Intramolecular radical additions to quinolines

Article abstract of DOI:10.1016/S0040-4020(02)00295-8

The paper is concerned with intramolecular radical additions to quinolines. Radical additions to C-2, C-3 and C-4 of a quinoline have all been shown to proceed under neutral conditions. In each case formation of heteroaromatic products, rather than dihydroquinolines, was observed (implicating the so called oxidative tin hydride pathway).

Full text of DOI:10.1016/S0040-4020(02)00295-8

TETRAHEDRON
Pergamon
Tetrahedron 58 .2002) 3387±3400
Intramolecular radical additions to quinolines
David C. Harrowven,a,p Benjamin J. Suttona and Steven Coultonb
aDepartment of Chemistry, The University of Southampton, Southampton SO17 1BJ, UK
bGlaxoSmithKline, NewFrontiers Science Park %North), Third Avenue, Harlow, Essex CM19 5AW, UK
Received 30 November 2001; revised 11 February 2002; accepted 7 March 2002
AbstractÐThe paper isconcerned with intramolecular radical additionsto quinolines. Radical additionsto C-2, C-3 and C-4 of a quinoline
have all been shown to proceed under neutral conditions. In each case formation of heteroaromatic products, rather than dihydroquinolines,
was observed .implicating the so called oxidative tin hydride pathway). q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
of publicationsappeared showing that radical additionsto
the C-4 and C-2 carbonsof quinoline predominated in
acidic media.3 Several extensions followed leading to a
number of high yielding and regioselective methods for the
functionalisation of quinolines; the seminal contributions of
Minisci being particularly noteworthy.4 In thispaper we
report our development of some intramolecular variants of
the reaction .Scheme 1).5 Notably, these studies show that
6-exo/endo-trig radical cyclisations to C-2, C-3 and C-4 of a
quinoline are often ef®cient processes at neutral pH.
Radical additionsto quinolineshave a long, if chequered,
history. First described by Hey and Walker in 1948, the
addition of a phenyl radical to quinoline wasfound to be
low yielding and lacking in selectivity.1 A decade later,
Pausacker con®rmed that the thermal decomposition of
dibenzoyl peroxide in quinoline gave productsarisng
from Phz additionsto each of the C-2 to C-8 carbon centres.
Though 8-phenylquinoline wasidenti®ed asthe major
component of thismixture, it wasproduced in such a pitiful
yield .ca. 10% yield based on dibenzoyl peroxide; ,1%
based on quinoline) that the reaction was of no synthetic
value.2 Thus it remained an academic curiosity until a series
2. Results and discussion
All attemptsto effect cyclisation reactionsleading to ®ve
membered ringsfailed, yielding only the productsof halide
reduction .Scheme 2). Thisobesrvation wasnot entirely
unexpected as it con®rmed a suspicion that the 5-exo/
endo-trig cyclisation mode is more akin to a 5-endo-trig
process than a 5-exo-trig process.6
The incorporation of an additional carbon in the tethering
chain gave more encouraging results. Thus, treatment of cis-
azastilbene 5 with tributyltin hydride under radical forming
conditionsled to a three component mixture from which the
C-2 addition product 7 .24%) and C-4 addition product 8
.46%) were readily separated. Accompanying these
materialswas trans-azastilbene 9 .17%).7 Itsformation,
and a need to use a near stoichiometric quantity of the
initiator to drive the reaction to completion, suggested an
inef®cient homolysis of the carbon to bromine bond. Indeed,
through the simple expedient of switching the halide from
bromine to iodine, a separable 3:2 mixture of the cyclisation
products 7 and 8 wasgiven in near quantitative yield and the
reaction required only 10 mol% of the initiator .Scheme 3).
Scheme 1.
Keywords: radicals and radical reactions; quinolines; nitrogen heterocycles;
cyclisation.
Corresponding author. Tel.: 144-23-8059-3302; fax: 144-23-8059-
3781; e-mail: dch2@soton.ac.uk
The cyclisations of 10 and 11, where a saturated two carbon
chain conjoined the quinoline and aryl halide, were then
examined. Treatment of bromide 10 with tributyltin hydride
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020.02)00295-8

3388
D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
Scheme 2.
Scheme 3.
under standard radical forming conditions led to a complex
product mixture from which the two cyclisation products 12
.18%) and 13 .15%), recovered starting material .27%) and
dihydroazastilbene 14 .10%) could be isolated. A mixed
many aliphatic signals, was also given. Attempts to identify
the componentsof thismixture prove intractable. With
iodide 11 the reaction proved more ef®cient, yielding
dihydrobenzo[c]acridine 12 and dihydrobenzo[k]phenan-
thridine 13 in 23 and 51% yield, respectively .Scheme 4).
1
fraction, the H and 13C NMR spectra of which showed
Scheme 4.

D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
3389
Scheme 5.
The increased yield of 13 relative to 12 when iodide 11 was
used suggests that the unidenti®ed products in the reaction
with bromide 10 were derived from reduction of 13 or its
cyclisation precursor, vide infra. Notably, and in contrast to
the related radical cyclisation to a pyridine, no products
derived from the 5-exo-trig .ipso-addition) pathway were
detected .Scheme 4).6
course, with dihydrobenzo[i]phenanthridine 25 being
given in 67% yield .Scheme 6).
2.1. A note on the mechanism ofnon-reducing radical
reactions mediated by tributyltin hydride
Finally, a referee asked that we comment on an apparent
dichotomy between our results and a report by Allin et al.7
in which it wastsated that `In the Bu 3SnH mediated
oxidative cyclisations reported in the literature, greater
than 1 equiv. of AIBN isrequired suggesting that AIBN is
involved with a H-abstraction mechanism for this step'.8
Though this is undoubtedly true for some reactions, many
results were overlooked in reaching that conclusion,
A series of cyclisations to C-3 of a quinoline were also
investigated. Thus, while treatment of cis-azastilbene 15
with tributyltin hydride under standard radical forming
conditionsreturned a mixture of cis- and trans-15, the corre-
sponding iodide 17 gave benzo[a]acridine 16 in 42% yield.
Dihydroazastilbenes 18 and 20 also underwent cyclisation
leading to 19 in 62 and 70% yield, respectively .Scheme 5).
5,9
including our preliminary communication of thiswork.
Most notably, non-reducing radical reactions mediated by
tributyltin hydride generally require ,10 mol% of AIBN
when iodides are used as substrates and substantially more
when bromides or selenides are used as substrates.9 Thisis
best illustrated by the cyclisation reactions of 5 and 6 .and
14 and 15 in Ref. 9x).
The cyclisation of aryl iodide 21, in which the radical
precursor was tethered at C-4 of the quinoline by a cis-
alkene, proved less ef®cient. In this case alkene isomerisa-
tion outpaced homolysis of the carbon to iodine bond/
cyclisation, leading to a product mixture comprising of the
trans-azastilbene 23 .55% yield) and the C-3 addition
product 22 .35% yield). With the corresponding dihydro-
azastilbene 24, cyclisation again became the dominant
Our rationale isthat two propagation esquencesare in
operation and that the dominant course is dictated by the
Scheme 6.

3390
D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
Scheme 8.
Scheme 7.
nature of the substrate. Thus, for substrates akin to iodide 6,
initiation follows the classical mechanism. However, once
the reaction is underway, we suggest that the dominant
course followed is that depicted in Scheme 7. Cyclisation
of 29 isfollowed by losof a proton from intermediate 28.
The resulting radical anion 26 then givesup an electron to 6
yielding the aromatic product 8 and radical anion 27. Loss
of iodide from 27 next gives 29, thereby propagating the
chain reaction. Finally, the hydrogen iodide formed asa
by-product .and presumed to be tied up as a salt in this
case) reacts with tributyltin hydride to produce tributyltin
iodide and a molecule of hydrogen.
product ratio when these materials are good electron
acceptors.
3. Conclusions
In conclusion, we have shown that:
² Intramolecular 6-exo/endo-trig radical cyclisations to
C-2, C-3 and C-4 of a quinoline are all facile processes
and outpace the alternative ipso-cyclisation .5-exo-trig)
pathways.
² Radical cyclisations to quinolines follow a non-reducing
course and can be effected at neutral pH.8
Single electron transfer to a bromide .or selenide) is much
less facile than to an iodide. Hence, for substrates akin to 5
the sequence outlined in Scheme 7 becomes less signi®cant.
After classical initiation and cyclisation, we suggest that
intermediate 28 loses a proton to some acceptor .A) in the
system .which might be the substrate, the initiator or a
product) giving radical anion 26 and AH1. A single electron
transfer from 26 to AH1 then givesthe product 8 and a
radical intermediate AHz. The chain reaction isthen
propagated by a hydrogen atom abstraction from tributyltin
hydride by AHz .Scheme 8).
² Cyclisation reactions that employ aryl iodides generally
proceed more ef®ciently than the corresponding reaction
with an aryl bromide. They also require less AIBN.
² When a cis-alkene is used to conjoin the radical precursor
and quinoline at C-2 or C-4, isomerisation of the alkene
competeswith carbon to halogen bond homolysiswhen
10
tributyltin hydride isused asa mediator.
² 5-exo/endo-Trig radical cyclisations to quinolines fail
and thusappear to be more akin to 5- endo-trig processes
than 5-exo-trig processes.
Work isongoing to probe the mechanism in more detail asat
thistime our thoughtsare based more on conjecture than
scienti®c rigour. Nonetheless, the proposal provides a
working hypothesis that is consistent with the results
disclosed to date. It also provides an explanation as to
why iodides usually give superior yields to bromides in
such processes and how the halide can in¯uence the
4. Experimental
4.1. General remarks
Melting pointswere recorded on a Reichert melting point
apparatususing a Comark digital temperature probe and are

D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
3391
uncorrected. Samples for combustion analysis and melting
4.2. Preparation ofsubstrates +Schemes 9±11)
point determination were freshly recrystallised from the
solvent indicated in parentheses after the mp. UV spectra
were recorded on a Shimadzu UV-1601 spectrometer. IR
spectra were recorded using a Bio-Rad FTS 135 Fourier
transform infrared spectrometer equipped with a Golden
Gate Single Re¯ection Diamond ATR .N.B. IR data were
attained directly from solid samples). NMR spectra were
recorded on a Bruker AM250 .operating at 250 MHz for
1H and at 67.5 MHz for 13C), or a Bruker AC300 .operating
4.2.1. a-+2-Bromophenyl)-3-quinolinemethanol 1. t-Butyl-
lithium .1.25 M in hexane, 5.9 mL, 7.38 mmol) wasadded
dropwise over 10 min to a solution of 3-bromoquinoline
.1.0 mL, 1.53 g, 7.35 mmol) in Et2O .20 mL) at 21008C.
After 2 h a solution of 2-bromobenzaldehyde .0.87 mL,
1.38 g, 7.45 mmol) in Et2O .20 mL) wasadded. After warm-
ing to 2608C over 2 h, brine .90 mL) and THF .50 mL) were
added. The organic phase was separated, dried .MgSO4),
®ltered and concentrated in vacuo. The residues were puri®ed
by column chromatography .silica, chloroform) to give the
title product 1 .1.78 g, 5.65 mmol, 77%) asa white solid; mp
153±1558C .Et2O/petrol); IR .solid, cm21) nmax 3061 br. w,
2831 w, 2701 w, 1579 w, 1496 m, 1464 m, 1380 w, 1284 w,
1162 m, 1071 m, 1008 w; UV .MeOH, nm) lmax .1max) 318
.3770), 304 .3330), 290 .3200); 1H NMR .300 MHz, CDCl3)
dH 8.74 .1H, d, Jˆ2.2 Hz, ArH), 8.11 .1H, br. s, ArH), 7.99
.1H, d, Jˆ8.1 Hz, ArH), 7.74±7.47 .5H, m, 5£ArH), 7.33
.1H, app. t, Jˆ7.4 Hz, ArH), 7.14 .1H, app. td, Jˆ8.1,
1.5 Hz, ArH), 6.35 .1H, s, CHOH), 5.44 .1H, s, OH); 13C
NMR .75 MHz, CDCl3) dC 150.3 .CH), 147.0 .C), 142.1 .C),
135.8 .C), 134.3 .CH), 133.0 .CH), 129.8 .CH), 129.5 .CH),
128.7 .CH), 128.7 .CH), 128.2 .CH), 128.1 .CH), 127.9 .C),
127.0 .CH), 122.8 .C), 72.6 .CHOH); LRMS .APCI) 316
.83%, [MH.81Br)]1), 314 .100%, [MH.79Br)]1), 298 .12%,
[MH.81Br)2H2O]1), 296 .12%, [MH.79Br)2H2O]1), 234
.18%, [MH2HBr]1); HRMS .EI) m/z Found: M1:
313.0096, C16H1279BrNO requires313.0102; Anal. Found:
C, 61.13; H, 3.87; N, 4.35; C16H12BrNO requiresC, 61.17;
H, 3.85; N, 4.46.
1
at 300 MHz for H and at 75 MHz for 13C), or a Bruker
1
AM400 .operating at 400 MHz for H and at 100 MHz for
13C). Chemical shifts .dH) are reported asvaluesin partsper
million relative to tetramethylsilane .dH 0.00, dC 0.00),
CDCl3 .dC 77.2) or residual CHCl3 .dH 7.27). Mass spectra
attained using atmospheric pressure chemical ionisation
.APCI) or electrospray .ES) were recorded on a Micromass
Platform quadrupole mass analyser with an electrospray ion
source. The eluent was distilled acetonitrile and experi-
mentswere conducted at a ¯ow rate of 200 mL min21. Elec-
tron impact .EI) mass spectra were recorded on a VG
Analytical 70-250-SE normal geometry double focusing
mass spectrometer using 70 eV ionisation energy and a
2008C source temperature. High-resolution mass spectra
.HRMS) were recorded on the same instrument giving a
resolution of 104.
All reactionswere magnetically tsirred under an inert
atmosphere. Reactions were monitored by thin layer
chromatography using Macherey±Nagel Alugram Sil G/
UV254 precoated aluminium foil platesof layer thicknes
0.25 mm. Compounds were visualised ®rstly by UV irradia-
tion, then by exposure to iodine vapour and ®nally by heat-
ing plates exposed to solutions of phosphomolybdic acid in
ethanol or basi®ed aqueous potassium permanganate.
Column chromatography was performed on Sorbsil 60 silica
.230±400 mesh), slurry packed and run under low pressure.
4.2.2. +2-Bromophenyl)-3-quinolinyl-methanone 3. The
alcohol 1 .500 mg, 1.59 mmol) and activated manganese
dioxide .4.00 g, 46 mmol) were stirred in dichloromethane
.50 mL) at ambient temperature under an argon atmosphere
for 24 h. After ®ltration through celite and concentration in
vacuo, the organic residues were recrystallised from ether to
give 3 .468 mg, 1.50 mmol, 94%) asa white solid; mp 129±
1318C .Et2O); IR .solid, cm21) nmax 3031 w, 2926 w, 1665 s,
1614 m, 1594 w, 1566 m, 1489 w, 1459 w, 1365 s, 1290 s,
1240 m, 1152 w, 1117 w, 1018 w; UV .MeOH, nm) lmax
.1max) 292 .9930), 251 .38,000); 1H NMR .300 MHz,
CDCl3) dH 9.37 .1H, d, Jˆ1.8 Hz, ArH), 8.50 .1H, d,
Jˆ1.8 Hz, ArH), 8.21 .1H, d, Jˆ8.8 Hz, ArH), 7.93±7.86
.2H, m, 2£ArH), 7.72 .1H, d, Jˆ7.4 Hz, ArH), 7.64 .1H,
app. t, Jˆ7.4 Hz, ArH), 7.54±7.42 .3H, m, 3£ArH); 13C
NMR .75 MHz, CDCl3) dC 194.6 .CvO), 150.0 .CH),
149.8 .C), 139.8 .CH), 139.7 .C), 133.5 .CH), 132.5
.CH), 131.9 .CH), 129.6 .CH), 129.5 .CH), 129.3 .CH),
128.6 .C), 127.7 .CH), 127.6 .CH), 126.8 .C), 119.7 .C);
LRMS .APCI) 355 .24%, [MH.81Br)1MeCN]1), 353
.20%, [MH.79Br)1MeCN]1), 314 .100%, [MH.81Br)]1),
312 .95%, [MH.79Br)]1), 259 .10%); HRMS .EI) m/z
Found M1: 310.9950, C16H1079BrNO requires310.9946;
Anal. Found: C, 61.65; H, 3.23; N, 4.49; C16H10BrNO
requiresC, 61.56; H, 3.23; N, 4.49.
Tetrahydrofuran was dried by distillation over sodium and
benzophenone. Toluene wasdried by ditsillation over
sodium. Dichloromethane was dried by distillation over
calcium hydride. Ether refersto diethyl ether and petrol
refersto the fraction of petroleum ether in the boiling
point range 40±608C. 5-Bromo-6-.bromomethyl)-1,3-
benzodioxole 31, mp 92±948C .chloroform) [lit. 88±898C;
91±928C],11,12 wasprepared by the method of Padwa et al. 11
[.6-Bromo-1,3-benzodioxole-5-yl)-methyl]-triphenylphos-
phonium bromide 32, mp 275±2798C .EtOH) [Lit. 278±
2808C .xylene)],13 wasprepared by the method of Harrow-
ven et al.14
4.2.3. 3-Quinolinecarbaldehyde. t-Butyllithium .1.25 M in
hexane, 5.9 mL, 7.38 mmol) wasadded dropwies over
5 min to a cooled .21008C) solution of 3-bromoquinoline
.1.0 mL, 1.53 g, 7.35 mmol) in Et2O .20 mL). After 2 h,
DMF .2 mL, 1.89 g, 25.8 mmol) wasadded, dropwies
Scheme 9. Reagents: .a) t-BuLi then 2-bromobenzaldehyde; .b) MnO2;
.c) t-BuLi then DMF.

3392
D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
over 5 min. The solution was warmed to 2608C over 4 h
then brine .50 mL) and THF .20 mL) were added. After
warming to ambient temperature the aqueousphaes was
separated and extracted with Et2O .20 mL). The combined
organic phases were dried .MgSO4) and concentrated in
vacuo. The resulting residues were recrystallised from
ether to give the title compound .704 mg, 4.48 mmol,
61%) asa white crystalline solid; mp 70±72 8C .ether/petrol)
[Lit. 718C .EtOH); 708C .H2O)];15,16 IR .DCM, cm21) nmax
3047 w, 2835 w, 1700 s, 1618 s, 1596 m, 1572 m, 1498 m,
1372 m, 1272 s, 1210 m, 1165 m, 1125 m; UV .MeOH, nm)
lmax .1max) 315 .250), 282 .410), 246 .1330), 227 .2680);
1H NMR .300 MHz, CDCl3) dH 10.27 .1H, s, CHO), 9.38
.1H, br. s, ArH), 8.65 .1H, d, Jˆ1.5 Hz, ArH), 8.21 .1H, d,
Jˆ8.1 Hz, ArH), 8.01 .1H, d, Jˆ8.1 Hz, ArH), 7.90 .1H,
app. t, Jˆ7.4 Hz, ArH), 7.68 .1H, app. t, Jˆ7.7 Hz, ArH);
13C NMR .75 MHz, CDCl3) dC 190.8 .CHO), 150.6 .C),
149.1 .CH), 140.2 .CH), 132.7 .CH), 129.7 .CH), 129.4
.CH), 128.6 .C), 127.9 .CH), 127.0 .C); LRMS .CI) 158
.100%, [MH]1), 157 .42%, [M]1), 129 .26%,
[MH2CHO]1). These data were consistent with reported
literature values.
127.2 .CH), 126.9 .CH), 114.9 .C), 112.9 .CH), 109.9 .CH),
101.9 .OCH2O) with one quaternary C obscured; LRMS
.ES) 356 .16%, [MH.81Br)]1), 354 .16%, [MH.79Br)]1);
Anal. Found: C, 60.85; H, 3.41; N, 3.85; C18H12BrNO2
requiresC, 61.04; H, 3.41; N, 3.95; then trans-5 .252 mg,
0.71 mmol, 24%) asa white solid; mp 175±177 8C .EtOH);
IR .solid, cm21) nmax 3065 w, 2897 w, 1501 m, 1475 s, 1411
w, 1240 m, 1115 w, 1038 m; UV .MeOH, nm) lmax .1max
)
337 .19,100), 309 .20,200), 281 .23,600); 1H NMR
.300 MHz, CDCl3) dH 9.11 .1H, s, ArH), 8.20 .1H, s,
ArH), 8.12 .1H, d, Jˆ8.8 Hz, ArH), 7.85 .1H, d,
Jˆ8.1 Hz, ArH), 7.70 .1H, app. t, Jˆ7.4 Hz, ArH), 7.62
.1H, d, Jˆ16.2 Hz, CHvCH), 7.57 .1H, app. t, Jˆ7.4 Hz,
ArH), 7.20 .1H, s, ArH), 7.07 .1H, s, ArH), 7.02 .1H, d,
Jˆ16.2 Hz, CHvCH), 6.03 .2H, s, OCH2O); 13C NMR
.75 MHz, CDCl3) dC 149.4 .CH), 148.4 .C), 147.9 .C),
147.3 .C), 132.5 .CH), 130.2 .C), 129.9 .C), 129.5 .CH),
129.4 .CH), 129.1 .CH), 128.1 .C), 127.9 .CH), 127.1 .CH),
126.1 .CH), 115.8 .C), 112.9 .CH), 105.8 .CH), 102.0
.OCH2O); LRMS .ES) 397 .13%, [MH.81Br)1CH3CN]1),
395 .MH.79Br)1CH3CN]1), 356 .100%, [MH.81Br)]1), 354
.96%, [MH.79Br)]1); Anal. Found: C, 60.71; H, 3.40; N,
3.83; C18H12BrNO2 requiresC, 61.04; H, 3.41; N, 3.95.
4.2.5. 3-[2-+6-Bromo-1,3-benzodioxol-5-yl)-ethyl]-quino-
line 10. A solution of cis- and trans-azastilbenes 5 .12:5,
901 mg, 2.54 mmol), tosyl hydrazine .2.90 g, 15.6 mmol)
and sodium acetate .1.28 g, 15.6 mmol) in THF .15 mL)
and water .15 mL) washeated at re¯ux for 72 h then cooled
to ambient temperature and partitioned between saturated
potassium carbonate .30 mL) and ether .15 mL). The
aqueousphaes wasextracted with ether .3 £20 mL) then
the combined organic phases were dried .MgSO4) and
concentrated in vacuo. The residues were recrystallised
from ether to give dihydroazastilbene 10 .532 mg,
1.49 mmol, 59%) as a white crystalline solid; mp 115±
1178C .EtOH); IR .solid, cm21) nmax 2899 w, 1501 m,
1475 s, 1236 m, 1119 w, 1038 m; UV .MeOH, nm) lmax
Scheme 10. Reagents: .a) Br2, AcOH; .b) PPh3; .c) NaH, 3-quinolinecar-
boxaldehyde; .d) NH2NHTs, NaOAc; .e) NaH, 2-quinolinecarboxaldehyde.
1
.1max) 318 .6820), 304 .10,100), 292 .11,900); H NMR
.300 MHz, CDCl3) dH 8.77 .1H, d, Jˆ2.2 Hz, ArH), 8.09
.1H, d, Jˆ8.8 Hz, ArH), 7.92 .1H, br. s, ArH), 7.76 .1H, d,
Jˆ8.1 Hz, ArH), 7.67 .1H, app. t, Jˆ7.4 Hz, ArH), 7.52
.1H, app. t, Jˆ7.4 Hz, ArH), 7.01 .1H, s, ArH), 6.64 .1H,
s , AHr ), 5.93 .2H, s, OCH2O), 3.03 .4H, s, CH2CH2); 13C
NMR .75 MHz, CDCl3) dC 152.1 .CH), 147.5 .C), 147.1
.C), 147.1 .C), 134.6 .CH), 134.0 .C), 133.2 .C), 129.4
.CH), 128.9 .CH), 128.2 .C), 127.5 .CH), 126.8 .CH),
114.6 .C), 113.0 .CH), 110.2 .CH), 101.8 .OCH2O), 38.0
.CH2), 33.8 .CH2); LRMS .ES) 358 .100%, [MH.81Br)]1),
356 .98%, [MH.79Br)]1), 140 .20%), 127 .25%); Anal.
Found: C, 60.36; H, 3.96; N, 3.82; C18H14BrNO2 requires
C, 60.69; H, 3.96; N, 3.93.
4.2.4. 3-[+Z)-2-+6-Bromo-1,3-benzodioxol-5-yl)-1-ethenyl]-
quinoline, cis-5, and 3-[+E)-2-+6-bromo-1,3-benzodioxol-
5-yl)-1-ethenyl]-quinoline, trans-5. NaH .176 mg,
4.40 mmol, 60% dispersion in oil) was washed with THF
.10 mL) then suspended in THF .25 mL) at 08C. The phos-
phonium salt 32 .2.04 g, 3.66 mmol) wasadded and the
reaction warmed to room temperature over 18 h then
re-cooled to 08C. 3-Quinolinecarbaldehyde .500 mg,
3.02 mmol) wasthen added and after 3 h precipitated tri-
phenylphosphine oxide was removed by ®ltration. The
®ltrate wasconcentrated in vacuo and puri®ed by column
chromatography .silica, 30:70, Et2O/petrol) to give ®rstly
cis-5 .638 mg, 1.80 mmol, 60%) as a white crystalline solid;
mp 115±1178C .EtOH); IR .solid, cm21) nmax 3012 w, 2896
w, 1616 w, 1567 w, 1500 m, 1475 s, 1423 m, 1230 m, 1037
m; UV .MeOH, nm) lmax .1max) 300 .12,200), 275 .13,800);
1H NMR .300 MHz, CDCl3) dH 8.69 .1H, s, ArH), 8.04 .1H,
d, Jˆ8.8 Hz, ArH), 7.96 .1H, s, ArH), 7.74±7.66 .2H, m,
2£ArH), 7.52 .1H, app. t, Jˆ7.4 Hz, ArH), 7.10 .1H, s,
ArH), 6.75 .2H, s, CHvCH), 6.59 .1H, s, ArH), 5.92 .2H,
s , OCH2O); 13C NMR .75 MHz, CDCl3) dC 151.0 .CH),
148.2 .C), 147.4 .C), 146.7 .C), 135.4 .CH), 131.9 .CH),
130.1 .C), 129.7 .C), 129.5 .CH), 129.1 .CH), 127.8 .CH),
4.2.6. 2-[+Z)-2-+6-Bromo-1,3-benzodioxol-5-yl)-1-ethenyl]-
quinoline 15. NaH .176 mg, 4.40 mmol, 60% dispersion in
oil) was washed with THF .10 mL) then suspended in THF
.25 mL) at 08C. The phosphonium salt 32 .2.04 g,
3.66 mmol) wasadded followed after 2 h by 2-quinoline-
carbaldehyde .500 mg, 3.02 mmol). After a further 3 h the
precipitated triphenylphosphine oxide was removed by
®ltration. The ®ltrate wasconcentrated in vacuo and puri®ed
by column chromatography .silica, 20:80, ethyl acetate/
petrol) to give 15 .1.01 g, 2.84 mmol, 88%) asa white

D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
3393
solid; mp 96±988C .EtOH); IR .solid, cm21) nmax 3055 w,
2897 w, 1614 w, 1594 m, 1554 w, 1500 s, 1474 s, 1416 m,
1232 m, 1036 m; UV .MeOH, nm) lmax .1max) 331 .10,100),
235 .23,700); 1H NMR .300 MHz, CDCl3) dH 8.06 .1H, d,
Jˆ8.1 Hz, ArH), 7.90 .1H, d, Jˆ8.1 Hz, ArH), 7.77±7.68
.2H, m, 2£ArH), 7.50 .1H, app. t, Jˆ7.4 Hz, ArH), 7.17
.1H, d, Jˆ8.1 Hz, ArH), 7.09 .1H, s, ArH), 6.93 .2H, s,
vCH), 6.66 .1H, s, ArH), 5.92 .2H, s, OCH2O); 13C
NMR .75 MHz, CDCl3) dC 156.1 .C), 148.3 .C), 148.1
.C), 147.1 .C), 135.5 .CH), 133.6 .CH), 131.6 .CH),
130.1 .C), 129.6 .CH), 129.2 .CH), 127.5 .CH), 126.9
.C), 126.5 .CH), 122.0 .CH), 115.0 .C), 112.7 .CH),
110.6 .CH), 101.8 .OCH2O); LRMS .ES) 356 .100%,
[MH.81Br)]1), 354 .98%, [MH.79Br)]1), 144 .41%,
[C10H9NH]1); Anal. Found: C, 60.86; H, 3.42; N, 3.94;
C18H12BrNO2 requiresC, 61.04; H, 3.41; N, 3.95.
4.2.8. +6-Iodo-1,3-benzodioxol-5-yl)-methanol 33. To a
cooled .258C) solution of piperonyl alcohol 30 .9.3 g,
61.1 mmol) in CHCl3 .130 mL) were added iodine
.17.3 g, 68.0 mmol) and silver tri¯uroacetate .15.0 g,
67.9 mmol). After stirring for 30 min the reaction was
®ltered through Celitew. The ®ltrate waswashed with satu-
rated Na2S2O3 .100 mL), dried .MgSO4) and concentrated
in vacuo to a light yellow solid. Recrystallisation from
CHCl3 gave iodide 33 .14.7 g, 52.8 mmol, 87%) asa
white crystalline solid; mp 110±1128C .CHCl3) [Lit. 108±
1098C .CHCl3)].17
4.2.9. 5-+Bromomethyl)-6-iodo-1,3-benzodioxole 34.
Concentrated HBr .48%, 40 mL) wasslowly added to the
alcohol 33 .10.1 g, 36.3 mmol) and the resulting suspension
stirred for 2 h at rt then extracted with DCM .3£100 mL).
The combined organic phases were washed with Na2CO3
.2 M, 50 mL), dried .MgSO4) and concentrated in vacuo
to give benzyl bromide 34 .11.2 g, 32.9 mmol, 90%) asa
white solid; mp 72±738C .EtOH) [lit. 728C].17
4.2.7. 2-[2-+6-Bromo-1,3-benzodioxol-5-yl)ethyl]quino-
line 18. A solution of cis-azastilbene 15 .667 mg,
1.88 mmol), tosyl hydrazine .2.90 g, 15.6 mmol) and
sodium acetate .1.28 g, 15.6 mmol) in THF .15 mL) and
water .15 mL) washeated at re¯ux for 72 h then cooled to
ambient temperature. The reaction waspartitioned between
saturated potassium carbonate .30 mL) and ether .30 mL).
The aqueousphase wasextracted with ether .3 £30 mL) then
the combined organic phases were dried .MgSO4) and
concentrated in vacuo. The residues were puri®ed by
column chromatography .silica, 30:70, Et2O/petrol) to
give dihydroazastilbene 18 .590 mg, 1.66 mmol, 88%) as
a white crystalline solid; mp 108±1108C .Et2O/petrol); IR
.solid, cm21) nmax 3050 w, 2892 w, 1600 w, 1502 m, 1475 s,
1233 m, 1113 m, 1038 m; UV .MeOH, nm) lmax .1max) 316
.4550), 302 .6420), 290 .6610); 1H NMR .300 MHz,
CDCl3) dH 8.09 .1H, d, Jˆ8.1 Hz, ArH), 8.06 .1H, d,
Jˆ8.1 Hz, ArH), 7.80 .1H, d, Jˆ8.1 Hz, ArH), 7.71 .1H,
app. t, Jˆ7.7 Hz, ArH), 7.51 .1H, app. t, Jˆ7.4 Hz, ArH),
7.29 .1H, d, Jˆ8.1 Hz, ArH), 7.02 .1H, s, ArH), 6.75 .1H, s,
ArH), 5.93 .2H, s, OCH2O), 3.25±3.18 .4H, m, CH2CH2);
13C NMR .75 MHz, CDCl3) dC 161.5 .C), 148.1 .C), 147.5
.C), 146.9 .C), 136.5 .CH), 133.9 .C), 129.6 .CH), 129.0
.CH), 127.7 .CH), 127.0 .C), 126.0 .CH), 121.7 .CH), 114.6
.C), 112.9 .CH), 110.4 .CH), 101.7 .OCH2O), 39.5 .CH2),
36.3 .CH2); LRMS .ES) 358 .97%, [MH.81Br)]1), 356
.100%, [MH.79Br)]1), 153 .32%), 146 .32%), 143 .45%),
127 .60%); Anal. Found: C, 60.52; H, 3.97; N, 3.82;
C18H14BrNO2 requiresC, 60.69; H, 3.96; N, 3.93.
4.2.10. Bromo-[+6-iodo-1,3-benzodioxol-5-yl)-methyl]-
triphenylphosphorane 35. A solution of bromide 34
.11.0 g, 32.3 mmol) and triphenylphosphine .8.7 g,
33.0 mmol) in xylene .50 mL) washeated at 100 8C for
24 h. The resultant white precipitate was collected by ®ltra-
tion, washed with cold xylene .2£20 mL) and cold petrol
.2£20 mL), then recrystallised from EtOH/Et2O to give the
phosphonium salt 35 .18.6 g, 30.8 mmol, 95%) asa white
crystalline solid; mp 268±2728C .EtOH); IR .solid, cm21
nmax 2848 w, 1584 w, 1498 m, 1480 m, 1470 m, 1432 w,
1246 s, 1236 s, 1109 s, 1036 s; UV .MeOH, nm) lmax .1max
)
)
1
302 .4420), 275 .4830), 268 .5430); H NMR .300 MHz,
CDCl3) dH 7.81±7.61 .15H, m, 15£ArH), 7.02 .1H, s, ArH),
6.92 .1H, d, Jˆ2.2 Hz, ArH), 5.92 .2H, s, OCH2O), 5.45
.2H, d, Jˆ13.2 Hz, ArCH2PPh3Br); 13C NMR .75 MHz,
CDCl3) dC 148.9 .C), 148.8 .C), 135.3 .JC±Pˆ3.4 Hz,
3£CH),
134.4
.JC±Pˆ10.2 Hz,
6£CH),
130.3
.JC±Pˆ12.4 Hz, 6£CH), 123.4 .JC±Pˆ10.2 Hz, C), 118.5
.JC±Pˆ3.4 Hz, CH), 117.1 .JC±Pˆ84.8 Hz, 3£C), 111.5
.JC±Pˆ3.4 Hz, CH), 102.3 .OCH2O), 93.4 .JC±Pˆ7.9 Hz,
C), 35.7 .JC±Pˆ48.6 Hz, CH2); LRMS .ES) 524 .28%),
523 .100%; [M2Br]1).
4.2.11. 3-[+Z)-2-+6-Iodo-1,3-benzodioxol-5-yl)-1-ethenyl]-
quinoline cis-6 and 3-[+E)-2-+6-iodo-1,3-benzodioxol-5-
yl)-1-ethenyl]-quinoline
trans-6.
NaH
.176 mg,
4.40 mmol, 60% dispersion in oil) was washed with THF
.10 mL) then suspended in THF .30 mL) at 08C. Phos-
phonium salt 35 .2.00 g, 3.32 mmol) wasadded and the
reaction mixture wasallowed to warm to rt over 2 h then
re-cooled to 08C. 3-Quinolinecarbaldehyde .500 mg,
3.02 mmol) wasthen added and after 2 h precipitated tri-
phenylphosphine oxide was removed by ®ltration. The
®ltrate wasconcentrated in vacuo and puri®ed by column
chromatography .silica, 50:50, Et2O/petrol) and fractional
crystallisation from aqueous ethanol to give ®rstly cis-6
.610 mg, 1.52 mmol, 48%) as a yellow crystalline solid;
mp 118±1208C .EtOH/H2O); IR .solid, cm21) nmax 1493
m, 1473 s, 1426 w, 1257 m, 1222 m, 1230 m, 1038 m;
UV .MeOH, nm) lmax .1max) 291 .9130); 1H NMR
.300 MHz, CDCl3) dH 8.65 .1H, s, ArH), 8.02 .1H, d,
Jˆ8.8 Hz, ArH), 7.91 .1H, s, ArH), 7.69 .1H, app. t,
Scheme 11. Reagents: .a) I2, AgO2CCF3; .b) HBr; .c) PPh3; .d) NaH,
3-quinolinecarboxaldehyde; .e) NH2NHTs, NaOAc; .f) NaH, 2-quinoline-
carboxaldehyde; .g) NaH, 4-quinolinecarboxaldehyde.

3394
D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
Jˆ7.7 Hz, ArH), 7.66 .1H, d, Jˆ8.1 Hz, ArH), 7.50 .1H,
app. t, Jˆ7.4 Hz, ArH), 7.33 .1H, s, ArH), 6.70 .1H, d,
Jˆ11.8 Hz, vCH), 6.64 .1H, d, Jˆ11.8 Hz, vCH), 6.59
.1H, s, ArH), 5.91 .2H, s, OCH2O); 13C NMR .75 MHz,
CDCl3) dC 151.1 .CH), 148.5 .C), 148.2 .C), 146.8 .C),
135.9 .CH), 135.3 .CH), 134.2 .C), 129.5 .C), 129.4
.CH), 129.2 .CH), 127.8 .CH), 127.8 .C), 127.1 .CH),
126.8 .CH), 118.6 .CH), 109.7 .CH), 101.7 .OCH2O),
88.1 .C); LRMS .ES) 443 .20%, [MH1MeCN]1), 402
.83%, [MH]1), 127 .100%); Anal. Found: C, 53.60; H,
3.02; N, 3.44; C18H12INO2 requiresC, 53.89; H, 3.01; N,
3.49; then trans-6 .610 mg, 1.52 mmol, 48%) asa yellow
crystalline solid; mp 177±1798C .EtOH/H2O); IR .solid,
cm21) nmax 2897 w, 1500 m, 1473 s, 1406 w, 1231 s,
1114 w, 1038 m; UV .MeOH, nm) lmax .1max) 346
wasadded, followed after 2 h by 2-quinolinecarbaldehyde
.500 mg, 3.18 mmol). After a further 2 h precipitated tri-
phenylphosphine oxide was removed by ®ltration. The
®ltrate wasconcentrated in vacuo and puri®ed by column
chromatography .silica, ether) to give 17 .1.10 g,
2.74 mmol, 92%) as a white crystalline solid; mp 129±
1318C .EtOH); IR .solid, cm21) nmax 3057 w, 2915 w,
1614 w, 1596 m, 1556 w, 1499 s, 1477 s, 1434 m, 1241 s,
1036 s; UV .MeOH, nm) lmax .1max) 330 .12,400), 302
1
.12,200), 243 .33,400); H NMR .300 MHz, CDCl3) dH
8.06 .1H, d, Jˆ8.1 Hz, ArH), 7.90 .1H, d, Jˆ8.8 Hz,
ArH), 7.76±7.69 .2H, m, 2£ArH), 7.52 .1H, app. t,
Jˆ7.4 Hz, ArH), 7.35 .1H, s, ArH), 7.11 .1H, d,
Jˆ8.8 Hz, ArH), 6.90 .1H, d, Jˆ12.5 Hz, vCH), 6.83
.1H, d, Jˆ12.5 Hz, vCH), 6.66 .1H, s, ArH), 5.94 .2H, s,
OCH2O); 13C NMR .75 MHz, CDCl3) dC 156.2 .C), 148.4
.C), 148.4 .C), 137.9 .CH), 135.6 .CH), 134.3 .C), 131.6
.CH), 129.7 .CH), 129.3 .CH), 127.7 .CH), 127.0 .C), 126.7
.CH), 122.2 .CH), 118.6 .CH), 110.6 .CH), 101.9 .OCH2O),
88.2 .C) with one quaternary C obscured; LRMS .ES) 402
.100%, [MH]1), 127 .43%); Anal. Found: C, 53.91; H, 3.02;
N, 3.39; C18H12INO2 requiresC, 53.89; H, 3.01; N, 3.49.
1
.25,880), 317 .23,090), 283 .28,130), 256 .29,490); H
NMR .300 MHz, CDCl3) dH 9.12 .1H, s, ArH), 8.17 .1H,
s , AHr), 8.10 .1H, d, Jˆ8.1 Hz, ArH), 7.84 .1H, d,
Jˆ8.1 Hz, ArH), 7.69 .1H, app. t, Jˆ7.4 Hz, ArH), 7.56
.1H, app. t, Jˆ7.4 Hz, ArH), 7.48 .1H, d, Jˆ16.2 Hz,
vCH), 7.32 .1H, s, ArH), 7.19 .1H, s, ArH), 6.95 .1H, d,
Jˆ16.2 Hz, vCH), 6.02 .2H, s, OCH2O); 13C NMR
.75 MHz, CDCl3) dC 149.6 .CH), 148.9 .C), 148.5 .C),
147.5 .C), 134.4 .CH), 133.2 .C), 132.3 .CH), 130.0 .C),
129.3 .CH), 129.3 .CH), 128.1 .C), 127.9 .CH), 127.1 .CH),
126.5 .CH), 118.8 .CH), 105.7 .CH), 101.9 .OCH2O), 89.7
.C); LRMS .ES) 443 .10%, [MH1MeCN]1), 402 .34%,
[MH]1), 127 .100%); Anal. Found: C, 53.60; H, 2.95; N,
3.31; C18H12INO2 requiresC, 53.89; H, 3.01; N, 3.49.
4.2.14. 2[-2-+6-Iodo-1,3-benzodioxol-5-yl)-1-ethyl]quino-
line 20. A solution of azastilbene 17 .1.10 g, 2.74 mmol),
tosyl hydrazine .2.90 g, 15.6 mmol) and sodium acetate
.1.28 g, 15.6 mmol) in THF .15 mL) and water .15 mL)
washeated at re¯ux for 72 h then cooled to ambient
temperature. The reaction waspartitioned between saturated
potassium carbonate .60 mL) and ether .30 mL) then
separated. The aqueous phase was extracted with ether
.2£30 mL) then the combined organic phases were dried
.MgSO4), concentrated in vacuo and puri®ed by recrystal-
lisation from ethanol to give dihydroazastilbene 20
.993 mg, 2.46 mmol, 90%) asa white crytsalline oslid;
mp 139±1418C .EtOH); IR .solid, cm21) nmax 2896 w,
1621 w, 1598 w, 1499 m, 1473 s, 1226 s, 1116 m, 1041
m; UV .MeOH, nm) lmax .1max) 316 .5620), 303 .7590),
4.2.12. 3-[2-+6-Iodo-1,3-benzodioxol-5-yl)-ethyl]-quino-
line 11. A solution of cis- and trans-azastilbenes 6 .1:1,
400 mg, 0.997 mmol), tosyl hydrazine .2.90 g, 15.6 mmol)
and sodium acetate .1.28 g, 15.6 mmol) in THF .15 mL)
and water .15 mL) washeated at re¯ux for 24 h then cooled
to ambient temperature. The reaction mixture waspar-
titioned between saturated potassium carbonate .60 mL)
and ether .30 mL) and separated. The aqueous phase was
extracted with ether .4£30 mL) then the combined organic
phases were dried .MgSO4), concentrated in vacuo and
puri®ed by column chromatography .silica, Et2O) to give
dihydroazastilbene 11 .398 mg, 0.987 mmol, 99%) asa
white crystalline solid; mp 115±1178C .EtOH/H2O); IR
.solid, cm21) nmax 1498 m, 1471 s, 1235 m, 1121 w, 1039
m; UV .MeOH, nm) lmax .1max) 318 .4800), 304 .7340),
1
293 .7160); H NMR .300 MHz, CDCl3) dH 8.09 .1H, d,
Jˆ8.1 Hz, ArH), 8.09 .1H, d, Jˆ8.8 Hz, ArH), 7.81 .1H, d,
Jˆ8.1 Hz, ArH), 7.72 .1H, app. t, Jˆ7.4 Hz, ArH), 7.52
.1H, app. t, Jˆ7.4 Hz, ArH), 7.34 .1H, d, Jˆ8.8 Hz,
ArH), 7.27 .1H, s, ArH), 6.80 .1H, s, ArH), 5.95 .2H, s,
OCH2O), 3.27±3.14 .4H, m, CH2CH2); 13C NMR .75 MHz,
CDCl3) dC 161.4 .C), 148.6 .C), 148.1 .C), 147.0 .C), 137.4
.C), 136.5 .CH), 129.6 .CH), 129.0 .CH), 127.7 .CH), 127.0
.C), 126.0 .CH), 121.7 .CH), 118.7 .CH), 109.7 .CH), 101.7
.OCH2O), 88.0 .C), 40.9 .CH2), 39.8 .CH2); LRMS .ES)
404 .100%, [MH]1), 127 .24%); Anal. Found: C, 53.65; H,
3.48; N, 3.45; C18H14INO2 requiresC, 53.62; H, 3.50; N,
3.47.
1
297 .7460); H NMR .300 MHz, CDCl3) dH 8.80 .1H, s,
ArH), 8.09 .1H, d, Jˆ8.8 Hz, ArH), 7.93 .1H, s, ArH), 7.76
.1H, d, Jˆ7.4 Hz, ArH), 7.67 .1H, app. t, Jˆ7.7 Hz, ArH),
7.52 .1H, app. t, Jˆ7.4 Hz, ArH), 7.24 .1H, s, ArH), 6.68
.1H, s, ArH), 5.92 .2H, s, OCH2O), 3.01 .4H, s, CH2CH2);
13C NMR .75 MHz, CDCl3) dC 152.1 .CH), 148.7 .C),
147.2 .C), 147.1 .C), 136.7 .C), 134.6 .CH), 133.8 .C),
129.4 .CH), 128.9 .CH), 128.2 .C), 127.5 .CH), 126.8
.CH), 118.8 .CH), 109.6 .CH), 101.7 .OCH2O), 87.9 .CI),
42.5 .CH2), 34.1 .CH2); LRMS .ES) 445 .15%,
[MH1MeCN]1), 405 .18%, [MH.13C)]1), 404 .100%,
[MH]1), 127 .71%); Anal. Found: C, 53.78; H, 3.52; N,
3.33; C18H14INO2 requiresC, 53.62; H, 3.50; N, 3.47.
4.2.15. 4-[+E)-2-+6-Iodo-1,3-benzodioxol-5-yl)-1-ethenyl]-
quinoline trans-21 and 4-[+Z)-2-+6-iodo-1,3-benzodioxol-
5-yl)-1-ethenyl]quinoline
cis-21.
NaH
.176 mg,
4.40 mmol, 60% dispersion in oil) was washed with THF
.10 mL) then suspended in THF .25 mL) at 08C. Phos-
phonium salt 35 .2.00 g, 3.32 mmol) wasadded, followed
after 2 h by 4-quinolinecarbaldehyde .500 mg, 3.18 mmol).
After a further 2 h precipitated triphenylphosphine oxide
wasremoved by ®ltration. The ®ltrate wasconcentrated in
vacuo and puri®ed by column chromatography .silica,
ether) to give a 1:1 mixture of cis- and trans-21 .1.07 g,
4.2.13. 2-[+Z)-2-+6-Iodo-1,3-benzodioxol-5-yl)-1-ethenyl]-
quinoline 17. NaH .154 mg, 3.85 mmol, 60% dispersion in
oil) was washed with THF .10 mL) then suspended in THF
.25 mL) at 08C. Phosphonium salt 35 .1.80 g, 2.98 mmol)

D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
3395
2.67 mmol, 84%). Fractional crystallisation from methanol
yielded ®rstly trans-21 asa pale orange oslid .510 mg,
1.27 mmol, 40%); mp 175±1768C .MeOH); IR .solid,
cm21) nmax 2896 w, 1621 w, 1598 w, 1499 m, 1473 s,
.CH), 101.6 .OCH2O), 87.6 .C), 41.2 .CH2), 32.9 .CH2);
LRMS .ES) 445 .15%, [MH1MeCN]1), 404 .100%,
[MH]1), 153 .15%), 144 .16%); Anal. Found: C, 53.70;
H, 3.51; N, 3.41; C18H14INO2 requiresC, 53.62; H, 3.50;
N, 3.47.
1226 s, 1116 m, 1041 m; UV .MeOH, nm) lmax .1max
)
356 .19,430), 232 .39,860); 1H NMR .250 MHz,
d6-DMSO) dH 8.91 .1H, d, Jˆ4.6 Hz, ArH), 8.53 .1H, d,
Jˆ7.6 Hz, ArH), 8.05 .1H, dd, Jˆ7.9, 0.9 Hz, ArH), 7.94
.1H, d, Jˆ15.9 Hz, vCH), 7.80 .1H, app. td, Jˆ7.6, 1.3 Hz,
ArH), 7.80 .1H, s, ArH), 7.73 .1H, d, Jˆ4.4 Hz, ArH), 7.66
.1H, app. td, Jˆ7.6, 1.3 Hz, ArH), 7.51 .1H, d, Jˆ15.8 Hz,
vCHR), 7.50 .1H, s, ArH), 6.14 .2H, s, OCH2O); 13C NMR
.63 MHz, d6-DMSO) dC 150.7 .CH), 149.2 .C), 149.1 .C),
148.7 .C), 142.4 .C), 138.1 .CH), 132.7 .C), 129.9 .CH),
129.9 .CH), 126.9 .CH), 126.1 .C), 124.7 .CH), 124.5 .CH),
118.6 .CH), 117.0 .CH), 107.2 .CH), 102.5 .OCH2O), 91.5
.C); LRMS .APCI) 403 .19%, [MH .13C)]1), 402 .100%,
[MH]1), 279 .14%); Anal. Found: C, 53.75; H, 2.98; N,
3.39; C18H12INO2 requiresC, 53.89; H, 3.01; N, 3.49;
then from the mother liquor cis-21 .500 mg, 1.25 mmol,
39%) asa pale yellow oslid; mp 112±113 8C .EtOH); IR
.solid, cm21) nmax 1496 m, 1471 s, 1427 w, 1240 s, 1223
m, 1192 w, 1140 w, 1112 w, 1034 s; UV .MeOH, nm) lmax
4.3. Radical reactions
4.3.1. a-Phenyl-3-quinolinemethanol 2. A stirred solution
of aryl bromide 1 .300 mg, 0.95 mmol), Bu3SnH .0.25 mL,
280 mg, 0.96 mmol) and AIBN .20 mg, 0.122 mmol) in
toluene .30 mL) washeated at 80 8C under nitrogen for 5 h
then cooled to rt. Saturated KF .25 mL) and water .25 mL)
were added and the two phase mixture was stirred
vigorously for 18 h. The organic phase was separated,
dried .MgSO4), concentrated in vacuo and puri®ed by
column chromatography .silica, 97:3, CHCl3/MeOH) to
yield the title compound 2 .112 mg, 0.48 mmol, 50%) asa
white solid; mp 136±1388C .CHCl3); IR .solid, cm21) nmax
3146 br. m, 3001 w, 2846 w, 1619 w, 1579 w, 1495 m, 1439
w, 1374 w, 1329 m, 1307 w, 1230 m, 1124 m, 1081 w, 1052
w; UV .MeOH, nm) lmax .1max) 318 .2700), 304 .2350),
291 .2240), 269 .2630); 1H NMR .300 MHz, d6-DMSO) dH
8.91 .1H, s, ArH), 8.34±8.33 .2H, m, 2£ArH), 7.99 .2H,
app. t, Jˆ7.4 Hz, ArH), 7.71 .1H, app. t, Jˆ7.7 Hz, ArH),
7.58 .1H, app. t, Jˆ7.7 Hz, ArH), 7.50±7.21 .4H, m,
4£ArH), 6.29 .1H, d, Jˆ3.7 Hz, CHOH), 6.01 .1H, d,
Jˆ3.7 Hz, OH); 13C NMR .75 MHz, d6-DMSO) dC 150.2
.CH), 146.8 .C), 144.8 .C), 138.5 .C), 132.2 .CH), 129.2
.CH), 128.7 .CH), 128.4 .2£CH), 128.2 .CH), 127.5 .C),
127.2 .CH), 126.8 .CH), 126.5 .2£CH), 72.5 .CHOH);
LRMS .CI) 277 .8%, [MH1MeCN]1), 275 .6%,
[MH2H21MeCN]1), 237 .15%), 236 .100%, [MH]1),
234 .16%, [MH2H2]1), 218 .18%, [MH2H2O]1); HRMS
.EI) Found: M1, 235.0994, C16H13NO requires235.0997;
Anal. Found: C, 81.69; H, 5.57; N, 5.96; C16H13NO requires
C, 81.68; H, 5.57; N, 5.95.
1
.1max) 303 .7910); H NMR .400 MHz, CDCl3) dH 8.74
.1H, d, Jˆ4.4 Hz, ArH), 8.14 .1H, d, Jˆ8.1 Hz, ArH),
8.05 .1H, d, Jˆ8.1 Hz, ArH), 7.75 .1H, t, Jˆ7.0 Hz,
ArH), 7.58 .1H, t, Jˆ7.0 Hz, ArH), 7.28 .1H, s, ArH),
7.10 .1H, d, Jˆ4.4 Hz, ArH), 7.03 .1H, d, Jˆ11.8 Hz,
vCH), 6.89 .1H, d, Jˆ11.8 Hz, vCH), 6.28 .1H, s,
ArH), 5.84 .2H, s, OCH2O); 13C NMR .63 MHz, CDCl3)
dC 149.8 .CH), 148.2 .C), 148.1 .C), 142.9 .C), 138.4 .CH),
133.2 .C), 129.9 .CH), 129.7 .CH), 126.8 .CH), 126.8 .C),
126.0 .CH), 124.4 .CH), 121.2 .CH), 118.3 .CH), 118.3 .C),
109.8 .CH), 101.6 .CH2), 88.4 .Ar, C); LRMS .APCI) 403
.18%, [MH .13C)]1), 402 .86%, [MH]1), 153 .85%), 127
.100%); Anal. Found: C, 53.74; H, 2.94; N, 3.45;
C18H12INO2 requiresC, 53.89; H, 3.01; N, 3.49.
4.2.16. 4-[2-+6-Iodo-1,3-benzodioxol-5-yl)-1-ethyl]quino-
line 24. A solution of cis- and trans-azastilbenes 21 .ratio
1:1, 780 mg, 1.94 mmol), tosyl hydrazine .2.90 g,
15.6 mmol) and sodium acetate .1.28 g, 15.6 mmol) in
THF .15 mL) and water .15 mL) washeated at re¯ux for
72 h then cooled to ambient temperature. The reaction was
partitioned between 2 M potassium carbonate .30 mL) and
ether .50 mL). The aqueousphase wasextracted with ether
.2£50 mL) then the combined organic phases were dried
.MgSO4), concentrated in vacuo and puri®ed by column
chromatography .silica, ether) to give dihydroazastilbene
24 .678 mg, 1.68 mmol, 87%) asa white crystalline solid;
mp 98±1008C .ether/petrol); IR .solid, cm21) nmax 2896 w,
1592 w, 1502 m, 1474 s, 1227 s, 1110 m, 1038 s; UV
.MeOH, nm) lmax .1max) 314 .2990), 300 .7870), 290
.8880); 1H NMR .300 MHz, CDCl3) dH 8.81 .1H, d,
Jˆ4.4 Hz, ArH), 8.14 .1H, d, Jˆ8.8 Hz, ArH), 8.14 .1H,
d, Jˆ8.8 Hz, ArH), 7.71 .1H, app. t, Jˆ7.7 Hz, ArH), 7.57
.1H, app. t, Jˆ7.4 Hz, ArH), 7.27 .1H, s, ArH), 7.23 .1H, d,
Jˆ4.4 Hz, ArH), 6.75 .1H, s, ArH), 5.93 .2H, s, OCH2O),
3.30±3.25 .2H, app. dd, Jˆ9.9, 6.3 Hz, CH2), 3.07±3.02
.2H, app. dd, Jˆ9.6, 5.9 Hz CH2); 13C NMR .75 MHz,
CDCl3) dC 150.4 .CH), 148.6 .C), 148.3 .C), 147.1 .C),
146.9 .C), 136.8 .C), 130.3 .CH), 129.2 .CH), 127.5 .C),
126.5 .CH), 123.6 .CH), 121.0 .CH), 118.7 .CH), 109.4
4.3.2. Phenyl-3-quinolinyl-methanone 4. A stirred solu-
tion of aryl bromide 3 .129 mg, 0.413 mmol), Bu3SnH
.0.14 mL, 151 mg, 0.519 mmol) and AIBN .10 mg,
0.061 mmol) in toluene .40 mL) washeated at 80 8C under
nitrogen for 48 h then cooled to rt. Saturated KF .20 mL)
and water .20 mL) were added and the two phase mixture
was stirred vigorously for 48 h. The organic phase was sepa-
rated, dried .MgSO4), concentrated in vacuo and puri®ed by
column chromatography .silica, 1:1, Et2O/petrol) to yield
the title compound 4 .72 mg, 0.31 mmol, 75%) asa white
solid; mp 75±768C .petrol) [Lit. 76±788C];18 Anal. Found:
C, 82.11; H, 4.79; N, 6.02; C16H11NO requiresC, 82.38; H,
4.75; N, 6.00. Spectral data were in accord with literature
values.
4.3.3. [1,3]Dioxolo[40,50:4,5]benzo[c]acridine 7, [1,3]-
dioxolo[40,50:4,5]benzo[k]phenanthridine 8 and 3-[+E)-
2-+1,3-benzodioxol-5-yl)-1-ethenyl]-quinoline 9. A stirred
solution of aryl bromide 5 .250 mg, 0.706 mmol), Bu3SnH
.0.23 mL, 249 mg, 0.853 mmol) and AIBN .100 mg,
0.609 mmol) in toluene .80 mL) washeated at 80 8C under
nitrogen for 18 h then cooled to rt. Saturated KF .25 mL)
and water .25 mL) were added and the two phase mixture
was stirred vigorously for 8 h. The organic phase was
separated, dried .MgSO4), concentrated in vacuo and

3396
D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
puri®ed by column chromatography .silica, 1:1 Et2O/petrol)
to yield ®rstly [1,3]dioxolo[40,50:4,5]benzo[c]acridine 7
.47 mg, 0.172 mmol, 24%), then 3-[.E)-2-.1,3-benzo-
dioxol-5-yl)-1-ethenyl]quinoline 9 .35 mg, 0.127 mmol,
18%) asa white solid; mp 117±119 8C .EtOH); IR .solid,
cm21) nmax 3032 w, 2894 w, 1502 s, 1490 s, 1445 m, 1253 s,
1039 m; UV .MeOH, nm) lmax .1max) 336 .28,900), 308
1.0 Hz, ArH), 7.86±7.79 .3H, m, 3£ArH), 7.72 .1H, ddd,
Jˆ8.5, 7.0, 1.5 Hz, ArH), 7.34 .1H, s, ArH), 6.19 .2H, s,
OCH2O); nOe .400 MHz, CDCl3) irradiation of the signal at
dH 9.29 led to nOe enhancement at dH 7.86±7.79. Irradia-
tion of the signal at dH 8.50 led to nOe enhancement at dH
8.96. Irradiation of the signal at dH 7.34 led to nOe enhance-
ment at dH 7.86±7.79; 13C NMR .100 MHz, CDCl3) dC
153.2 .CH), 149.2 .C), 148.9 .C), 146.7 .C), 133.1 .C),
130.9 .C), 130.6 .CH), 128.4 .CH), 128.4 .CH), 126.9
.CH), 126.7 .CH), 125.6 .C), 125.0 .C), 125.0 .C), 124.2
.CH), 106.1 .CH), 105.8 .CH), 102.2 .OCH2O); LRMS .ES)
275 .17%, [MH.13C)]1), 274 .100%, [MH]1); Anal. Found:
C, 78.63; H, 4.04; N, 5.10; C18H11NO2 requiresC, 79.11; H,
4.06; N, 5.13.
1
.19,000), 282 .25,200); H NMR .400 MHz, CDCl3) dH
9.02 .1H, d, Jˆ2.0 Hz, ArH), 8.06 .1H, d, Jˆ2.0 Hz,
ArH), 8.01 .1H, d, Jˆ8.5 Hz, ArH), 7.74 .1H, d,
Jˆ8.0 Hz, ArH), 7.60 .1H, ddd, Jˆ8.5, 7.0, 1.5 Hz, ArH),
7.47 .1H, ddd, Jˆ8.0, 7.0, 1.0 Hz, ArH), 7.18 .1H, d,
Jˆ16.6 Hz, vCH), 7.06 .1H, d, Jˆ1.5 Hz, ArH), 7.02
.1H, d, Jˆ16.1 Hz, vCH), 6.95 .1H, dd, Jˆ8.0, 1.5 Hz,
ArH), 6.77 .1H, d, Jˆ8.0 Hz, ArH), 5.94 .2H, s, OCH2O);
13C NMR .100 MHz, CDCl3) dC 148.0 .CH), 146.9 .C),
146.5 .C), 146.0 .C), 130.4 .CH), 129.9 .C), 129.2 .CH),
129.0 .C), 127.9 .CH), 127.6 .CH), 126.7 .C), 126.3 .CH),
125.6 .CH), 122.1 .CH), 120.5 .CH), 107.1 .CH), 104.2
.CH), 99.9 .OCH2O); LRMS .ES) 317 .9%,
[MH1MeCN]1), 276 .100%, [MH]1), 140 .17%), 127
.22%); HRMS .ES1) Found MH1: 276.1009, C18H14NO2
requires276.1019; and ®nally [1,3]dioxolo[4 0,50:
4,5]benzo[k]phenanthridine 8 .89 mg, 0.326 mmol, 46%).
Alternatively, a stirred solution of aryl iodide 6 .100 mg,
0.249 mmol), Bu3SnH .0.08 mL, 87 mg, 0.297 mmol) and
AIBN .4 mg, 0.024 mmol) in toluene .20 mL) washeated at
808C under nitrogen for 18 h then cooled to rt. Saturated KF
.25 mL) and water .25 mL) were added and the two phase
mixture was stirred vigorously for 24 h. The organic phase
wasseparated, dried .MgSO 4), concentrated in vacuo and
puri®ed by column chromatography .silica, 1:1 Et2O/petrol)
to yield ®rstly [1,3]dioxolo[40,50:4,5]benzo[c]acridine 7
.26 mg, 0.095 mmol, 38%) asa white oslid; mp 180±
1828C .Et2O/petrol); IR .solid, cm21) nmax 1487 m, 1464
s, 1405 m, 1278 m, 1232 m, 1039 m; UV .MeOH, nm) lmax
.1max) 385 .7620), 366 .8340), 350 .6290), 307 .59,500),
4.3.4. 5,6-Dihydro[1,3]dioxolo[40,50:4,5]benzo[c]acridine
12, 7,8-dihydro[1,3]dioxolo[40,50:4,5]benzo[k]phenan-
thridine 13 and 3-[2-+1,3-benzodioxol-5-yl)-1-ethyl]quino-
line 14. A stirred solution of aryl iodide 11 .750 mg,
1.86 mmol), Bu3SnH .0.70 mL, 757 mg, 2.60 mmol) and
AIBN .30 mg, 0.183 mmol) in toluene .170 mL) washeated
at 808C under nitrogen for 36 h then cooled to rt. Saturated
KF .50 mL) and water .50 mL) were added and the two
phase mixture was stirred vigorously for 36 h. The organic
phase was separated, dried .MgSO4), concentrated in vacuo
and puri®ed by column chromatography .silica, Et2O) to
yield ®rstly 12 as a white crystalline solid .116 mg,
0.421 mmol, 23%); mp 138±1408C .Et2O/petrol); IR
.solid, cm21) nmax 2894 w, 2835 w, 1612 w, 1484 s, 1449
m, 1405 m, 1376 m, 1268 s, 1226 m, 1036 s; UV .MeOH,
nm) lmax .1max) 359 .30,200), 320 .10,100), 275 .19,700),
252 .29,900); 1H NMR .300 MHz, CDCl3) dH 8.10 .1H, d,
Jˆ8.1 Hz, ArH), 8.08 .1H, s, ArH), 7.86 .1H, s, ArH), 7.72
.1H, d, Jˆ8.1 Hz, ArH), 7.64 .1H, app. t, Jˆ7.4 Hz, ArH),
7.46 .1H, app. t, Jˆ7.4 Hz, ArH), 6.74 .1H, s, ArH), 6.01
.2H, s, OCH2O), 3.08 .2H, app. t, Jˆ7.0 Hz, CH2), 2.91
.2H, app. t, Jˆ6.6 Hz, CH2); 13C NMR .75 MHz, CDCl3)
dC 153.2 .C), 148.9 .C), 147.5 .C), 147.3 .C), 134.5 .C),
133.4 .CH), 130.0 .C), 129.1 .CH), 128.9 .C), 128.6 .CH),
127.6 .C), 126.9 .CH), 125.7 .CH), 108.0 .CH), 106.2 .CH),
101.2 .OCH2O), 28.9 .CH2), 28.5 .CH2); LRMS .ES) 277
.18%, [MH.13C)]1), 276 .100%, [MH]1); Anal. Found: C,
78.39; H, 4.74; N, 5.03; C18H13NO2 requiresC, 78.53; H,
1
282 .59,600); H NMR .400 MHz, CDCl3) dH 8.92 .1H, s,
ArH), 8.64 .1H, s, ArH), 8.34 .1H, d, Jˆ8.8 Hz, ArH), 8.02
.1H, d, Jˆ8.0 Hz, ArH), 7.81 .1H, app. t, Jˆ7.7 Hz, ArH),
7.68 .1H, d, Jˆ8.8 Hz, ArH), 7.60 .1H, d, Jˆ8.8 Hz, ArH),
7.57 .1H, app. t, Jˆ7.7 Hz, ArH), 7.24 .1H, s, ArH), 6.17
.2H, s, OCH2O); nOe .400 MHz, CDCl3) irradiation of the
signal at dH 8.92 caused no nOe enhancement. Irradiation of
the signal at dH 8.64 led to nOe enhancement at dH 8.02 and
dH 7.68. Irradiation of the signal at dH 7.24 led to nOe
enhancement at dH 7.60; 13C NMR .100 MHz, CDCl3) dC
149.3 .C), 148.2 .C), 147.7 .C), 147.2 .C), 135.1 .CH),
130.4 .C), 129.6 .CH), 129.6 .CH), 127.8 .CH), 127.1
.CH), 126.6 .C), 125.5 .CH), 124.6 .C), 124.1 .CH),
105.7 .CH), 103.9 .CH), 101.6 .OCH2O) with one quatern-
ary C obscured; LRMS .ES) 275 .17%, [MH.13C)]1), 274
.100%, [MH]1), 153 .41%), 127 .48%); HRMS .ES1)
Found MH1: 274.0865, C18H12NO2 requires274.0868;
then
[1,3]dioxolo[40,50:4,5]benzo[k]phenanthridine
8
.39 mg, 0.143 mmol, 57%) asa white oslid; mp 200±
2028C .EtOH); IR .solid, cm21) nmax 3062 w, 2903 w,
1578 w, 1501 m, 1476 s, 1450 m, 1385 w, 1365 w, 1249
s, 1037 m; UV .MeOH, nm) lmax .1max) 382 .2430), 363
1
.2320), 332 .5730), 303 .10,200), 282 .31,200); H NMR
.400 MHz, CDCl3) dH 9.29 .1H, s, ArH), 8.96 .1H, d,
Jˆ8.5 Hz, ArH), 8.50 .1H, s, ArH), 8.32 .1H, dd, Jˆ8.0,

D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
3397
4.76; N, 5.09; then 13 .260 mg, 0.944 mmol, 51%) asa
white crystalline solid; mp 144±1468C .CH2Cl2/petrol); IR
.solid, cm21) nmax 2898 w, 1618 w, 1562 m, 1501 s, 1485 s,
1419 w, 1389 m, 1283 m, 1224 s, 1167 m, 1041 s; UV
.MeOH, nm) lmax .1max) 353 .7880), 327 .5060), 243
.15,800); 1H NMR .400 MHz, CDCl3) dH 8.84 .1H, s,
ArH), 8.47 .1H, d, Jˆ8.5 Hz, ArH), 8.17 .1H, d,
Jˆ8.0 Hz, ArH), 7.72 .1H, app. t, Jˆ7.3 Hz, ArH), 7.59
.1H, app. t, Jˆ7.5 Hz, ArH), 7.53 .1H, s, ArH), 6.95 .1H,
s , AHr ), 6.09 .2H, s, OCH2O), 2.94±2.91 .2H, m, CH2),
2.86±2.82 .2H, m, CH2); nOe .400 MHz, CDCl3) irradiation
of the signal at dH 8.84 led to nOe enhancement at dH 2.94±
2.91. Irradiation of the signal at dH 7.53 led to nOe enhance-
ment at dH 8.47. Irradiation of the signal at dH 6.95 led to
nOe enhancement at dH 2.86±2.82; 13C NMR .100 MHz,
CDCl3) dC 151.1 .CH), 150.0 .C), 148.7 .C), 147.4 .C),
140.4 .C), 136.1 .C), 131.3 .CH), 131.0 .C), 129.1 .CH),
127.5 .CH), 126.6 .C), 126.1 .CH), 125.4 .C), 110.7 .CH),
109.9 .CH), 102.4 .OCH2O), 30.3 .CH2), 27.7 .CH2);
LRMS .ES) 277 .18%, [MH.13C)]1), 276 .100%, [MH]1),
242 .16%); Anal. Found: C, 78.22; H, 4.76; N, 5.00;
C18H13NO2 requiresC, 78.53; H, 4.76; N, 5.09.
one CH obscured; LRMS .ES) 279 .19%, [MH.13C)]1),
278 .100%, [MH]1); HRMS .ES1) Found MH1:
278.1176, C18H16NO2 requires278.1167.
4.3.5. Attempted radical cyclisation of2[+ Z)-2-+6-bromo-
1,3-benzodioxol-5-yl)-1-ethenyl]quinoline 15. The alkene
15 .116 mg, 0.327 mmol) in toluene .80 mL) wastsirred
under nitrogen at 808C with Bu3SnH .0.10 mL, 108 mg,
0.371 mmol) and AIBN .15 mg, 0.091 mmol) for 48 h.
The resulting mixture was cooled to room temperature, stir-
red for 18 h with saturated KF .50 mL) then separated. The
organic phase was dried .MgSO4), concentrated and puri®ed
by column chromatography .silica, 50:50, ether/petrol) to
yield a mixture of cis-15 and trans-15. Fractional crystal-
lisation from ethanol gave trans-15 .16 mg, 0.0451 mmol,
14%) asa white crystalline solid; mp 198±200 8C .EtOH);
IR .solid, cm21) nmax 1597 m, 1486 s, 1412 w, 1308 w, 1265
m, 1242 m, 1232, m, 1119 m, 1034 s; UV .MeOH, nm) lmax
1
.1max) 351 .18,460), 252 .19,900); H NMR .300 MHz,
CDCl3) dH 8.14 .1H, d, Jˆ8.8 Hz, ArH), 8.09 .1H, d,
Jˆ8.8 Hz, ArH), 7.93 .1H, d, Jˆ16.2 Hz, vCH), 7.80
.1H, d, Jˆ8.1 Hz, ArH), 7.75 .1H, d, Jˆ8.8 Hz, ArH),
7.72 .1H, t, Jˆ7.4 Hz, ArH), 7.51 .1H, t, Jˆ7.4 Hz, ArH),
7.29 .1H, s, ArH), 7.23 .1H, d, Jˆ16.2 Hz, vCH), 7.08
.1H, s, ArH), 6.03 .2H, s, OCH2O); 13C NMR .75 MHz,
CDCl3) dC 155.9 .C), 148.8 .C), 148.2 .C), 147.9 .C),
136.4 .CH), 132.8 .CH), 130.2 .CH), 129.8 .CH), 129.7
.C), 129.2 .CH), 127.5 .CH), 127.3 .C), 126.3 .CH),
118.8 .CH), 116.4 .C), 112.9 .CH), 106.1 .CH), 102.0
.CH2); LRMS .ES) 356 .86%, [M.81Br)1H]1), 354 .80%,
[M.79Br)1H]1), 276 .17%), 152 .100%); HRMS .ES1)
Found MH1: 354.0124, C18H13NO279Br requires354.0116;
concentration of the mother liquor furnished cis-15 .95 mg,
0.268 mmol, 82%).
Alternatively, a stirred solution of aryl bromide 10 .286 mg,
0.803 mmol), Bu3SnH .0.30 mL, 325 mg, 1.11 mmol) and
AIBN .10 mg, 0.061 mmol) in toluene .120 mL) washeated
at 808C under nitrogen for 24 h then cooled to rt. Saturated
KF .25 mL) and water .25 mL) were added and the two
phase mixture was stirred vigorously for 24 h. The phases
were separated and the aqueous phase extracted with ether
.2£50 mL). The combined organic phases were dried
.MgSO4), concentrated in vacuo and puri®ed by column
chromatography .silica, gradient elution 0:100!80:20
ether/petrol) to yield ®rstly 12 .40 mg, 0.15 mmol, 18%);
then an inseparable mixed fraction .38 mg); then recovered
10 .71 mg, 27%) and ®nally a mixed fraction comprising of
13 and 14. Fractional crystallisation from ethanol gave 13
.33 mg, 0.12 mmol, 15%). Finally, 14 .22 mg, 0.08 mmol,
10%) wasioslated from the mother liquor; mp 91±93 8C
.EtOH); IR .solid, cm21) nmax 1500 m, 1483 s, 1440 m,
1360 w, 1241 s, 1190 w, 1038 s; UV .MeOH, nm) lmax
.1max) 318 .4510), 304 .4210), 285 .7310), 233 .37,410);
1H NMR .300 MHz, CDCl3) dH 8.73 .1H, d, Jˆ2.2 Hz,
ArH), 8.09 .1H, d, Jˆ8.1 Hz, ArH), 7.88 .1H, s, ArH),
7.76 .1H, d, Jˆ8.1 Hz, ArH), 7.68 .1H, t, Jˆ7.4 Hz,
ArH), 7.53 .1H, t, Jˆ7.7 Hz, ArH), 6.72 .1H, d,
Jˆ8.1 Hz, ArH), 6.71 .1H, s, ArH), 6.60 .1H, d,
Jˆ8.1 Hz, ArH), 5.93 .2H, s, OCH2O), 3.10±3.05 .2H, m,
CH2CH2), 2.97±2.92 .2H, m, CH2CH2); 13C NMR .75 MHz,
CDCl3) dC 151.9 .CH), 147.7 .C), 146.8 .C), 145.9 .C),
134.5 .CH), 134.1 .C), 129.1 .CH), 128.7 .CH), 128.1
.C), 127.4 .CH), 126.6 .CH), 121.4 .CH), 108.9 .CH),
108.2 .CH), 100.9 .CH2), 37.2 .CH2), 35.3 .CH2), with
4.3.6. [1,3]Dioxolo[40,50:4,5]benzo[a]acridine 16. A stir-
red solution of aryl iodide 17 .500 mg, 1.25 mmol),
Bu3SnH .1.62 mL, 1.75 g, 6.01 mmol) and AIBN
.120 mg, 0.73 mmol) in toluene .100 mL) washeated at
808C under nitrogen for 72 h then cooled to rt. Saturated
KF .40 mL) and water .40 mL) were added and the two
phase mixture was stirred vigorously for 36 h then sepa-
rated. The aqueousphaes wasextracted with ether
.2£100 mL) then the combined organic phases were dried
.MgSO4), concentrated in vacuo and puri®ed by column
chromatography .silica, Et2O) to give 16 .142 mg,
0.52 mmol, 42%) asa yellow crytsalline oslid; mp 215±
2178C .Et2O/petrol); IR .solid, cm21) nmax 3045 w, 2946
w, 1737 w, 1633 w, 1618 w, 1504 m, 1470 s, 1394 w,
1371 m, 1271 m, 1252 s, 1039 s; UV .MeOH, nm) lmax
.1max) 385 .10,740), 366 .10,190), 309 .7172), 295

3398
D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
1
.53,370), 284 .63,090), 242 .60,200); H NMR .400 MHz,
CDCl3) dH 9.13 .1H, s, ArH), 8.17 .1H, d, Jˆ8.5 Hz, ArH),
8.02 .1H, s, ArH), 7.98 .1H, d, Jˆ8.0 Hz, ArH), 7.87 .1H, d,
Jˆ9.0 Hz, ArH), 7.77 .1H, d, Jˆ9.5 Hz, ArH), 7.72 .1H,
app. t, Jˆ8.3 Hz, ArH), 7.51 .1H, app. t, Jˆ7.5 Hz, ArH),
7.17 .1H, s, ArH), 6.06 .2H, s, OCH2O); nOe .400 MHz,
CDCl3) irradiation of the signal at dH 9.13 led to nOe
enhancement at dH 8.02 and dH 7.98. Irradiation of the
signal at dH 7.17 led to nOe enhancement at dH 7.77; 13C
NMR .75 MHz, CDCl3) dC 149.2 .C), 149.1 .C), 148.7 .C),
148.3 .C), 132.4 .CH), 130.5 .CH), 130.2 .CH), 129.4 .CH),
128.6 .CH), 127.8 .C), 127.1 .CH), 126.8 .C), 126.3 .CH),
124.4 .C), 107.1 .CH), 102.1 .CH), 102.1 .OCH2O), with
one quaternary C obscured; LRMS .ES) 274 .8%, [MH]1),
123 .100%); Anal. Found: C, 78.79; H, 4.07; N, 5.09;
C18H11NO2 requiresC, 79.11; H, 4.06; N, 5.13.
the signal at dH 8.19 led to nOe enhancement at dH 7.81 and
dH 7.33. Irradiation of the signal at dH 3.24 led to nOe
enhancement at dH 2.97. Irradiation of the signal at dH
2.97 led to nOe enhancement at dH 6.77 and dH 3.24; 13C
NMR .75 MHz, CDCl3) dC 159.1 .C), 148.0 .C), 147.5
.C), 146.7 .C), 132.1 .C), 129.1 .CH), 128.6 .CH), 128.5
.CH), 128.4 .C), 128.2 .C), 127.8 .CH), 126.8 .C), 126.2
.CH), 108.8 .CH), 104.6 .CH), 101.4 .OCH2O), 33.2
.ArCH2), 28.9 .ArCH2); LRMS .ES) 276 .100%,
[MH]1), 153 .35%), 130 .22%); Anal. Found: C, 78.10;
H, 4.83; N, 5.03; C18H13NO2 requiresC, 78.53; H, 4.76;
N, 5.09.
4.3.8. [1,3]Dioxolo[4050:4,5]benzo[i]phenanthridine 22
and 4-[+E)-2-+1,3-benzodioxol-5-yl)-1-ethenyl]-quinoline
23. A stirred solution of aryl iodide 21 .600 mg,
1.50 mmol), Bu3SnH .0.55 mL, 595 mg, 2.04 mmol) and
AIBN .20 mg, 0.122 mmol) in toluene .120 mL) washeated
at 808C under nitrogen for 24 h then cooled to rt. Saturated
KF .50 mL) and water .50 mL) were added and the two
phase mixture was stirred vigorously for 18 h then sepa-
rated. The organic phase was dried .MgSO4), concentrated
in vacuo and puri®ed by column chromatography .silica,
Et2O) to yield ®rstly recovered starting material 21
.40 mg, 0.10 mmol, 7%) then a mixture of the cyclised
product 22 and the reduced product 23. These materials
were separated by fractional crystallisation from EtOH to
yield ®rstly 22 .142 mg, 0.52 mmol, 35%) asa white solid;
mp 237±2398C .EtOH); IR .solid, cm21) nmax 1744 m, 1701
m, 1470 s, 1370 m, 1356 m, 1230 s, 1190 m, 1030 m; UV
.MeOH, nm) lmax .1max) 372 .10,340), 354 .8740), 329
4.3.7. 5,6-Dihydro[1,3]dioxolo[40,50:4,5]benzo[a]acridine
19. A stirred solution of aryl bromide 18 .91 mg,
0.255 mmol), Bu3SnH .0.10 mL, 108 mg, 0.371 mmol)
and AIBN .10 mg, 0.06 mmol) in toluene .80 mL) was
heated at 808C under nitrogen for 18 h then cooled to rt.
Saturated KF .25 mL) and water .25 mL) were added and
the two phase mixture was stirred vigorously for 24 h then
separated. The aqueous phase was extracted with ether
.50 mL) and the combined organic phases were dried
.MgSO4), concentrated in vacuo and puri®ed by column
chromatography .silica, 1:1 Et2O/petrol) to give the title
compound 19 .43 mg, 0.156 mmol, 62%) asa white solid.
Alternatively, a stirred solution of aryl iodide 20 .570 mg,
1.41 mmol), Bu3SnH .0.46 mL, 498 mg, 1.71 mmol) and
AIBN .20 mg, 0.122 mmol) in toluene .80 mL) washeated
at 808C under nitrogen for 24 h then cooled to rt. Saturated
KF .25 mL) and water .25 mL) were added and the two
phase mixture was stirred vigorously for 36 h then sepa-
rated. The aqueousphaes wasextracted with ether
.50 mL), then the combined organic phases were dried
.MgSO4), concentrated in vacuo and puri®ed by column
chromatography .silica, 1:1, Et2O/petrol) to yield 19
.270 mg, 0.98 mmol, 70%) asa white crytsalline oslid;
mp 168±1708C .EtOH); IR .solid, cm21) nmax 3042 w,
2948 w, 2891 w, 1619 w, 1502 m, 1482 s, 1383 m, 1363
1
.11,250), 307 .14,690), 254 .39,010); H NMR .400 MHz,
CDCl3) dH 10.02 .1H, s, ArH), 8.64 .1H, dd, Jˆ8.0, 1.0 Hz,
ArH), 8.50 .1H, d, Jˆ9.0 Hz, ArH), 8.25 .1H, dd, Jˆ8.0,
1.5 Hz, ArH), 8.23 .1H, s, ArH), 8.05 .1H, d, Jˆ8.5 Hz,
ArH), 7.77 .1H, app. td, Jˆ7.5, 1.5 Hz, ArH), 7.71 .1H,
app. td, Jˆ7.5, 1.0 Hz, ArH), 7.33 .1H, s, ArH), 6.17 .2H,
s , OCH2O); 13C NMR .100 MHz, CDCl3) dC 148.2 .C),
146.9 .C), 146.8 .CH), 143.5 .C), 130.0 .CH), 129.8 .C),
128.8 .CH), 127.9 .C), 127.2 .CH), 125.8 .CH), 125.7 .C),
123.1 .C), 121.3 .CH), 120.4 .C), 117.0 .CH), 104.4 .CH),
100.5 .OCH2O), 98.6 .CH); LRMS .APCI) 275 .20%,
[MH.13C)]1), 274 .100%, [MH]1); HRMS .ES1) Found
MH1: 274.0863, C18H12NO2 requires274.0867; then 23
.226 mg, 0.82 mmol, 55%) asa white oslid; mp 117±
1188C .EtOH); IR .solid, cm21) nmax 1575 w, 1501 m,
1489 w, 1446 m, 1253 s, 1197 m, 1038 s; UV .MeOH,
m, 1250 m, 1222 m, 1038 s; UV .MeOH, nm) lmax .1m1ax
)
357 .13,500), 322 .10,700), 309 .7970), 278 .17,400); H
NMR .300 MHz, CDCl3) dH 8.19 .1H, s, ArH), 8.02 .1H, d,
Jˆ8.1 Hz, ArH), 7.81 .1H, d, Jˆ8.1 Hz, ArH), 7.64 .1H,
app. t, Jˆ7.4 Hz, ArH), 7.48 .1H, app. t, Jˆ7.4 Hz, ArH),
7.33 .1H, s, ArH), 6.77 .1H, s, ArH), 6.00 .2H, s, OCH2O),
3.24 .2H, app. t, Jˆ7.0 Hz, ArCH2), 2.97 .2H, app. t,
Jˆ7.0 Hz, ArCH2); nOe .400 MHz, CDCl3) irradiation of
1
nm) lmax .1max) 316 .7430), 304 .7430), 227 .27,020); H
NMR .400 MHz, CDCl3) dH 8.88 .1H, d, Jˆ4.5 Hz, ArH),
8.20 .1H, d, Jˆ8.4 Hz, ArH), 8.12 .1H, d, Jˆ8.4 Hz, ArH),
7.73 .1H, app. t, Jˆ7.6 Hz, ArH), 7.64 .1H, d, Jˆ16.0 Hz,
vCH), 7.58 .1H, app. t, Jˆ7.4 Hz, ArH), 7.56 .1H, d,
Jˆ4.2 Hz, ArH), 7.26 .1H, d, Jˆ16.0 Hz, vCH), 7.19
.1H, s, ArH), 7.05 .1H, d, Jˆ7.9 Hz, ArH), 6.86 .1H, d,
Jˆ8.0 Hz, ArH), 6.02 .2H, s, OCH2O); 13C NMR
.63 MHz, CDCl3) dC 150.2 .CH), 148.8 .C), 148.4 .C),
148.3 .C), 143.0 .C), 134.7 .CH), 131.1 .C), 130.2 .CH),
129.3 .CH), 126.4 .CH), 126.4 .C), 123.4 .CH), 122.6 .CH),
121.0 .CH), 116.8 .CH), 108.6 .CH), 105.9 .CH), 101.4
.OCH2O); LRMS .APCI) 277 .19%, [MH.13C)]1), 276
.100%, [MH]1), 158 .32%); Anal. Found: C, 78.13; H,
4.70; N, 5.08; C18H13NO2 requiresC, 78.53; H, 4.76; N,
5.09.

D. C. Harrowven et al. / Tetrahedron 58 %2002) 3387±3400
3399
4.3.9. 5,6-Dihydro-[1,3]dioxolo[40,50:4,5]benzo[i]phenan-
thridine 25. A stirred solution of aryl iodide 24 .415 mg,
1.03 mmol), Bu3SnH .0.40 mL, 433 mg, 1.48 mmol) and
AIBN .40 mg, 0.24 mmol) in toluene .80 mL) washeated
at 808C under nitrogen for 48 h then cooled to rt. Saturated
KF .40 mL) and water .40 mL) were added and the two
phase mixture was stirred vigorously for 24 h then sepa-
rated. The aqueousphaes wasextracted with ether
1989, 28, 489. For recent examples see .b) Russell, G. A.;
Rajaratnam, R.; Wang, L. J.; Shi, B. Z.; Kim, B. H.; Yao,
C. F. J. Am. Chem. Soc. 1993, 115, 10596. .c) Russell,
G. A.; Wang, L. J.; Yao, C. F. J. Org. Chem. 1995, 60, 5390.
5. Harrowven, D. C.; Sutton, B. J.; Coulton, S. Tetrahedron Lett.
2001, 42, 2907.
6. Harrowven, D. C.; Sutton, B. J.; Coulton, S. Tetrahedron Lett.
2001, 42, 9061.
7. Allin, S. M.; Barton, W. R. S.; Bowman, W. R.; McInally, T.
Tetrahedron Lett. 2001, 42, 7887.
.2£50 mL) then the combined organic phases were dried
.MgSO4), concentrated in vacuo and puri®ed by column
chromatography .silica, Et2O) to yield the title compound
25 .190 mg, 0.69 mmol, 67%) asa white oslid; mp 138±
1408C .DCM/petrol); IR .solid, cm21) nmax 2900 w, 1687 w,
1502 m, 1486 s, 1471 s, 1366 m, 1267 m, 1232 s, 1038 s; UV
.MeOH, nm) lmax .1max) 357 .7910), 269 .18,140), 239
.16,620); 1H NMR .300 MHz, CDCl3) dH 9.15 .1H, s,
ArH), 8.08 .1H, d, Jˆ8.8 Hz, ArH), 8.03 .1H, d,
Jˆ8.1 Hz, ArH), 7.64 .1H, app. t, Jˆ7.4 Hz, ArH), 7.54
.1H, app. t, Jˆ7.7 Hz, ArH), 7.35 .1H, s, ArH), 6.77 .1H,
s , AHr ), 5.97 .2H, s, OCH2O), 3.21 .2H, t, Jˆ7.6 Hz,
ArCH2), 2.87 .2H, t, Jˆ7.6 Hz, ArCH2); nOe .400 MHz,
CDCl3) irradiation of the signal at dH 9.15 led to nOe
enhancement at dH 7.35. Irradiation of the signal at dH
7.35 led to nOe enhancement at dH 9.15. Irradiation of the
signal at dH 3.21 led to nOe enhancement at dH 8.03 and dH
2.87. Irradiation of the signal at dH 2.87 led to nOe enhance-
ment at dH 6.77 and dH 3.21; 13C NMR .75 MHz, CDCl3) dC
147.3 .C), 147.2 .C), 146.9 .C), 146.5 .CH), 140.6 .C),
130.9 .C), 129.9 .CH), 128.6 .CH), 126.9 .C), 126.7
.CH), 126.4 .C), 125.8 .C), 123.4 .CH), 108.7 .CH),
104.2 .CH), 101.2 .OCH2O), 27.9 .ArCH2), 23.3 .ArCH2);
LRMS .ES) 317 .22%, [MH1MeCN]1), 276 .100%,
[MH]1), 168 .22%), 153 .64%), 144 .33%); HRMS .ES)
Found MH1: 276.1026, C18H14NO2 requires276.1024.
8. The term `oxidative cyclisations' is often used to describe
reactionsmediated by a tributyltin hydride in which a radical
cyclisation step is followed by the loss of a hydrogen atom in
the absence of an added oxidising agent. The term is rather
misleading as the overall reaction proceeds with the loss of
HX to form a s-bond and likewise there is no change in
oxidation level in the cyclisation step.
9. For examplesof non-reducing radical reactionsmediated by
tributyltin hydride see: .a) Murphy, J. A.; Sherburn, M. S.
Tetrahedron Lett. 1990, 31, 3495. .b) Murphy, J. A.; Sherburn,
M. S. Tetrahedron 1991, 47, 4077. .c) Motherwell, W. B.;
Pennell, A. M. K. J. Chem. Soc., Chem. Commun. 1991,
877. .d) Bowman, W. R.; Heaney, H.; Jordan, B. M. Tetra-
hedron 1991, 47, 10119. .e) Antonio, Y.; De La Cruz, M. E.;
Galeazzi, E.; Guzman, A.; Bray, B. L.; Greenhouse, R.; Kurz,
L. J.; Lustig, D. A.; Maddox, M. L.; Muchowski, J. M. Can. J.
Chem. 1994, 72, 15. .f) Curran, D. P.; Liu, H. J. Chem. Soc.,
Perkin Trans. 1 1994, 1377. .g) Beckwith, A. L. J.; Storey,
J. M. D. J. Chem. Soc., Chem. Commun. 1995, 977. .h) da
Mata, M. L. E. N.; Motherwell, W. B.; Ujjainwalla, F. Tetra-
hedron Lett. 1997, 38, 137. .i) da Mata, M. L. E. N.; Mother-
well, W. B.; Ujjainwalla, F. Tetrahedron Lett. 1997, 38, 141.
.j) Rosa, A. M.; Lobo, A. M.; Branco, P. S.; Prabhakar, S.;
Pereira, A. M. D. L. Tetrahedron 1997, 53, 269. .k) Rosa,
A. M.; Lobo, A. M.; Branco, P. S.; Prabhakar, S. Tetrahedron
1997, 53, 285. .l) Rosa, A. M.; Lobo, A. M.; Branco, P. S.;
Â
Prabhakar, S.; Sa-da-Costa, M. Tetrahedron 1997, 53, 299.
Â
.m) Hagan, D. J.; Gimenez-Arnau, E.; Schwalbe, C. H.;
Stevens, M. F. G. J. Chem. Soc., Perkin Trans. 1 1997,
2739. .n) Moody, C. J.; Norton, C. L. J. Chem. Soc., Perkin
Trans. 1 1997, 2639. .o) Ho, T. C. T.; Jones, K. Tetrahedron
1997, 53, 8287. .p) Josien, H.; Ko, S.-B.; Bom, D.; Curran,
D. P. Chem. Eur. J. 1998, 4, 67. .q) Tsuge, C.; Halta, T.;
Tsuchiyama, H. Chem. Lett. 1998, 155. .r) Crich, D.;
Hwang, J.-T. J. Org. Chem. 1998, 63, 2765. .s) Padwa, A.;
Dimitroff, M.; Waterson, A. G.; Wu, T. J. Org. Chem. 1998,
63, 3986. .t) Harrowven, D. C.; Nunn, M. I. T. Tetrahedron
Lett. 1998, 39, 5875. .u) Nadin, A.; Harrison, T. Tetrahedron
Lett. 1999, 40, 4073. .v) Aldabbagh, F.; Bowman, W. R.
Tetrahedron 1999, 55, 4109. .w) Aldabbagh, F.; Bowman,
W. R.; Mann, E.; Slawin, A. M. Z. Tetrahedron 1999, 55,
8111. .x) Bowman, W. R.; Mann, E.; Parr, J. J. Chem. Soc.,
Perkin Trans. 1 2000, 2991. .y) Harrowven, D. C.; Nunn,
M. I. T.; Newman, N. A.; Fenwick, D. Tetrahedron Lett.
2001, 42, 961. .z) Harrowven, D. C.; Nunn, M. I. T.; Blumire,
N. J.; Fenwick, D. Tetrahedron 2001, 57, 4447.
Acknowledgements
The authorsthank GlaxoSmithKline and the EPSRC for a
CASE award .to B. J. S.) and Joan Street and Neil Wellsfor
some invaluable nOe studies.
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