-nitrophenyl)methyl] triphenylphosphonium bromide (2). Treatment of 3-
methoxy-2-nitrobenzylbromide (1.48 g, 6.05 mmol) with PPh3 (1.74 g, 6.64 mmol) in toluene (15
mL) as described for 1 (100 oC, 12 h), gave after work up 2 (2.67 g, 5.26 mmol, 87%) as white
solid. mp=213-215 oC; 1H NMR (600 MHz, DMSO-d6) δ 7.92 (t, J=7.8 Hz, 3H), 7.74 (dt, J=7.8, 3.6
Hz, 6H), 7.63 (dd, J=8.4, 7.2 Hz, 6H), 7.42 (t, J=8.4 Hz, 1H), 7.35 (d, J=9.0 Hz, 1H), 6.66 (dd, J=8.4,
2.4 Hz, 1H), 5.10 (d, J=15.0 Hz, 2H), 3.84 (s, 3H); 13C NMR (150 MHz, DMSO-d6) δ 151.4 (d, JCP=2.2
Hz), 140.9(d, JCP=6.9 Hz), 135.3 (d, JCP=3.4 Hz), 133.9 (d, JCP=10.2 Hz), 132.1 (d, JCP=3.4 Hz), 130.2
(d, JCP=12.6 Hz), 123.1 (d, JCP=4.6 Hz), 121.8 (d, JCP=7.9 Hz), 117.1 (d, JCP=84.6 Hz), 114.3 (d,
JCP=2.2 Hz), 57.0, 25.3 (d, JCP=49.2 Hz); IR (ATR) 1536, 1433, 1281, 1108, 685 cm-1; HRMS (ESI,
negative ion mode) calcd for C26H23BrNO3P (M-) 507.0599, found 507.0628.
[(4-Bromo-2-nitrophenyl)methyl] triphenylphosphonium bromide (3). Treatment of 4-
bromo-2-nitrobenzylbromide (208 mg, 0.705 mmol) with PPh3 (203 mg, 0.774 mmol) in toluene
(8 mL) as described for 1 (100 oC, 8 h), gave after work up 3 (393 mg, 0.705 mmol, 100%) as a
white solid. mp=242-244 oC; 1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J=2.0 Hz, 1H), 7.97-7.90 (m,
3H), 7.92(d, J=1.6 Hz, 1H), 7.77-7.72 (m, 6H), 7.66-7.61 (m, 6H), 7.31 (dd, J=8.0, 2.4 Hz, 1H), 5.42
(d, J=15.2 Hz, 2H); 13C NMR (150 MHz, DMSO-d6) δ 148.8 (d, JCP=6.1 Hz), 137.3 (d, JCP=3.0 Hz),
135.3 (d, JCP=3.0 Hz), 133.9 (d, JCP=10.6 Hz), 130.3 (d, JCP=12.1 Hz), 128.4 (d, JCP=2.3 Hz), 123.1 (d,
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JCP=8.4 Hz), 122.6 (d, JCP=4.5 Hz), 117.4, 116.6, 26.4 (d, JCP=49.3 Hz); IR (ATR) 1521, 1367, 1346,
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1284, 1066, 852 cm-1; HRMS (ESI) calcd for C25H20Br2NO2P (M-Br) 476.0415, found 476.0416.
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3-(5-Bromo-2-nitrophenyl)-2-propenal (5) and E,E-5-(5-Bromo-2-nitrophenyl)-2,4-
pentadienal (16). A mixture of 5-bromo-2-nitrobenzaldehyde (600 mg, 2.61 mmol),
(formylmethyl)triphenylphosphonium chloride (1.78 mg, 5.22 mmol) and DMAP (956 mg, 7.82
mmol) in CHCl3 (36 mL) was stirred at ambient temperature for 4 h followed by heating at reflux
for 3 h. After cooling to ambient temperature, the solvent was removed under reduced pressure
and the resulting crude product was purified by chromatography (hexane/EtOAc, 95:5) to afford,
in order of elution, 5 (337 mg, 1.32 mmol, 51%) and 16 (153 mg, 0.542 mmol, 21%) both as pale
yellow solids. Analytical data for 5: mp=135-137 °C; 1H NMR (600 MHz, CDCl3) δ 9.78 (d, J=7.2
Hz, 1H), 8.01 (d, J=3.0 Hz, 1H), 7.99 (d, J=9.6 Hz, 1H), 7.80 (d, J=1.8 Hz, 1H), 7.73 (dd, J=9.0, 1.8
Hz, 1H), 6.61 (dd, J=15.5, 7.8 Hz, 1H); 13C NMR (150 MHz, CDCl3) δ 192.5, 146.5, 145.7, 133.9,
133.4, 132.0, 131.9, 128.8, 126.7; IR (ATR) 1675, 1521, 1345, 1098, 834 cm-1; HRMS (ESI,
negative ion mode) calcd for C9H6BrNO3 (M-) 254.9531, found 254.9530.
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Analytical data for 16: mp=127-129 °C; 1H NMR (600 MHz, CDCl3) δ 9.68 (d, J=7.8 Hz, 1H), 7.92
(d, J=8.4 Hz, 1H), 7.84 (d, J=2.4 Hz, 1H), 7.62 (dd, J=9.0, 2.4 Hz, 1H), 7.50 (d, J=15.6 Hz, 1H), 7.30
(dd, J=15.6, 10.8 Hz, 1H), 6.96 (dd, J=15.6, 11.4 Hz, 1H), 6.36 (dd, J=15.6, 7.8 Hz, 1H); 13C NMR
(150 MHz, CDCl3) δ 193.2, 149.8, 146.6, 135.0, 134.1, 133.1, 132.5, 131.8, 131.4, 128.4, 126.6; IR
(ATR) 3417, 1676, 1512, 1345, 1334, 1117, 983 cm-1; HRMS (ESI, negative ion mode) calcd for
C11H8BrNO3 (M-) 280.9688, found 280.9709.
E,E-1-(2-Chloro-6-nitrophenyl)-4-(2-nitrophenyl)-1,3-butadiene (7). A solution of freshly
prepared sodium ethoxide (NaOEt, 1.5 M in EtOH, 6 mL, 9.0 mmol) was added drop wise to a
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solution of 4 (389 mg, 2.20 mmol) and 1 (1.13 g, 2.20 mmol) in absolute EtOH (9 mL) at ambient
temperature. The reaction mixture turned dark purple slowly changing to red. After 36 h at
ambient temperature, water (30 mL) was added, and the mixture was extracted with EtOAc (3 x
15 mL). The combined organic phases were dried (MgSO4), filtered, and the solvents were
removed under reduced pressure. The residue was purified by chromatography (hexane/EtOAc,
9:1, then 8:2) to give 7 (399 mg, 1.21 mmol, 55%) as an orange solid. mp=153-155 oC; 1H NMR
(400 MHz, CDCl3) δ 7.92 (dd, J=8.0, 0.8 Hz, 1H), 7.90 (dd, J=8.4, 1.2 Hz, 1H), 7.82 (dd, J=8.4, 1.2 Hz,
1H), 7.73-7.63 (m, 3H), 7.60 (td, J=7.2, 0.4 Hz, 1H), 7.51 (td, J=8.0, 0.8 Hz, 1H), 7.46-7.32 (m, 6H),
7.19 (d, J=15.2 Hz, 1H), 7.17 (d, J=15.2 Hz, 1H), 6.93 (dd, J=13.4, 10.0 Hz, 1H), 6.83 (d, J=15.6 Hz,
1H), 6.73-6.59 (m, 3H), 6.40 (dd, J=15.2, 10.0 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 150.7,
150.3, 147.9, 147.8, 136.6, 135.7, 135.1, 133.7, 133.6, 133.2, 133.0, 133.0, 132.9, 132.2, 132.0,
130.8, 130.2, 130.2, 129.7, 128.9, 128.4, 128.4, 128.3, 128.3, 127.9, 127.7, 125.8, 124.7, 124.6,
124.3, 122.5, 122.4; IR (ATR) 1515, 1343, 986, 751, 725 cm-1; HRMS (ESI) calcd for C16H12ClN2O4
(M+H+) 331.0486, found 331.0480.
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EE/ZE-1-(3-Methoxy-2-nitrophenyl)-4-(2-nitrophenyl)-1,3-butadiene (8). Treatment of a
solution of 4 (300 mg, 1.69 mmol) and 2 (861 mg, 1.69 mmol) in EtOH (18 mL) with NaOEt (1.7
M, 11 mL, 18.7 mmol), as described for 7 (24 h), gave after work up and chromatography
(hexane/EtOAc, 8:2, then 7:3) 8 (354 mg, 1.08 mmol, 64%, EE/ZE=1:1) as an orange solid.
mp=130-135 oC; 1H NMR (600 MHz, DMSO-d6) δ 7.97-7.95 (m, 3H), 7.76 (dd, J=7.9, 1.4 Hz, 1H),
7.71 (dd, J=7.8, 1.3 Hz, 1H), 7.68 (dd, J=7.9, 1.3 Hz, 1H), 7.59 (t, J=8.3 Hz, 1H), 7.56-7.51 (m, 4H),
7.41-7.30 (m, 3H), 7.25 (dd, J=8.3, 0.8 Hz, 1H), 7.17 (d, J=15.2 Hz, 1H), 7.16 (d, J=7.9 Hz, 1H), 7.13
(d, J=15.2 Hz, 1H), 7.03 (dd, J=15.2, 11.5 Hz, 1H), 6.73 (t, J=11.4 Hz, 1H), 6.59 (d, J=15.5 Hz, 1H),
6.45 (d, J=11.3 Hz, 1H), 3.92 (s, 3H), 3.90 (s, 3H); 13C NMR (150 MHz, CDCl3, major and minor) δ
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150.3, 150.2, 147.9, 147.8, 139.9, 139.7, 134.4, 133.9, 133.6, 133.5, 133.2, 131.6, 131.3, 130.9,
130.9, 130.8, 129.3, 129.1, 129.1, 128.9, 128.7, 128.3, 128.2, 127.7, 125.5, 124.4, 124.4, 124.1,
121.9, 117.4, 112.8, 112.5, 56.7, 56.7; IR (ATR) 1519, 1369, 1343, 1285, 1063 cm-1; HRMS (ESI)
calcd for C17H15N2O5 (M+H+) 327.0981, found 327.0976.
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EE/EZ-1-(4-Bromo-2-nitrophenyl)-4-(2-nitrophenyl)-1,3-butadiene (9). Treatment of a
solution of 4 (51 mg, 0.29 mmol) and 3 (155 mg, 0.278 mmol) in EtOH (7 mL) with NaOEt (1.7 M,
7 mL, 11.9 mmol), as described for 7 (36 h), gave after work up and chromatography
(hexane/EtOAc, 9:1) 9 (78.4 mg, 0.209 mmol, 73%, EE/EZ=1:2) as an orange solid. NMR data
from the EE/EZ=1:2 mixture of 9: mp=141-142 oC; 1H NMR (600 MHz, DMSO-d6) δ 8.32 (d, J=2.1
Hz, 1H), 8.19 (d, J=2.1 Hz, 0.5H), 7.99-7.94 (m, 3H), 7.91 (dd, J=8.6, 2.0 Hz, 0.5H), 7.78 (dd, J=8.0,
1.3 Hz, 1H), 7.72 (t, J=6.7 Hz, 0.5H), 7.65 (dd, J=7.4, 0.7 Hz, 1H), 7.54-7.50 (m, 3H), 7.38 (dd,
J=15.1, 10.5 Hz, 0.5H), 7.31 (dd, J=14.9, 10.6 Hz, 0.5H), 7.17-7.14 (m, 1.5H), 7.05-6.98 (m, 1.5H),
6.79 (d, J=11.4 Hz, 1H), 7.73 (t, J=11.2 Hz, 1H); 13C NMR (150 MHz, DMSO-d6) δ 148.3, 148.2,
147.9, 147.8, 136.3, 135.8, 134.6, 134.0, 133.7, 133.3, 133.2, 131.8, 130.9, 130.7, 130.4, 130.2,
129.3, 129.0, 128.9, 128.9, 128.5, 128.2, 128.2, 127.7, 127.2, 127.1, 126.9, 122.4, 124.3, 120.7,
120.6;52 IR (ATR) 3027, 1520, 1347, 1217, 748 cm-1; HRMS (ESI) calcd for C16H12BrN2O4 (M+H+)
374.9980, found 374.9975.
EZ/EE-1-(4-Bromo-2-nitro-nitrophenyl)-4-(5-bromo-2-nitrophenyl)-1,3-butadiene (10).
Treatment of a solution of 5 (320 mg, 1.25 mmol) with 3 (696 mg, 1.25 mmol) with NaOEt (2.0 M
in EtOH, 2.81 mL, 5.62 mmol) in EtOH (16 mL), as described for 7 (24 h) gave after work up and
chromatography (hexane/EtOAc, 9:1) 10 (424 mg, 0.934 mmol, 75%, EZ/EE=7:1) as an orange
solid. mp=159-162 °C; 1H NMR data from the EZ/EE=7:1 mixture of 10, major isomer: 1H NMR
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(600 MHz, CDCl3) δ 8.29 (d, J=1.8 Hz, 1H), 7.83 (d, J=8.6 Hz, 1H), 7.78 (dd, J=8.3, 1.8 Hz, 1H), 7.60
(d, J=2.0 Hz, 1H), 7.51 (dd, J=8.8, 1.9 Hz, 1H), 7.35 (d, J=8.1 Hz, 1H), 7.22 (d, J=15.3 Hz, 1H), 6.90
(d, J=11.2 Hz, 1H), 6.78 (dd, J=15.2, 11.2 Hz, 1H), 6.64 (t, J=11.4 Hz, 1H); partial 1H NMR data for
minor isomer: 1H NMR (600 MHz, CDCl3) δ 8.11 (d, J=1.6 Hz, 1H), 7.87 (d, J=2.5 Hz, 1H), 7.73 (dd,
J=9.1, 1.8 Hz, 1H), 7.62 (d, J=8.3 Hz. 1H), 7.54 (dd, J=8.6, 1.7 Hz, 1H), 7.02-6.96 (m, 2H); 13C NMR
(150 MHz, DMSO-d6) δ 148.1, 148.0, 146.4, 146.3, 136.3, 136.2, 134.4, 134.2, 134.0, 133.7, 133.6,
131.5, 131.4, 131.0, 130.9, 130.8, 130.0, 129.5, 129.3, 129.2, 128.8, 128.6, 128.1, 128.1, 128.0,
127.8, 126.5, 126.4, 126.4, 126.3, 121.9, 121.7; IR (ATR) 3381, 1589, 1517, 1335, 748 cm-1; HRMS
(ESI, negative ion mode) calcd for C16H10Br2N2O4 (M-) 451.9007, found 451.9018.
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2,2’-Bi-1H-indole (11). 1,4-Di(2-nitrophenyl)-1,3-butadiene (6)53 (51 mg, 0.17 mmol), Pd(dba)2
(6 mg, 0.01 mmol), dppp (4 mg, 0.01 mmol) and phen (5 mg, 0.02 mmol) were dissolved in
anhydrous DMF (1 mL) in a threaded ACE glass pressure tube. The tube was fitted with a
pressure head, and the solution was saturated with carbon monoxide (four cycles of 6 atm of
CO). The reaction mixture was heated at 120 oC under CO (6 atm) until all starting material was
consumed (60 h), as judged by TLC (hexanes/EtOAc, 9:1). Brine (10 mL) was added and the red-
brown solution was extracted with EtOAc (3x20 mL). The combined organic phases were dried
(MgSO4), filtered, and the solvent was removed under reduced pressure. The resulting crude
product was purified by chromatography (hexane/EtOAc, 19:1) to afford 11 (29 mg, 0.13 mmol,
73%) as a white solid. mp 310-313 oC (lit.54 mp 310-312 oC).
4-Chloro-2,2’-bi-1H-indole (12). Treatment of a solution of 7 (297 mg, 0.898 mmol) in DMF (2
mL) with Pd(dba)2 (36 mg, 0.063 mmol), dppp (26 mg, 0.063 mmol) and phen (23 mg, 0.126
mmol), as described for 11 (6 atm CO, 120 oC, 40 h), gave after work up and chromatography
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(hexane/EtOAc, 9:1) 12 (226 mg, 0.846 mmol, 94%) as a white solid. mp=186-187 oC; 1H NMR
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(400 MHz, Acetone-d6) δ 11.03 (br s, 1H), 10.81 (br, s, 1H), 7.60 (dd, J=7.6, 0.8 Hz, 1H), 7.46 (dd,
J=8.0, 0.8 Hz, 1H), 7.39 (ddd, J=7.2, 2.4, 0.8 Hz, 1H), 7.18 (td, J=7.6, 0.4 Hz, 1H), 7.16 (t, J=7.6 Hz,
1H), 7.14-7.05 (m, 4H), 7.01 (dd, J=2.4, 0.8 Hz, 1H); 13C NMR (100 MHz, Acetone-d6) δ 138.9,
138.3, 133.3, 131.5, 129.8, 128.6, 125.7, 123.5, 123.2, 121.2, 120.7, 120.1, 111.9, 110.8, 100.2,
97.6; IR (ATR) 3409, 3063, 1334, 1185, 747 cm-1; HRMS (ESI) calcd for C16H12ClN2 (M+H+)
267.0689, found 267.0686.
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7-Methoxy-2,2’-bi-1H-indole (13). Treatment of a solution of 8 (86 mg, 0.26 mmol) in DMF (2
mL) with Pd(dba)2 (11 mg, 0.018 mmol), dppp, (8 mg, 0.018 mmol) and phen (23 mg, 0.126
mmol), as described for 11 (CO 6 atm, 120 oC, 72 h), gave after work up and chromatography
(hexane/EtOAc, 9:1) 13 (64 mg, 0.24 mmol, 93%) as a white solid. mp=228-229 oC; 1H NMR (400
MHz, Acetone-d6) δ 10.68, (br, s, 1H), 10.58 (br, s, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.42 (dd, J=8.0 Hz,
1.2 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 7.13 (td, J=6.8, 1.2 Hz, 1H), 7.11 (d, J=1.2 Hz, 1H), 7.04 (td,
J=6.8, 1.2 Hz, 1H), 6.98 (d, J=8.0 Hz, 1H), 6.94 (d, J=2.4 Hz, 1H), 6.68 (d, J=7.6 Hz, 1H), 3.94 (s, 3H);
13C NMR (100 MHz, Acetone-d6) δ 147.2, 138.1, 132.3, 132.1, 131.3, 130.0, 128.3, 122.7, 121.2,
121.0, 120.5, 113.8, 111.8, 103.7, 100.2, 100.0, 55.6; IR (ATR) 3346, 1580, 1344, 1252, 1094, 729
cm-1; HRMS (ESI) calcd for C17H15N2O (M+H+) 263.1184, found 263.1184.
6-Bromo-2,2’-bi-1H-indole (14). Treatment of a solution of 9 (72 mg, 0.19 mmol) in DMF (1.5
mL) with Pd(dba)2 (8 mg, 0.013 mmol), dppp, (6 mg, 0.013 mmol) and phen (5 mg, 0.027 mmol),
as described for 11 (CO 6 atm, 120 oC, 49 h), gave after work up and chromatography
(hexane/EtOAc, 1:9) 14 (44 mg, 0.142 mmol, 74%) as a white solid. mp=251-252 oC; 1H NMR
(400 MHz, Acetone-d6) δ 10.93 (s, 1H), 10.79 (s, 1H), 7.58 (s, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.51 (d,
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J=8.0 Hz, 1H), 7.41 (dd, J=7.6, 0.8 Hz, 1H), 7.17 (dd, J=8.8, 2.0 Hz, 1H), 7.14 (dd, J=8.4, 1.2 Hz, 1H),
7.04 (t with further fine splittings, J=7.2 Hz, 1H), 6.96 (br s, 2H); 13C NMR (100 MHz, Acetone-d6)
δ 138.9, 138.2, 133.4, 131.7, 129.8, 129.0, 123.6, 123.1, 122.5, 121.1, 120.6, 115.6, 114.5, 111.9,
100.0, 99.5; IR (ATR) 3425, 1386, 1338, 1218, 741 cm-1; HRMS (ESI) calcd for C16H12BrN2 (M+H+)
311.0183, found 311.0176.
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5,6’-Dibromo-2,2’-bi-1H-indole (15). Treatment of a solution of 10 (100 mg, 0.220 mmol) in
the presence of Pd(dba)2 (8.9 mg, 0.015 mmol), dppp (6.4 mg, 0.015 mmol) and phen (5.6 mg,
0.031 mmol) in DMF (1.5 mL) with CO (6 atm), as described for 11 (120 oC , 58 h), gave after
work up and chromatography (hexane/EtOAc, 9:1) 15 (61.3 mg, 0.157 mmol, 71%) as a white
solid. mp=275-276 °C; 1H NMR (600 MHz, CDCl3/DMSO-d6) δ 11.73 (br, s, 1H), 11.69 (br, s, 1H),
7.74 (s, 1H), 7.53 (s, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.34 (d, J=9.0 Hz, 1H), 7.19 (dd, J=8.4, 1.8 Hz, 1H),
7.12 (dd, J=8.4, 1.8 Hz, 1H), 6.94 (s, 1H), 6.90 (s, 1H); 13C NMR (150 MHz, CDCl3/DMSO-d6) δ
137.8, 135.6, 132.2, 131.6, 130.2, 127.3, 124.1, 122.3, 122.1, 121.6, 114.4, 113.5, 112.8, 111.9,
99.0, 98.3; IR (ATR) 3416, 1599, 1437, 1332, 802 cm-1; HRMS (ESI) calcd for C16H11Br2N2 (M+H+)
388.9289, found 388.9286.
Tributyl(1-(2-nitrophenyl)ethenyl)tin (22). Tributyltin hydride (742 mg, 2.55 mmol) was
added drop wise, at ambient temperature, to a solution of PdCl2(PPh3)2 (119 mg, 0.170 mmol)
and 1-ethynyl-2-nitrobenzene (17)55 (250 mg, 1.70 mmol) in THF (5 mL). The dark brown
reaction mixture was stirred for 34 h followed by removal of the solvent under reduced
pressure. Purification by chromatography (hexane/EtOAc, 95:5) gave 22 (707 mg, 1.61 mmol,
95%) as a pale green oil. 1H NMR (600 MHz, CDCl3) δ 7.99 (dd, J = 8.4, 1.2 Hz, 1H), 7.52 (dt, J =
7.8, 1.2 Hz, 1H), 7.31 (dt, J = 7.2, 1.2 Hz, 1H), 7.11 (dd, J = 7.8, 1.2 Hz, 1H), 5.74 (d, J = 3.0 Hz, 1H),
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5.45 (d, J = 2.4 Hz, 1H), 1.43-1.48 (m, 6H), 1.26 (sext, J = 7.8 Hz, 6H), 0.91-0.94 (m, 6H), 0.86 (t, J =
7.2 Hz, 9H); 13C NMR (150 MHz, CDCl3) δ 154.6, 146.0, 144.3, 133.2, 129.7, 126.3, 126.0, 124.3,
28.8, 27.3, 13.6, 10.9; IR (ATR) 2922, 1518, 1339, 1038 cm-1; HRMS (ESI) calcd for
C20H34NO2120Sn (M+H+) 440.1606, found 440.1607.
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Tributyl(1-(5-benzyloxy-2-nitrophenyl)ethenyl)tin (23). Treatment of 1816 (1.30 g, 5.15
mmol) in dry THF (15 mL) with tributyltin hydride (2.30 g, 7.90 mmol) in the presence of
PdCl2(PPh3)2 (362 mg, 0.515 mmol), as described for 22 (24 h), gave after solvent removal and
chromatography (hexane/EtOAc, 9:1) 23 (2.70 g, 4.96 mmol, 96%) as a brown viscous oil. 1H
NMR (400 MHz, CDCl3) δ 8.10 (d, J=9.2 Hz, 1H), 7.45-7.33 (m, 5H), 6.86 (dd, J=9.2, 2.4 Hz, 1H),
6.63 (d, J=2.0 Hz, 1H), 5.72 (d, J=2.4 Hz, 1H), 5.41 (d, J=2.0 Hz, 1H), 5.14 (s, 2H), 1.56-1.37 (m,
6H), 1.27 (sext, J=7.2 Hz, 6H), 0.95 – 0.84 (m, 15H); 13C NMR (100 MHz, CDCl3) δ 162.3, 155.7,
147.6, 139.1, 135.6, 128.7, 128.4, 127.5, 127.1, 124.8, 114.6, 112.7,70.5, 28.8, 27.3, 13.6, 11.0; IR
(ATR) 2954, 2922, 1567, 1329, 1283, 1243, 1228, 694 cm-1; HRMS calcd for C27H40NO3120Sn
(M+H+) 546.2030, found 546.2030.
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Tributyl(1-(4-chloro-2-nitrophenyl)ethenyl)tin (24). Treatment of a solution of 19 (215
mg, 1.18 mmol) in THF (3 mL) with tributyltin hydride (577 mg, 1.78 mmol) in the presence of
PdCl2(PPh3)2 (83.1 mg, 0.118 mmol), as described for 22 (24 h), gave after solvent removal and
chromatography (hexane/EtOAc, 19:1) 24 (537 mg, 1.13 mmol, 96%) as a brown viscous oil. 1H
NMR (400 MHz, CDCl3) δ 7.99 (d, J=2.0 Hz, 1H), 7.48 (dd, J=8.4, 2.4 Hz, 1H), 7.05 (d, J=8.0, Hz, 1H),
5.73 (d, J=2.4 Hz, 1H), 5.46 (d, J=2.4 Hz, 1H), 1.51-1.43 (m, 6H), 1.30 (sext, J=8.0 Hz, 6H), 0.99-
0.82 (m, 15H); 13C NMR (100 MHz, CDCl3) δ 153.6, 146.1, 142.8, 133.2, 131.8, 130.8, 126.8, 124.2,
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28.8, 27.2, 13.6, 10.9; IR (ATR) 2954, 2922, 1567, 1329, 1283, 1243, 1228, 694 cm-1; HRMS (ESI)
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calcd for C20H33ClNO2120Sn (M+H+) 474.1222, found 474.1225.
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Tributyl(1-(4-carbomethoxy-2-nitrophenyl)ethenyl)tin (25). Treatment of a solution of 20
(100 mg, 0.487 mmol) in THF (2 mL) with tributyltin hydride (213 mg, 0.731 mmol) in the
presence of PdCl2(PPh3)2 (34 mg, 0.049 mmol), as described for 22 (35 h) gave after solvent
removal and chromatography (hexane/EtOAc, 19:1) 25 (189 mg, 0.380 mmol, 78%) as a brown
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viscous oil. H NMR (400 MHz, CDCl3) δ 8.63 (d, J=1.6 Hz, 1H), 8.15 (dd, J=7.6, 1.6 Hz, 1H), 7.17
(d, J=8.0 Hz, 1H), 5.75 (d, J=2.8 Hz, 1H), 5.48 (d, J=2.8 Hz, 1H), 3.96 (s, 3H), 1.51-1.43 (m, 6H),
1.25 (sext, J=7.2 Hz, 6H), 0.94-0.90 (m, 6H), 0.85 (t, J=6.8 Hz, 9H); 13C NMR (100 MHz, CDCl3) δ
165.0, 154.1, 148.7, 145.8, 133.5, 129.9, 128.6, 126.4, 125.6, 52.4, 28.7, 27.2, 13.6, 11.0; IR (ATR)
2954, 2922, 1567, 1329, 1283, 1243, 1228, 694 cm-1; HRMS (ESI) calcd for C22H36NO4120Sn
(M+H+) 498.1666, found 498.1670.
Tributyl(1-(4-methoxy-2-nitrophenyl)ethenyl)tin (26). Treatment of a solution of 2158 (1.10
g, 6.21 mmol) in THF (130 mL) with tributyltin hydride (2.71 g, 9.31 mmol) in the presence of
PdCl2(PPh3)2 (436 mg, 0.621 mmol), as described for 22 (32 h), gave after solvent removal and
chromatography (hexane/EtOAc, 9:1) 26 (2.62 g, 5.58 mmol, 90%) as a brown viscous oil. 1H
NMR (400 MHz, CDCl3) δ 7.52 (d, J=2.8 Hz, 1H), 7.10 (dd, J=8.4, 2.8 Hz, 1H), 7.01 (d, J=8.0,Hz, 1H),
5.72 (d, J=2.4 Hz, 1H), 5.42 (d, J=2.8 Hz, 1H), 3.86 (s, 3H), 1.51-1.32 (m, 6H), 1.26 (sext, J=7.6 Hz,
,6H), 0.98-0.82 (m, 15H); 13C NMR (100 MHz, CDCl3) δ 157.9, 154.3, 146.1, 136.8, 130.7, 126.1,
120.6, 108.2, 55.8, 28.8, 27.3, 13.6, 10.8; IR (ATR) 2924, 1521, 1341, 1303, 1034 cm-1; HRMS
(ESI) calcd for C21H26NO3120Sn (M+H+-C4H8) 412.0935, found 412.0931.
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2,3-Di(2-nitrophenyl)-1,3-butadiene (27).16 To a solution of 22 (348 mg, 0.794 mmol) in DMF
(10 mL) was added PdCl2(PPh3)2 (28 mg, 0.040 mmol), PPh3 (21 mg, 0.080 mmol) and CuI (113
mg, 0.595 mmol). The reaction was stirred at ambient temperature for 36 h. Et2O (30 mL) was
added and the organic phase was washed with NH4OH (10%, aqueous, 3 X 30 mL), H2O (30 mL),
and brine (30 mL). The organic phase was dried (MgSO4), filtered, and the solvents were
removed under reduced pressure. The resulting solid was purified by chromatography
(hexane/EtOAc, 95:5) to afford 27 (78 mg, 0.263 mmol, 67%) as a dark yellow solid. mp=122-
124 oC; 1H NMR (600 MHz, CDCl3) δ 7.98 (dd, J=8.4, 1.2 Hz, 2H), 7.66 (dt, J=7.8, 1.2 Hz, 2H), 7.61
(dd, J=7.8, 1.2 Hz, 2H), 7.52 (dt, J=7.2, 1.2 Hz, 2H), 5.15 (s, 2H), 4.92 (s, 2H); 13C NMR (150 MHz,
CDCl3) δ 149.0, 145.2, 135.3, 132.9, 132.4, 128.7, 124.0, 118.3; IR (ATR) 1514, 1332, 911, 790,
749, 697 cm-1; HRMS (ESI) calcd for C16H12N2NaO4 (M+Na+) 319.0695, found 319.0690.
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2,3-Di(5-benzyloxy-2-nitrophenyl)-1,3-butadiene (28). Treatment of 23 (103 mg, 0.189
mmol) in DMF (1.5 mL) with Pd(dba)2 (7.2 mg, 0.013 mmol), PPh3 (14 mg, 0.053 mmol), and CuI
(36 mg, 0.189 mmol), as described for 27 (28 h), gave after work up and chromatography59
(hexane/EtOAc, 9:1) 28 (37.6 mg, 0.074 mmol, 78%) as a white solid. mp=158-160 oC; 1H NMR
(400 MHz, CDCl3) δ 8.08 (d, J=9.2, Hz, 1H), 7.48-7.36 (m, 5H), 7.17 (d, J=2.8 Hz, 1H), 7.02 (dd,
J=9.6, 3.2 Hz, 1H), 5.19 (s, 2H), 5.08 (s, 1H), 4.88 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 162.2,
145.6, 141.7, 138.3, 135.5, 128.7, 128.4, 127.8, 126.8, 117.5, 117.1, 114.9, 70.7; IR (ATR) 1573,
1513, 1343, 1230, 1007 cm-1; HRMS (ESI) calcd for C30H25N2O6 (M+H+) 509.1713, found
509.1715.
2,3-Di(4-chloro-2-nitrophenyl)-1,3-butadiene (29). To a slurry of copper chloride (210 mg,
2.12 mmol) in DMF (2 mL) in a round-bottomed flask covered with aluminum foil to exclude
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light was added a solution of 24 (400 mg, 0.846 mmol) in DMF (2 mL). The resulting mixture was
stirred at ambient temperature for 1 h. A saturated solution of NH4Cl (aqueous, 4 mL) was added
and the mixture was allowed to stir for an additional hour. The mixture was diluted with EtOAc
(30 mL), was washed with H2O (3 x 30 mL) and brine (20 mL). The organic phase was dried
(MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was
purified by chromatography59 (hexane/EtOAc, 9:1) affording 29 (124 mg, 0.340 mmol, 80%) as a
white solid. mp=182 oC; 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 2.0, Hz, 1H), 7.64 (dd, J=8.0, 1.6
Hz 1H), 7.54 (d, J = 8.4 Hz, 1H), 5.15 (s, 1H), 4.92 (s, 1H); 13 C NMR (100 MHz, DMSO-d6) δ 149.2,
143.4, 133.5, 133.3, 133.2, 132.6, 124.1, 119.4; IR (ATR) 3086, 1523, 1344, 914, 700 cm-1; HRMS
(ESI, negative ion mode) calcd for C16H10Cl2N2O4 (M-) 364.0018, found 364.0048.
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2,3-Di(4-carbomethoxy-2-nitrophenyl)-1,3-butadiene (30). Treatment of 25 (400 mg, 0.806
mmol) with CuCl (207 mg, 2.10 mmol) in DMF (2 mL), as described for 29 (3 h), gave after work
up and chromatography59 (hexane/EtOAc, 9:1), 30 (306 mg, 0.742 mmol, 92%) as a white solid.
mp=187-188 oC; 1H NMR (400 MHz, CDCl3) δ 8.60 (d, J=1.2, Hz, 1H), 8.29 (dd, J=7.6, 1.2 Hz 1H),
7.68 (d, J=8.0 Hz, 1H), 5.18 (s, 1H), 5.20 (s, 2H), 4.92 (s, 1H), 3.98 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 164.7, 148.9, 144.2, 139.0, 133.5, 132.6, 131.2, 125.3, 118.9, 52.8; IR (ATR) 1721, 1532,
1358, 1288, 1219 cm-1; HRMS (ESI, negative ion mode) calcd for C20H16N2O8 (M-) 412.0907,
found 412.0937.
2,3-Di(4-methoxy-2-nitrophenyl)-1,3-butadiene (31). Treatment of 26 (100 mg, 0.214 mmol)
in the presence of CuCl (55 mg, 0.56 mmol), in DMF (1.5 mL), as described for 29 (2 h), gave after
work up and chromatography59 (hexane/EtOAc, 9:1) 31 (37.1 mg, 0.104 mmol, 98%) as a white
solid. mp=163.5-164 oC; 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J=9.2, Hz, 1H), 7.47 (d, J=2.4, Hz 1H),
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7.17 (dd, J=8.8 2.8 Hz, 1H), 5.09 (s, 1H), 4.90 (s, 1H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
159.3, 149.5, 145.3, 133.2, 127.6, 119.3, 118.0, 108.8, 55.9; IR (ATR) 1521, 1340, 1308, 1278,
1028 cm-1; HRMS (ESI) calcd for C18H17N2O6 (M+H+) 357.1087, found 357.1081.
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3,3’-Bi-1H-indole (32).60 Treatment of a solution of 27 (93.0 mg, 0.314 mmol) in the presence
of Pd(dba)2 (18.1 mg, 0.031 mmol), dppp (13.0 mg, 0.031 mmol), and phen (11.4 mg, 0.063
mmol), and in DMF (1.5 mL) with CO (6 atm), as described for 11 (120 oC, 36 h) gave, after
chromatography (hexane/EtOAc, 7:3), 32 (65.1 mg, 0.280 mmol, 89%) as a white solid. All data
in accordance with previously reported values.
5,5’-Dibenzyloxy-3,3’-Bi-1H-indole (33). Treatment of a solution of 28 (100 mg, 0.197 mmol)
in the presence of Pd(dba)2 (9 mg, 0.016 mmol), dppp (6 mg, 0.016 mmol) phen (6 mg, 0.031
mmol) in DMF (2 mL) with CO (6 atm), as described for 11 (72 h), gave after work up and
chromatography (hexane/EtOAc; 7:3) 33 (76.3 mg, 0.172 mmol, 87%) as a white solid.
mp=125-126 oC; 1H NMR (400 MHz, CDCl3) δ 8.10 (br, s, 1H), 7.46 (d, J=6.8, Hz, 2H), 7.39-7.31
(m, 6H), 7.02 (dd, J=8.8, 2.4 Hz, 1H), 5.07 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 153.5, 137.6,
131.6, 128.4, 127.7, 127.6, 127.3, 122.4, 113.2, 111.9, 110.7, 103.6, 71.0; IR (ATR) 3406, 1452,
1186, 1151, 794 cm-1; HRMS (ESI, negative mode) calcd for C30H24N2O2 (M-) 444.1838, found
444.1834.
6,6’-Dichloro-3,3’-Bi-1H-indole (34). Treatment of a solution of 29 (23 mg, 0.064 mmol) in the
presence of Pd(dba)2 (4 mg, 0.006 mmol), dppp (4 mg, 0.006 mmol), and phen (2 mg, 0.013
mmol) in DMF (1.5 mL) with CO (6 atm), as described for 11 (72 h), gave after work up and
chromatography (hexane/EtOAc, 7:3) 34 (190 mg, 0.063 mmol, 100%) as a white solid. mp=225-
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226 oC; 1H NMR (400 MHz, Acetone-d6) δ 10.52 (s, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.69 (d, J=2.4 Hz,
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1H), 7.53 (d, J=2.0 Hz, 1H), 7.09 (dd, J=8.4, 2.0 Hz, 1H); 13C NMR (100 MHz, Acetone-d6) δ 138.1,
127.9, 126.3, 123.9, 121.7, 120.4, 112.2, 111.1; IR (ATR) 3411, 1448, 1376, 1227, 914, 802 cm-1;
HRMS (ESI) calcd for C16H11Cl2N2 (M+H+) 301.0299, found 301.0292.
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6,6’-Carbomethoxy-3,3’-Bi-1H-indole (35). Treatment of a solution of 30 (100 mg, 0.243
mmol) in the presence of Pd(dba)2 (10 mg, 0.017 mmol), dppp (7 mg, 0.017 mmol) and phen (6
mg, 0.034 mmol) in DMF (2 mL) with CO (6 atm), as described for 11 (44 h), gave after work up
and chromatography (hexane/EtOAc, 1:1) 35 (84.3 mg, 0.242 mmol, 100%) as a white solid. mp
= 300-301 oC; 1H NMR (400 MHz, CDCl3/DMSO-d6) δ 11.67 (br, s, 1H), 8.13 (s with further fine
splittings, 1H), 7.96 (d, J=2.4 Hz, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.69 (dd, J=8.4, 1.6 Hz, 1H), 3.87 (s,
3H); 13C NMR (100 MHz, CDCl3/DMSO-d6 ) δ 167.1, 135.5, 129.2, 125.7, 122.3, 119.5, 118.9,
113.6, 109.5, 51.4; IR (ATR) 3305, 1689, 1436, 1319, 1227 cm-1; HRMS (ESI) calcd for C20H17N2O4
(M+H+) 349.1188, found 349.1182.
6,6’-Dimethoxy-3,3’-Bi-1H-indole (36). Treatment of a solution of 31 (421 mg, 1.18 mmol) in
the presence of Pd(dba)2 (47 mg, 0.083 mmol), dppp (34 mg, 0.083 mmol), and phen (30 mg,
0.17 mmol) in DMF (2.5 mL) with CO (6 atm), as described for 11 (30 h), gave after work up and
chromatography (hexane/EtOAc, 1:1) 36 (221 mg, 0.757 mmol, 64%) as a white solid. mp=282-
284 oC; 1H NMR (400 MHz, DMSO-d6) δ 10.90 (s, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.46 (d, J=2.0 Hz, 1H),
6.92 (d, J=2.4 Hz, 1H), 6.70 (dd, J=8.4, 1.6 Hz, 1H), 3.79 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ
155.5, 137.1, 120.3, 120.2, 120.1, 109.8, 108.9, 94.5, 55.1; IR (ATR) 3379, 1626, 1298, 1155, 1026
cm-1; HRMS (ESI) calcd for C18H17N2O2 (M+H+) 293.1290, found 293.1284.
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Tributyl(1-(3-nitro-2-pyridyl)ethenyl)tin (38). Treatment of a solution of 3761 (100 mg,
0.675 mmol) in THF (2 mL) with tributyltin hydride (295 mg, 1.01 mmol) in the presence of
PdCl2(PPh3)2 (47 mg, 0.068 mmol), as described for 22 (36 h), gave after solvent removal and
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chromatography (hexane/EtOAc, 9:1), 38 (181 mg, 0.412 mmol, 61%) as a brown viscous oil. 1H
NMR (400 MHz, CDCl3) δ 8.70 (dd, J=4.8, 1.6 Hz, 1H), 8.10 (dd, J=8.4, 1.6 Hz, 1H), 7.24 (dd, J=8.0,
4.4 Hz, 1H), 5.95 (d, J=2.8 Hz, 1H), 5.64 (d, J=2.4 Hz, 1H), 1.49-1.43 (m, 6H), 1.30-125 (m, 6H),
1.00-0.83 (m, 15H); 13C NMR (100 MHz, CDCl3) δ 159.6, 153.4, 152.0, 143.8, 131.8, 129.1, 120.7,
28.7, 27.2, 13.6, 10.9; (ATR) 2956, 2924, 1526, 1352, 808 cm-1; HRMS (ESI) calcd for
C19H33N2O2120Sn (M+H+) 441.1564, found 441.1558.
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2,3-Di(3-nitro-2-pyridyl)-1,3-butadiene (39). Treatment of 38 (500 mg, 1.14 mmol) with CuCl
(282 mg, 2.85 mmol) in DMF (3 mL), as described for 29 (5 h), gave after work up and
chromatography59 (hexane/EtOAc, 1:1) 39 (91.4 mg, 0.306 mmol, 54%) as a white solid.
mp=198-199 oC; 1H NMR (400 MHz, CDCl3) δ 8.88 (dd, J=4.8, 1.6 Hz, 1H), 8.22 (dd, J=8.4, 1.6 Hz
1H), 7.48 (dd, J=8.4, 4.8 Hz, 1H), 5.40 (s, 1H), 5.24 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 152.6,
152.4, 146.4, 143.6, 132.0, 123.2, 120.0; IR (ATR) 3019, 1522, 1361, 1217, 932 cm-1; HRMS (ESI)
calcd for C14H11N4O4 (M+H+) 299.0780, found 299.0774.
3,3’-Bi-1H-pyrrolo[3,2-b]pyridine (40). Treatment of a solution of 39 (90 mg, 0.302 mmol) in
the presence of Pd(dba)2 (12 mg, 0.021 mmol), dppp (9 mg, 0.021 mmol), and phen (8 mg, 0.042
mmol) in DMF (2 mL) with CO (6 atm), as described for 11 (36 h), gave after work up and
chromatography (EtOAc) 40 (52.3 mg, 0.223 mmol, 74%) as a white solid. mp=309-310 oC; 1H
NMR (400 MHz, DMSO-d6) δ 11.26 (s, 1H), 8.63 (d, J=2.4 Hz, 1H), 8.44 (dd, J=4.8, 1.6 Hz, 1H), 7.81
(dd, J=8.0, 1.2 Hz, 1H), 7.16 (dd, J=8.4, 4.8 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ 143.7, 142.1,
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128.6, 125.6, 118.5, 116.3, 108 .9; IR (ATR) 3088, 3019, 1522, 1361, 1217 cm-1; HRMS (ESI) calcd
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for C14H11N4 (M+H+) 235.0984, found 235.0978.
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2-(1-Bromo-1-ethenyl)-5-methoxy-1-nitrobenzene (42). A mixture of 2-(2-trimethylsilyl-1-
ethynyl)-5-methoxy-1-nitrobenzene (41)62 (756 mg, 3.03 mmol) and HBr (aq.-48%, 1.10 mL) in
3-pentanone (7 mL) was stirred at 100 oC for 2 h. After cooling to ambient temperature, the dark
brown solution was diluted with EtOAc (15 mL) and the organic phase was washed with water
(3x15 mL), dried (MgSO4), filtered, and the filtrate was concentrated under reduced pressure.
The resulting brown oil was purified by chromatography (hexane/EtOAc, 95:5) to give 42 (446
mg, 1.73 mmol, 57%) as a brown oil. 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J=2.0 Hz, 1H), 7.37 (d,
J=8.4 Hz, 1H), 7.10 (dd, J=8.4, 2.8 Hz, 1H), 5.84 (d, J=2.4 Hz, 1H), 5.82 (d, J=2.4 Hz, 1H), 3.89 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 160.2, 148.2, 132.2, 127.5, 124.3, 121.2, 118.8, 109.4, 56.0; IR
(ATR) 1611, 1526, 1352, 1245, 1029 cm-1; HRMS (ESI) calcd for C9H9BrNO3 (M+H+) 257.9765,
found 257.9763.
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2-(4-Methoxy-2-nitrophenyl)-3-(2-nitrophenyl)-1,3-butadiene (43). To a mixture of 42
(320 mg, 1.24 mmol), CuI (307 mg, 1.61 mmol), CsF (382 mg, 2.52 mmol) and Pd(PPh3)4 (143
mg, 0.124 mmol) in DMF (3 mL) was added, under a N2 atmosphere, a solution of 22 (706 mg,
1.61 mmol) in DMF (3 mL). The resulting mixture was stirred at 70 oC for 12 h. The mixture was
cooled to ambient temperature and EtOAc (30 mL) was added. The mixture was washed with
water (5x20 mL) and brine (20 mL), and the organic phase was dried (MgSO4), filtered, and the
filtrate was concentrated under reduced pressure. The resulting brown oil was purified by
chromatography59 (hexane/EtOAc, 95:5) to give, in order of elution, 27 (66 mg, 0.22 mmol, 28%)
as a white solid and 43 (247 mg, 0.756 mmol, 61%) as a yellow solid. mp=91-95 oC; 1H NMR (400
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MHz, CDCl3) δ 7.96 (dd, J=8.4, 1.2 Hz, 1H), 7.65 (dt, J=8.4, 1.2 Hz, 1H), 7.59 (dd, J=8.0, 1.6 Hz, 1H),
7.52-7.47 (m, 3H), 7.19 (dd, J=8.4, 2.8 Hz, 1H), 5.12 (d, J=2.8 Hz, 2H), 4.93 (s, 1H), 4.88 (s, 1H),
3.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.3, 149.4,148.9, 145.4, 145.0, 135.4, 133.1, 132.9,
132.3, 128.6, 127.3, 123.9, 119.2, 118.1, 117.9, 108.8, 55.8; IR (ATR) 1520, 1351, 1233, 1027, 910
cm-1; HRMS (ESI) calcd for C17H15N2O5 (M+H+) 327.0981, found 327.0979.
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6-Methoxy-3,3’-Bi-1H-indole (44). Treatment of a solution of 43 (200 mg, 0.613 mmol) in the
presence of Pd2(dba)3 (56 mg, 0.061 mmol), dppp (26 mg, 0.063 mmol), and phen (22 mg, 0.123
mmol) in DMF (1.5 mL) with CO (6 atm), as described for 11 (30 h), gave after work up and
chromatography (hexane/EtOAc, 7:3 then 1:1) 44 (161 mg, 0.613 mmol, 100%) as a white solid.
mp=252 oC (dec.); 1H NMR (400 MHz, DMSO-d6) δ 11.11 (br s, 1H), 10.93 (br s, 1H), 7.77 (d, J=7.6
Hz, 1H), 7.64 (d, J=8.4 Hz, 1H), 7.61 (d, J=2.4 Hz, 1H), 7.49 (d, J=2.4 Hz, 1H), 7.43 (d, J=8.0 Hz, 1H),
7.13 (t, J=7.2 Hz, 1H), 7.05 (t, J=7.2 Hz, 1H), 6.94 (d, J=2.4 Hz, 1H), 6.72 (dd, J=8.4, 2.4 Hz, 1H),
3.80 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 155.6, 137.1, 136.4, 126.0, 121.6, 121.2, 120.4,
120.3, 120.2, 119.6, 118.8, 111.5, 109.9, 109.7, 108.9, 94.5, 55.2; IR (ATR) 3395, 1629, 1454,
1239, 1105 cm-1; HRMS (ESI) calcd for C17H15N2O (M+H+) 263.1184, found 263.1180.
[(5-Bromo-2-nitrophenyl)methyl] triphenylphosphonium bromide (46).63 Treatment of 5-
bromo-2-nitrobenzyl bromide (486 mg, 1.65 mmol) with PPh3 (519 mg, 1.977 mmol) in toluene
(6 mL) as described for 1 (100 oC, 10 h), gave after work up 46 (918 mg, 1.647 mmol, 100%) as a
white solid. mp=249-250 °C, 1H NMR (600 MHz, DMSO-d6) δ 7.97 (d, J=9.0 Hz, 1H), 7.93 (td, J=8.4,
1.8 Hz, 3H), 7.87 (dt, J=7.2, 2.4 Hz, 1H), 7.75 (dt, J=8.4, 3.6 Hz, 6H), 7.67-7.64 (m, 6H), 7.56 (d,
J=2.4 Hz, 1H), 5.47 (d, J=15.0 Hz, 2H); 13C NMR (150 MHz, DMSO-d6) δ 147.3 (d, JCP=5.7 Hz), 136.3
(d, JCP=10.3 Hz), 136.3, 135.4, 134.0 (d, JCP=10.3 Hz), 133.3, 127.9 (d, JCP=4.5 Hz), 127.8, 125.9 (d,
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