Biradicals from thermolysis of N-[2-(1-alkynyl)phenyl]-N'- phenylcarbodiimides and their subsequent transformations to 6H-indolo[2,3- b]quinolines

Article abstract of DOI:10.1021/jo981845k

Thermolysis of the carbodiimide 9a in γ-terpinene at 138 °C produced 2-(phenylamino)quinoline (11a, 49%) and the parent 6H-indolo[2,3-b]quinoline (14a, 16%). Apparently, 11a was produced via the biradical 10a followed by hydrogen-atom abstraction from γ-terpinene. A two-step biradical pathway through 12a or a one-step intramolecular Diels-Alder reaction could furnish 13a, which then underwent tautomerization to give 14a. With the carbodiimide 9b having a trimethylsilyl substituent at the acetylenic terminus, thermolysis in refluxing p-xylene at 138 °C produced the 6H-indolo[2,3- b]quinoline 14b (86%) exclusively. Treatment of 14b with 6 N NaOH in refluxing ethanol then furnished 14a in 92% yield. Similarly, the 6H- indolo[2,3-b]quinolines 14c-f were obtained from thermolysis of the carbodiimides 9c-f. The use of the aza-Wittig reaction between 4- methoxyphenyl isocyanate and the iminophosphoranes 2d and 2f to produce the corresponding carbodiimides followed by thermolysis furnished the 6H- indolo[2,3-b]quinolines 16d and 16f having a methoxy substituent at the C-2 position. Thermolysis of the carbodiimides 25a and 25b produced 26a and 26b having two indoloquinoline units connected at the 11 and 11' positions with either a three-carbon or a five-carbon tether. Using 1,4-phenylene diisocyanate for the aza-Wittig reaction with 2 equiv of the iminophosphorane 2g followed by thermolysis furnished 31 (66%) having two indoloquinoline units incorporated in the seven fused rings.

Full text of DOI:10.1021/jo981845k

J . Org. Chem. 1999, 64, 925-932
925
Bir a d ica ls fr om Th er m olysis of
N-[2-(1-Alk yn yl)p h en yl]-N′-p h en ylca r bod iim id es a n d Th eir
Su bsequ en t Tr a n sfor m a tion s to 6H-In d olo[2,3-b]qu in olin es†
Chongsheng Shi, Quan Zhang, and Kung K. Wang*
Department of Chemistry, West Virginia University, Morgantown, West Virginia 26506-6045
Received September 10, 1998
Thermolysis of the carbodiimide 9a in γ-terpinene at 138 °C produced 2-(phenylamino)quinoline
(11a , 49%) and the parent 6H-indolo[2,3-b]quinoline (14a , 16%). Apparently, 11a was produced
via the biradical 10a followed by hydrogen-atom abstraction from γ-terpinene. A two-step biradical
pathway through 12a or a one-step intramolecular Diels-Alder reaction could furnish 13a , which
then underwent tautomerization to give 14a . With the carbodiimide 9b having a trimethylsilyl
substituent at the acetylenic terminus, thermolysis in refluxing p-xylene at 138 °C produced the
6H-indolo[2,3-b]quinoline 14b (86%) exclusively. Treatment of 14b with 6 N NaOH in refluxing
ethanol then furnished 14a in 92% yield. Similarly, the 6H-indolo[2,3-b]quinolines 14c-f were
obtained from thermolysis of the carbodiimides 9c-f. The use of the aza-Wittig reaction between
4-methoxyphenyl isocyanate and the iminophosphoranes 2d and 2f to produce the corresponding
carbodiimides followed by thermolysis furnished the 6H-indolo[2,3-b]quinolines 16d and 16f having
a methoxy substituent at the C-2 position. Thermolysis of the carbodiimides 25a and 25b produced
26a and 26b having two indoloquinoline units connected at the 11 and 11′ positions with either a
three-carbon or a five-carbon tether. Using 1,4-phenylene diisocyanate for the aza-Wittig reaction
with 2 equiv of the iminophosphorane 2g followed by thermolysis furnished 31 (66%) having two
indoloquinoline units incorporated in the seven fused rings.
In tr od u ction
ketenes5 to biradical species have been extensively
studied, the biradical-forming reactions involving other
heteroatoms in the conjugated systems are rare.6 The
ability to produce 4a from 3a demonstrates the feasibility
of placing a nitrogen atom in the conjugated system for
the generation of biradicals under mild thermal condi-
tions and provides a new avenue for the design of novel
DNA-cleaving agents.7
Interestingly, when 3b (R ) SiMe3) was heated under
refluxing benzene, the benzocarbazole 8b was produced
exclusively (t1/2 ) 0.89 h at 72 °C). Presumably, the
reaction proceeded through a different cascade sequence
involving an initial formation of a five-membered ring
to produce biradical 6b followed by an intramolecular
radical-radical combination to form 7b and a subsequent
tautomerization to furnish 8b. While a one-step intramo-
lecular Diels-Alder reaction of 3b could also produce 7b
as reported previously in several analogous systems,8 the
presence of a sterically demanding trimethylsilyl group
We recently reported the use of iminophosphoranes 2,
readily prepared from treatment of 2-(1-alkynyl)anilines
1 with dibromotriphenylphosphorane (Ph3PBr2), for the
aza-Wittig reaction with diphenylketene to produce N-[2-
(1-alkynyl)phenyl]ketenimines 3 (Scheme 1).1 The keten-
imines 3 then were converted to the quinolines 5 and/or
the 5H-benzo[b]carbazoles 8 depending on the nature of
the substituent at the acetylenic terminus under mild
thermal conditions. A similar study was also reported by
Schmittel, Engels, and co-workers recently.2 In the
presence of an excess of 1,4-cyclohexadiene (1,4-CHD) as
a hydrogen-atom donor, 3a (R ) H) was converted to the
quinoline 5a (t1/2 ) 0.37 h at 22 °C) in 49% yield.
Apparently, the reaction proceeds through an initial
cycloaromatization reaction to form the biradical 4a
followed by hydrogen-atom abstraction from 1,4-CHD.
The transformation from 3a to 4a represents a new
example of a growing list of the thermally induced
biradical-forming cycloaromatization reactions. While the
Bergman cyclization of (Z)-3-hexene-1,5-diynes (ene-
diynes),3 the Myers cyclization of (Z)-1,2,4-heptatrien-6-
ynes (enyne-allenes),4 and the Moore cyclization of enyne-
(4) (a) Myers, A. G.; Kuo, E. Y.; Finney, N. S. J . Am. Chem. Soc.
1989, 111, 8057-8059. (b) Myers, A. G.; Dragovich, P. S. J . Am. Chem.
Soc. 1989, 111, 9130-9132. (c) Nagata, R.; Yamanaka, H.; Okazaki,
E.; Saito, I. Tetrahedron Lett. 1989, 30, 4995-4998. (d) Nagata, R.;
Yamanaka, H.; Murahashi, E.; Saito, I. Tetrahedron Lett. 1990, 31,
2907-2910. (e) Wang, K. K.; Wang, Z.; Tarli, A.; Gannett, P. J . Am.
Chem. Soc. 1996, 118, 10783-10791 and references therein. (f)
Grissom, J . W.; Klingberg, D.; Huang, D.; Slattery, B. J . J . Org. Chem.
1997, 62, 603-626 and references therein.
† Presented at the 216th National Meeting of the American Chemical
Society, Boston, MA, August 26, 1998; ORGN 584.
(1) Shi, C.; Wang, K. K. J . Org. Chem. 1998, 63, 3517-3520.
(2) Schmittel, M.; Steffen, J .-P.; Angel, M. A. W.; Engels, B.;
Lennartz, C.; Hanrath, M. Angew. Chem., Int. Ed. Engl. 1998, 37,
1562-1564.
(3) (a) J ones, R. R.; Bergman, R. G. J . Am. Chem. Soc. 1972, 94,
660-661. (b) Lockhart, T. P.; Comita, P. B.; Bergman, R. G. J . Am.
Chem. Soc. 1981, 103, 4082-4090. (c) Bharucha, K. N.; Marsh, R. M.;
Minto, R. E.; Bergman, R. G. J . Am. Chem. Soc. 1992, 114, 3120-
3121. For recent reviews, see: (d) Wang, K. K. Chem. Rev. 1996, 96,
207-222. (e) Grissom, J . W.; Gunawardena, G. U.; Klingberg, D.;
Huang. D. Tetrahedron 1996, 52, 6453-6518.
(5) (a) Moore, H. W.; Yerxa, B. R. Chemtracts 1992, 273-313. (b)
Tarli, A.; Wang, K. K. J . Org. Chem. 1997, 62, 8841-8847.
(6) (a) David, W. M.; Kerwin, S. M. J . Am. Chem. Soc. 1997, 119,
1464-1465. (b) Hoffner, J .; Schottelius, M. J .; Feichtinger, D.; Chen,
P. J . Am. Chem. Soc. 1998, 120, 376-385. (c) Braverman, S.; Duar,
Y.; Freund, M. Isr. J . Chem. 1985, 26, 108-114.
(7) (a) Maier, M. E. Synlett 1995, 13-26. (b) Nicolaou, K. C.; Dai,
W.-H. Angew. Chem., Int. Ed. Engl. 1991, 30, 1387-1416.
(8) (a) Differding, E.; Ghosez, L. Tetrahedron Lett. 1985, 26, 1647-
1650. (b) Molina, P.; Alajar´ın, M.; Vidal, A.; Sa´nchez-Andrada, P. J .
Org. Chem. 1992, 57, 929-939.
10.1021/jo981845k CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/05/1999

926 J . Org. Chem., Vol. 64, No. 3, 1999
Shi et al.
Sch em e 1
Sch em e 2
of 3e (R ) t-Bu) and 3f (R ) Ph), the benzocarbazoles 8e
and 8f were produced exclusively. The presence of a
sterically demanding tert-butyl group at the acetylenic
terminus of 3e makes the formation of 7e via the
concerted intramolecular Diels-Alder reaction unlikely.
A logical extension of this work involves replacing the
ketenimine moiety in 3 with other heterocumulenes.
Carbodiimide appears to be an excellent candidate for
such a substitution. We now report our findings of using
N-[2-(1-alkynyl)phenyl]-N′-phenylcarbodiimides 9 to pro-
duce biradicals and their subsequent transformations to
2-(phenylamino)quinoline (11a ) and 6H-indolo[2,3-b]-
quinolines 14 (Scheme 2).13 Recently, there has been a
surge of interest in developing new synthetic pathways
to 6H-indolo[2,3-b]quinolines8b,14 because several mem-
bers of this group of compounds have been found to
possess interesting biological activities.15
at the acetylenic terminus makes the concerted process
unlikely to occur under mild thermal conditions. The
reaction was directed toward 8b presumably because of
the emergence of a severe nonbonded steric interaction
in 4b (R ) SiMe3)9 and the ability of the trimethylsilyl
group in stabilizing an adjacent radical site in 6b.10 Such
a change of the reaction pathway was also observed in a
similar study2 and in several analogous cases of ring
closures of enyne-allenes9,11 and enyne-ketenes.12 Treat-
ment of 8b with 1 N HCl at 40 °C for 1 h produced the
desilylated adduct 8a (>81% yield). It is worth noting
that 8a could not be obtained from 3a directly. With the
ketenimine 3d (R ) Pr), both the quinoline 5d (58%) and
the benzocarbazole 8d (33%) were produced. In the cases
Resu lts a n d Discu ssion
It was interesting to learn that carbodiimide 9a had
already been prepared previously by treatment of imi-
(9) Gillmann, T.; Hulsen, T.; Massa, W.; Wocadlo, S. Synlett 1995,
1257-1259.
(10) Wilt, J . W.; Aznavoorian, P. M. J . Org. Chem. 1978, 43, 1285-
1286.
(13) After the original manuscript had been submitted for publica-
tion, a similar study was reported: Schmittel, M.; Steffen, J .-P.; Engels,
B.; Lennartz, C.; Hanrath, M. Angew. Chem., Int. Ed. Engl. 1998, 37,
2371-2373.
(14) (a) Molina, P.; Alajar´ın, M.; Vidal, A. J . Chem. Soc., Chem.
Commun. 1990, 1277-1279. (b) Saito, T.; Ohmori, H.; Furuno, E.;
Motoki, S. J . Chem. Soc., Chem. Commun. 1992, 22-24. (c) Saito, T.;
Ohmori, H.; Ohkubo, T.; Motoki, S. J . Chem. Soc., Chem. Commun.
1993, 1802-1803.
(15) (a) Peczyn´ska-Czoch, W.; Pognan, F.; Kaczmarek, L.; Boratyn´-
ski, J . J . Med. Chem. 1994, 37, 3503-3510. (b) Kaczmarek, L.; Balicki,
R.; Nantka-Namirski, P.; Peczyn´ska-Czoch, W.; Mordarski, M. Arch.
Pharm. (Weinheim) 1988, 321, 463-467.
(11) (a) Schmittel, M.; Steffen, J .-P.; Auer, D.; Maywald, M.Tetra-
hedron Lett. 1997, 38, 6177-6180. (b) Schmittel, M.; Strittmatter, M.;
Kiau, S. Angew. Chem., Int. Ed. Engl. 1996, 35, 1843-1845. (c)
Schmittel, M.; Kiau, S.; Siebert, T.; Strittmatter, M. Tetrahedron Lett.
1996, 37, 7691-7694. (d) Schmittel, M.; Strittmatter, M.; Vollmann,
K.; Kiau, S. Tetrahedron Lett. 1996, 37, 999-1002. (e) Schmittel, M.;
Maywald, M.; Strittmatter, M. Synlett 1997, 165-166. (f) Schmittel,
M.; Strittmatter, M.; Kiau, S. Tetrahedron Lett. 1995, 36, 4975-4978.
(g) Garcia, J . G.; Ramos, B.; Pratt, L. M.; Rodriguez, A. Tetrahedron
Lett. 1995, 36, 7391-7394.
(12) Foland, L. D.; Karlsson, J . O.; Perri, S. T.; Schwabe, R.; Xu, S.
L.; Patil, S.; Moore, H. W. J . Am. Chem. Soc. 1989, 111, 975-989.

Thermolysis of N-[2-(1-Alkynyl)phenyl]-N′-phenylcarbodiimides
J . Org. Chem., Vol. 64, No. 3, 1999 927
nophosphorane 2a (R ) H) with phenyl isocyanate.16
Thermolysis of 9a in toluene at 160 °C in a sealed tube
furnished 2-(phenylamino)quinoline (11a , 40%) and the
parent 6H-indolo[2,3-b]quinoline (14a , 19%).16 We were
able to reproduce similar results by heating 9a , isolated
in 83% yield from treatment of 2a with phenyl isocyanate,
in γ-terpinene at 138 °C to afford 11a (49%) and 14a
(16%). Apparently, 11a was produced via the biradical
10a followed by hydrogen-atom abstraction from γ-ter-
pinene. A two-step biradical pathway through 12a or a
one-step intramolecular Diels-Alder reaction could fur-
nish 13a , which then underwent tautomerization to give
14a . Several analogous examples in which a carbon-
carbon double bond replaces the triple bond in 9 for the
intramolecular Diels-Alder reaction have been
reported.8b,14 The indoloquinoline 14a was used as an
immediate precursor for the synthesis of a naturally
occurring alkaloid, 5-methyl-5H-indolo[2,3-b]quinoline
(15a ) (eq 1),15,16 which was isolated from the roots of the
West African plant Cryptolepis sanguinolenta17 and was
found to possess interesting biological activities.15
Sch em e 3
to the ketenimine 3d (R ) Pr), which furnished the
quinoline 5d preferentially. In addition, the carbodiimide
9d is thermally less labile than the ketenimine 3d , and
a higher temperature is needed to promote the reaction.
Treatment of 2d with phenyl isocyanate in refluxing
p-xylene without isolation of 9d also afforded 14d directly
in a one-step operation in 72% yield. With 9e having a
sterically very demanding tert-butyl group, thermolysis
in refluxing p-xylene for 14 h produced the indoloquino-
line 14e (76%). Again, the presence of a tert-butyl group
at the acetylenic terminus of 9e makes the formation of
13e via the concerted intramolecular Diels-Alder reac-
tion unlikely. With a phenyl substituent at the acetylenic
terminus of 9f, thermolysis under refluxing benzene (80
°C) for 4 h was sufficient to induce the transformation
to 14f18 in 91% yield. Direct thermolysis of the reaction
mixture of 2f and phenyl isocyanate in refluxing benzene
without isolation of 9f also afforded 14f in 67% yield.
The reaction sequence outlined in Scheme 2 could
provide an efficient route to the indoloquinoline 14a if
the competing pathway toward the quinoline 11a could
be suppressed. The result with 3b suggests that a
trimethylsilyl group at the acetylenic terminus could
serve as a surrogate for the hydrogen atom in directing
the reaction toward the indoloquinoline 14b. A subse-
quent protodesilylation reaction could lead to 14a . It was
gratifying to observe that thermolysis of 9b, obtained in
71% from 2b and phenyl isocyanate, in refluxing p-xylene
at 138 °C produced 14b in 86% yield. Similarly, heating
the reaction mixture of 2b and phenyl isocyanate in
refluxing p-xylene without isolation of 9b also gave 14b
(61%) in a single operation. Treatment of 14b with 6 N
NaOH in refluxing ethanol for 12 h then furnished 14a
in 92% yield.
4-Methoxyphenyl isocyanate was also used for the aza-
Wittig reaction with 2d and 2f. Thermolysis of the
reaction mixtures furnished the indoloquinolines 16d and
16f8b having a methoxy substituent at the C-2 position
(eq 2).
When 9c was subjected to thermolysis in p-xylene at
138 °C for 4 h, the indoloquinoline 14c (77%) was
produced exclusively, indicating a preferential formation
of 13c for subsequent tautomerization to 14c. The
corresponding quinoline 11c (R ) Me) was not detected.
Direct thermolysis of the reaction mixture of 2c and
phenyl isocyanate in refluxing p-xylene without isolation
of 9c also afforded 14c (59%) in a single operation. It was
reported that 14c could serve as the immediate precursor
of 5,11-dimethyl-5H-indolo[2,3-b]quinoline (15c) (eq 1),
which was found to display a strong antibacterial, anti-
mycotic, and cytotoxic activity in vitro, as well as
significant antitumor properties in vivo.15
An alternative pathway to the carbodiimides 9 was also
developed (Scheme 3). The Pd-catalyzed cross-coupling
reaction between 17 and 1-alkynes furnished methyl 2-(1-
alkynyl)benzoates 18, which were hydrolyzed to afford
19. Treatment of 19 with diphenyl phosphorazidate
Similarly, when 9d having a propyl group at the
acetylenic terminus was heated either in refluxing p-
xylene or in γ-terpinene at 138 °C, the indoloquinoline
14d (89%) was produced exclusively, in sharp contrast
(17) (a) Sharaf, M. H. M.; Schiff, P. L., J r.; Tackie, A. N.; Phoebe,
C. H., J r.; Martin, G. E. J . Heterocycl. Chem. 1996, 33, 239-243. (b)
Cimanga, K.; De Bruyne, T.; Pieters, L.; Claeys, M.; Vlietinck, A.
Tetrahedron Lett. 1996, 37, 1703-1706.
(16) Alajar´ın, M.; Molina, P.; Vidal, A. J . Nat. Prod. 1997, 60, 747-
748.
(18) Marsili, A. Tetrahedron 1968, 24, 4981-4991.

928 J . Org. Chem., Vol. 64, No. 3, 1999
Shi et al.
Sch em e 4
Sch em e 5
(DPPA)19 produced 2-(1-alkynyl)phenyl isocyanates 20.
The subsequent aza-Wittig reactions with the iminophos-
phorane 2120 then gave 9d and 9f. Thermolysis of the
reaction mixtures of 20d and 20f with 21 in refluxing
p-xylene also produced the indoloquinolines 14d (50%)
and 14f (55%), respectively.
It is straightforward to adopt the synthetic sequence
outlined in Scheme 2 for the preparation of 26a and 26b
(Scheme 4) as potential bifunctional DNA intercalating
agents.21 The use of the diacetylenes 22a and 22b for
cross coupling with 2 equiv of 2-iodoaniline eventually
allowed the connection of the two indoloquinoline units
in 26a and 26b with either a three-carbon or a five-
carbon tether at the 11 and 11′ positions. The imino-
phosphoranes 24a and 24b were generated in situ from
treatment of 23a and 23b with 2 equiv of Ph3PBr2 for
the subsequent aza-Wittig reaction with 2 equiv of phenyl
isocyanate, producing the carbodiimides 25a and 25b in
49% and 54% overall yield, respectively. It was possible
to isolate the iminophosphoranes 24a (20%) and 24b
(29%) by column chromatography (silica gel) albeit
significant decomposition on the column. Treatment of
the isolated 24a with 2 equiv of phenyl isocyanate
produced 25a in 72% yield. Thermolysis of 25a and 25b
in refluxing p-xylene then furnished 26a (74%) and 26b
(77%), respectively.
Treatment of 1,4-phenylene diisocyanate with 2 equiv
of 2g for the aza-Wittig reaction produced 27 in situ,
which on thermolysis in refluxing p-xylene furnished 31
(66%) having two indoloquinoline units incorporated in
the seven fused rings (Scheme 5). It was also possible to
isolate 27 by column chromatography (silica gel) in 44%
yield. The presence of the two n-octyl groups in 31 greatly
enhances its solubility in organic solvents.
The structure assignment of 31 is based on high-
1
resolution mass spectra, the H and 13C NMR spectra,
and the NOE studies. The molecular ion was detected
on a high-resolution mass spectrometer (m/z ) 582.3698).
1
The H and 13C NMR spectra showed the right number
of signals and pattern of multiplicity consistent with the
structure of 31. Interestingly, the 1H NMR spectrum
(Figure 1) exhibited two sets of signals with equal
intensity at δ 4.00 (2 H, ddd, J ) 12.9, 8.7, 4.2 Hz) and
3.74 (2 H, dt, J ) 13.4, 8.0 Hz), indicating that the
benzylic hydrogens are diastereotopic. The benzylic hy-
drogens are diastereotopic because the fused ring struc-
ture in 31 is helical due to nonbonded steric interactions
of the two n-octyl groups. This is reminiscent of the
structures of the 4,5-dimethylphenanthrenes, which have
been shown to possess a helical twist.22 The signals of
the benzylic hydrogens in DMSO-d6 remained well
separated and exhibited no line broadening even at 110
(19) (a) Shioiri, T.; Ninomiya, K.; Yamada, S.-i. J . Am. Chem. Soc.
1972, 94, 6203-6205. (b) Ninomiya, K.; Shioiri, T.; Yamada, S.
Tetrahedron 1974, 30, 2151-2157. (c) Rigby, J . H.; Balasubramanian,
N. J . Org. Chem. 1989, 54, 224-228.
(20) Horner, L.; Oediger, H. J ustus Liebigs Ann. Chem. 1959, 627,
142-162.
(21) Gribble, G. W.; Saulnier, M. G. J . Chem. Soc., Chem. Commun.
1984, 168-169.

Thermolysis of N-[2-(1-Alkynyl)phenyl]-N′-phenylcarbodiimides
J . Org. Chem., Vol. 64, No. 3, 1999 929
faster than that of tautomerization of 28 to 32 (Scheme
6). Without a prior tautomerization, the biradical 29 has
no choice but to cyclize to form 30, producing 31 after
two subsequent tautomerization reactions. Had the in-
termediate 28 underwent a tautomerization reaction to
form 32 prior to the second indoloquinoline formation,
one could have expected a preferential ring closure
leading to 33 without nonbonded steric interactions
between the two n-octyl groups. It is worth noting that
the indoloquinoline 31 having an extended aromatic ring
structure is potentially capable of intercalating DNA.23
Con clu sion s
Thermolysis of the carbodiimides 9 represents a new
way of generating biradicals from unsaturated molecules
having two nitrogen atoms in the conjugated system. The
cascade sequence outlined in Scheme 2 also provides an
efficient pathway to 6H-indolo[2,3-b]quinolines. The pos-
sibility of placing a wide variety of substituents at various
positions of the 6H-indolo[2,3-b]quinoline structure by
selecting suitable fragments for assembly is an especially
attractive feature of this synthetic route.
F igu r e 1. Partial 1H NMR spectrum of the indoloquinoline
31 in CDCl3.
Exp er im en ta l Section
Diethyl ether (Et2O) was distilled from benzophenone ketyl
prior to use. Triethylamine was distilled from CaH2. The 2-(1-
alkynyl)anilines 1 (83-100% yield) were prepared from 2-io-
doaniline according to the reported procedures.1,24 2-Iodo-
aniline was purchased from Oakwood Products, Inc., and was
used as received. 1-Alkynes were obtained from Farchan
Laboratories, Inc., and were used without further purification.
Iminophosphoranes 2 were prepared according to the reported
procedure.1,14a Dibromotriphenylphosphorane (Ph3PBr2), phen-
yl isocyanate, 4-methoxyphenyl isocyanate, 1,4-phenylene
diisocyanate, diphenyl phosphorazidate (DPPA), Pd(PPh3)2Cl2,
Pd(PPh3)4, p-xylene (anhydrous), N,N-dimethylformamide
(DMF), N,N-diisopropylethylamine, and γ-terpinene were
purchased from Aldrich and were used as received. Methyl
2-iodobenzoate was purchased from Lancaster. Melting points
are uncorrected. 1H (270 MHz) and 13C (67.9 MHz) NMR
spectra were recorded in CDCl3 using CHCl3 (1H δ 7.26) or
CDCl3 (13C δ 77.00) as internal standard unless otherwise
indicated.
2-(1-P r op yn yl)a n ilin e (1c). A suspension of 2.190 g of
2-iodoaniline (10.0 mmol), 0.190 g of copper(I) iodide (1.00
mmol), and 0.562 g of Pd(PPh3)2Cl2 (0.800 mmol) in 50 mL of
triethylamine was cooled to -78 °C under a nitrogen atmo-
sphere and degassed by freeze-pump-thaw. After the reaction
mixture was allowed to warm to room temperature, 672 mL
of gaseous propyne (27 mmol) was introduced with a gastight
syringe, and the resulting mixture was stirred at room
temperature for 27 h. The reaction mixture was then concen-
trated, and 200 mL of diethyl ether was added. The solid
suspension was removed by filtration, and the filtrate was
washed with water, dried over MgSO4, and concentrated. The
residue was purified by column chromatography (silica gel/
10% diethyl ether in hexanes) to furnish 1.310 g of 1c (10.0
mmol, 100%) as a yellow oil: IR (neat) 3469, 3374, 2044, 1614,
749 cm-1; 1H δ 7.25 (1 H, dd, J ) 8.2, 1.5 Hz), 7.08 (1 H, td, J
) 7.7, 1.5 Hz), 6.69-6.64 (2 H, m), 4.18 (2 H, br s), 2.11 (3 H,
s); 13C δ 147.61, 131.92, 128.74, 117.76, 114.10, 108.85, 90.96,
76.13, 4.51; MS m/z 131 (M+), 130, 103, 77.
Sch em e 6
°C, indicating that the rate of the helix inversion is
relatively slow on the NMR time scale even at 110 °C. A
significant nuclear Overhauser effect was observed be-
tween the doublet aromatic signal at δ 8.28 and the
benzylic signal at δ 4.00. However, the nuclear Over-
hauser effect was negligible with the benzylic signal at
δ 3.74. In addition, no NOE interaction between the
singlet aromatic signal at δ 8.23 and the two benzylic
signals was observed.
The observation of two sets of benzylic signals and the
lack of the NOE interaction with the singlet aromatic
signal at δ 8.23 preclude the cycloaromatized isomer 33
depicted in Scheme 6 as the reaction product. Because
33 has essentially a planar ring structure, one would
1
expect the H NMR signal of the benzylic hydrogens of
33 to be a simple triplet as in the case of 14d . Further-
more, one would also expect a strong NOE interaction
between the benzylic hydrogens and the singlet aromatic
hydrogens.
(23) (a) Pindur, U.; Erfanian-Abdoust, H. Liebigs Ann. Chem. 1988,
803-805. (b) Pindur, U.; Erfanian-Abdoust, H. Chem. Rev. 1989, 89,
1681-1689.
The preferential formation of 31 is presumably because
the rate of transformation from 28 to 30 (Scheme 5) is
(24) (a) Villemin, D.; Goussu, D. Heterocycles 1989, 29, 1255-1261.
(b) Arcadi, A.; Cacchi, S.; Marinelli, F. Tetrahedron Lett. 1989, 30,
2581-2584. (c) Iritani, K.; Matsubara, S.; Utimoto. K. Tetrahedron Lett.
1988, 29, 1799-1802.
(22) (a) Armstrong, R. N.; Ammon, H. L.; Darnow, J . N. J . Am.
Chem. Soc. 1987, 109, 2077-2082. (b) Newman, M. S.; Hussey, A. S.
J . Am. Chem. Soc. 1947, 69, 3023-3027.

930 J . Org. Chem., Vol. 64, No. 3, 1999
Shi et al.
2-(1-P r op yn yl)-N-(t r ip h en ylp h osp h or a n ylid en e)b en -
zen a m in e (2c). To 4.220 g of Ph3PBr2 (10.0 mmol) were added
1.310 g of 1c (10.0 mmol), 2.78 mL of anhydrous triethylamine,
and 100 mL of anhydrous benzene under a nitrogen atmo-
sphere. The reaction mixture was heated under reflux for 4 h.
The white triethylammonium bromide precipitate was re-
moved by filtration, and the filtrate was concentrated. The
residue was purified by column chromatography (silica gel/
40-60% diethyl ether in hexanes) to furnish 2.776 g (7.10
mmol, 71%) of 2c as colorless crystals: IR (KBr) 3088, 1605,
734 cm-1; 1H δ 7.9-7.77 (6 H, m), 7.6-7.4 (9 H, m), 7.30 (1 H,
dt, J ) 7.4, 2.0 Hz), 6.82 (1 H, td, J ) 7.7, 1.6 Hz), 6.58 (1 H,
t, J ) 7.4 Hz), 6.49 (1 H, d, J ) 8.2 Hz), 2.16 (3 H, s); 13C δ
152.48, 132.68 (d, J ) 9.8 Hz), 132.65, 131.54 (d, J ) 2.6 Hz),
131.38 (d, J ) 100.5 Hz), 128.43 (d, J ) 11.9 Hz), 127.68,
121.58 (d, J ) 9.3 Hz), 119.32 (d, J ) 21.2 Hz), 117.08, 87.70,
80.76, 4.95.
11-(Tr im eth ylsilyl)-6H-in d olo[2,3-b]qu in olin e (14b). A
solution of 0.216 g of 9b (0.745 mmol) in 3.0 mL of p-xylene
was heated under reflux for 5 h. The reaction mixture was
then concentrated, and the residue was purified by flash
chromatography (silica gel/20-50% diethyl ether in hexanes)
to afford 0.186 g (0.641 mmol, 86%) of 14b as bright pale yellow
crystals: mp 247-248 °C; IR (KBr) 3060, 1252, 864, 842, 743
1
cm-1; H δ 11.79 (1 H, br s, NH), 8.53 (1 H, d, J ) 8.4 Hz),
8.26 (1 H, d, J ) 7.9 Hz), 8.24 (1 H, dd, J ) 7.9, 1.1 Hz), 7.78
(1 H, ddd, J ) 8.2, 6.8, 1.3 Hz), 7.60-7.46 (3 H, m), 7.28 (1 H,
ddd, J ) 8.2, 6.9, 1.6 Hz), 0.80 (9 H, s); 13C δ 152.14, 145.15,
144.57, 141.81, 129.21, 128.46, 128.38, 127.81, 127.12, 126.44,
125.18, 122.21, 121.54, 119.17, 110.87, 2.57; MS m/z 290 (M+),
275, 259, 245, 231, 218, 73; HRMS calcd for C18H18N2Si
290.1239, found 290.1242.
The indoloquinoline 14b (61% yield) was also synthesized
in a one-pot operation from 2b and phenyl isocyanate without
isolation of 9b.
N-(2-Eth yn ylph en yl)-N′-ph en ylcar bodiim ide (9a).16 The
following procedure for the preparation of 9a is representative.
To 0.377 g of 2a (1.00 mmol) was introduced a solution of 0.119
g of phenyl isocyanate (1.00 mmol) in 15 mL of anhydrous
benzene via cannula under a nitrogen atmosphere at room
temperature. After 1 h, the reaction mixture was concentrated
in vacuo, and the residue was purified by column chromatog-
raphy (silica gel/5% diethyl ether in hexanes) to furnish 0.181
g (0.83 mmol, 83%) of 9a as a yellow oil: IR (neat) 3285, 2258,
11-P r op yl-6H-in d olo[2,3-b]qu in olin e (14d ). A solution of
0.368 g of 9d (1.42 mmol) in 4.0 mL of p-xylene was heated
under reflux for 5 h. The reaction mixture was then concen-
trated, and the residue was purified by flash chromatography
(silica gel/20-50% diethyl ether in hexanes) to afford 0.329 g
(1.27 mmol, 89%) of 14d as golden yellow crystals: mp 245-
1
246 °C; IR (KBr) 3455, 1611, 739 cm-1; H δ 12.23 (1 H, br s,
NH), 8.30 (1 H, d, J ) 8.4 Hz), 8.22 (1 H, d, J ) 8.2 Hz), 8.17
(1 H, d, J ) 7.9 Hz), 7.77 (1 H, d, J ) 7.6 Hz), 7.6-7.48 (3 H,
m), 7.31 (1 H, t, J ) 7.6 Hz), 3.65 (2 H, t, J ) 8.0 Hz), 1.98 (2
H, sextet, J ) 7.6 Hz), 1.24 (3 H, t, J ) 7.4 Hz); 13C δ 153.44,
146.26, 144.31, 141.38, 128.71, 127.45, 127.04, 124.17, 123.41,
122.67, 121.39, 119.99, 116.63, 110.93, 30.93, 22.92, 14.70; MS
m/z 260 (M+), 231. Anal. Calcd for C18H16N2: C, 83.05; H, 6.19;
N, 10.76. Found: C, 82.86; H, 6.16; N, 10.67.
1
2139, 2103, 1592, 754, 689 cm-1; H δ 7.49 (1 H, dd, J ) 7.6,
1.4 Hz), 7.37-7.28 (3 H, m), 7.25-7.10 (5 H, m), 3.26 (1 H, s);
13C δ 140.58, 138.34, 133.60, 129.90, 129.37, 125.50, 125.14,
124.47, 124.40, 118.30, 83.88, 80.19; MS m/z 218 (M+), 190,
114, 89, 77; HRMS calcd for C15H10N2 218.0844, found 218.0837.
N-[2-(1-P en tyn yl)p h en yl]-N′-p h en ylca r bod iim id e (9d ).
The same procedure was repeated as described for 9a except
that 0.871 g of 2d (2.08 mmol) was treated with 0.248 g of
phenyl isocyanate (2.08 mmol) in 30 mL of anhydrous benzene
to afford 0.427 g (1.64 mmol, 79%) of 9d as a yellow oil: IR
The indoloquinoline 14d (72% yield) was also synthesized
in a one-pot operation from 2d and phenyl isocyanate without
isolation of 9d .
1
(neat) 2247, 2143, 2107, 1592, 756, 689 cm-1; H δ 7.44 (1H,
Alternatively, 14d was also synthesized by treatment of 20d
with 21. To 0.247 g of the iminophosphorane 2120 (0.700 mmol)
in 10 mL of p-xylene was introduced via cannula a solution of
0.13 g of 2-(1-pentynyl)phenyl isocyanate (20d , 0.70 mmol) in
10 mL of p-xylene under a nitrogen atmosphere. After 2 h at
room temperature, the reaction mixture was heated under
reflux for 12 h. The reaction mixture was then concentrated,
and the residue was purified by flash chromatography (silica
gel/30% diethyl ether in hexanes) to afford 0.091 g (0.35 mmol,
50%) of 14d .
dd, J ) 7.9, 1.5 Hz), 7.4-7.08 (8 H, m), 2.10 (2 H, t, J ) 7.2
Hz), 1.46 (2 H, sextet, J ) 7.3 Hz), 0.93 (3 H, t, J ) 7.3 Hz);
13C δ 139.16, 138.72, 133.65, 133.01, 129.25, 128.39, 125.12,
125.05, 124.25, 124.19, 120.78, 98.70, 76.87, 21.69, 21.53,
13.40; MS m/z 260 (M+), 245, 231, 218; HRMS calcd for
C
18H16N2 260.1314, found 260.1312.
Alternatively, 9d was also synthesized by treatment of 20d
with 21. To 0.247 g of the iminophosphorane 2120 (0.700 mmol)
in 10 mL of anhydrous benzene was introduced via cannula a
solution of 0.13 g of 2-(1-pentynyl)phenyl isocyanate 20d (0.70
mmol) in 10 mL of dry benzene under a nitrogen atmosphere
at room temperature. After 1 h, the reaction mixture was
concentrated in vacuo, and the residue was purified by flash
column chromatography (silica gel/7% benzene in hexanes) to
afford 0.093 g (0.358 mmol, 51%) of 9d .
2-Meth oxy-11-p r op yl-6H-in d olo[2,3-b]qu in olin e (16d ).
To a solution of 0.650 g of 2d (1.55 mmol) in 10 mL of
anhydrous p-xylene was added via cannula a solution of 0.231
g of 4-methoxyphenyl isocyanate (1.55 mmol) in 10 mL of
anhydrous p-xylene under a nitrogen atmosphere. The reaction
mixture was heated under reflux for 5 h and then concen-
trated. The residue was purified by flash chromatography
(silica gel/20-50% diethyl ether in hexanes) to afford 0.212 g
(0.731 mmol, 47%) of 16d as a pale yellow solid: mp 236-238
°C; IR (KBr) 3417, 1633, 1613, 1232, 823, 724 cm-1; 1H δ 9.66
(1 H, br s, NH), 8.18 (1 H, d, J ) 7.9 Hz), 8.04 (1 H, d, J ) 9.2
Hz), 7.56-7.49 (3 H, m), 7.45 (1 H, dd, J ) 9.2, 2.6 Hz), 7.34-
7.28 (1 H, m), 4.01 (3 H, s), 3.62 (2 H, t, J ) 8.0 Hz), 1.98 (2
H, sextet, J ) 7.6 Hz), 1.23 (3 H, d, J ) 7.4 Hz); 13C (DMSO-
d6) δ 154.70, 151.30, 142.14, 141.53, 141.34, 128.97, 127.31,
123.25, 120.56, 120.27, 119.44, 115.43, 110.68, 102.60, 55.37,
29.95, 22.27, 14.21; MS m/z 290 (M+), 275, 261, 246, 218;
HRMS calcd for C19H18N2O 290.1419, found 290.1420.
Meth yl 2-(1-P en tyn yl)ben zoa te (18d ). To a degassed
solution containing 1.755 g of Pd(PPh3)2Cl2 (2.50 mmol), 0.488
g of CuI (2.56 mmol), 6.55 g of methyl 2-iodobenzoate (17, 25.0
mmol), and 14.0 mL of N,N-diisopropylethylamine (80.4 mmol)
in 80 mL of DMF was added via cannula a degassed solution
of 3.4 g (4.9 mL) of 1-pentyne (50 mmol) in 25 mL of DMF.
After 24 h at room temperature, the reaction mixture was
poured into a flask containing 200 mL of a saturated NH4Cl
solution and 200 mL of pentane. After filtration, the organic
layer was separated, washed with water, dried over MgSO4,
and concentrated. The residue was distilled in vacuo to afford
2-(P h en yla m in o)qu in olin e (11a )8b,16 a n d 6H-In d olo[2,3-
b]qu in olin e (14a ).15,16 A solution of 0.182 g (0.835 mmol) of
9a in 2.0 mL of γ-terpinene was heated under a nitrogen
atmosphere at 138 °C for 14 h. After the reaction mixture was
cooled to room temperature, a pale yellow solid precipitated
out of the solution and coated the inside wall of the flask. The
γ-terpinene solution was removed with a pipet, and the
remaining solid was washed with benzene and dried in vacuo
to give 0.029 g (0.13 mmol, 16%) of 14a (mp 338-340 °C (lit.16
mp 342-346 °C)) as a pale yellow solid. The combined solution
of benzene and γ-terpinene was concentrated in vacuo, and
the residue was purified by preparative thin-layer chroma-
tography (silica gel/40% diethyl ether in hexanes) to furnish
0.090 g (0.41 mmol, 49%) of 11a (mp 101-103 °C (lit.8b 103-
104 °C)) as a yellow solid.
The indoloquinoline 14a was also obtained by heating a
suspension of 0.076 g of 14b (0.26 mmol) over 0.5 mL of a 6 N
sodium hydroxide solution and 0.5 mL of ethanol under reflux
for 12 h. Then, the reaction mixture was cooled to room
temperature, and 0.5 mL of water was added. The supernatant
liquid was removed with a pipet, and the residue was washed
with water and dichloromethane to give 0.053 g of 14a (0.24
mmol, 92%).

Thermolysis of N-[2-(1-Alkynyl)phenyl]-N′-phenylcarbodiimides
5.00 g (24.8 mmol, 99%) of 18d as a light yellow oil: IR (neat)
J . Org. Chem., Vol. 64, No. 3, 1999 931
triethylamine, and 40 mL of anhydrous benzene was heated
under reflux for 5 h. Triethylammonium bromide was removed
by filtration, and the filtrate was concentrated. The crude 24a
was used directly without further purification. To the crude
24a in 20 mL of anhydrous benzene was introduced via
cannula a solution of 0.953 g (8.01 mmol) of phenyl isocyanate
in 60 mL of anhydrous benzene under a nitrogen atmosphere
at room temperature. After 4 h, the reaction mixture was
concentrated in vacuo, and the residue was purified by column
chromatography (silica gel/5% diethyl ether in hexanes) to
afford 0.941 g (1.98 mmol, 49% overall yield from 23a ) of 25a
2234, 1731, 757, 702 cm-1 1H δ 7.84 (1 H, dd, J ) 7.9, 1.5
;
Hz), 7.47 (1 H, dd, J ) 7.8, 1.4 Hz), 7.36 (1 H, td, J ) 7.7, 1.5
Hz), 7.25 (1 H, td, J ) 7.4, 1.5 Hz), 3.86 (3 H, s), 2.41 (2 H, t,
J ) 7.1 Hz), 1.62 (2 H, sextet, J ) 7.2 Hz), 1.03 (3 H, t, J )
7.4 Hz); 13C δ 166.74, 133.99, 131.74, 131.26, 129.92, 126.92,
124.28, 95.61, 79.21, 51.80, 21.97, 21.57, 13.36; MS m/z 202
(M+), 174, 159, 143.
2-(1-P en tyn yl)ben zoic Acid (19d ). A solution of 5.000 g
(24.75 mmol) of 18d in 30 mL of THF and 140 mL of 1 N NaOH
was heated at 50 °C for 12 h. The reaction mixture was cooled
in an ice-water bath and was acidified with dilute HCl. The
organic layer was separated, washed with water, dried over
MgSO4, and concentrated. The residue was purified by recrys-
tallization from 50% of diethyl ether in hexanes to afford 4.354
g (23.16 mmol, 94%) of 19d as pale yellow needles: IR 2962,
as a yellow oil: IR (neat) 2136, 2102, 1590, 1482, 754 cm-1
;
1H δ 7.37 (2 H, dd, J ) 7.7, 1.7 Hz), 7.3-7.18 (10 H, m), 7.13-
7.06 (6 H, m), 2.11 (4 H, t, J ) 7.2 Hz), 1.48 (2 H, quintet, J
) 7.2 Hz); 13C δ 139.05, 138.78, 133.69, 133.11, 129.34, 128.64,
125.20, 124.33, 124.22, 120.54, 97.51, 77.35, 26.94, 18.93; MS
m/z 476 (M+), 359, 277, 194; HRMS calcd for C33H24N4
476.2001, found 476.2012.
1
2234, 1692, 757 cm-1; H δ 11.4 (1 H, br), 8.06 (1 H, dd, J )
7.9, 1.1 Hz), 7.55 (1 H, dd, J ) 7.7, 1.2 Hz), 7.48 (1 H, td, J )
7.4, 1.5 Hz), 7.35 (1 H, td, J ) 7.4, 1.5 Hz), 2.47 (2 H, t, J )
7.0 Hz), 1.68 (2 H, sextet, J ) 7.4 Hz), 1.09 (3 H, t, J ) 7.4
Hz); 13C δ 171.53, 134.31, 132.34, 131.06, 130.64, 127.27,
124.91, 97.24, 79.00, 21.95, 21.77, 13.50; MS m/z 188 (M+),
160, 159, 131, 118; HRMS calcd for C12H12O2 188.0837, found
188.0829.
The carbodiimide 25a was also obtained by treatment of the
purified 24a with phenyl isocyanate. To 0.156 g of 24a (0.196
mmol) in 10 mL of anhydrous benzene was introduced via
cannula a solution of 0.047 g of phenyl isocyanate (0.39 mmol)
in 5 mL of anhydrous benzene under a nitrogen atmosphere
at room temperature. After 4 h, the reaction mixture was
concentrated in vacuo, and the residue was purified by flash
chromatography (silica gel/2% diethyl ether in hexanes) to
afford 0.067 g (0.141 mmol, 72%) of 25a .
2-(1-P en tyn yl)p h en yl Isocya n a te (20d ). To a solution of
3.22 g (17.1 mmol) of 19d in 30 mL of anhydrous benzene were
added 2.4 mL of triethylamine and 3.83 mL (17.8 mmol) of
DPPA. After 3 h at room temperature, the reaction mixture
was heated at reflux for 2 h until the nitrogen gas evolution
had ceased. The reaction mixture was then washed with a
saturated NH4Cl solution, water, dried over MgSO4, and
concentrated. The residue was purified by flash chromatog-
raphy (silica gel/3% diethyl ether in hexanes) to afford 2.48 g
(13.41 mmol, 78%) of 20d as a colorless oil: IR (neat) 2244,
In d oloqu in olin e 26a . A solution of 0.246 g (0.52 mmol) of
25a in 80 mL of p-xylene was heated under reflux for 5 h. After
the reaction mixture was cooled to room temperature, the
yellow precipitate was separated by centrifugation. After two
cycles of heating the precipitate in 20 mL of p-xylene at 60 °C
followed by centrifugation and decanting the supernatant
liquid, the remaining solid was pumped to dryness in vacuo
to afford 0.183 g (0.384 mmol, 74%) of 26a as a yellow solid:
IR 1699, 870, 755 cm-1; 1H (DMSO-d6) δ 11.69 (2 H, br s, NH),
8.56 (2 H, d, J ) 8.3 Hz), 7.99 (2 H, d, J ) 8.4 Hz), 7.75-7.68
(4 H, m), 7.51 (2 H, t, J ) 7.6 Hz), 7.40 (4 H, d, J ) 3.9 Hz),
6.95 (2 H, m, J ) 4.2 Hz), 3.96 (4 H, t, J ) 7.3 Hz), 2.33 (2 H,
m); 13C (DMSO-d6) δ 153.02, 147.01, 143.06, 141.86, 129.11,
128.23, 128.03, 124.90, 123.72, 123.45, 123.26, 120.70, 119.95,
116.00, 111.28, 30.16, 28.28; MS m/z 476 (M+), 401, 375, 277,
245, 232; HRMS calcd for C33H24N4 476.2001, found 476.2025.
Ca r bod iim id e 27. To 2.876 g (5.88 mmol) of 2g in 10 mL
of anhydrous benzene was introduced via cannula a solution
of 0.471 g (2.94 mmol) of 1,4-phenylene diisocyanate in 60 mL
of anhydrous benzene under a nitrogen atmosphere at room
temperature. After 2 h, the reaction mixture was concentrated
in vacuo, and the residue was purified by column chromatog-
raphy (silica gel/2% diethyl ether in hexanes) to afford 0.75 g
(1.29 mmol, 44%) of 27 as a colorless liquid: IR 2103, 836,
1599, 1506, 755 cm-1 1H δ 7.40 (1 H, dd, J ) 7.7, 1.7 Hz),
;
7.20 (1 H, td, J ) 7.2, 1.7 Hz), 7.10 (1 H, td, J ) 7.5, 1.5 Hz),
7.00 (1 H, dd, J ) 7.9, 1.2 Hz), 2.50 (2 H, t, J ) 7.1 Hz), 1.72
(2 H, sextet, J ) 7.2 Hz), 1.10 (3 H, t, J ) 7.4 Hz); 13C δ 135.10,
131.95, 128.38, 127.38, 125.10, 123.19, 121.52, 99.38, 76.36,
21.62, 21.49, 13.46; MS m/z 185 (M+), 170, 156, 130, 128;
HRMS calcd for C12H11NO 185.0841, found 185.0849.
An ilin e 23a . To a degassed solution containing 0.702 g of
Pd(PPh3)2Cl2 (1.00 mmol), 0.19 g of CuI (1.00 mmol), 4.60 g of
2-iodoaniline (21.0 mmol), and 80 mL of Et3N was added 1.17
mL of 1,6-heptadiyne (22a , 10.2 mmol). After 16 h at room
temperature, the reaction mixture was heated at 45 °C for 8
h. Then the reaction mixture was poured into a flask contain-
ing 200 mL of a saturated NH4Cl solution and 100 mL of Et2O.
After filtration, the organic layer was separated, washed with
water, dried over MgSO4, and concentrated. The residue was
purified by flash column chromatography (silica gel/50%
diethyl ether in hexanes) to furnish 2.415 g (8.814 mmol, 86%)
755 cm-1; H δ 7.39 (2 H, dm, J ) 7.7, 2 Hz), 7.22 (2 H, td, J
1
of 23a as a yellow oil: IR (neat) 3467, 3371, 1612, 748 cm-1
;
) 6.9, 1.7 Hz), 7.17 (4 H, s), 7.10 (4 H, t, J ) 7.2 Hz), 2.13 (4
H, t, J ) 6.9 Hz), 1.43 (4 H, quintet, J ) 7.2 Hz), 1.24 (20 H,
br), 0.87 (6 H, t, J ) 6.6 Hz); 13C δ 138.56, 136.28, 133.70,
133.10, 128.48, 125.33, 125.12, 124.36, 120.91, 99.10, 76.79,
31.83, 29.19, 29.12, 28.99, 28.36, 22.66, 19.80, 14.11.
1H δ 7.30 (2 H, dd, J ) 8.0, 1.4 Hz), 7.13 (2 H, td, J ) 8.5, 1.5
Hz), 6.74-6.69 (4 H, m), 4.21 (4 H, br s, NH), 2.69 (4 H, t, J
) 6.9 Hz), 1.94 (2 H, quintet, J ) 7.0 Hz), 13C δ 147.61, 131.92,
128.88, 117.66, 114.06, 108.37, 94.22, 77.77, 27.82, 18.70; MS
m/z 274 (M+), 207, 191, 144, 131.
In d oloqu in olin e 31. To a solution of 0.14 g (0.286 mmol)
of 2g in 10 mL of anhydrous p-xylene was added via cannula
a solution of 0.023 g (0.144 mmol) of 1,4-phenylene diisocy-
anate in 50 mL of anhydrous p-xylene under a nitrogen
atmosphere at room temperature. After 1 h, the reaction
mixture was heated under reflux for 6 h. The reaction mixture
was then concentrated, and the residue was purified by column
chromatography (silica gel/20% diethyl ether and 5% ethanol
in hexanes) to afford 0.055 g (0.094 mmol, 66%) of 31 as a
yellow solid: IR 1600, 818, 735 cm-1; 1H δ 11.08 (2 H, s), 8.28
(2 H, d, J ) 7.9 Hz), 8.23 (2 H, s), 7.74 (2 H, d, J ) 8.1 Hz),
7.62 (2 H, t, J ) 7.4 Hz), 7.43 (2 H, t, J ) 7.3 Hz), 4.00 (2 H,
ddd, J ) 12.9, 8.7, 4.2 Hz), 3.74 (2 H, dt, J ) 13.4, 8.0 Hz),
1.79 (2 H, br), 1.62 (2 H, br), 1.15-0.82 (20 H, m), 0.67 (6 H,
Im in op h osp h or a n e 24a . The reaction mixture of 0.965 g
(3.52 mmol) of 23a , 3.12 g (7.39 mmol) of Ph3PBr2, 2.0 mL of
anhydrous triethylamine, and 30 mL of anhydrous benzene
was heated under reflux for 5 h. Triethylammonium bromide
was removed by filtration, and the filtrate was concentrated.
The residue was purified through a short column (silica gel/
40% diethyl ether and 5% ethanol in hexanes) to afford 0.565
g (0.711 mmol, 20%) of 24a as colorless crystals: IR 1583, 1477,
1435, 694 cm-1; 1H δ 7.81 (12 H, m), 7.44 (18 H, m), 7.32 (2 H,
dt, J ) 7.7, 2.1 Hz), 6.84 (2 H, td, J ) 7.7, 1.6 Hz), 6.59 (2 H,
t, J ) 7.2 Hz), 6.52 (2 H, d, J ) 7.9 Hz), 2.72 (4 H, t, J ) 7.2
Hz), 2.07 (2 H, quintet, J ) 7.2 Hz); 13C δ 152.27, 133.94,
132.64 (d, J ) 9.8 Hz), 131.56 (d, J ) 2.6 Hz), 131.15 (d, J )
99.9 Hz), 128.44 (d, J ) 11.9 Hz), 127.68, 121.63 (d, J ) 9.3
Hz), 119.39 (d, J ) 22.3 Hz), 117.13, 91.67, 81.97, 29.05, 19.68.
Ca r bod iim id e 25a . A mixture of 1.096 g (4.00 mmol) of
23a , 3.518 g (8.33 mmol) of Ph3PBr2, 2.2 mL of anhydrous
1
t, J ) 7.0 Hz); H (DMSO-d6) δ 11.96 (2 H, s), 8.23 (2 H, d, J
) 8.1 Hz), 7.90 (2 H, s), 7.58 (2 H, d, J ) 7.3 Hz), 7.53 (2 H, t,
J ) 8.1 Hz), 7.32 (2 H, t, J ) 6.9 Hz), 3.96 (2 H, m), 3.59 (2 H,
m), 1.48 (2 H, br), 1.22 (2 H, br), 1.05-0.56 (26 H, m); 13C δ

932 J . Org. Chem., Vol. 64, No. 3, 1999
Shi et al.
152.01, 145.65, 140.35, 130.17, 126.97, 123.39, 121.49, 120.40,
119.74, 115.05, 111.28, 33.89, 31.58, 29.90, 29.18, 28.87, 22.41,
13.94; 13C (DMSO-d6) δ 151.98, 146.07, 144.40, 140.96, 130.85,
127.20, 123.61, 120.94, 120.37, 119.43, 113.94, 111.59, 32.70,
31.47, 29.48, 28.66, 28.38, 28.24, 22.33, 14.31; MS m/z 582
(M+), 469, 384, 371, 272; HRMS calcd for C40H46N4 582.3722,
found 582.3698.
of the National Science Foundation (CHE-9618676) is
gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, spectroscopic and analytical data for 2g, 9b,c,e,f,
14c,e,f, 16f, 18f, 19f, 20f, 23b, 24b, 25b, and 26b, and 1H
and 13C NMR spectra for compounds 1c,g, 2c,g, 9a -f, 14b-f,
16d ,f, 18d ,f, 19d ,f, 20d ,f, 23a ,b, 24a ,b, 25a ,b, 26a ,b, 27, and
31 (76 pages). See any current masthead page for ordering
and Internet access information.
Ack n ow led gm en t. We thank Professor Peter Gan-
nett (School of Pharmacy, West Virginia University) for
performing the NOE experiments. The financial support
J O981845K