Gas-phase domino cyclization of phosphonium ylides leading to the total synthesis of Eustifoline D

Article abstract of DOI:10.1016/j.tetlet.2017.09.073

Six stabilised phosphonium ylides bearing ortho-benzylaminophenyl and cinnamoyl (or a heterocyclic analogue) groups have been prepared and upon flash vacuum pyrolysis at 800 °C were found to undergo cascade cyclization processes to give mainly 3-styrylquinolines but also in some cases ring-fused carbazoles and other fused-ring heterocyclic products. By starting with an appropriate ring-methylated precursor the natural product Eustifoline D was obtained in 19% yield in the pyrolysis in addition to the 3-(2-furylethenyl)quinoline (46%).

Full text of DOI:10.1016/j.tetlet.2017.09.073

Accepted Manuscript
Gas-phase domino cyclisation of phosphonium ylides leading to the total syn-
thesis of Eustifoline D
R. Alan Aitken, Lorna Murray
PII:
S0040-4039(17)31209-1
https://doi.org/10.1016/j.tetlet.2017.09.073
TETL 49343
DOI:
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
11 August 2017
18 September 2017
25 September 2017
Please cite this article as: Aitken, R.A., Murray, L., Gas-phase domino cyclisation of phosphonium ylides leading
to the total synthesis of Eustifoline D, Tetrahedron Letters (2017), doi: https://doi.org/10.1016/j.tetlet.2017.09.073
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Gas-phase domino cyclisation of
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R. Alan Aitken and Lorna Murray

1
Tetrahedron Letters
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Gas-phase domino cyclisation of phosphonium ylides leading to the total
synthesis of Eustifoline D
R. Alan Aitkena, * and Lorna Murraya
a EaStCHEM School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, U.K.
* e-mail: raa@st-and.ac.uk
ARTICLE INFO
ABSTRACT
Article history:
Received
Six stabilised phosphonium ylides bearing ortho-benzylaminophenyl and cinnamoyl (or a
heterocyclic analogue) groups have been prepared and upon flash vacuum pyrolysis at 800 °C
were found to undergo cascade cyclization processes to give mainly 3-styrylquinolines but also
in some cases ring-fused carbazoles and other fused-ring heterocyclic products. By starting with
an appropriate ring-methylated precursor the natural product Eustifoline D was obtained in 19%
yield in the pyrolysis in addition to the 3-(2-furylethenyl)quinoline (46%).
Received in revised form
Accepted
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved.
Cyclization
Gas-phase reaction
Phosphorus ylides
Fused-ring systems
Radical reaction
There has been considerable recent interest in the application
of flash vacuum pyrolysis (FVP) to the synthesis of a wide range
other carbazole alkaloids, some of which possess useful
medicinal activity. This activity has attracted a good deal of
synthetic interest in such carbazole alkaloids,12 but to date there
have only been two
of heterocyclic compounds,1 and despite
a
common
misapprehension that the technique involves overly harsh
conditions which are incompatible with sensitive functional
groups, it has been used in natural product synthesis in a few
cases.2 In previous work, we have combined the pyrolytic
generation of an alkyne functional group from an oxo-stabilised
phosphonium ylide with the generation of an ortho phenoxy or
phenylthio radical, leading to intramolecular cyclization to give
benzofurans and benzothiophenes (Scheme 1).3,4 This was later
extended to domino cyclization methods leading to tri- and tetra-
cyclic fused ring heterocycles.5,6 More recent developments have
included the observation of an eight-stage cascade process,7 the
synthesis of thieno[2,3-b]pyridines,8 and an application of this
approach to the formation of benzopyranones.9 However all these
studies have involved O or S as the cyclizing atom and the
corresponding process involving cyclization of N to give indoles
is much less developed. There is only one report of this process,
and it shows that the situation is complicated in the case of N-
methyl ylides by the possibility of N to C transfer of the reactive
centre leading to quinoline products rather than the expected N-
methylindoles in some cases.10 Despite this problem, ring-fused
carbazoles were obtained and among these was N-
methylfuro[2,3-c]carbazole 1 (Scheme 2) which was obtained in
65% yield by FVP of the appropriate ylide at 700 °C.
We noticed that this was isomeric with the natural product
Eustifoline D, 2 isolated in 1990 by Furukawa and co-workers11
from the shrub Murraya euchrestifolia Hayata along with many
Scheme 1. Summary of previous cyclizations with OMe and
SMe as the radical-generating group

2
Tetrahedron Letters
previous syntheses of 2.13,14 These both involve initial
butyllithium, with phosphonium salt 6 and we had to resort to the
less convenient sodium hydride. This route also suffers from the
drawback that half of the phosphonium salt is wasted in the
inevitable "transylidation"22 that accompanies the use of an acid
chloride for acylation, effectively absorbing HCl from the
initially formed acylphosphonium salt to regenerate 0.5 equiv. of
the chloride corresponding to 6. Substituting the appropriate N-
carbazole synthesis followed by installation of the furan ring in
the last steps. Herein, we report a new and conceptually distinct
synthesis of 2 in which the two central rings of the target
compound are formed by cyclization onto an alkyne in a single
gas-phase step from a precursor already containing the remaining
benzene and furan rings. Similar cascade cyclization processes
Scheme 2. Structures of previously obtained 1 and the
isomeric natural product target 2
leading to tetracyclic fused ring products have recently been
reported for alkynes containing aromatic OMe groups with
cyclizations initiated by a carbodiimide,15 isocyanate16 or
iodine,17 SMe groups and iodination with18 or without19 a gold
catalyst, and NMe2 groups with iodine20 or a palladium or copper
catalyst.21
In our previous work,10 there was always an N-methyl group
present, but it was found that either N-methanesulfonyl or N-
benzyl could act as a suitable radical-generating leaving group.
To test whether having both of these groups present might lead to
an aminyl radical for cyclization and ultimate loss of the other
group to form the NH product, ylide 7 was prepared as shown in
Scheme 3.
Scheme 4. Synthesis of the model ylides 12a-d and ring-
methylated phosphonium salt 24
acylbenzotriazole, as first applied in synthesis of peptide-derived
ylides,23 overcomes this problem. An improved synthetic route
(Scheme 4) was thus developed and used to access the four
model ylides 12a-d, which were designed to explore the viability
of the cascade cyclization to give tetracyclic NH carbazole
products as well as the compatibility with the presence of a ring
methyl substituent (12b). These compounds were obtained as
stable highly crystalline solids but their analysis by NMR
spectroscopy was difficult due to restricted rotation, meaning that
satisfactory 13C NMR data could only be obtained at 55 °C. Once
this data was obtained however, the highly consistent pattern of
31P coupling provided good confirmation of the structures, and
the low value of 6 Hz for 2JP–CO meant that the Ph3PO elimination
was likely to be successful.24,25
When ylides 12a–d were subjected to FVP, the desired
elimination of Ph3PO readily occurred but the pattern of
heterocyclic products obtained was more complex than expected.
At the low temperature of 500 °C, FVP of furyl compound 12c
Scheme 3. Synthesis and FVP of ylide 7
Table 1. Products from the FVP of ylides 12a-d at 800 °C
Comp
ound
12a
Isolated Yield (%)
When this was subjected to FVP at 700 °C, the required
benzo[c]carbazole 8 was formed albeit in only 14% yield.
X
16
18
18
19 E-20 Z-20 21
35
CH=CH
–
–
9
–
The presence of the N-methanesulfonyl group led to
competitive deprotonation when using the typical base, n-

3
12b
12c
CMe=CH
O
–
–
–
–
31
39
21
2
–
–
12d
S
15
–
–
35
6
5
10
25
Scheme 5. Proposed mechanisms for the pyrolysis of 12a-d to give 13, 16, 18, 19, 20 and 21
gave a moderate yield of enyne 13, thus confirming the
occurrence of the desired initial step. When the temperature
was increased, complete reaction was achieved at 800 °C to
give Ph3PO, bibenzyl and a variety of heterocyclic products
(Scheme 5, Table 1).
FVP at 800 °C gave a mixture of two compounds, which
were readily separable by chromatography: E-3-alkenyl-6-
methylquinoline 26 (46%) and Eustifoline D 2 (19%). The
latter showed H NMR data which was in close agreement
with the naturally-derived material (Table 2).11
1
It appears that the initially formed aminyl radical 14
equilibrates with the isomeric benzylic C-centred radical 15,
and in fact the latter is favoured compared to the
corresponding situation with N-methyl.10 Thus, although
some cyclization of 14 leading to the ring-fused carbazoles
16 was observed for the phenyl 12a and thienyl 12d
substituted compounds, the major products in all four cases
were the (E)- and (Z)-3-alkenylquinolines 20. Perhaps the
most surprising observation is that these are generally
formed with loss of the 2-phenyl group and only for the furyl
12c case are products 18 and 19 obtained in which the
phenyl group is retained. It appears that the initial cyclization
product 17 generally prefers to eliminate benzene and only in
the furyl case do the alternative routes with retention of the
phenyl dominate. Only for 12d is a further cyclization with
loss of benzene observed to give a low yield of the novel
thieno[2,3-k]phenanthridine 21d.
In summary, the FVP at 800 °C of 2-(N,N-
dibenzylamino)phenylcinnamoyl ylides 12 proceeds mainly
Despite the rather unpromising outcome of these model
studies, we proceeded with synthesis of the ring-methylated
phosphonium salt 24 required for Eustifoline D, as shown in
Scheme 3, starting from 5-methylanthranilic acid.26,27
Treatment of this salt with n-butyllithium followed by the
(furylethenoyl)benzotriazole gave ylide 25 (Scheme 6). To
our pleasant surprise, and in contrast to the behaviour of 12c,

4
Tetrahedron
We thank EPSRC (UK) for a DTA studentship (Grant No.
EP/P501768/1).
Supplementary data
Supplementary data associated with this article (full
experimental and characterisation details and copies of NMR
spectra) can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2017
References and notes
1.
2.
Aitken, R. A.; Boubalouta, Y. In Adv. Heterocycl. Chem., Vol.
115; Scriven, E. F. V.; Ramsden, C. A., Eds.; Elsevier: Oxford,
2015, 93–150.
Harras M, Milius W, Aitken RA, Schobert R. J. Org. Chem. 2017;
82: 579–587.
3.
4.
Aitken RA, Burns G. Tetrahedron Lett. 1987; 28: 3717–3718.
Aitken RA, Burns G. J. Chem. Soc., Perkin Trans. 1 1994; 2455–
2460.
5.
6.
Aitken RA, Bradbury CK, Burns G, Morrison JJ. Synlett 1995; 53–
54.
Aitken RA, Burns G, Morrison JJ. J. Chem. Soc., Perkin Trans. 1
1998; 3937–3941.
7.
8.
9.
Aitken RA, Garnett AN. Synlett 2001; 228–229.
Aitken RA, Garnett AN. New J. Chem. 2009; 33: 2402–2404.
Aitken RA, Chang D. Heterocycles 2016; 93: 164–184.
10. Aitken RA, Murray L. J. Org. Chem. 2008; 73: 9781–9783.
11. Ito C, Furukawa H. Chem. Pharm. Bull. 1990; 38: 1548–1550.
12. Schmidt AW, Reddy KR, Knölker H-J. Chem. Rev. 2012; 112:
3193–3328.
Scheme 6. Synthesis and FVP of ylide 25
13. Forke R, Krahl MP, Krause T, Schlechtenger G, Knölker H-J.
Synlett 2007; 268–272.
to give the corresponding (E)- and (Z)-3-styrylquinolines
20, although ring-fused carbazoles 16 are also formed in
some cases as well as other products such as thieno[2,3-
k]phenanthridine 21. Only for the furan-derived compound
12c is there retention of one N-benzyl-derived phenyl group
in the products 18 and 19. Addition of a 5-methyl substituent
unexpectedly alters the behaviour and gives the (E)-3-
alkenylquinoline 26 together with the desired natural product
2 which is thus formed in five steps from 5-methylanthranilic
acid.
14. Lebold TP, Kerr MA. Org. Lett. 2007; 9: 1883–1886.
15. Li H, Petersen JL, Wang KK. J. Org. Chem. 2003; 68: 5512–5518.
16. Li H, Yang H, Petersen JL, Wang KK. J. Org. Chem. 2004; 69:
4500–4508.
17. Chen C-C, Wu M-Y, Chen H-Y, Wu M-J. J. Org. Chem. 2017; 82:
6071–6081.
18. Chen C-C, Chen C-M, Wu M-J. J. Org. Chem. 2014; 79: 4704–
4711.
19. Ferrara G, Jin T, Akhtaruzzaman M, Islam A, Han L, Jiang H,
Yamamoto Y. Tetrahedron Lett. 2012; 53: 1946–1950.
20. Chen C-C, Yang S-C, Wu M-J. J. Org. Chem. 2011; 76: 10269–
10274.
21. Chen C-C, Chin L-Y, Yang S-C, Wu M-J. Org. Lett. 2010; 12:
5652–5655.
22. Bestmann H-J, Arnason B. Chem. Ber. 1962; 95 1513–.
23. Katritzky AR, Vincek A, Suzuki K. Arkivoc 2005; part v: 116–
126.
Table 2. Comparison of experimental and literature 1H
NMR data for 2 (400 MHz, CDCl3)
Signal
H-1
H-2
H-4
H-5
NH
Observed
7.33 (dd, J = 2, 1 Hz) 7.23 (dd, J = 2, 1 Hz)
7.81 (d, J = 2 Hz) 7.81 (d, J = 2 Hz)
7.58 (dd, J = 9, 1 Hz) 7.58 (dd, J = 9, 1 Hz)
Lit.11
24. Aitken RA, Hérion H, Janosi A, Karodia N, Raut SV, Seth S,
Shannon IJ, Smith FC. J. Chem. Soc., Perkin Trans. 1 1994; 2467–
2472.
25. Aitken RA, Boubalouta Y, Chang D, Cleghorn LP, Gray IP,
Karodia N, Reid EJ, Slawin AMZ. Tetrahedron 2017; 73:
(TET28967)
26. Dunn GE, Prysiazniuk R. Can. J. Chem. 1961; 39: 285–296.
27. Typical experimental procedures:
7.36 (d, J = 9 Hz)
8.12 (br)
7.35 (d, J = 9 Hz)
8.12 (br)
Benzyl 2-(N,N-dibenzylamino)-5-methylbenzoate 22
Potassium carbonate (23.77 g, 171.9 mmol) and 2-amino-5-
methylbenzoic acid (6.50 g, 43.0 mmol) were added to a stirred
mixture of methanol:water (5:1, 240 mL) and benzyl bromide
(23.53 g, 16.36 mL, 137.7 mmol) was added. The mixture was
heated under reflux for 3 h and the solvent mixture was removed
by evaporation. Water (150 mL) was added to the residue and the
mixture was extracted using ethyl acetate (2 × 100 mL). The
combined organic fractions were washed with water, dried and
evaporated to give a dark brown oil which was triturated with
diethyl ether. The solid was filtered off and found to be 2-(N,N-
dibenzylamino)-5-methylbenzoic acid (4.39 g, 31%) mp 141–142
ºC; 1H NMR (300 MHz, CDCl3): δ = 7.34 (m, 2 H), 7.29–7.25 (m,
6 H), 7.19–7.17 (m, 4 H), 7.07 (d, J = 8 Hz, 1 H, H-3), 4.15 (s, 4
H, 2 × CH2N), 2.36 (s, 3 H, Me). The filtrate was evaporated to
H-7
H-8
Me
7.40 (d, J = 8 Hz)
(under CHCl3)
2.58 (s)
7.40 (d, J = 8 Hz)
7.26 (dd, J = 8, 2 Hz)
2.58 (s)
H-10
7.97 (br s)
7.97 (br s)
Acknowledgments
give
a mixture of desired product, benzyl bromide and

5
tribenzylamine by 1H NMR. The oil was kugelrohr distilled to give
benzyl bromide (bp 90 °C/3 Torr), tribenzylamine (bp 150 °C/3
Torr) and the desired product 22 was obtained as the residue (6.95
g, 39%). IR: 1721 (CO), 1487, 1364, 1126, 1066, 952, 689 cm-1. 1H
NMR (300 MHz, CDCl3): δ = 7.50–7.17 (m, 16 H), 7.02 (ddd, J =
8, 2, 1 Hz, 1 H, H-4) 6.80 (d, J = 8 Hz, 1 H, H-3), 5.34 (s, 2 H,
OCH2), 4.13 (s, 4 H, 2 NCH2), 2.21 (s, 3 H, Me). 13C NMR (100
MHz, CDCl3): δ = 168.3 (CO), 148.2 (C), 138.1 (2 C), 135.9 (C),
132.4 (CH), 131.3 (CH), 130.7 (C), 128.51 (CH), 128.48 (CH),
128.3 (6 CH), 128.1 (4 CH), 126.8 (2 CH), 125.6 (C), 121.7 (2
CH), 66.7 (OCH2), 57.2 (2 NCH2), 20.4 (Me). MS (ESI+): m/z (%)
= 443.98 (100) [M+Na]+, 422.05 (20) [M+H]+. HRMS (ESI+): m/z
calcd for C29H28NO2 [M+H]+: 422.2120; found: 422.2110.
+21.6. MS (ESI+): m/z (%) 562.15 (100) [M–Br]+. HRMS (ESI+):
m/z calcd for C40H37NP [M–Br]+: 562.2664; found: 562.2675.
Anal. Calcd for C40H37BrNP: C, 74.76; H, 5.80; N, 2.18. Found: C,
74.54; H, 6.45; N, 2.24.
[(2-(N,N-Dibenzylamino)-5-methylphenyl)(3-(2-
furyl)propenoyl)methylene]triphenylphosphorane 25
A suspension of salt 24 (3.00 g, 4.67 mmol) in THF (10 mL) was
stirred under nitrogen while a solution of n-BuLi in hexanes (0.23
mL, 2.04 M, 4.67 mmol) was added. The resulting brightly
coloured solution was stirred for 2 h and a solution of N-(3-(2-
furyl)propenoyl)benzotriazole (1.12 g, 4.67 mmol) in THF (5 mL)
was added and the mixture stirred for a further 18 h. Water (20
mL) was added to the solution and the mixture was extracted using
ethyl acetate (2 × 20 mL). The combined extracts were washed
with water, dried and evaporated. The resulting solid was
recrystallised (Et2O/EtOAc) to give 25 (1.49 g, 44%) as yellow
crystals, mp 203–204 °C. IR: 1724, 1630, 1540, 1339, 1090, 739
2-(N,N-Dibenzylamino)-5-methylbenzyl alcohol 23
Under a nitrogen atmosphere, a solution of 22 (8.00 g, 19.0 mmol)
in dry THF (70 mL) was added dropwise to a stirred suspension of
LiAlH4 (0.79 g, 20.8 mmol) in dry THF (10 mL) and the resulting
mixture was stirred at room temperature for 18 h. To destroy the
excess of LiAlH4, water (0.80 mL) in THF (5.6 mL) was added to
the mixture followed by a 15% sodium hydroxide solution (0.80
mL) and finally water (2.40 mL). The suspension was stirred for
0.5 h and MgSO4 was added and stirred overnight. The mixture
was filtered through celite, the solid washed with ethyl acetate and
the combined filtrate and washings evaporated to give 23 (4.69 g,
82%) as a pale yellow oil. IR: 3379 (OH), 1601, 1501, 1358, 1191,
-1
cm . 1H NMR (400 MHz, CDCl3): δ = 7.75–7.28 (m, 15 H), 7.23–
7.06 (m, 10 H), 7.02 (d, J = 15 Hz, 1 H, CH=CH), 6.87–6.79 (m, 4
H), 6.47 (d, J = 8 Hz, 1 H, H-3 of Ar), 6.25 (dd, J = 3, 2 Hz, 1 H,
furyl H-4), 6.23 (d, J = 3 Hz, 1 H, furyl H-3), 4.11 (d, J = 14 Hz, 2
H, NCH2), 3.94 (d, J = 14 Hz, 2 H, NCH2), 2.19 (s, 3 H, Me); 13C
NMR (300 MHz, CDCl3): δ (55 °C) = 179.2 (d, J = 6 Hz, CO),
153.4 (furyl C-2), 151.4 (d, J = 5 Hz, Ar C-2), 142.5 (furyl C-5),
139.2 (d, J = 5 Hz, CH), 137.1 (2 C), 133.9 (br d, J = 10 Hz, C-2
of PPh), 132.2 (d, J = 10 Hz, Ar C-1), 131.5 (br d, J = 3 Hz, C-4 of
PPh), 129.6 (4 CH), 128.3 (br d, J = 12 Hz, C-3 of PPh), 127.7 (4
CH), 127.9 (d, J = 2 Hz, CH), 126.3 (2 CH), 127.1 (d, J = 90 Hz,
C-1 of PPh), 125.5 (d, J = 13 Hz, CO-CH), 124.3 (CH), 122.6 (d, J
= 2 Hz, CH), 122.5 (d, J = 2 Hz, CH), 111.5 (furyl CH), 111.0
(furyl CH), 74.3 (d, J = 107 Hz, C=P), 54.5 (2 NCH2), 20.4 (CH3).
31P NMR (162 MHz, CDCl3): δ = +16.5. MS (ESI+): m/z (%) =
682.02 (100) [M+H]+. HRMS (ESI+): m/z calcd for C47H41NO2P
[M+H]+: 682.2875; found: 682.2888.
-1
1
1036 cm . H NMR (400 MHz, CDCl3): δ = 7.29–7.18 (m, 10 H),
7.13 (d, J = 8 Hz, 1 H, H-4 of Ar), 7.03 (dd, J = 8, 2 Hz, 1 H, H-3
of Ar), 6.97 (d, J = 2 Hz, 1 H, H-6 of Ar), 4.60 (s, 2 H, CH2O),
4.26 (br s, 1 H, OH), 4.03 (s, 4 H, 2 NCH2), 2.28 (s, 3 H, Me). 13C
NMR (100 MHz, CDCl3): δ = 146.5 (C), 137.5 (2 C), 136.7 (C),
134.7 (C), 129.3 (4 CH), 129.2 (CH), 128.5 (CH), 128.3 (4 CH),
127.3 (2 CH), 123.5 (CH), 63.9 (CH2O), 58.6 (2 NCH2), 20.9
(Me). MS (EI): m/z (%) = 317.18 (5) [M]+, 226.11 (100) [M–
CH2Ph]+. HRMS (ESI+): m/z calcd for C22H23NO [M]+: 317.1780;
found: 317.1783.
FVP of ylide 25 to give 26 and Eustifoline D
Ylide 25 (154 mg, 0.32 mmol) was subjected to FVP at 800 °C and
2–3 × 10–2 torr. NMR analysis of the crude product showed a
mixture of Ph3PO, bibenzyl and other products. The mixture was
purified by preparative TLC (50:50 diethyl ether:petroleum ether)
to give (E)-3-(2-(2-furyl)ethenyl)-6-methylquinoline 26 (24.4 mg,
46%) as dark brown oil. 1H NMR (400 MHz, CDCl3): δ = 9.00 (d,
J = 2 Hz, 1 H, H-2), 8.01 (d, J = 2 Hz, 1 H, H-4), 7.96 (d, J = 8 Hz,
1 H, H-8), 7.55 (br s, 1 H, furyl), 7.49 (dd, J = 8, 2 Hz, 1 H, H-7),
7.44 (d, J = 2 Hz, 1 H, H-5), 7.16 and 7.09 (AB pattern, J = 16 Hz,
2 H), 6.67–6.43 (m, 2 H, furyl), 2.53 (s, 3 H, Me). MS (ESI+): m/z
(2-(N,N-Dibenzylamino)-5-
methylbenzyl)triphenylphosphonium bromide 24
A stirred solution of alcohol 23 (4.00 g, 12.6 mmol) in toluene (50
mL) was heated to 60 °C and phosphorus tribromide (1.19 g, 0.42
mL, 4.4 mmol) was added dropwise over 0.5 h. The solution was
stirred at 60 °C for 2 h and at rt for 16 h. The mixture was added to
water (30 mL) and the organic layer separated, washed with water
(2 × 20 mL) and dried. The dried organic solution was heated at
reflux with triphenylphosphine (3.30 g, 12.6 mmol) for 8 h. The
precipitate was filtered off, washed with diethyl ether and oven
dried to give 24 (4.5 g, 67%) as a white powder, mp 201–203 °C.
(%)
=
236.07 (100) [M+H]+. HRMS (ESI+): m/z calcd for
C16H14NO [M+H]+: 236.1075; found: 236.1068.
1
IR: 1430, 1373, 1107, 739, 690 cm-1; H NMR (300 MHz, CDCl3):
Also isolated was 9-methylfuro[2,3-c]carbazole 2 (Eustifoline D)
as a brown oil (9.5 mg, 19%). 1H NMR (400 MHz, CDCl3): δ =
8.12 (br s, 1 H, NH), 7.97 (br s, 1 H, H-10), 7.81 (d, J = 2 Hz, 1 H,
H-2), 7.58 (dd, J = 9, 1 Hz, 1 H, H-4), 7.40 (d, J = 8 Hz, 1 H, H-7),
7.36 (d, J = 9 Hz, 1 H, H-5), 7.33 (dd, J = 2, 1 Hz, 1 H, H-1),
[under chloroform, from lit.,11 7.26 (dd, J = 8, 1 Hz, 1 H, H-8)],
2.58 (s, 3 H, Me).
δ = 7.79 (t, J = 8 Hz, 3 H), 7.63 (td, J = 8, 3 Hz, 6 H), 7.48–7.38
(m, 6 H), 7.56–7.17 (m, 6 H), 7.11 (br dd, J = 8, 2 Hz, 1 H, H-3 of
Ar), 6.94 (d, J = 8 Hz, 1 H, H-4 of Ar), 6.89-6.85 (m, 4 H), 6.56
(br d, J = 2 Hz, 1 H, H-6 of Ar), 4.75 (d, J = 14 Hz, 2 H, CH2P),
3.65 (s, 4 H, 2 NCH2), 2.05 (s, 3 H, Me). 13C NMR (100 MHz,
CDCl3): δ = 148.9 (d, J = 7 Hz, C-2 of Ar), 136.9 (C), 136.7 (2 C),
135.4 (d, J = 2 Hz, C-4 of PPh), 135.3 (CH), 134.1 (CH), 134.0 (d,
J = 9 Hz, C-2 of PPh), 130.4 (d, J = 12 Hz, C-3 of PPh), 129.1 (4
CH), 128.2 (4 CH), 127.5 (2 CH), 125.4 (CH), 124.1 (d, J 7, C-1
of Ar), 117.9 (d, J = 86 Hz, C-1 of PPh), 57.8 (2 NCH2), 25.0 (d, J
= 50 Hz, CH2P), 20.8 (Me). 31P NMR (162 MHz, CDCl3): δ =

6
Tetrahedron
•
•
•
•
Six different stabilised phosphorus ylides
suitable for cascade cyclisation have been
prepared
Pyrolysis mainly gives styrylquinolines
accompanied by other fused-ring quinolines
and carbazoles
With a ring methyl present the quinoline is
accompanied by the furocarbazole natural
product Eustifoline D
Eustifoline D is formed in 5 steps from 5-
methylanthranilic acid