Novel indole-fused, medium-sized ring heterocycles via chloroacetamide photochemistry

Article abstract of DOI:10.3987/com-99-8737

Syntheses of derivatives of three novel indole-fused systems based on indolo[2,1-d][1,5]benzodiazocine, indolo[7,7a,1-d,e][1,6]benzodiazonine and pyrrolo[2,3-b]indolo[5,5a,6-b,a]quinazoline, the first two including 8- and 9-membered ring heterocycles, are

Full text of DOI:10.3987/com-99-8737

HETEROCYCLES, Vol. 53, No. 2, 2000, pp. 277 - 290, Received, 16th August, 1999
NOVEL INDOLE-FUSED, MEDIUM-SIZED RING HETEROCYCLES VIA
CHLOROACETAMIDE PHOTOCHEMISTRY
a
b
c
c
John B. Bremner, Henry F. Russell, Brian W. Skelton, and Allan H. White
a Department of Chemistry, University of Wollongong, Wollongong, 2522 NSW,
Australia
b Johnson C. Smith University, Charlotte, North Carolina, 28216, USA
c Department of Chemistry, University of Western Australia, Nedlands,
Western Australia 6907, Australia
Abstract - Syntheses of derivatives of three novel indole-fused systems based on
indolo[2,1-d][1,5]benzodiazocine, indolo[7,7a,1-d,e][1,6]benzodiazonine and
pyrrolo[2,3-b]indolo[5,5a,6-b,a]quinazoline, the first two including 8- and 9-
membered ring heterocycles, are described. These derivatives resulted from the
photo-induced cyclization of the respective chloroacetamide precursors prepared
via N-alkylation of the appropriate indole with 2-nitrobenzyl bromide,
subsequent nitro group reduction and then N-chloroacetylation. Structural and
stereochemical features of these new ring system derivatives are discussed.
The use of chloroacetamide derivatives as substrates for photocyclization is a proven method for making a
1,2
variety of nitrogen heterocyclic systems, especially medium-ring lactams.
This type of cyclization has
been used on a variety of indolic systems to yield not only indolobenzazepines but also
3-7
indolobenzazocine and indolobenzazonine skeletons.
As part of a program to access novel fused indole
structures for pharmacological screening, we have investigated new applications of this photo-induced
cyclization of chloroacetamide derivatives. In particular, chloroacetamide systems linked to the 1-
position of indole were targeted in an effort to access the new indolo[2,1-d][1,5]benzodiazocine skeleton
containing an indole-fused 8-membered ring.
The particular precursor chloroacetamides (4a-c) required were prepared from the respective anilines (3a-
c) which were accessed in turn from the indoles (1a-c) via the N-alkylated derivatives (2a-c) (Scheme 1).
8-11
Initial attempts to alkylate indole (1a) using 2-nitrobenzyl chloride via several published routes
were
unsuccessful yielding instead chloride self-condensation products. It is probable that this was due
primarily to the acidity of the benzylic hydrogens which allowed the indole anion to act more as a base
than a nucleophile. Switching to the corresponding 2-nitrobenzyl bromide and using a modification of the
12
procedure of Ho, alleviated the problem and alkylation products (2a-c) were obtained in reasonable
yield. The subsequent reductions to 3a-c and chloroacetylations with chloroacetyl chloride to 4a-c were
accomplished under mild conditions. The structures of the products in Scheme 1 were confirmed by
NMR spectroscopic analysis and MS.
Photolysis of the chloroacetamides (4a-c) was conducted in 50% acetonitrile-water solution using a 16W
mercury lamp (Scheme 2). As anticipated from electronic considerations consequent on photo-induced
single electron transfer from the indolic moiety, 4b reacted significantly faster than 4a (4 hours versus 8
hours), while 4c required at least 16 hours to complete reaction. The methoxy series gave higher yields
as expected because of the stabilising effect of the electron releasing methoxy group on the intermediate
indolic radical cation. The yields in the fluoro series were somewhat poorer probably due to radical cation
destabilization by the fluoro atom.

Not only were the expected benzodiazocine products (5a-c) produced but, in addition, two other new ring
systems resulted: an indolo[7,7a,1-d,e][1,6]benzodiazonine (6a-c) and a pyrrolo[2,3-b]indolo[5,5a,6-
b,a]quinazoline (7a-c). A significant portion of the latter skeleton is a hexahydropyrrolo[2,3-b]indole
which is shared with a range of alkaloids including the acetylcholinesterase inhibitor, physostigmine, and
the securamines (plus flustramines) isolated from marine bryozoans which show interesting biological
13-15
activity.
R
R
NO2
2a 77%
2b 81%
2c 71%
NaH
5°C
N
NO2
N
H
CH2Br
DMF
-60°C
1a-c
H2
Pd/C
THF
1-4
a
R
H
b
c
OCH3
F
R
R
ClCH2COCl
3a 36%
3b 94%
3c 81%
N
NH2
N
NHCOCH2Cl
5°C
DCM
4a 82%
4b 43%
4c 80%
Scheme 1
9
R
R
2
1
8
4
hν
11
6a 39%
6b 43%
6c 28%
16W Hg lamp, N
N
2
N
4a-c
+
O
6
13
MeCN/H O
2
5a 16%
5b 14%
5c 14%
NH
O
N
H
4
9
___________
+
5-7
a
b
R
H
OCH
H
R
13b
13c
1
12
3
H
c
F
7a 18%
7b 22%
7c 13%
N
N
O
8
4
Scheme 2
Separation of the derivatives of 5, 6 and 7 from the photosylates was accomplished by column
chromatography. Derivatives (7a-c) had higher R s and eluted cleanly for all series. Derivatives of 5 and 6
f
had lower and very close R s and complete separation was more difficult, especially for 5c and 6c.
f
However, enough pure material was obtained for characterization.

1
Yields of both 5a-c and 6a-c were determined based upon isolated material plus H-NMR analysis of the
residual mixtures using the clearly separated signals for the CH adjacent to the carbonyl which occured
2
around δ 3.50 as a sharp singlet; the indolic 3-proton which occured between δ 6.30 and δ 6.50 as either a
singlet (5a-c) or a doublet (6a-c); and the lactam N-H proton which appeared as a broadened singlet
generally below δ 8.20.
The structures of 5a-c and 6a-c were initially deduced from the NMR spectra which show a singlet for H-
8 in the region of δ 6.50 for 5a-c, while for 6a-c the corresponding signal (H-2) is a doublet analogous to
those for the N-substituted indole precursors. This signal is not present in the spectra of (7a-c) since
these protons are now on a dihydroindolic moiety. For the fluoro analogs, ortho and meta proton-F19
o
m
1
2
(J H-F and J H-F) and F19-C13 (J and J ) couplings gave rise to more complex signals in both the
proton and carbon-13 NMR spectra.
The basic structure of 7a-c was initially determined by 2D-COSY analysis. The COSY spectrum of 7a
revealed the specific couplings of most of the protons. For the aliphatic protons the two H-1 protons
(doublet at δ 2.80 and doublet of doublets at δ 3.18) showed cross peaks to each other and to the H-13b
multiplet at δ 3.90; H-13b showed cross peaks not only to both protons in the 1-position but also to the
H-13c doublet (δ 5.44) and at least one aromatic proton (probably H-7). The H-8 methylene protons
(doublets at δ 4.63 and 4.75) correlated strongly only to each other. The aromatic protons also showed
several specific correlations in two fairly distinct groupings: one between δ 6.50 to 7.20 and another from
δ 7.00 to 8.20. The upfield group showed four sets of cross peaks the clearest of which were those
between H-10 (doublet at δ 6.59) and H-12 (doublet of doublets of doublets at δ 6.79). The downfield
group had one clear correlation between the doublet at δ 8.20 (H-4) and a doublet of doublets of doublets
at δ 7.22 (H-5). The doublet at δ 8.20 in 7a was ascribed to H-4, consistant with the deshielding effect
expected from the lactam carbonyl group.
The COSY spectrum of 7b showed identical correlations for the aliphatic protons and somewhat more
detailed correlations for the aromatic region with the H-13 proton (δ 6.78) showing cross peaks to the
signal at δ 6.71 for the H-11 proton. The H-10 and H-11 protons showed strong mutual cross peaks.
There were also cross peaks for H-13 showing a correlation to H-13b. The H-4 proton was again
obvious at δ 8.22 with clear cross peaks to the other three protons of its ring.
Structures of a representative of each structural series (5b, 6a and 7a) were confirmed unequivocally by
16
X-Ray crystallography as shown in Figures 1, 2, and 3; for each figure, 50% ellipsoids are shown for
the non-hydrogen atoms, together with skeletal numbering, and hydrogen atoms have arbitrary radii of
0.1Å. Non-hydrogen atom coordinates and equivalent isotropic thermal parameters for 5b, 6a and 7a are
given in the corresponding Tables 1, 2 and 3; in the case of 6a, four molecules were present in the
asymmetric unit cell, and only molecule 1 is given here.16 The study of 7a confirmed the 13a-13b ring
junction as cis and the overall structure correlated extremely well with the “butterfly shaped” structure
predicted by molecular modelling (Merck Force Field)17 for 7a wherein, in vacuo, this compound with the
cis ring junction has a strain energy of only 24.89 kJ/mol; the compound with the trans ring junction has a
much higher calculated strain energy of 137.61 kJ/mol.
The mechanism leading to the cyclization products most probably involves photo-induced, single electron
transfer (S.E.T.) and subsequent chloride ion loss to give a resonance stabilized intermediate which can
then cyclize via three pathways as indicated in Figure 4.

Table 1. Non-hydrogen atom coordinates and equivalent isotropic
thermal parameters of 5b.
Atom
x
y
z
2
U
Å
eq
C(1)
C(2)
C(3)
C(4)
C(4a)
N(5)
C(6)
O(6)
C(7)
C(7a)
C(8)
C(8a)
C(9)
C(10)
O(10)
C(101
)
0.2302(2)
0.2253(2)
0.0522(2)
-0.1146(2)
-0.1091(2)
-0.2824(1)
-0.3364(2)
-0.4814(1)
-0.2221(2)
-0.0703(2)
-0.0334(2)
0.1388(2)
0.2501(2)
0.4125(2)
0.5184(1)
0.6847(2)
0.56835(6) 0.2255(1)
0.63814(7) 0.2121(1)
0.67080(7) 0.1638(1)
0.63449(6) 0.1340(1)
0.56454(6) 0.1500(1)
0.52812(5) 0.1152(1)
0.48286(6) 0.1930(1)
0.44858(4) 0.14745(8)
0.47809(6) 0.3408(1)
0.42516(6) 0.3770(1)
0.37949(6) 0.4807(1)
0.34489(6) 0.4850(1)
0.29552(6) 0.5687(1)
0.27301(6) 0.5414(1)
0.22552(4) 0.62961(9)
0.20013(7) 0.6042(2)
0.0256(7)
0.0286(7)
0.0298(8)
0.0271(7)
0.0223(7)
0.0247(6)
0.0217(6)
0.0259(5)
0.0228(7)
0.0207(6)
0.0219(7)
0.0206(6)
0.0228(7)
0.0228(7)
0.0295(5)
0.0314(8)
Figure 1. Molecular projection of 5b
normal to the phenyl ring.
C(11)
C(12)
C(12a)
N(13)
C(14)
C(14a)
0.4643(2)
0.3575(2)
0.1978(2)
0.0705(1)
0.0726(2)
0.0639(2)
0.29744(6) 0.4310(1)
0.34682(6) 0.3483(1)
0.37115(5) 0.3777(1)
0.42107(5) 0.3144(1)
0.45408(6) 0.1890(1)
0.53031(6) 0.1916(1)
0.0253(7)
0.0255(7)
0.0210(6)
0.0213(5)
0.0229(7)
0.0215(6)
Table 2. Non-hydrogen atom coordinates and equivalent
isotropic thermal parameters of 6a (molecule 1)
2
Atom
x
y
z
U
Å
eq
C(11)
C(12)
C(12a)
C(13)
C(14)
C(15)
C(15a)
C(16)
C(17)
O(17)
N(18)
C(18a)
C(19)
C(110)
C(111)
C(112)
-0.0240(4)
-0.0099(5)
0.0865(4)
0.1419(5)
0.2369(5)
0.0901(5)
0.0701(5)
-0.0127(5)
-0.0659(5)
-0.1418(5)
1.2353(4) 0.037(5)
1.3236(4) 0.036(5)
1.3311(4) 0.034(5)
1.4043(4) 0.037(5)
1.3885(4) 0.039(5)
1.2984(4) 0.036(5)
1.2240(4) 0.029(5)
1.1257(4) 0.032(5)
1.0891(4) 0.032(5)
1.1300(3) 0.035(3)
1.0058(3) 0.032(4)
0.9602(4) 0.031(5)
0.8684(4) 0.039(5)
0.8216(5) 0.046(6)
0.8679(5) 0.048(6)
0.9574(5) 0.039(5)
1.0056(4) 0.032(5)
1.1004(4) 0.037(5)
1.1824(3) 0.032(4)
1.2418(4) 0.027(4)
0.2824(5) - 0.1636(5)
0.2310(4)
0.2901(4)
0.2567(4)
0.2651(3)
0.2226(4)
0.1993(4)
0.2550(5)
0.2354(5)
0.1593(5)
0.1006(5)
-0.1124(4)
-0.1289(4)
-0.1911(4)
-0.2832(3)
-0.1449(4)
-0.0369(4)
-0.0084(5)
0.0964(5)
0.1710(5)
0.1421(5)
0.0373(5)
0.0070(5)
0.0267(4)
-0.0392(4)
C(112a) 0.1188(4)
C(113)
N(114)
0.0493(4)
0.0612(3)
C(114a) 0.1311(4)
Figure 2. Molecular projection of 6a
(molecule 1) normal to the phenyl ring.

Table 3. Non-hydrogen atom coordinates and equivalent
isotropic thermal parameters of 7a.
Atom
x
y
z
2
U
Å
eq
C(1)
C(2)
O(2)
N(3)
C(3a)
C(4)
C(5)
C(6)
C(7)
0.3084(3)
0.4824(3)
0.5178(2)
0.5937(2)
0.7792(3)
0.8523(3)
1.0304(3)
1.1339(3)
1.0633(3)
0.8887(3)
0.8210(3)
0.6537(2)
0.6720(3)
0.8217(3)
0.7981(3)
0.6314(4)
0.4822(3)
0.5023(3)
0.3646(3)
0.5049(3)
0.4222(2)
0.3918(1)
0.4415(1)
0.2987(1)
0.2479(2)
0.2630(2)
0.2055(2)
0.1310(2)
0.1181(2)
0.1784(1)
0.1659(2)
0.2476(1)
0.3722(2)
0.4231(2)
0.5478(2)
0.6188(2)
0.5663(2)
0.4426(2)
0.3627(2)
0.2535(2)
0.2000(1)
0.2506(1)
0.31092(7)
0.21659(7)
0.23902(9)
0.3115(1)
0.3316(1)
0.2812(1)
0.2087(1)
0.1862(1)
0.1057(1)
0.08742(8)
0.05900(9)
0.01514(9)
-0.0108(1)
0.0075(1)
0.0520(1)
0.07744(9)
0.12508(9)
0.14576(9)
0.0222(9)
0.0198(8)
0.0271(7)
0.0190(7)
0.0196(8)
0.0233(8)
0.028(1)
0.0276(9)
0.0240(9)
0.0198(8)
0.0239(9)
0.0208(7)
0.0211(8)
0.0255(9)
0.031(1)
C(7a)
C(8)
N(9)
C(9a)
C(10)
C(11)
C(12)
C(13)
C(13a)
C(13b)
C(13c)
0.033(1)
0.028(1)
0.0222(8)
0.0222(9)
0.0200(8)
Figure 3. Molecular projection of 7a
normal to the phenyl ring
4a-c
1. hν; S.E.T.
2. -Cl-
R
b
•
R
R
CH2
•
•
•
⊕
N
CH2
NHCO
CO
⊕
N
a
⊕
N
•
•
NH
CH2
H2C
H2C
H
• CH2CON
a;-H+
b
-H+
5a-c
-H+
6a-c
7a-c
Figure 4. Pathways to cyclization products.
Photolysis of the readily available chloroacetamides (4a-c) provides an entry to a number of novel
heterocyclic systems.
EXPERIMENTAL PROCEDURE
General Procedures:
All melting points were determined using a Reichert hot-stage melting point apparatus and are
1
13
uncorrected. The H and C NMR were determined at 300.73 and 75.63 MHz respectively with a

Varian Unity-300 spectrometer. Unless otherwise stated, the spectra were obtained from solutions in
CDCl and referenced to TMS (proton) and chloroform mid-line (77) (carbon). Chemical shifts of the
3
1
outer peaks are given for specified multiplet patterns in the H-NMR spectra. MS (CI) were obtained
using Shimadzu QP-5000 spectrometer and the direct insertion technique with an electron beam energy of
o
70 eV and a source temperature of 250 C. In the CI MS, isobutane was used as the ionizing gas. High
+
resolution (CI) MS (for MH ) were run using a VG Autospec spectrometer operating at 70 eV and
o
source temperature 250 C with PFK reference and methane as the ionizing gas. IR spectra were recorded
on a BOMEM MB-154 FTIR using KBr discs. TLC was performed on Merck silica gel 60 F
on
254
aluminum sheets or Merck aluminum oxide 60 F
on aluminum sheets. R values were recorded from
f
254
the center of spots. All chromatographic solvent proportions are volume for volume. Column
chromatography was performed using Merck Kieselgel 60 silica gel or Merck aluminum oxide 60 F
254
neutral (Type E) under medium pressure. Solvents were removed under reduced pressure by rotary
evaporation, and organic solvent extracts were dried with anhydrous Na SO . Light petroleum had a
2
4
o
boiling range of 60-80 C. In addition to the standard abbreviations of this journal we use: DCM
(dichloromethane), EtOAc (ethyl acetate), MeOH (methanol), and EtOH (ethanol).
Alkylation Procedure
1-[2-Nitrophenyl)methyl]-1H-indole (2a)
A stirred suspension of sodium hydride (1.3g of ca 50% dispersion in mineral oil; 0.65g ; 27.1 mmol) in
o
dry DMF (25 mL) under a N atmosphere was cooled to 0-5 C and 1H-indole (1a) (2.9 g, 25 mmol) in
2
DMF solution (75 mL) was added dropwise, with stirring over 30 min. Stirring was continued with
cooling for a further 30 min and then to rt for 2 h. At this point excess DMF (275 mL) was added to
ensure solution of the indole sodium salt at -60oC and the resulting yellowish solution was cooled to -
60oC in a dry ice/ acetone bath. To the cold solution a solution of 2-nitrobenzyl bromide (6.85 g, 32
mmol) in DMF (25 mL) was added dropwise and the deep red mixture allowed to stir overnight with
warming to rt. Approximately 95% of the DMF was removed under high vacuum from the resulting pale
yellow slurry and the remainder was poured into a mixture of water and ice (400 mL). The slightly
gummy solid was allowed to stir rapidly for 4 h, suction filtered, washed with cold water, and air dried to
give 2a (6.9g) as a dull yellow solid. Recrystallization from ethanol gave 2a (total yield 4.85 g, 77%) as
o
1
yellow crystals; mp 90.5-92 C. H-NMR (CDCl ) δ: 5.75 (s, 2H, CH N), 6.47 (dd, J = 4.4 Hz, J = 9.3
3
2
Hz, 1H, H-6’), 6.63 (d, J = 3.2 Hz, 1H, H-3), 7.10-7.19 (m, 4H, H-2, H-6, H-5, and H-4’), 7.35-7.44 (m,
13
2H, H-7 and H-5’), 7.69 (d, J = 8.6 Hz, 1H, H-4), 8.16 (d, J = 9.5 Hz, 1H, H-3’). C-NMR (CDCl ) δ:
3
47.53 (CH ), 102.68 (C-3), 109.42 (C-7); 120.00, 121.19, 122.18, 125.14, 128.16, 128.30, 128.42 (all
2
ArC-H), 128.73 (C-3a); 133.52 (C-1’), 134.14 (C-3’), 136.27 (C-7a), 147.14 (C-NO2). HRMS(CI) m/z
(accurate MS 253.0979, C H N O requires 253.0977).
15 13
2 2
The above procedure was followed for the preparations of 2b and 2c with the modifications noted below.
5-Methoxy-1-[2-nitrophenyl)methyl]-1H-indole (2b)
This compound was prepared from 5-methoxy-1H-indole (1b) (1.47g, 10 mmol). The resulting gummy
material was taken up in DCM, the aqueous layer extracted with DCM (3 x 50 mL), the combined
extracts dried, and evaporated under vacuum to give an orange oil. Trituration under diethyl ether yielded
a tan crystalline product (total yield 1.7g) Recrystallization from ethanol gave 2b (0.5g 20%) as yellow
o
crystals; mp 117-119 C. A repeat of this procedure on 0.04 mole scale resulted in a 81% yield of 2b.

1
H-NMR (CDCl ) δ: 3.85 (s, 3H, CH O), 5.75 (s, 2H, CH N), 6.45 (d, J = 9.0 Hz, 1H, H-6’), 6.55 (dd,
3
3
2
J = 0.7 Hz, J = 3.2 Hz, 1H, H-3), 6.82 (dd, J = 2.4 Hz, J = 8.8 Hz, 1H, Ar), 7.02 (d, J = 8.8 Hz, 1H, Ar),
13
7.1-7.2 (m, 2H, H-2 and Ar), 7.36-7.42 (m, 2H, Ar), 8.16 (d, J = 9.5 Hz, 1H, H-3’). C-NMR (CDCl )
3
δ: 47.72 (CH ), 55.82 (CH ), 102.21 (ArC-H), 102.88 (C-3), 110.20 (ArC-H), 112.49 (C-7), 125.13 (C-
2
3
2), 128.17 (ArC-H), 128.30 (ArC-H), 129.01 (ArC-H), 129.19 (C-3a), 131.54 (C-7a), 134.16 (ArC-H),
134.30 (C-1’), 147.11 (C-NO2), 154.45 (C-OCH ). HRMS(CI) m/z (accurate MS 283.1074,
3
C H N O requires 283.1083).
16 15
2 3
5-Fluoro-1-[2-nitrophenyl]methyl]-1H-indole (2c)
This compound was prepared from 5-fluoro-1H-indole (1c) (5.4 g, 40 mmol). The resulting orange oil
was taken up in hot methanol, allowed to crystallize, and filtered, and the filtrate concentrated to yield a
second crop of crystals. The total yield of yellow crystalline (2c) was 6.7 g (71%); mp 118-119°C
1
(methanol). H-NMR (CDCl ) δ: 5.75 (s, 2H, CH N), 6.47 (dd, J = 4.2 or 5.6 Hz, J = 9.3 Hz, 1H, H-
3
2
6’), 6.59 (d, J = 3.2 Hz, 1H, H-3), 6.91 (ddd, J = 2.4 Hz, J = 8.8 Hz, J = 9.3 Hz, 1H, Ar), 7.05 (dd, J =
4.2 Hz, J = 8.8 Hz, 1H, Ar), 7.18 (d, J = 3.2 Hz, 1H, H-2), 7.32 (dd, J = 2.4 Hz, J = 9.5 Hz, 1H, Ar),
13
7.38-7.48 (m, 2H, Ar), 8.17 (d, J = 9.5 Hz, 1H, H-3’).
C-NMR (CDCl ) δ: 47.86 (CH ), 102.56
3 2
13 19
(ArC-H), 102.62 (C-3), 105.98 (d, J = 23 Hz, C -F , C-6), 110.04 (ArC-H), 110.18 (ArC-H), 110.98
13 19
(d, J = 26 Hz, C -F , C-4), 110.80 ArC-H), 125.27 (C-2), 127.98 (ArC-H), 128.48 (ArC-H), 128.92
(C-3a), 130.08 (ArC-H), 132.81 (ArC-H), 133.90 (C-1’), 134.27 (C-7a), 147.02 (NO2), 158.10 (d, J =
13 19
233 Hz, C -F , C-F). HRMS(CI) m/z (accurate MS 271.0875, C H N O F requires 271.0883).
15 12
2 2
Reduction Procedure
1-[(2-Aminophenyl)methyl]-1H-indole (3a)
A solution of 2a (4.15 g, 16.5 mmol), 10% Pd/C (1 g), and 2 drops of conc. HCl in THF (100 mL) was
stirred under an H atmosphere at rt overnight. The catalyst was removed by filtration, washed with
2
DCM (5 x 10 mL), and the filtrate dried and evaporated to give an orange oil. The oil was taken up in
minimal hot ethanol and the crystals obtained suction filtered to yield 3a as a tan crystalline solid (1.3 g,
o
1
36 %) pure by TLC (silica gel; hexane/DCM, 1:1); mp 79-80.5 C (ethanol). H-NMR (CDCl ) δ: 3.45
3
(s, 2H, NH ), 5.15 (s, 2H, CH ), 6.51 (dd, J = 0.7 Hz, J = 3.2 Hz, 1H, H-3), 6.65 (d, J = 8.1 Hz, 1H, H-
2
2
3’), 6.75 (ddd, J = 1.0 Hz, J = 7.3 Hz, J = 7.6 Hz, 1H, Ar), 6.90 (d, J = 9.3 Hz, 1H, Ar), 6.99 (d, J = 3.2
Hz, 1H, H-2), 7.09-7.24 (m, 3H, H-2, H-5 and H-6), 7.38 (d, J = 7.3 Hz, 1H, H-7), 7.65 (d, J = 7.3 Hz,
13
1H, H-4).
C-NMR (CDCl ) δ: 47.45 (CH ), 101.99 (C-3), 109.46 (C-7); 116.32, 118.91, 119.71,
3 2
121.08, 121.78, 127.25 (all ArC-H); 128.83 (C-3a), 129.20 (ArC-H), 129.75 (ArC-H), 136.33 (C-7a),
144.88 (C-NH ). HRMS(CI) m/z (accurate MS 223.1225, C H N requires 223.1235).
2
15 15 2
The above procedure was followed for the preparation of 3b and 3c with the modifications noted below.
1-[2-Aminophenyl]methyl]-5-methoxy-1H-indole (3b)
Starting from compound (2b) on a 4 mmol scale a crude orange oil was obtained which was taken up in
hot ethanol (3 mL) and the crystals obtained suction filtered to yield a tan solid (0.5g). The filtrate was
reduced under vacuum to yield further solid product (0.45g). The total yield of tan crystalline (2b) was
1
0.95 g (94%); mp 118-120°C (ethanol). H-NMR (CDCl ) δ: 3.45 (s, 2H, NH ), 3.83 (s, 3H, CH O),
3
2
3

5.15 (s, 2H, CH ), 6.40 (dd, J = 0.7 Hz, J = 3.2 Hz, 1H, H-3), 6.67 (d, J = 8.1 Hz, 1H, Ar), 6.76 (ddd, J
2
= 1.0 Hz, J = 7.3 Hz, J = 7.3 Hz, 1H, Ar), 6.86 (dd, J = 2.4 Hz, J = 8.8 Hz, 1H, Ar), 7.94-7.0 (m with
prominent d, J = 3.2 Hz, 2H, H-2 and Ar), 7.10 (d, J = 2.2 Hz, 1H, Ar), 7.15 (ddd, J = 1.22 Hz, J = 7.8
13
Hz, J = 9.0 Hz, 1H, Ar), 7.26 (d, J = 8.8 Hz, 1H, Ar).
C-NMR (CDCl ) δ: 47.75 (CH ), 55.86
3 2
(CH ), 101.56 (ArC-H), 102.83 (C-3); 110.24, 112.06, 116.34, 118.92 (all ArC-H); 121.13 (C-1’),
3
127.86 (C-2), 129.20 (C-3a), 129.25 (ArC-H), 129.74 (ArC-H), 131.71 (C-7a), 144.92 (C-NH ), 154.26
2
(C-OCH ). HRMS(CI) m/z (accurate MS 253.1333, C H N O requires 253.1341)
3
16 17 2
1-[2-Aminophenyl)methyl]-5-fluoro-1H-indole (3c)
Starting from compound (2c) on a 23 mmol scale the resulting orange oil was taken up in DCM, washed
with dilute NaHCO , the solvent dried and evaporated. Column chromatography on silica gel
3
(hexane/DCM, 1:1) eluted the product as a pale green oil (4.63 g) which slowly crystallized. A portion
o
1
was recrystallized from methanol to give 3c (3.36 g, 61%) as off-white crystals; mp 81-82.5 C. H-
NMR (CDCl ) δ: 3.48 (s, 2H, NH ), 5.15 (s, 2H, CH ), 6.48 (d, J = 3.2 Hz, 1H, H-3), 6.70 (d, J = 8.1
3
2
2
Hz, 1H, Ar), 6.77 (ddd, J = 1.0 Hz, J = 7.3 Hz, J = 7.6 Hz, 1H, Ar), 6.86-7.0 (m, 2H, Ar), 7.06 (d, J =
13
3.2 Hz, 1H, H-2), 7.17 (ddd, J = 1.2 Hz, J = 7.6 Hz, J = 7.8 Hz, 1H, Ar), 7.23-7.31 (m, 2H, Ar).
C-
NMR(CDCl ) δ: 47.79 (CH ), 101.87 (ArC-H), 101.93 (C-3), 105.50 (ArC-H), 105.79 (d, J = 24 Hz,
3
2
13 19
13 19
C -F , C-6), 109.98 (ArC-H), 110.19 (d, J = 21 Hz, C -F , C-4), 110.20 (ArC-H), 116.41 (ArC-H),
119.02 (ArC-H), 120.75 (C-3a), 128.90 (ArC-H), 129.34 (ArC-H), 129.66 (ArC-H), 132,92 (C-7a),
13 19
144.80 (C-NH ), 157.95 (d, J = 234, C -F ,C-F). HRMS(CI) m/z (accurate MS 241.1134,
2
C H N F requires 241.1141).
15 14
2
Chloroacetylation Procedure
N-[(2-(1’-1H-Indolyl)methyl)phenyl]chloroacetamide (4a)
A stirred suspension of 3a (0.33 g, 1.5 mmol) and sodium carbonate (0.6 g, 5.6 mmol) in dry DCM (15
o
mL) was cooled to 0-5 C and chloroacetyl chloride (0.43 g, 3.7 mmol) in DCM (8 mL) was added in 0.5
mL portions over 10 min. Stirring was continued with cooling for a further 30 min. and the reaction then
allowed to warm to rt with stirring overnight. Distilled water (50 mL) was added to the reaction, the
layers separated, and the aqeous layer extracted with DCM (3 x 10 mL). The extracts were combined,
dried and solvent removed under vacuum to yield a pale yellow oil which yielded an off-white solid.
o
1
Recrystallization from methanol gave 4a (0.36 g, 82%) as colorless, fluffy crystals; mp 120-122 C. H-
NMR (CDCl ) δ: 4.05 (s, 2H, CH2Cl), 5.30 (s, 2H, benzylic), 6.55 (d, J = 2.7 Hz, 1H, H-3), 7.00 (d, J
3
= 3.2 Hz, 1H, H-2), 7.05 (d, J = 7.3 Hz, 1H, Ar), 7.1-7.3 (m, 4H, Ar), 7.34 (ddd, J = 1.2 Hz, J = 7.3 Hz,
13
J = 8.1 Hz, 1H, H-6), 7.64 (d, J = 9.0 Hz, 1H, Ar), 7.66 (d, J = 8.6, 1H, H-4), 8.00 (s, 1H, N-H).
C-
NMR (CDCl ) δ: 42.68 (CH2 benzyl), 47.33 (CH2Cl), 102.59 (C-3), 109.56 (C-7), 119.93 (Ar), 121.15
3
(C-1’), 121.96 (C-3’), 125.05 (C-2), 126.99 (C-3a); 127.4, 128.84, 128.93, 129.18, 130.42 (all ArC-H);
134.14 (C-7a), 136.40 (C-NH), 164.56 (CO). HRMS(CI) m/z (accurate MS 299.0948, C H N OCl
17 16
2
requires 299.0951). Anal. Calcd for C H N O Cl: C, 68.44; H, 5.07; N, 9.40. Found: C, 68.44; H,
17 15
2
5.17; N, 9.45.
The above procedure was followed for the preparations of 4b and 4c with the modifications noted below.

N-{2-[1’-(5’-Methoxy-1H-indolyl)methyl]phenyl}chloroacetamide (4b)
This product was prepared from compound (3b) (3.78 g, 15 mmol) to yield a pale orange oil which was
chromatographed on silica gel (light petroleum/DCM, 3:7) to give 4b as an off-white solid.
o
1
Recrystallization from methanol gave 4b (2.1 g, 43%) as colorless crystals; mp 132-133 C. H-NMR
(CDCl ) δ: 3.83 (s, 3H, CH O), 4.03 (s, 2H, CH2Cl), 5.23 (s, 2H, benzylic), 6.47 (d, J = 3.2 Hz, 1H, H-
3
3
3), 6.84 (dd, J = 2.4 Hz, J = 9.0 Hz, 1H, Ar), 6.96 (d, J = 3.2 Hz, 1H, H-2), 7.04 (d, J =7.6 Hz, 1H, Ar),
7.10 (d, J = 2.4 Hz, 1H, Ar), 7.14 (d, J = 8.8 Hz, 1H, Ar), 7.20 (ddd, J = 1.2 Hz, J = 7.8 Hz, J = 8.8 Hz,
1H, Ar), 7.35 (ddd, J = 1.2 Hz, J = 7.8 Hz, J = 8.8 Hz, 1H, Ar), 7.63 (d, J = 7.6 Hz, 1H, H-3’), 8.01 (s,
13
1H, N-H). C-NMR (CDCl ) δ: 42.68 (CH2), 47.57 (CH2), 55.81 (CH ), 102.13 (ArC-H), 102.82 (C-
3
3
3), 110.33 (ArC-H), 112.22 (C-7), 124.96 (ArC-H), 126.93 (C-2); 128.02, 128.94, 129.15, 129.29 (all
ArC-H); 130.36 (C-3a), 131.73 (C-7a), 134.18 (C-NH-), 154.35 (C-OCH ), 164.56 (CO). HRMS(CI)
3
m/z (accurate MS 329.1033, C H N O 35Cl requires 329.1057). Anal. Calcd for C H N O Cl: C,
18 18
2
2
18 17 2 2
65.83; H, 5.22; N, 8.54. Found: C, 65.83; H, 5.13; N, 8.10.
N-{2-[1’-(5’-Fluoro-1H-indolyl)methyl]phenyl}chloroacetamide (4c)
This product was prepared from compound (3c) (3.36g, 14 mmol) to yield a pale orange solid.
Trituration under DCM gave 4c as a white solid (3.2 g). The filtrate was concentrated and recrystallized
o
from methanol to yield further 4c (0.35 g) for a total yield of pure 4c of 3.55 g (80%); mp 142-143 C.
1
H-NMR (CDCl ) δ: 4.06 (s, 2H, CH2Cl), 5.27 (s, 2H, benzylic), 6.95 (dd, J = 0.7 Hz, J = 3.2 Hz, 1H,
3
H-3), 6.92 (ddd, J = 2.4 Hz, J = 9.0 Hz, J = 9.0 Hz, 1H, Ar), 7.01 (d, J = 7.8 Hz, 1H, Ar), 7.04 (d, J =
3.2 Hz, 1H, H-2), 7.12-7.25 (m, 2H, Ar), 7.28 (dd, J = 2.4 Hz, J = 9.5 Hz, 1H, Ar), 7.37 (ddd, J = 1.2
13
Hz, J = 7.6 Hz, J = 7.8 Hz, 1H, Ar), 7.60 (d, J = 8.1 Hz, 1H, Ar), 8.02 (s, 1H, N-H).
C-NMR
13 19
(CDCl ) δ: 42.67 (CH2), 47.58 (CH2), 102.38 (ArC-H), 102.44 (C-3), 105.86 (d, J = 24 Hz, C -F , C-
3
13 19
6), 110.31 (ArC-H), 110.33 (d, J = 26 Hz, C -F , C-4), 125.18 (C-2), 127.16 (ArC-H), 129.03 (ArC-
13 19
H), 129.10 (ArC-H), 130.38 (C-1’), 132.95 (C-3a), 133.95 (C-NH), 158.00 (d, J = 234 Hz, C -F , C5-
F), 164.60 (CO). HRMS(CI) m/z (accurate MS 317.0834, C H N OF35Cl requires 317.0857).
17 15
2
General Information and Procedure for the Photolyses
The photolyses were conducted in a large quartz immersion well reactor (Model RQ 400) supplied by
Photochemical Reactors Ltd., U.K. The lamp (16W) was housed internally and the solution was
saturated with N before and during photolysis.
2
A solution of 4a, b or c in 50% acetonitrile/water v/v (360 mL) was purged with nitrogen for 30 min and
then irradiated at rt with continued nitrogen purge for the indicated number of hours. The orange solution
was made basic to pH 9-10 with 1 M NaOH and the acetonitrile removed under vacuum, The resulting
yellowish slurry was suction filtered and the crude material obtained taken up in DCM (50 mL). Water
(200 mL) was added to the filtrate and this was extracted with DCM (3 x 50 mL). The DCM extracts
were combined with the crude product DCM solution, dried over anhydrous sodium sulfate, and solvent
removed under vacuum to give the photolysates as orange foams or gums.
Photolysis of N-[(2-(1’-1H-Indolyl)methyl)phenyl]chloroacetamide (4a)
The solution of 4a (0.299, 1.0 mmol) was photolysed for 8 h. TLC (silica gel, MeOH/DCM, 5:95)
indicated a multi-component mixture with three major spots (R s: 0.84, 0.43 and 0.38). This procedure
f

was repeated twice more (on 1.5 mmol and 2 mmol scales) to yield a total of 1.5 g of orange gum. The
gum was chromatographed on silica with DCM to give five fractions: 1 (24 mg, R 0.93 - starting material
f
4a); 2 (200 mg, R 0.84); 3 (100 mg, R 0.43); 4 (325 mg - mixture of R 0.43 and 0.38); and 5 (175 mg, R
f
f
f
f
0.38). Fractions 2, 3 and 5 represent the following isolated yields: 7a (200 mg, 18%), 5a (100 mg, 9%),
and 6a (175 mg, 16%), all of which have a molecular MS of 262. These yields are based upon actual 4a
photolysed (5 mmol - fraction 1, 0.8 mmol). 1H- NMR analysis of (fraction 4) indicated this two
component mixture contained further 5a (75 mg, 7%) and 6a (250 mg, 23%) giving total percentage yields
of these products of 16% and 39% respectively.
Fraction 2 was identified as 13b,13c-dihydro-8H-pyrrolo[2,3-b]indolo[5,5a,6-b,a]quinazolin-2(1H)-one
o
1
(7a) which was recrystallized from methanol to give colorless crystals; mp 195-197 C. H-NMR
(CDCl ) δ: 2.80 (d, J = 17.1 Hz, 1H, H-1), 3.18 (dd, J = 17.1 Hz, J = 7.8 Hz, 1H, H-1), 3.90 (m, 1H, H-
3
13b), 4.63 (d, J = 17.7 Hz, 1H, H-8), 4.75 (d, J = 17.7 Hz, 1H, H-8), 5.44 (d, J = 6.4 Hz, 1H, H-13c),
6.59 (d, J = 8.1 Hz, 1H, H-10), 6.79 (ddd, J = 0.7 Hz, J = 6.6 Hz, J = 7.3 Hz, 1H, H-12), 7.06-7.20 (m,
4H, H-6, H-7, H-11, H-13), 7.22 (ddd, J = 1.7 Hz, J = 8.3 Hz, J = 8.8 Hz, 1H, H-5), 8.20 (d, J = 8.3 Hz,
13
1H, H-4). C-NMR (CDCl ) δ: 38.06 (CH2, C-1), 38.22 (CH2, C-13b), 45.08 (CH2N, C-8), 76.34 (C-
3
13c), 108.46 (ArC-H), 119.48 (ArC-H), 120.19 (ArC-H), 123.94 (ArC); 124.10, 124.60, 125.77, 126.98,
128.74 (all ArC-H); 129.58 (C-7a), 134.58 (ArC-H), 149.61 (ArC-H), 170.79 (CO). HRMS(CI) m/z
(accurate MS 263.1184, C H N O requires 263.1184). Anal. Calcd for C H N O: C, 77.83; H,
17 15
2
17 14 2
5.38; N, 10.68. Found: C, 78.22; H, 5.30; N, 10.10.
Fraction 3 was identified as 5,14-dihydroindolo[2,1-d][1,5]benzodiazocin-6(7H)-one (5a) which was
o
recrystallized from methanol to give off-white crystals; mp 268-270 C. IR (KBr) ν : 3247 (NH),
max
-1
1
1662 (C=O) cm . H-NMR (CDCl ) δ: 3.57 (s, 2H, CH2CO), 5.14 (s, 2H, benzylic), 6.39 (s, 1H, H-8),
3
7.11 (m, 1H, Ar), 7.27 (ddd, J = 1.2 Hz, J = 4.9 Hz, J = 7.1 Hz, 1H, Ar), 7.29 (dd, J = 1.2 Hz, J = 4.2
Hz, 1H, Ar), 7.34 (dd, J = 1.5 Hz, J = 7.6 Hz, 1H, Ar), 7.37-7.40 (m, 1H, Ar), 7.44 (dd, J = 1.7 Hz, J =
13
7.6 Hz, 1H, Ar), 7.47-7.58 (m, 2H, Ar), 8.50 (s, 1H, N-H).
C-NMR (CDCl ) δ: 35.00 (CH2, C-14),
3
45.28 (CH2, C-7), 103.45 (C-8); 108.70, 119.79, 120.41, 121.56, 125.49 (all ArC-H); 127.85 (C-7a),
128.59 (ArC-H), 130.10 (ArC-H), 131.45 (ArC), 131.83 (ArC), 132.23 (ArC-H), 137.75 (ArC), 138.21
(C-11a), 171.06 (CO). HRMS(CI) m/z (accurate MS 263.1176, C H N O requires 263.1184). Anal.
17 15
2
Calcd for C H N O: C, 77.83; H, 5.38; N, 10.68. Found: C, 77.32; H, 5.36; N, 9.96.
17 14
2
Fraction 5 was identified as 8,13-dihydroindolo[7,7a,1,-d,e][1,6]benzodiazonin-7(6H)-one (6a) which
o
was recrystallized from methanol to give off-white crystals; mp 266-268 C. IR (KBr) ν : 3185 (NH),
max
-1
1
1663 (C=O) cm . H-NMR (CDCl ) δ: 3.53 (s, 2H, CH2CO), 5.11 (s, 2H, benzylic), 6.50 (d, J = 3.2
3
Hz, 1H, H-2), 6.98 (m with prominent d, J = 7.1 Hz, 2H, Ar), 7.19 (d, J = 3.2 Hz, 1H, H-1), 7.27-7.42
13
(m, 3H, Ar), 7.50 (dd, J = 1.9 Hz, J = 7.1 Hz, 1H, Ar), 7.67 (m, 1H, Ar), 8.50 (s, 1H, N-H).
C-NMR
(CDCl ) δ: 39.23 (CH2, C-13), 49.07 (CH2, C-6), 102.75 (C-2), 119.01 (ArC); 120.27, 120.41, 127.18,
3
127.44, 128.45, 129.54 (all ArC-H); 131.17 (C-2a), 131.37 (ArC-H), 132.73 (ArC-H), 137.19 (ArC),
138.25 (ArC), 138.35 (C-14a), 176.68 (CO). HRMS(CI) m/z (accurate MS 263.1193, C H N O
17 15
2
requires 263.1184). Anal. Calcd for C H N O: C, 77.83; H, 5.38; N, 10.68. Found: C, 78.06; H,
17 14
2
5.42; N, 10.37.
Photolysis of N-{2-[1’-(5’-Methoxy-1H-indolyl)methyl]phenyl}chloroacetamide (4b)
The solution of 4b (0.299, 1.0 mmol) was photolysed for 4 h. TLC (silica gel; EtOAc/DCM,1:9)
indicated a four component mixture with three major components (R s: 0.64, 0.32 and 0.24). The
f

photolysis was repeated once more and then twice at a 1.5 mmol scale to yield a total of 1.57 g of
photosylate as an orange gum. The gum was chromatographed on silica (EtOAc/DCM,1:9) to give 5
main fractions: 1 (73 mg, R 0.8 - starting material); 2 (302 mg, R 0.64); 3 (187 mg, R 0.32); 4 (41 mg -
f
f
f
mixture of R 0.32 and 0.24); and 5 (556 mg, R 0.24). Fractions 2, 3 and 5 represent the following
f
f
isolated yields: 7b (302 mg, 22%), 5b (187 mg, 14%) and 6b (556 mg 40%) respectively, all of which
have a molecular MS of 292. These yields are based upon actual 4b photolysed (5 mmol - fraction 1,
1
0.25 mmol). H-NMR analysis of fraction 4 indicated this two component mixture contained further 5b
(6 mg, 0.4%) and 6b (35 mg, 3%) giving total percentage yields of these products of 14% and 43%
respectively.
Fraction
2
was
identified
as
13b,13c-dihydro-12-methoxy-8H-pyrrolo[2,3-b]indolo[5,5a,6-
o
b,a]quinazolin-2(1H)-one (7b). Recrystallization from methanol gave colorless crystals; mp 209-211 C.
IR (KBr) ν : 1689 (C=O) cm . H-NMR (CDCl ) δ: 2.80 (d, J = 16.8 Hz, 1H, H-1), 3.16 (dd, J =
-1
1
max
3
16.8 Hz, J = 7.8 Hz, 1H, H-1), 3.73 (s, 3H, CH3O), 3.89 (m, 1H, H-13b), 4.55 (d, J = 17.8 Hz, 1H,
benzylic), 4.74 (d, J = 17.83 Hz, 1H, benzylic), 5.43 (d, J = 6.1 Hz, 1H, H-13c), 6.50 (d, J = 8.6 Hz, 1H,
H-10), 6.71 (dd, J = 2.0 Hz, J = 8.6 Hz, 1H, H-11), 6.78 (m, 1H, H-13), 7.06-7.20 (m, 2H, H-6, H-7),
13
7.23 (m with prominent d, J = 9.5 Hz, 1H, H-5), 8.22 (d, J = 9.5, 1H, H-4).
C-NMR (CDCl ) δ:
3
38.10 (C-1), 38.82 (C-13b), 45.66 (CH ,N, C-8), 56.01 (CH O), 77.71 (C-13c); 109.17, 112.01, 113.73,
2
3
120.33, 124.29, 125.05, 126.05, 127.19 (all ArC-H); 131.15, 134.88, 143.85, 154.11 (all ArC), 170.89
(CO). HRMS(CI) m/z (accurate MS 293.1284, C H N O requires 293.1290). Anal. Calcd for
18 17
2 2
C18H16N2O2: C, 73.94; H, 5.52; N, 9.59. Found: C, 74.28; H, 5.51; N, 9.21.
Fraction 3 has been identified as 5,14-dihydro-10-methoxyindolo[2,1-d][1,5]benzodiazocin-6(7H)-one
o
(5b). Recrystallization from methanol gave off-white crystals; mp 238-239.5 C. IR (KBr) ν : 3153
max
-1
1
(NH), 1669 (C=O) cm . H-NMR (CDCl ) δ: 3.54 (s, 2H, CH2CO),3.89 (s, 3H, CH3O), 5.09 (s, 2H,
3
benzylic), 6.31 (s, 1H, H-8), 6.91 (dd, J = 2.4 Hz, J = 9.0 Hz, 1H, H-11), 7.02 (d, J = 2.4 Hz, 1H, H-9),
7.28 (dd, J = 1.2 Hz, J = 7.6 Hz, 1H, Ar), 7.34-7.40 (m, 2H, Ar), 7.45 (dd, J = 1.7 Hz, J = 7.6 Hz, 1H,
13
Ar), 7.54 (dd, J = 1.7 Hz, J = 7.3 Hz, 1H, Ar), 8.52 (s, 1H, N-H). C-NMR (CDCl ) δ: 35.01 (CH2,
3
C-14), 45.51 (CH2, C-7), 55.88 (CH O), 102.19 (C-8); 103.11, 109.44, 119.60, 125.48 (all ArC-H);
3
128.19 (C-8a), 128.61, 130.08, 131.46 (ArC), 132.23 (ArC-H), 132.33 (ArC-H), 133.10 (ArC), 138.13
(ArC), 154.14 (ArC), 170.90 (CO). HRMS(CI) m/z (accurate MS 293.1283, C H N O requires
18 17
2 2
293.1290). Anal. Calcd for C H N O : C, 73.94; H, 5.52; N, 9.59. Found: C, 74.08; H, 5.43; N, 9.11.
18 16
2 2
Fraction 5 has been identified as 8,13-dihydro-4-methoxyindolo[7,7a,1-d,e][1,6]benzodiazonin-7(6H)-one
o
(6b). Recrystallization from methanol gave crystals with a pink tinge; mp 233-235 C. IR (KBr) ν
:
max
-1
1
3178 (NH), 1667 (C=O) cm . H-NMR (CDCl ) δ: 3.47 (s, 2H, CH2CO), 3.80 (s, 3H, CH O), 5.07
3
3
(s, 2H, benzylic), 6.41 (d, J = 3.2 Hz, 1H, H-2), 6.72 (d, J = 2.2 Hz, 1H, H-5), 6.95 (d, J = 2.2 Hz, 1H,
H-3), 7.15 (d, J = 2.9 Hz, 1H, H-1), 7.27-7.42 (m, 3H, Ar), 7.65 (dd, J = 6.3 Hz, J = 9.0 Hz, 1H, Ar ),
13
8.45 (s, 1H, N-H). C-NMR (CDCl ) δ: 39.10 (CH2, C-13), 49.11 (CH2, C-6), 55.74 (CH O), 101.88
3
3
(C-2), 116.98 (ArC-H), 119.88 (ArC); 127.44, 128.52, 129.55, 131.46 (all ArC-H); 131.81 (ArC), 133.40
(ArC-H); 133.50, 137.10, 138.27, 154.10 (all ArC), 176.23 (CO). HRMS(CI) m/z (accurate MS
293.1298, C H N O requires 293.1290). Anal. Calcd for C H N O : C, 73.94; H, 5.52; N, 9.59.
18 17
2
2
18 16 2 2
Found: C, 74.54; H, 5.55; N, 9.36.

Photolysis of N-{2-[1'-(5'-Fluoro-1H-indolyl)methyl]phenyl}chloroacetamide (4c)
The solution of 4c (0.95, 3.0 mmol) was photolysed for 16 h. TLC (silica gel: DCM) indicated a three
component mixture (R s: 0.7, 0.52 and 0.15). This photolysis was repeated twice more at the same scale
f
to yield a total of 2.49 g of photolysate as an orange gum. The gum was triturated with ether to give a tan
solid (1.45 g) whose TLC indicated two possible components. The ether was evaporated to give a foam
(1.08 g) consisting of starting material and the R 0.52 component. Column chromatography of this foam
f
on silica (DCM) gave 2 major fractions: 1 (228 mg, R 0.72 - starting material), and 2 (241 mg, R 0.52,
f
f
7c). The above tan solid was chromatographed on silica (EtOAc/DCM, 1:9) to give two major fractions:
2’(97 mg, R 0.52, 7c) and 3’(720 mg, R 0.15). Fraction 3’was found to be two components (R s 0.63
f
f
f
and 0.56) upon TLC with double development (neutral alumina: benzene/DCM, 1:9). The combined
yield of 7c was 338 mg, 18%). Fration 3’ represents yields of 5c and 6c in the mixture of 14% and 28%
respectively. These yields were based upon actual 4c photolysed (5 mmol - fraction 1, 0.7 mmol) and
1
H-NMR analysis of three pertinent signals (fraction 3’).
Fraction 2 was identified as 12-fluoro-13b,13c-dihydro-8H-pyrrolo[2,3-b]indolo[5,5a,6-b,a]quinazolin-
o
2(1H)-one (7c). Recrystallization from methanol gave colorless crystals; mp 215-217 C. IR (KBr) ν
:
max
-1
1
1689 (C=O) cm . H-NMR (CDCl ) δ: 2.78 (d, J = 16.9 Hz, 1H, H-1), 3.19 (dd, J = 16.9 Hz, J = 7.8
3
Hz, 1H, H-1), 3.91 (m, 1H, H-13b), 4.56 (d, J = 17.8 Hz, 1H, H-8), 4.76 (d, J = 17.8 Hz, 1H, H-8), 5.43
(d, J = 6.1 Hz, 1H, H-13c), 6.50 (dd, J = 3.9 Hz (H-F), J = 8.6 Hz, 1H, H-11), 6.82-6.94 (m, 2H, H-10,
13
H-13), 7.08-7.28 (m, 3H, H-5, H-6, H-7), 8.22 (d, J = 8.1 Hz, 1H, H-4). C-NMR (CDCl ) δ: 38.04
3
(C-1), 38.56 (C-13b), 45.62 (C-8), 77.63 (C-13c), 109.00 (ArC-H), 109.09 (ArC-H), 112.52 (d, J = 25
13 19
13 19
Hz, C -F , C11-F), 115.13 (d, J = 23 Hz, C -F , C13-F), 120.41 (ArC-H), 123.96 (ArC), 124.46
(ArC-H), 126.05 (ArC-H), 127.31 (ArC-H), 131.29 (ArC), 131.39 (ArC), 134.72 (ArC), 146.00 (ArC)),
13 19
157.37 (d, J = 237Hz, C -F , C12-F), 170.05 (CO). HRMS(CI) m/z (accurate MS 281.1093,
C H N OF requires 281.1090). Anal. Calcd for C17H13N2OF: C, 72.85; H, 4.67; N, 9.99. Found: C,
17 14
2
73.36; H, 4.83; N, 10.13.
A portion (100 mg) of the fraction 3 mixture was rechromatographed on alumina (DCM) to give small
amounts of two compounds.
The first was identified as 10-fluoro-5,14-dihydroindolo[2,1-
d][1,5]benzodiazocin-6(7H)-one (5c) (15mg). Recrystallization from methanol gave 5c (4 mg) colorless
o
-1
1
crystals; mp 276-278 C. IR (KBr) ν : 3191 (NH), 1689 (C=O) cm . H-NMR (CDCl ) δ: 3.56 (s,
max
3
2H, CH2CO), 5.14 (s, 2H, benzylic), 6.36 (s, 1H, H-8), 7.00 (ddd, J = 2.5 Hz, J = 9.1 Hz, J = 9.1 Hz(H-
F), 1H, H-11), 7.20 (dd, J = 2.5 Hz, J = 9.4 Hz(H-F), 1H, H-9), 7.30 (d, J = 7.8 Hz, 1H, H-1), 7.36-7.42
(m, 2H, ArH), 7.46 (ddd, J = 1.3 Hz, J = 7.6 Hz, J = 7.6 Hz, 1H, H-2), 7.55 (dd, J = 1.3 Hz, J = 7.5 Hz,
13
1H, H-4), 8.10 (s, 1H, N-H). C-NMR (CDCl ) δ: 35.00 (CH2), 45.60 (CH2), 103.41 (ArC-H), 103.46
3
13 19
(ArC-H), 105.25 (d, J = 24 Hz, C -F , C9-F), 109.23 (ArC-H), 109.32 (ArC-H), 109.80 (d, J = 26 Hz,
C -F , C11-F), 125.55 (ArC-H), 128.13 (ArC), 128.78 (ArC-H), 130.29 (ArC-H), 131.29 (ArC),
132.27 (ArC-H), 133.46 (ArC), 134.39 (ArC), 138.04 (ArC), 157.87 (d, J = 234 Hz, C -F , C10-F),
13 19
13 19
170.31 (CO). HRMS(CI) m/z (accurate MS 281.1092, C H N OF requires 281.1090).
17 14
2
The second compound was identified as 4-fluoro-8,13-dihydroindolo[7,7a,1-d,e][1,6]benzodiazonin-
7(6H)-one (6c) (30 mg). Recrystallization from methanol gave 6c (15 mg) as colorless crystals; mp 258-
o
-1
1
262 C. IR (KBr) ν : 3189 (NH), 1663 (C=O) cm . H-NMR (CDCl ) δ: 3.50 (s, 2H, CH2CO),
max
3
5.11 (s, 2H, benzylic), 6.46 (d, J = 3.2 Hz, 1H, H-2), 6.84 (dd, J = 2.4 Hz, J = 9.7 Hz(H-F), 1H, H-5),
7.14 (dd, J = 2.4 Hz, J = 8.8 Hz(H-F), 1H, H-3), 7.23 (d, J = 3.2 Hz, 1H, H-1), 7.31-7.34 (m with
prominent d, J = 9.3 Hz, 1H, H-10), 7.38-7.44 (m, 2H, H-11, H-12), 7.54 (m with prominent d, J = 9.3

13
Hz, 1H, H-9), 7.97 (s, 1H, N-H). C-NMR (CDCl ) δ: 38.82 (CH2), 49.15 (CH2), 102.37 (ArC-H),
3
13 19
13 19
102.42 (ArC-H), 104.77 (d, J = 22 Hz, C -F , C5-F), 115.13 (d, J = 26 Hz, C -F , C3-F), 120.07 (d,
13 19
J = 9 Hz, C -F , C5a-F); 127.46, 128.71, 129.76, 131.48, 134.38 (all ArC-H); 134.96 (ArC), 136.92
(ArC), 138.04 (ArC), 157.47 (d, J = 237 Hz, C -F , C4-F), 175.63 (CO). HRMS(CI) m/z (accurate
13 19
MS 281.1099, C H N OF requires 281.1090).
17 14
2
ACKNOWLEDGEMENTS
We acknowledge support from The National Institutes of Health, via Fogarty Minority International
Research Training (MIRT) Grant T37 TW00030-03, and the University of Wollongong for this work.
Support of this study abroad program by Johnson C. Smith University and the University of
Wollongong is also gratefully acknowledged, as is support from the ARC. We also thank Dr. John Korth
and Mr. Larry Hick for their assistance in running the MS, Dr. Renate Griffith for the molecular
modelling, and Ms Chris Dixon for assistance with the infra red spectra.
REFERENCES AND NOTES
1. R. J. Sundberg, in Organic Photochemistry, ed. by A. Padwa, Marcel Dekker, New York, 1983, 6,
121.
2. R. Rezaie, J. B. Bremner, G. K. Blanch, B. W. Skelton, and A. H. White, Heterocycles, 1995, 41, 959.
3. S. Naruto and O. Yonemitsu, Chem. Pharm. Bull., 1980, 28, 900.
4. J. Bosch, M. Amat, E. Sanfeliu, and M. A. Miranda, Tetrahedron, 1985, 41, 2557.
5. S. E. Klohr and J. M. Cassady, Synth. Commun., 1988, 18, 671.
6. A. L. Beck, M. Mascal, C. J. Moody, A. M. A. Slawin, D. J. Williams, and W. J. Coates, J. Chem.
Soc., Perkin Trans. 1, 1992, 797.
7. A. L. Beck, M. Mascal, C. J. Moody, and W. J Coates, J. Chem. Soc., Perkin Trans. I, 1992, 813.
8. B. Cardillo, G. Casnati, A. Pochini, and A. Ricca, Tetrahedron, 1967, 23, 3771.
9. G. M. Rubottom and J. C. Chabala, Synthesis, 1972, 566.
10. H. Heaney and S. V. Ley, J. Chem. Soc., Perkin Trans. I, 1973, 499.
11. Y. Kikugawa and Y. Miyake, Synthesis, 1981, 461.
12. C. Y. Ho, W. E. Hageman, and F. J. Persico, J. Med. Chem., 1986, 29, 1118.
13. M. Bruncko, D. Crich, and R. Samy, J. Org. Chem., 1994, 59, 5543.
14. M. S. Morales-Rios, O. R. Suarez-Castillo, and P. Joseph-Nathan, J. Org.Chem., 1999, 64, 1086.
15. L. Rahbaek, U. Anthoni, C. Christophersen, P. H. Nielsen, and B. O. Petersen, J. Org. Chem., 1996,
61, 887.
16. Structure Determinations: Full spheres (2θmax = 58˚) of area-detector diffractometer data were
measured at ca. 153 K (Bruker AXS instrument; monochromatic Mo Kα radiation, λ = 0.71073 Å; ω
scans) yielding Nt(otal) reflections, reducing to N unique, via the proprietary software, No with F> 4σ (F)
being considered 'observed' and used in the full matrix least squares refinement, refining anisotropic
thermal parameter forms for O,N,C and (x, y, z, Uiso)H for 5b, 7a, the latter parameters constrained at
estimates for 6a. Conventional residuals R, Rw (statistical weights) on |F| are recorded at convergence.
Neutral atom complex scattering factors were used within the Xtal 3.5 program system (S. R. Hall, G. S.
D. King, and J. M. Stewart, University of Western Australia, Lamb, Perth, 1997). Full crystallographic
data tables for 5b, 6a, and 7a are available from the Cambridge Crystallographic Data Centre.
Crystal/refinement data
–
5b – C18H16N2O2, M = 292.3. Monoclinic, space group P21/c
(C25h, No.14), a = 7.3956(8), b = 19.819(2), c = 10.423(1) Å, β = 107.402(3)˚, V = 1457.8 Å3. Dc (Z =
4) = 1.332 g cm-3; F(000) = 616. µMo = 0.88 cm-1; specimen: 0.40 x 0.20 x 0.06 mm (plate; no
correction). Nt = 16863, N = 3671 (Rint = 0.023), No = 2959; R = 0.038, Rw = 0.048; nυ=263, |Δρmax
|

= 0.30(2) e Å-3.
6a – C17H14N2O, M = 262.3. Triclinic, space group P1 (C1i , No.2) , a = 14.404(3), b = 14.594(3), c =
15.350(3) Å, α = 69.588(3), β = 70.769(3), γ = 65.314(3)˚, V = 2683 Å3. Dc (Z = 8) = 1.299 g cm-3;
F(000) = 1104. µMo = 0.82 cm-1; specimen: 0.45 x 0.22 x 0.15 mm (no correction). Nt = 30460, N =
13141 (Rint = 0.046), No = 7944; R= 0.083, Rw = 0.11; nυ=723, |Δρmax| = 0.48(3) e Å-3.
7a – C17H14N2O, M = 262.3. Orthorhombic, space group P212121 (D24, No.19) , a = 6.735(1), b =
10.529(2), c = 17.909(4) Å, V = 1270 Å3. Dc (Z = 4) = 1.372 g cm-3; F(000) = 552. µMo = 0.85 cm-1;
specimen: 0.40 x 0.12 x 0.12 mm; 'T'min, max ('SADABS' 'empirical' absorption correction) = 0.84,
0.98. Nt = 14539, N = 1902 (Rint 0.030; 'Friedel pairs' merged after indecisive refinement of absolute
structure), No = 1672; R= 0.034, Rw = 0.039; nυ=238, |Δρmax| = 0.21 e Å-3.
17. Molecular modelling was performed on a Silicon Graphics 02 workstation using Spartan (v.5.0)
software by Wavefunction, Inc., Irvine, CA. The geometry of the compound was optimised in vacuo (as
an isolated molecule) using the Merck Force Field (MM FF94; T.A. Halgren, J. Computational Chem.,
1996, 17, 490 and following papers in the same issue) as implemented in Spartan.