Access to pyrrolo- and pyrido[1,2-α]indole derivatives by intramolecular nitrone cycloadditions. Effect of steric factors on the regioselective product formation

Article abstract of DOI:10.1021/jo000842g

On starting from N-allyl-substituted 2-indolecarbaldehydes and exploiting the intramolecular nitrone cycloaddition methodology, we synthesized a number of the title fused-ring indole derivatives in racemic as well as enantiopure form.

Full text of DOI:10.1021/jo000842g

8924
J . Org. Chem. 2000, 65, 8924-8932
Access to P yr r olo- a n d P yr id o[1,2-a ]in d ole Der iva tives by
In tr a m olecu la r Nitr on e Cycloa d d ition s. Effect of Ster ic F a ctor s on
th e Regioselective P r od u ct F or m a tion
Egle M. Beccalli,*,† Gianluigi Broggini,‡ Concetta La Rosa,† Daniele Passarella,§ Tullio Pilati,|
Alberto Terraneo,§ and Gaetano Zecchi‡
Istituto di Chimica Organica della Facolta` di Farmacia dell’Universita` di Milano, via Venezian 21,
20133 Milano, Italy, Dipartimento di Scienze Chimiche, Fisiche e Matematiche dell’Universita`
dell’Insubria, via Lucini 3, 22100 Como, Italy, Dipartimento di Chimica Organica e Industriale
dell’Universita` di Milano, via Golgi 19, 20133 Milano, Italy, and Centro CNR per le Relazioni tra
Struttura e Reattivita` Chimica, via Golgi 19, 20133 Milano, Italy
egle.beccalli@unimi.it
Received May 31, 2000
On starting from N-allyl-substituted 2-indolecarbaldehydes and exploiting the intramolecular
nitrone cycloaddition methodology, we synthesized a number of the title fused-ring indole derivatives
in racemic as well as enantiopure form.
Sch em e 1
In tr od u ction
The indole nucleus annulated to carbocyclic or hetero-
cyclic ring(s) is present in an astonishing variety of
natural products endowed with potent and multiform
biological activities.1-6 Hence, novel and efficient syn-
theses of such compounds still represent highly pursued
targets. In recent years, one of us has just reported
synthetic studies dealing with indole and carbazole
alkaloids,7-9 while some of us have successfully tried for
applications of the intramolecular nitrone cycloaddition
methodology.10,11 On these grounds, we have decided to
exploit the same methodology as a tool for the conversion
of simple and easily accessible indoles to more complex,
polycyclic indole derivatives structurally related to natu-
ral or synthetic bioactive compounds. In particular, we
have aimed at the construction of a functionalized ring
annulated to the 1,2-position of the indole nucleus in the
light of the fact that such a skeleton is present in
mitosenes and mitomycins. These compounds show an-
tibiotic and antitumor activity and inhibit bacterial cell
division through a mechanism of DNA alkylation.12-14 In
particular, mitomycin C is used in clinical cancer che-
motherapy.
Nitrones derived from 1-allyl-2-indolecarbaldehyde (1)
were perceived as suitable intermediates for our purpose
(Scheme 1).
* To whom correspondence should be addressed. Tel: (39) 02-
70601774. Fax: (39) 02-70638473.
† Istituto di Chimica Organica della Facolta` di Farmacia.
‡ Dipartimento di Scienze Chimiche, Fisiche e Matematiche.
§ Dipartimento di Chimica Organica e Industriale.
| Centro CNR.
(1) Lounasmaa, M.; Somersalo, P. In Progress in the Chemistry of
Organic Natural Products; Herz, W., Grisebach, H., Kirby, G. W., Eds.;
Springer-Verlag: Wien, 1979; Vol. 38, pp 1-45.
(2) Husson, H.-P. In The Alkaloids; Brossi, A., Ed; Academic Press:
London, 1985; Vol. 26, Chapter 1.
(3) Franck, R. W. In Progress in the Chemistry of Organic Natural
Products; Herz, W., Grisebach, H., Kirby, G. W., Tamm, Ch., Eds.;
Springer-Verlag: Wien, 1986; Vol. 50, pp 27-56.
(4) Remers, W. A.; Dorr, R. T. In Alkaloids: Chemical and Biological
Perspectives; Pelletier, S. W., Ed.; Wiley: New York, 1988; Vol. 6,
Chapter 1.
As a function of the regiochemical outcome of the
intramolecular cycloaddition, both pyrrolo- and pyrido-
[1,2-a]indole skeletons were accessible by the approach
here described.
Resu lts a n d Discu ssion
(5) Sza´ntay, C. In The Alkaloids; Cordell, G. A., Ed.; Academic
Press: London, 1998; Vol. 50, Chapter 10.
(6) Lounasmaa, M.; Hankinen, P.; Westersund, M. In The Alkaloids;
Cordell, G. A., Ed.; Academic Press: London, 1999; Vol. 52, Chapter
2.
Treatment of aldehyde 1 with benzylhydroxylamine,
carried out in diethyl ether at room temperature, allowed
the isolation of the pure nitrone 2 in 45% yield. Heating
(7) Beccalli, E. M.; Gelmi, M. L.; Marchesini, A. Tetrahedron 1998,
54, 6909.
(8) Beccalli, E. M.; Clerici, F.; Marchesini, A. Tetrahedron 1998, 54,
11675.
(12) Verboom, W.; Reinhoudt, D. N.; Lammerink, B. H. M.; Orle-
mans, E. O. M.; Van Veggel, F. C. J . M.; Lelieveld, P. Anti-Cancer Drug
Des. 1987, 2, 271.
(9) Beccalli, E. M.; Gelmi, M. L.; Marchesini, A. Eur. J . Org. Chem.
1999, 1421.
(10) Broggini, G.; Folcio, F.; Sardone, N.; Sonzogni, M.; Zecchi, G.
Tetrahedron: Asymmetry 1996, 7, 797.
(11) Arnone, A.; Broggini, G.; Passarella, D.; Terraneo, A.; Zecchi,
G. J . Org. Chem. 1998, 63, 9279.
(13) Verboom, W.; Orlemans, E. O. M.; Scheltinga, M. W.; Reinhoudt,
D. N.; Lelieveld, P.; Fiebig, H. H.; Winterhalter, B. R.; Double, J . A.;
Bibby, M. C. J . Med. Chem. 1989, 32, 1612.
(14) Maliepaard, M.; de Mol, N. J .; J anssen, L. H. M.; Hoogvliet, J .
C.; van der Neut, W.; Verboom, W.; Reinhoudt, D. N. J . Med. Chem.
1993, 36, 2091.
10.1021/jo000842g CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/01/2000

Access to Pyrrolo- and Pyrido[1,2-a]indole Derivatives
J . Org. Chem., Vol. 65, No. 26, 2000 8925
the latter in refluxing toluene resulted in a mixture of
the two regioisomeric cycloadducts 3 and 4, which were
isolated by column chromatography in 48 and 30% yield,
respectively. Structural assignments to the products
came from analytical and spectroscopic data. In particu-
lar, the 13C NMR spectrum of 4 shows triplet signals at
48.7, 60.3 and 72.6 ppm, thus indicating that all meth-
ylene groups are adjacent to heteroatom. It is not so in
the case of 3 because its 13C NMR spectrum has a triplet
signal at ca.. 30 ppm, which corresponds to a methylene
group adjacent to carbons.15,16 The cis junction of the two
new rings in both cycloadducts 3 and 4 is clearly the
consequence of geometric restraints imposed by the
intramolecular approach.
The preferred formation of the strained bridged-ring
species 3 is worthy of noting, particularly in light of the
behavior of C-(1-allyl-3-methylindol-2-yl)-N-methylni-
trone, which has been reported to give only a fused-ring
intramolecular cycloadduct.17,18 A possible explanation
followed from the inspection of molecular models. The
conformation of the reactant with the allyl moiety folded
toward the inside is rather crowded and plausibly
disfavored with respect to the conformation having the
allyl moiety oriented externally. However, the latter
conformation (which would originate 4) seems less suit-
able to the intramolecular approach of the π systems in
parallel planes and consequently may well be less reac-
tive than the former conformation (just leading to 3). To
support this view, we decided to perform a MM+ treat-
ment. Such a technique, often inadeguate to construct
transition states, was believed to be reliable in our case
because geometric constraints and steric factors more
than electronic features should be determinant to dif-
ferentiate the regioisomeric pathways. In light of theo-
retical studies of 1,3-dipolar cycloadditions,19-21 three
different hypotheses were taken into account: (i) a
synchronous approach with a distance of 2.85 Å for each
pair of reaction centers, (ii) an asynchronous approach
with the C-O distance shorter than the C-C one (2.7 vs
3.0 Å), and (iii) an asynchronous approach with the C-O
distance longer than the C-C one (3.0 vs 2.7 Å). For both
the bridged-ring and the fused-ring approaches, the
situation (ii) was found to be the most favorable. How-
ever, the fused-ring conformation B was higher in energy
by 0.4 kcal/mol with respect to the bridged-ring confor-
mation A (Figure 1). Such a difference in activation
energies should determine a product ratio 3:4 of ca. 1.7:
1.
F igu r e 1. “Bridged-ring” and “fused-ring” regioisomeric ap-
proaches for the intramolecular cycloadditions of nitrones 2
and 8.
Sch em e 2
Aiming to gain deeper information about the regio-
chemical aspect of the intramolecular cycloaddition, we
synthesized the cinnamyl-substituted aldehyde 7 and
treated it with benzylhydroxylamine (Scheme 2). The
reaction was rather difficult and required heating, so that
the corresponding nitrone 8 behave as a transient species.
Actually, after toluene refluxing for 5 days, the isolated
products were 9 (14%) and 10 (59%). Once again, by
means of MM+ computations, the asynchronous path
with the C-O distance shorter than the C-C one was
estimated as the most favored for both regioisomeric
possibilities. However, the fused-ring conformation D was
lower in energy by 0.7 kcal/mol with respect to the
bridged-ring conformation C (Figure 1). One can there-
fore deduce that the regioselective preference of nitrones
2 and 8 is markedly dependent on steric interactions. On
the other hand, the interplay between the intrinsic
stereoretention of concerted cycloadditions and the geo-
metric constraints due to the intramolecularity dictates
(15) Compound 3 exists as a 5:1 mixture of two conformers which
present differentiate NMR signals. They are plausibly due to hindered
inversion at the pyramidal nitrogen in accord with literature prece-
dents concerning encumbered isoxazolidines (see ref 16). A conforma-
tional study by the MM+ method has indicated that the invertomer
with the N-pendant in pseudoaxial position is more stable of 2.6 kcal/
mol in comparison to the one having the N-pendant in pseudoequatorial
position.
(16) Gru¨nanger, P.; Vita-Finzi, P. Isoxazoles; Wiley: New York,
1991; p 679.
(17) Bhuyan, P. J .; Boruah, R. C.; Sandhu, J . S. Tetrahedron Lett.
1989, 30, 1421. Baruah, B.; Prajapati, D.; Boruah, R. C.; Sandhu, J .
S. Synth. Commun. 1997, 27, 2563.
(18) Black, D. St. C.; Craig, D. C.; Deb-Das, R. B.; Kumar, N. Aust.
J . Chem. 1993, 46, 603.
(19) Hassner, A.; Maurya, R.; Padwa, A.; Bullock, W. H. J . Org.
Chem. 1991, 56, 2775.
(20) Annunziata, R.; Benaglia, M.; Cinquini, M.; Raimondi, L.
Tetrahedron 1993, 49, 8629.
(21) Houk, K. N.; Gonza´lez, J .; Li, Y. Acc. Chem. Res. 1995, 28, 81.

8926 J . Org. Chem., Vol. 65, No. 26, 2000
Beccalli et al.
Sch em e 3
the relative configuration of the three new stereocenters
of 9 and 10. Such a total stereoselection just constitutes
a remarkable advantage from the synthetic point of
view.22
The above cycloadducts were submitted to reductive
cleavage of the isoxazolidine ring in order to bring to light
its latent functionalities. Among the possible proce-
dures,23 we chose the catalytic hydrogenation having in
mind the concomitant debenzylation. The array of our
experimental findings is outlined in Scheme 3. In the case
of the bridged-ring substrates 3 and 9, the removal of a
benzylic group was incomplete when operating with Pd/C
in AcOH. On the other hand, when using Pd(OH)2 in
MeOH, the disappointing loss of the pseudobenzylic
amino group was observed.
The subsequent stage of our work was aimed at the
preparation of nonracemic compounds by means of the
enantiopure benzyl-like hydroxylamine 15 as the reaction
partner toward aldehydes 1 and 7 (Scheme 4). In both
cases, the intramolecular cycloaddition of the first-formed
nitrone 16 gave four isomeric products: two having a
bridged-ring structure and two having a fused-ring
structure. The proportions between the two kinds of
products practically matched those observed in the
intramolecular cycloadditions of the related N-benzylni-
trones 2 and 8. Within each pair of diastereoisomers, the
F igu r e 2. X-ray diffractometric analysis of fused-ring cy-
cloadducts 19a and 20b.
ratio deduced by the NMR spectrum of the product
mixture was approximatively 3:2, due to some degree of
asymmetric induction exerted by the chiral auxiliary. It
must be emphasized that the major bridged-ring product
arising from 16a exists as a mixture of two conformers
with different NMR signals, which give coalescence at
35 °C.
The distinction between the two diastereoisomeric
fused-ring structures was easily made by submitting 19a
and 20b to X-ray diffractometric analysis (Figure 2).24
In the case of the bridged-ring structures, where suitable
crystalline samples were not available, absolute configu-
rations were inferred from a conformational study as-
sociated with the comparative examination of the NMR
properties. We applied the MM+ procedure to the con-
formational analysis of the diastereoisomeric structures
17a and 18a . In both cases, two energy minima were
found in correspondence to the pseudoaxial and pseu-
doequatorial disposition of the N-pendant; however, the
(22) It remains to be noticed that compound 9 does not exhibit
splitting of the NMR signals, even at -60 °C, thus indicating the
existence of only one conformer. On the basis of MM+ computations,
the invertomer with the N-pendant in pseudoaxial position was shown
to be energetically favoured, as already found for the analogous
compound 3.
(24) Full details of the structure determinations have been deposited
at the Cambridge Crystallographic Data Centre (registration no CCDC
144431 for 19a and no CCDC 144432 for 20b). Copies of the data can
be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, U.K.
(23) Torssell, K. B. G. Nitrile Oxides, Nitrones, and Nitronates in
Organic Synthesis; VCH Publishers: New York, 1988.

Access to Pyrrolo- and Pyrido[1,2-a]indole Derivatives
J . Org. Chem., Vol. 65, No. 26, 2000 8927
Sch em e 4
Sch em e 5
F igu r e 3. Energy minimum conformations of the bridged-
ring cycloadducts 17 and 18 as inferred from MM+ computa-
tions.
Ta ble 1. Ch em ica l Sh ifts of th e P yr r olic Hyd r ogen in
Br id ged - a n d F u sed -Rin g Cycloa d d u cts 17-20
entry
17
18
19
20
a
6.53a
6.09b
6.42
5.98
5.93
6.31
b
5.94
5.08
6.18
a
b
Major conformer. Minor conformer.
first conformation was determined to be more stable by
0.7 kcal/mol in 17a and by 2.8 kcal/mol in 18a (Figure
3). The 1S,4R absolute configuration (17a ) was then
assigned to the diastereoisomer existing as a mixture of
two conformers. Such an assignment was corroborated
by the chemical shifts of the pyrrolic hydrogen, whose
upfield resonance reflects its positioning in the shielding
region of a phenyl ring, as demonstrated by the X-ray
analysis of 19a . The observed values (Table 1) are in
perfect agreement with the conformational formulas
depicted in Figure 3. In light of the full analogy of the
NMR data, we were able to confidently assign absolute
configurations in the case of 17b and 18b.
to catalytic hydrogenation. Once again, the choice of the
experimental conditions was subtle in order to realize a
selective reaction. The observed outcomes are sum-
marized in Scheme 5. The presence of a strong protic acid
was advisable, in the case of the bridged-ring cycload-
As the final stage of our work, we submitted the
optically active cycloadducts 17a , 18a , 19a ,b, and 20a ,b

8928 J . Org. Chem., Vol. 65, No. 26, 2000
Beccalli et al.
gel column with AcOEt as eluent to give 410 mg (45%) of 2:
mp 94-96 °C (diisopropyl ether); 1H NMR (δ, CDCl3, 300 MHz)
4.42 (overlapping, 2H), 4.72 (dd, J ) 1.2, 17.1 Hz, 1H), 5.06
(dd, J ) 1.2, 10.4 Hz, 1H), 5.10 (s, 2H), 5.82 (tdd, J ) 4.7,
10.4, 17.1 Hz, 1H), 7.10 (ddd, J ) 1.6, 6.3, 8.0 Hz, 1H), 7.20-
7.46 (overlapping, 8H), 7.68 (d, J ) 8.0 Hz, 1H), 8.21 (s, 1H);
MS m/z 290 (M+). Anal. Calcd for C19H18N2O: C, 78.59; H, 6.25;
N, 9.65. Found: C, 78.65; H, 6.28; N, 9.50.
ducts, to avoid long reaction times (several days). On the
other side, however, it facilitated the loss of the pseudo-
benzylic amino group as well as the hydrogenation of the
pyrrole nucleus. It is noteworthy that the formation of
22, which implies the creation of a new stereocenter, was
fully stereoselective, probably due to steric factors favor-
ing the anti disposition of the bridgehead hydrogen with
respect to the hydroxymethyl group. Such a configuration
has been elucidated by NOESY measurements.
In tr a m olecu la r Cycloa d d ition of Nitr on e 2. A solution
of 2 (540 mg, 1.8 mmol) in toluene (55 mL) was refluxed for
24 h. The solvent was evaporated under reduced pressure, and
the residue was chromatographed on a silica gel column with
AcOEt/light petroleum (1/1) as eluent. The first fractions gave
160 mg (30%) of (3aR*,10bR*)-1-benzyl-1,3a,4,10b-tetrahydro-
3H-isoxazolo[3′,4′:3,4]pyrrolo[1,2-a]indole (4): mp 131-132 °C
The enantiomeric purity was verified in the case of
1
amino alcohol (+)-14b on recording the H NMR spec-
trum in the presence of (R)-O-acetylmandelic acid and
in the case of alcohols (-)-21a and (-)-21b by treatment
1
1
with Mosher’s (R)-acid chloride and subsequent H NMR
(hexane-benzene); H NMR (δ, CDCl3, 300 MHz) 3.91 (dd, J
analysis.
) 4.2, 8.7 Hz, 1H), 3.99-4.07 (m, 1H), 4.11 (dd, J ) 3.6, 10.2
Hz, 1H), 4.12 and 4.19 (AB system, J ) 13.2 Hz, 2H), 4.27
(dd, J ) 8.1, 10.2 Hz, 1H), 4.35 (br s, 1H), 4.70 (br s, 1H), 6.13
(s, 1H), 7.06 (dd, J ) 7.1, 7.1 Hz, 1H), 7.14 (dd, J ) 7.0, 7.0
Hz, 1H), 7.28-7.46 (overlapping, 6H), 7.55 (d, J ) 7.8 Hz, 1H);
13C NMR (δ, CDCl3, 75 MHz) 48.68 (t), 50.85 (d), 60.34 (t),
67.29 (d), 72.56 (t), 94.97 (d), 109.68 (d), 119.62 (d), 121.18
(d), 127.55 (d), 128.46 (d), 129.11 (d), 132.58 (s), 133.22 (s),
137.02 (s), 141.21 (s); MS m/z 290 (M+). Anal. Calcd for
Con clu sion s
Although the results presented here show some degree
of variability, particularly as the final hydrogenation step
is concerned, there is no doubt that they are satisfactory
in view of the planned target. Actually, we succeeded in
synthesizing a number of enantiopure representatives of
the title fused-ring indole systems by way of a short and
efficient reaction sequence.
C
19H18N2O: C, 78.59; H, 6.25; N, 9.65. Found: C, 78.45; H,
6.39; N, 9.76. The last fractions contained 260 mg (48%) of
(1R*,4S*)-2-benzyl-1,2,4,5-tetrahydro-1,4-methanoindolo[2,1-
d][1,2,5]oxadiazepine (3): mp 131-132 °C (hexane-benzene);
1H NMR (δ, CDCl3, 300 MHz) major conformer 2.32 (d, J )
10.9 Hz, 1H), 2.85-3.00 (m, 1H), 3.57 and 3.67 (AB system, J
) 12.4 Hz, 2H), 4.03 (d, J ) 11.8 Hz, 1H), 4.27 (d, J ) 11.8
Hz, 1H), 4.50 (d, J ) 4.5 Hz, 1H), 4.93 (br d, J ) 6.5 Hz, 1H),
6.33 (br s, 1H), 7.10-7.37 (overlapping, 8H), 7.60-7.67 (m,
1H); minor conformer 2.32 (d, J ) 10.9 Hz, 1H), 2.75-2.85
(m, 1H), 3.57 and 3.67 (AB system, J ) 12.4 Hz, 2H), 3.89-
4.03 (m, 1H), 4.10-4.17 (m, 1H), 4.50 (d, J ) 4.5 Hz, 1H),
5.03-5.14 (m, 1H), 6.23 (br s, 1H), 7.10-7.37 (overlapping,
8H), 7.60-7.67 (m, 1H); 13C NMR (δ, CDCl3, 75 MHz) major
conformer 30.92 (t), 51.20 (t), 54.55 (t), 59.57 (d), 68.11 (d),
90.94 (d), 108.98 (d), 119.88 (d), 120.83 (d), 122.30 (d), 127.41
(d), 128.46 (d), 129.06 (d), 132.22 (s), 136.30 (s), 143.91 (s);
minor conformer 30.43 (t), 50.63 (t), 56.32 (t), 57.81 (d), 68.45
(d), 93.11 (d), 109.37 (d), 120.22 (d), 121.33 (d), 122.30 (d),
127.41 (d), 128.46 (d), 129.06 (d), 129.96 (s), 131.76 (s), 136.01
(s), 142.64 (s); MS m/z 290 (M+). Anal. Calcd for C19H18N2O:
C, 78.59; H, 6.25; N, 9.65. Found: C, 78.51; H, 6.18; N, 9.81.
1-Cin n a m yl-2-ca r beth oxyin d ole (5). Cinnamyl bromide
(3.15 g, 16 mmol), TEBA (110 mg, 0.5 mmol), and 50% NaOH
(20 mL) were added to a solution of 2-carbethoxyindole (2.00
g, 10 mmol) in benzene (64 mL). The mixture was vigorously
stirred at room temperature for 1 h. The organic layer was
separated, washed with water, and dried over Na2SO4. The
solvent was evaporated under reduced pressure to give 1.46 g
(48%) of 5: mp 72-73 °C (diisopropyl ether); 1H NMR (δ,
CDCl3, 300 MHz) 1.43 (t, J ) 7.1 Hz, 3H), 4.40 (q, J ) 7.1 Hz,
2H), 5.41 (d, J ) 4.0 Hz, 2H), 6.41 (overlapping, 2H), 7.15-
7.40 (overlapping, 8H), 7.46 (d, J ) 8.4 Hz, 1H), 7.79 (d, J )
8.0 Hz, 1H); IR (Nujol) 1710 cm-1; MS m/z 305 (M+). Anal.
Calcd for C20H19NO2: C, 78.66; H, 6.27; N, 4.59. Found: C,
78.59; H, 6.37; N, 4.40.
1-Cin n a m yl-2-h yd r oxym eth ylin d ole (6). A solution of 5
(220 mg, 0.73 mmol) in dry THF (5 mL) was dropped, under
N2, in a suspension of LiAlH4 (34 mg, 0.88 mmol) in dry THF
(40 mL) at 0 °C. The mixture was stirred at room temperature
for 2 h. MeOH (1 mL) was slowly added, and the solvent was
removed under reduced pressure. After addition of water (2
mL), the aqueous layer was adjusted to pH 7 with 0.1 M HCl
and extracted with CH2Cl2. The organic layer was dried over
Na2SO4 and evaporated to give 150 mg (78%) of 6: mp 99-
100 °C (diisopropyl ether); 1H NMR (δ, CDCl3, 300 MHz) 1.57
(br s, 1H, missing after deuteriation), 4.79 (s, 2H), 4.85 (d, J
) 3.4 Hz, 2H, s after deuteriation), 5.05 (d, J ) 3.1 Hz, 2H),
6.35-6.38 (overlapping, 2H), 6.53 (s, 1H), 7.13 (dd, J ) 7.0,
7.0 Hz, 1H), 7.21-7.32 (overlapping, 6H), 7.39 (d, J ) 8.1 Hz,
Exp er im en ta l Section
Melting points were measured in open capillary tubes and
are uncorrected. IR spectra were recorded using FT-IR spec-
trophotometer. 1H NMR and 13C NMR chemical shifts are
given in ppm downfield from SiMe4. Mass spectra were taken
at 70 eV by E. I. method. The optical rotations were deter-
mined on a digital polarimeter, with a 1 dm path length at 25
°C; concentrations (c) were reported in g/100 mL.
1-Allyl-2-h yd r oxym eth ylin d ole. A solution of 1-allyl-2-
carbethoxyindole25 (5.10 g, 21.1 mmol) in dry THF (40 mL)
was dropped, under N2, in an ice-cooled suspension of LiAlH4
(1.01 g, 26.6 mmol) in dry THF (40 mL). The mixture was
heated at reflux for 1 h. MeOH (10 mL) was slowly added and
the solvent was removed under reduced pressure. After
addition of water (20 mL), the aqueous layer was adjusted to
pH 7 with 0.1 M HCl and extracted with CH2Cl2. The organic
solution was dried over Na2SO4 and evaporated to give 3.23 g
(79%) of the title compound: oil; 1H NMR (δ, CDCl3, 300 MHz)
2.16 (br s, 1H, missing after deuteriation), 4.79 (s, 2H), 4.84-
4.90 (overlapping, 3H), 5.12 (dd, J ) 1.2, 10.1 Hz, 1H), 5.99
(tdd, J ) 4.9, 10.1, 17.4 Hz, 1H), 6.48 (s, 1H), 7.15 (dd, J )
7.4, 7.7 Hz, 1H), 7.20-7.41 (overlapping, 2H), 7.59 (d, J ) 7.7
Hz, 1H); IR (Nujol) 3325 cm-1; MS m/z 187 (M+). Anal. Calcd
for C12H13NO: C, 76.98; H, 7.00; N, 7.48. Found: C, 77.09; H,
6.87; N, 7.07.
1-Allylin d ole-2-ca r ba ld eh yd e (1). Activated MnO2 (28.4
g, 32.6 mmol) was added to a solution of 1-allyl-2-hydroxym-
ethylindole (3.23 g, 17.2 mmol) in CH2Cl2 (120 mL). The
mixture was stirred at room temperature for 3 h and filtered
over a short path of Celite, which was subsequently washed
with CH2Cl2 several times. The filtrate was evaporated to give
2.79 g (88%) of (1).26
N -[(1-Ally lin d o l-2-y l)m e t h y le n e ]b e n ze n e m e t h a n -
a m in e N-Oxid e (2). A suspension of N-benzylhydroxylamine
hydrochloride (660 mg, 4.1 mmol), Al2O3 (8.0 g), and NaHCO3
(570 mg, 6.8 mmol) in Et2O (40 mL) was stirred at room
temperature for 1 h. A solution of 1 (590 mg, 3.2 mmol) in
Et2O (20 mL) was added, and the resulting mixture was stirred
for 48 h. After filtration and evaporation of the solvent under
reduced pressure, the residue was chromatographed on a silica
(25) Hlasta, D. J .; Luttinger, D.; Perrone, M. H.; Silbernagel, M. J .;
Ward, S. J .; Haubrich, D. R. J . Med. Chem. 1987, 30, 1555.
(26) J ones, J . B.; Moody C. J . J . Chem. Soc., Perkin Trans. 1 1989,
2449.

Access to Pyrrolo- and Pyrido[1,2-a]indole Derivatives
J . Org. Chem., Vol. 65, No. 26, 2000 8929
1H), 7.64 (d, J ) 7.8 Hz, 1H); IR (Nujol) 3390 cm-1; MS m/z
263 (M+). Anal. Calcd for C18H17NO: C, 82.10; H, 6.51; N, 5.32.
Found: C, 81.98; H, 6.62; N, 5.37.
(dd, J ) 3.5, 12.3 Hz, 1H), 4.26 (dd, J ) 1.5, 12.3 Hz, 1H),
4.54-4.61 (m, 1H), 4.84 (dd, J ) 3.2, 3.2 Hz, 1H), 6.66 (s, 1H),
7.09 (dd, J ) 7.8, 8.0 Hz, 1H), 7.21 (dd, J ) 7.8, 7.8 Hz, 1H),
7.39 (d, J ) 8.0 Hz, 1H), 7.57 (d, J ) 7.8 Hz, 1H); 13C NMR (δ,
CD3OD, 75 MHz) 31.22 (t), 43.79 (d), 48.39 (t), 63.23 (d), 100.94
(d), 109.00 (d), 119.99 (d), 120.40 (d), 122.22 (d), 127.85 (s),
130.22 (s), 136.84 (s); IR (Nujol) 3160, 3200, 3300 cm-1; MS
m/z 202 (M+). Anal. Calcd for C12H14N2O: C, 71.26; H, 6.98;
N, 13.85. Found: C, 71.31; H, 7.15; N, 13.77.
Hyd r ogen a tion of 4 in AcOH. A mixture of 10% Pd/C (170
mg) and 4 (220 mg, 0.8 mmol) in AcOH (25 mL) was stirred
under H2 for 24 h. After filtration through Celite, the solvent
was removed under reduced pressure and the residue was
chromatographed on a silica gel column with chloroform/
methanol (9/1) as eluent to give 120 mg (78%) of (2R*,3R*)-
1-amino-2,3-dihydro-2-hydroxymethyl-1H-pyrrolo[1,2-a]in-
dole (14a ): mp 88-91 °C (diisopropyl ether); 1H NMR (δ,
CDCl3, 300 MHz) 2.51 (br s, 3H, missing after deuteriation),
3.17 (ddddd, J ) 4.0, 6.6, 7.2, 7.4, 8.2 Hz, 1H), 3.90 (dd, J )
7.2, 11.7 Hz, 1H), 3.98 (dd, J ) 4.0, 11.7 Hz, 1H), 4.02 (dd, J
) 6.6, 10.2 Hz, 1H), 4.13 (dd, J ) 8.2, 10.2 Hz, 1H), 4.75 (d, J
) 7.4 Hz, 1H), 6.28 (s, 1H), 7.08 (ddd, J ) 1.0, 6.9, 7.8 Hz,
1H), 7.16 (ddd, J ) 1.0, 6.9, 7.9 Hz, 1H) 7.25 (d, J ) 7.8 Hz,
1H), 7.58 (d, J ) 7.8 Hz, 1H); 13C NMR (δ, CDCl3, 75 MHz)
44.94 (t), 47.68 (d), 51.53 (d), 62.51 (t), 92.83 (d), 110.14 (d),
119.99 (d), 121.42 (d), 121.58 (d), 132.92 (s), 133.04 (s), 147.50
(s); IR (Nujol) 3040, 3275, 3345 cm-1; MS m/z 202 (M+). Anal.
Calcd for C12H14N2O: C, 71.26; H, 6.98; N, 13.85. Found: C,
71.15; H, 6.79; N, 13.67.
1-Cin n a m ylin d ole-2-ca r ba ld eh yd e (7). Activated MnO2
(940 mg, 10.8 mmol) was added to a solution of 6 (150 mg,
0.57 mmol) in CH2Cl2 (6 mL). The mixture was stirred at room
temperature for 12 h and filtered over a short path of Celite,
which was subsequently washed with CH2Cl2 several times.
The filtrate was evaporated to give 78 mg (52%) of 7: mp 71-
1
72 °C (diisopropyl ether); H NMR (δ, CDCl3, 300 MHz) 5.41
(d, J ) 4.9 Hz, 2H), 6.30-6.50 (overlapping, 2H), 7.18-7.35
(overlapping, 7H), 7.43-7.51 (overlapping, 2H), 7.79 (d, J )
8.1 Hz, 1H), 9.94 (s, 1H); IR (Nujol) 1670 cm-1; MS m/z 261
(M+). Anal. Calcd for C18H15NO: C, 82.73; H, 5.79; N, 5.36.
Found: C, 82.59; H, 5.87; N, 5.52.
Rea ction of 7 w ith N-Ben zylh yd r oxyla m in e. A suspen-
sion of 7 (460 mg, 1.8 mmol), N-benzylhydroxylamine hydro-
chloride (360 mg, 2.3 mmol), Al2O3 (4.2 g), and NaHCO3 (300
mg, 3.8 mmol) in toluene (130 mL) was refluxed for 5 d. After
filtration through Celite and evaporation of the solvent under
reduced pressure, the residue was chromatographed on a silica
gel column with toluene/AcOEt (19/1) as eluent. The first
fractions gave 92 mg (14%) of (1R*,4S*,12R*)-2-benzyl-12-
phenyl-1,2,4,5-tetrahydro-1,4-methanoindolo[2,1-d][1,2,5]oxa-
diazepine (9): mp 127-128 °C (hexane-benzene); 1H NMR
(δ, CDCl3, 300 MHz) 3.65 and 3.74 (AB system, J ) 14.3 Hz,
2H), 3.77 (s, 1H), 4.22 (dd, J ) 1.4, 11.9 Hz, 1H), 4.45 (dd, J
) 1.4, 11.9 Hz, 1H), 4.48 (s, 1H), 4.92 (br s, 1H), 6.35 (s, 1H),
7.15-7.45 (overlapping, 11H), 7.58-7.68 (overlapping, 3H); 13
C
NMR (δ, CDCl3, 75 MHz) 51.86 (t), 54.34 (d), 58.59 (t), 62.10
(d), 100.10 (d), 109.08 (d), 120.01 (d), 120.82 (d), 121.96 (d),
127.06 (d), 127.33 (d), 127.94 (s), 128.24 (d), 128.25 (d), 128.29
(d), 128.40 (d), 128.44 (d), 136.29 (s), 136.43 (s), 137.63 (s),
139.32 (s); MS m/z 366 (M+). Anal. Calcd for C25H22N2O: C,
81.94; H, 6.05; N, 7.64. Found: C, 81.91; H, 5.96; N, 7.45. The
last fractions contained 389 mg (59%) of (3R*,3aR*,10bR*)-1-
benzyl-3-phenyl-1,3a,4,10b-tetrahydro-3H-isoxazolo[3′,4′:3,4]-
pyrrolo[1,2-a]indole (10): mp 123-124 °C (hexane-benzene);
1H NMR (δ, CDCl3, 300 MHz) 3.92 (dddd, J ) 4.1, 7.1, 7.9, 8.0
Hz 1H), 4.20 (dd, J ) 8.0, 10.3 Hz, 1H), 4.26 and 4.39 (AB
system, J ) 13.1 Hz, 2H), 4.27 (dd, J ) 4.1, 10.3 Hz, 1H), 4.68
(d, J ) 7.9 Hz, 1H), 4.99 (d, J ) 7.1 Hz, 1H), 5.78 (br s, 1H),
7.07 (ddd, J ) 1.3, 8.0, 8.0 Hz, 1H), 7.15 (ddd, J ) 1.1, 7.2, 8.1
Hz, 1H), 7.23 (d, J ) 7.8 Hz, 1H), 7.30-7.49 (overlapping,
10H), 7.51 (d, J ) 7.8 Hz, 1H); 13C NMR (δ, CDCl3, 75 MHz)
47.34 (t), 59.95 (d), 62.32 (t), 69.44 (d), 86.31 (d), 95.63 (d),
110.36 (d), 120.33 (d), 121.90 (d), 127.41 (d), 128.36 (d), 129.09
(d), 129.12 (d), 129.16 (d), 129.39 (d), 130.40 (d), 133.27 (s),
133.71 (s), 137.14 (s), 139.14 (s), 141.50 (s); MS m/z 366 (M+).
Anal. Calcd for C25H22N2O: C, 81.94; H, 6.05; N, 7.64. Found:
C, 82.00; H, 6.21; N, 7.48.
Hyd r ogen a tion of 3 in MeOH. A mixture of 10% Pd-
(OH)2/C (95 mg) and 3 (100 mg, 0.34 mmol) in MeOH (10 mL)
was stirred under H2 for 24 h. After filtration through Celite,
the solvent was removed under reduced pressure and the
residue was chromatographed on a silica gel column with
AcOEt/light petroleum (1/1) as eluent. The first fraction gave
24 mg (37%) of 13: mp 94-96 °C (diisopropyl ether); 1H NMR
(δ, CDCl3, 300 MHz) 1.86 (br s, 1H, missing after deuteriation),
1.91-2.17 (overlapping, 2H), 2.97 (ddd, J ) 6.4, 7.0, 16.7 Hz,
1H), 3.18 (ddd, J ) 6.4, 7.4, 16.7 Hz, 1H), 3.90 (dd, J ) 6.1,
11.8 Hz, 1H), 4.24 (dd, J ) 4.6, 11.8 Hz, 1H), 4.36-4.44 (m,
1H), 6.23 (s, 1H), 7.08 (ddd, J ) 1.0, 7.0, 7.2 Hz, 1H), 7.14
(ddd, J ) 1.0, 7.0, 7.8 Hz, 1H), 7.25 (d, J ) 7.8 Hz, 1H), 7.53
(d, J ) 7.2 Hz, 1H); 13C NMR (δ, CDCl3, 75 MHz) 20.49 (t),
30.10 (t), 49.39 (t), 65.95 (d), 98.23 (d), 108.94 (d), 120.14 (d),
120.26 (d), 120.83 (d), 124.52 (s), 136.07 (s), 137.51 (s); IR
(Nujol) 3380 cm-1; MS m/z 187 (M+). Anal. Calcd for C12H13
-
NO: C, 76.98; H, 7.00; N, 7.48. Found: C, 77.11; H, 6.86; N,
7.62. Switching to methanol as eluant provided a second
fraction of 24 mg of 12 (34%).
Hyd r ogen a tion of 4 in MeOH. A mixture of 10% Pd-
(OH)2/C (95 mg) and 4 (100 mg, 0.35 mmol) in MeOH (10 mL)
was stirred under H2 for 24 h. After filtration through Celite,
the solvent was removed under reduced pressure and the
residue was chromatographed on a silica gel column with
chloroform/methanol (9/1) as eluent to give 32 mg (45%) of
(14a ).
Hyd r ogen a tion of 3 in AcOH. A mixture of 10% Pd/C (220
mg) and 3 (270 mg, 0.9 mmol) in AcOH (35 mL) was stirred
under H2 for 24 h. After filtration through Celite, the solvent
was removed under reduced pressure and the residue was
chromatographed on a silica gel column. Elution with chloro-
form/methanol (1/1) gave 53 mg (20%) of (7R*,9S*)-9-benzyl-
amino-7-hydroxy-6,7,8,9-tetrahydropyrido[1,2-a]indole (11a ):
Hyd r ogen a tion of 9 in AcOH. A mixture of 10% Pd/C (20
mg) and 9 (70 mg, 0.19 mmol) in AcOH (6 mL) was stirred
under H2 for 24 h. After filtration through Celite, the solvent
was removed under reduced pressure and the residue was
chromatographed on a silica gel column. Elution with toluene/
AcOEt (4/1) gave 32 mg (45%) of (7R*,8S*,9R*)-9-benzylamino-
7-hydroxy-8-phenyl-6,7,8,9-tetrahydropyrido[1,2-a ]indole
(11b): mp 121-122 °C (diisopropyl ether); 1H NMR (δ, CDCl3,
300 MHz) 3.37-3.49 (m, 1H), 3.56 and 3.81 (AB system, J )
13.5 Hz, 2H), 4.08 (dd, J ) 3.2, 12.1 Hz, 1H), 4.62-4.70
(overlapping, 2H), 4.91 (br s, 1H), 6.51 (s, 1H), 7.06 (overlap-
ping, 2H), 7.12-7.50 (overlapping, 9H), 7.68 (d, J ) 7.8 Hz,
1H), 7.72-7.78 (overlapping, 2H); 13C NMR (δ, CDCl3, 75 MHz)
44.74 (d), 51.03 (t), 52.10 (t), 55.25 (d), 67.39 (d), 102.08 (d),
109.61 (d), 120.19 (d), 120.48 (d), 121.80 (d), 127.17 (d), 127.42
(d), 127.82 (d), 128.37 (d), 128.50 (d), 129.04 (d), 135.26 (s),
1
mp 143-145 °C (diisopropyl ether); H NMR (δ, CDCl3, 300
MHz) 1.55 (br s, 2H, missing after deuteriation), 1.90 (ddd, J
) 3.0, 3.0, 14.4 Hz, 1H), 2.56 (ddd, J ) 2.4, 2.4, 14.4 Hz, 1H),
3.91 and 4.03 (AB system, J ) 13.0 Hz, 2H), 3.97 (dd, J )
12.0, 15.5 Hz, 1H), 4.41-4.44 (m, 1H), 4.51 (overlapping, 2H),
6.40 (s, 1H), 7.12 (dd, J ) 7.4, 7.8 Hz, 1H), 7.21 (dd, J ) 7.4,
7.8 Hz, 1H), 7.25-7.37 (overlapping, 6H), 7.58 (d, J ) 7.8 Hz,
1H); 13C NMR (δ, CDCl3, 75 MHz) 29.15 (t), 50.27 (d), 50.42
(t), 51.37 (t), 65.07 (d), 100.07 (d), 109.41 (d), 120.10 (d), 120.41
(d), 121.65 (d), 127.47 (d), 128.15 (d), 128.69 (d), 128.80 (s),
136.01 (s), 136.87 (s), 138.59 (s); IR (Nujol) 3250, 3290 cm-1
;
MS m/z 292 (M+). Anal. Calcd for C19H20N2O: C, 78.05; H, 6.89;
N, 9.58. Found: C, 77.89; H, 6.76; N, 9.71. Subsequent elution
gave 110 mg (61%) of (7R*,9S*)-9-amino-7-hydroxy-6,7,8,9-
tetrahydropyrido[1,2-a]indole (12): mp 144-146 °C (benzene-
137.07 (s), 138.66 (s), 139.01 (s); IR (Nujol) 3250, 3290 cm-1
;
1
hexane); H NMR (δ, CD3OD, 300 MHz) 2.31 (ddd, J ) 3.2,
MS m/z 368 (M+). Anal. Calcd for C25H24N2O: C, 81.49; H, 6.57;
3.2, 14.1 Hz, 1H), 2.39 (ddd, J ) 2.9, 3.3, 14.1 Hz, 1H), 4.11
N, 7.60. Found: C, 81.39; H, 6.71; N, 7.72.

8930 J . Org. Chem., Vol. 65, No. 26, 2000
Beccalli et al.
Hyd r ogen a tion of 10 in AcOH. A mixture of 10% Pd/C
(25 mg) and 10 (85 mg, 0.23 mmol) in AcOH (10 mL) was
stirred under H2 for 24 h. After filtration through Celite, the
solvent was removed under reduced pressure and the residue
was chromatographed on a silica gel column with chloroform/
methanol (4/1) as eluent to give 23 mg (36%) of (RR*,2R*,3R*)-
1-amino-2-(R-hydroxybenzyl)-2,3-dihydro-1H-pyrrolo[1,2-a]in-
128.85 (d), 132.47 (s), 133.48 (s), 143.19 (s); MS m/z 304 (M+).
Anal. Calcd for C20H20N2O: C, 78.92; H, 6.62; N, 9.20. Found:
C, 79.01; H, 6.69; N, 9.08. The third fraction gave 207 mg (27%)
of (-)-(RR,1S,4R)-2-(R-phenylethyl)-1,2,4,5-tetrahydro-1,4-
methanoindolo[2,1-d][1,2,5]oxadiazepine (17a ): mp 161-163
°C (hexane-benzene); [R]D ) -10.0 (c ) 0.10, CHCl3); 1H NMR
(δ, CDCl3, -10 °C, 300 MHz)28 major conformer 1.38 (d, J )
6.4 Hz, 3H), 2.35 (dd, J ) 1.5, 11.7 Hz, 1H), 2.87-2.99 (m,
1H), 3.22 (q, J ) 6.4 Hz, 1H), 4.02 (dd, J ) 3.6, 11.1 Hz, 1H),
4.16-4.39 (m, 1H), 4.80 (d, J ) 4.5 Hz, 1H), 4.88 (d, J ) 5.9
Hz, 1H), 6.53 (s, 1H), 7.05-7.48 (overlapping, 8H), 7.70 (d, J
) 7.5 Hz, 1H); minor conformer 1.51 (d, J ) 6.4 Hz, 3H), 2.20
(dd, J ) 1.5, 11.7 Hz, 1H), 2.66-2.78 (m, 1H), 3.86 (q, J ) 6.4,
1H), 4.02 (dd, J ) 3.6, 11.1 Hz, 1H), 4.16-4.39 (m, 1H), 4.40
(d, J ) 4.5 Hz, 1H), 5.19 (d, J ) 5.9 Hz, 1H), 6.09 (s, 1H),
7.05-7.48 (overlapping, 8H), 7.53 (d, J ) 7.5 Hz, 1H);1H NMR
(δ, CDCl3, 35 °C, 300 MHz) 1.48 (d, J ) 6.4 Hz, 3H), 2.26 (br
d, J ) 11.7 Hz, 1H), 2.81 (br s, 1H), 3.54 (br s, 1H), 3.97 (dd,
J ) 3.6, 11.1 Hz, 1H), 4.27 (d, J ) 11.1 Hz, 1H), 4.58 (br s,
1H), 4.99 (br s, 1H), 6.28 (br s, 1H), 7.02-7.50 (overlapping,
8H), 7.61 (d, J ) 7.5 Hz, 1H);13C NMR (δ, CDCl3, 75 MHz)
major conformer 21.48 (q), 36.08 (t), 50.60 (t), 54.86 (d), 63.09
(d), 71.75 (d), 99.94 (d), 109.09 (d), 119.72 (d), 120.45 (d), 121.55
(d), 126.60 (d), 127.10 (d), 128.44 (d), 134.56 (s), 135.78 (s),
143.82 (s); minor conformer 21.31 (q), 31.83 (t), 49.82 (t), 55.52
(d), 66.48 (d), 73.58 (d), 96.38 (d), 108.67 (d), 119.40 (d), 120.45
(d), 121.23 (d), 126.60 (d), 127.10 (d), 127.23 (s), 128.81 (d),
137.65 (s), 143.03 (s); MS m/z 304 (M+). Anal. Calcd for
1
dole (14b): oil; H NMR (δ, CDCl3, 300 MHz) 2.96 (br s, 3H,
missing after deuteriation), 3.31 (dddd, J ) 7.5, 7.7, 7.8, 8.7
Hz, 1H), 3.75-3.95 (overlapping, 2H), 4.70 (d, J ) 7.8 Hz, 1H),
4.93 (d, J ) 8.7 Hz, 1H), 6.30 (s, 1H), 7.04-7.21 (overlapping,
3H), 7.29-7.48 (overlapping, 5H), 7.57 (d, J ) 8.0 Hz, 1H);
13C NMR (δ, CDCl3, 75 MHz) 44.95 (t), 50.27 (d), 52.92 (d),
73.65 (d), 92.75 (d), 109.72 (d), 111.58 (d), 121.02 (d), 121.20
(d), 126.55 (d), 127.99 (d), 128.73 (d), 140.33 (s), 142.73 (s),
146.77 (s); MS m/z 278 (M+). Anal. Calcd for C18H18N2O: C,
77.67; H, 6.52; N, 10.06. Found: C, 77.58; H, 6.69; N, 9.98.
(R)-N-[(1-Allylin d ol-2-yl)m eth ylen e]-R-m eth ylben zen -
em eth a n a m in e N-oxid e (16a ). A suspension of (R)-N-R-
methylbenzylhydroxylamine (15)27 (480 mg, 2.7 mmol), alde-
hyde 1 (500 mg, 2.7 mmol) and Al2O3 (3.8 g) in Et2O (18 mL)
was stirred at room temperature for 48 h. After filtration and
evaporation of the solvent under reduced pressure, the residue
was chromatographed on a silica gel column with AcOEt/light
petroleum (3/5) as eluent to give 16a (310 mg, 38%): mp 124-
125 °C (diisopropyl ether); [R]D ) -68.2 (c ) 0.16, CHCl3); 1H
NMR (δ, CDCl3, 300 MHz) 1.92 (d, J ) 6.9 Hz, 3H), 4.63-
4.69 (overlapping, 2H), 4.78 (dd, J ) 1.2, 17.1 Hz, 1H), 5.08
(dd, J ) 1.2, 10.4 Hz, 1H), 5.20 (q, J ) 6.9 Hz, 1H), 5.85 (tdd,
J ) 4.7, 10.4, 17.1 Hz, 1H), 7.09 (ddd, J ) 1.7, 6.2, 7.9 Hz,
1H), 7.20-7.46 (overlapping, 8H), 7.66 (d, J ) 7.9 Hz, 1H),
8.21 (s, 1H); 13C NMR (δ, CDCl3, 75 MHz) 19.62 (q), 45.87 (t),
75.10 (d), 108.99 (d), 109.30 (d), 117.20 (s), 120.68 (d), 122.79
(d), 123.85 (d), 124.56 (d), 127.82 (d), 128.28 (d), 129.18 (d),
129.85 (s), 133.26 (d), 138.10 (s), 138.94 (s); MS m/z 304 (M+).
Anal. Calcd for C20H20N2O: C, 78.92; H, 6.62; N, 9.20. Found:
C, 79.11; H, 6.79; N, 9.03.
C
20H20N2O: C, 78.92; H, 6.62; N, 9.20. Found: C, 78.80; H,
6.44; N, 9.06. The last fraction contained 161 mg (21%) of (+)-
(RR,1R,4S)-2-(R-phenylethyl)-1,2,4,5-tetrahydro-1,4-metha-
noindolo[2,1-d][1,2,5]oxadiazepine (18a ): mp 181-183 °C
(hexane-benzene); [R]D ) +141.7 (c ) 0.22, CHCl3); 1H NMR
(δ, CDCl3, 300 MHz) 1.43 (d, J ) 6.3 Hz, 3H), 2.22 (br d, J )
11.2 Hz, 1H), 2.90 (br s, 1H), 3.38 (br s, 1H), 4.00 (br d, J )
11.8 Hz, 1H), 4.24-4.41 (overlapping, 2H), 4.99 (br d, J ) 5.8
Hz, 1H), 5.98 (br s, 1H), 7.16 (dd, J ) 7.6, 7.6 Hz, 1H), 7.21-
7.41 (overlapping, 7H), 7.63 (d, J ) 7.8 Hz, 1H); 13C NMR (δ,
CDCl3, 75 MHz) 23.08 (q), 36.29 (t), 50.82 (t), 55.26 (d), 63.66
(d), 72.23 (d), 100.85 (d), 108.81 (d), 119.72 (d), 120.68 (d),
121.64 (d), 127.33 (d), 127.59 (s), 127.87 (d), 128.30 (d), 135.05
(s), 136.21 (s), 143.09 (s); MS m/z 304 (M+). Anal. Calcd for
In tr a m olecu la r Cycloa d d ition of Nitr on e 16a . A solu-
tion of 16a (766 mg, 2.5 mmol) in toluene (80 mL) was refluxed
for 24 h. The solvent was evaporated under reduced pressure
and the residue was chromatographed on a silica gel column
with AcOEt/light petroleum (1/1) as eluent. The first fraction
gave 69 mg (9%) of (+)-(RR,3aR,10bR)-1-(R-phenylethyl)-1,-
3a,4,10b-tetrahydro-3H-isoxazolo[3′,4′:3,4]pyrrolo[1,2-a]in-
dole (20a ): mp 121-123 °C (hexane-benzene); [R]D ) +93.7
C
20H20N2O: C, 78.92; H, 6.62; N, 9.20. Found: C, 78.95; H,
6.49; N, 9.33.
Rea ction of Ald eh yd e 7 w ith (R)-N-R-Meth ylben zyl-
h yd r oxyla m in e (15). A suspension of 15 (620 mg, 4.6 mmol),
7 (1 g, 3.8 mmol), and Al2O3 (6.5 g) in toluene (24 mL) was
refluxed for 5 d. After filtration and evaporation of the solvent
under reduced pressure, the residue was chromatographed on
a silica gel column with toluene as eluent. The first fraction
gave 195 mg of a mixture (A) of two products which was
further elaborated as indicated below. The second fraction
contained 190 mg (13%) of (+)-(RR,3R,3aR,10bR)-1-(R-phe-
nylethyl)-3-phenyl-1,3a,4,10b-tetrahydro-3H-isoxazolo[3′,4′:
3,4]pyrrolo[1,2-a]indole (20b): mp 54-55 °C (diisopropyl
ether); [R]D ) +52.0 (c ) 0.10, CHCl3); 1H NMR (δ, CDCl3,
300 MHz) 1.63 (d, J ) 6.8 Hz, 3H), 3.66 (dddd, J ) 3.4, 7.2,
8.0, 8.8 Hz 1H), 4.08 (dd, J ) 8.0, 10.3 Hz, 1H), 4.21 (dd, J )
3.4, 10.3 Hz, 1H), 4.25 (q, J ) 6.8 Hz, 1H), 4.60 (d, J ) 8.8 Hz,
1H), 4.84 (d, J ) 7.2 Hz, 1H), 6.18 (s, 1H), 7.03 (ddd, J ) 1.1,
7.3, 7.4 Hz, 2H), 7.10 (ddd, J ) 1.0, 6.9, 7.3 Hz, 2H), 7.20 (d,
J ) 7.9 Hz, 2H), 7.24-7.38 (overlapping, 5H), 7.45 (d, J ) 7.4
Hz, 2H), 7.52 (d, J ) 8.0 Hz, 1H); 13C NMR (δ, CDCl3, 75 MHz)
21.68 (q), 46.89 (t), 59.82 (d), 65.93 (d), 85.47 (d), 95.94 (d),
110.15 (d), 120.19 (d), 121.80 (d), 127.11 (d), 127.84 (d), 128.12
(d), 128.68 (d), 128.83 (d), 129.08 (d), 133.15 (s), 133.57 (s),
139.34 (s), 142.20 (s); MS m/z 380 (M+). Anal. Calcd for
1
(c ) 0.47, CHCl3); H NMR (δ, CDCl3, 300 MHz) 1.62 (d, J )
6.6 Hz, 3H), 3.80 (dd, J ) 4.7, 8.4 Hz, 1H), 3.90 (ddddd, J )
3.4, 4.6, 7.6, 7.9, 8.0 Hz, 1H), 4.06 (dd, J ) 3.3, 10.3 Hz, 1H),
4.13 (q, J ) 6.6 Hz, 1H), 4.16 (dd, J ) 8.0, 10.3 Hz, 1H), 4.23
(dd, J ) 7.6, 8.4 Hz, 1H), 4.74 (d, J ) 7.9 Hz, 1H), 6.31 (s,
1H), 7.11 (ddd, J ) 1.3, 7.8, 8.0 Hz, 1H), 7.18 (ddd, J ) 1.1,
7.9, 8.1 Hz, 1H), 7.24 (d, J ) 7.9 Hz, 1H), 7.31 (d, J ) 8.1 Hz,
1H), 7.39 (dd, J ) 7.1, 7.6 Hz, 2H), 7.49 (d, J ) 7.1 Hz, 2H),
7.61 (d, J ) 7.6 Hz, 1H); 13C NMR (δ, CDCl3, 75 MHz) 22.61
(q), 48.03 (t), 51.11 (d), 63.09 (d), 65.04 (d), 72.06 (t), 95.47
(d), 109.65 (d), 119.58 (d), 121.08 (d), 127.17 (d), 127.33 (d),
127.41 (d), 128.36 (d), 132.59 (s), 133.12 (s), 140.21 (s), 142.93
(s); MS m/z 304 (M+). Anal. Calcd for C20H20N2O: C, 78.92; H,
6.62; N, 9.20. Found: C, 79.05; H, 6.51; N, 9.39. The second
fraction contained 130 mg (17%) of (-)-(RR,3aS,10bS)-1-(R-
phenylethyl)-1,3a,4,10b-tetrahydro-3H-isoxazolo[3′,4′:3,4] pyr-
rolo[1,2-a]indole (19a ): mp 182-184 °C (hexane-benzene);
[R]D ) -71.8 (c ) 0.12, CHCl3); 1H NMR (δ, CDCl3, 300 MHz)
1.53 (d, J ) 6.5 Hz, 3H), 3.88-4.02 (overlapping, 3H), 4.09
(dd, J ) 2.9, 10.3 Hz, 1H), 4.21 (dd, J ) 7.8, 10.3 Hz, 1H),
4.32 (dd, J ) 7.8, 7.8 Hz, 1H), 4.68-4.80 (m, 1H), 5.93 (br s,
1H), 7.03 (ddd, J ) 1.1, 7.4, 7.5 Hz, 1H), 7.10 (ddd, J ) 1.0,
7.1, 7.4 Hz, 1H), 7.18 (d, J ) 7.9 Hz, 1H), 7.34 (d, J ) 7.1 Hz,
1H), 7.40 (dd, J ) 7.1, 7.6 Hz, 2H), 7.45-7.52 (overlapping,
3H); 13C NMR (δ, CDCl3, 75 MHz) 22.19 (q), 48.90 (t), 49.95
(d), 64.03 (d), 66.21 (d), 71.96 (t), 94.34 (d), 109.64 (d), 119.51
(d), 120.89 (d), 121.12 (d), 127.57 (d), 127.92 (d), 128.47 (d),
C
26H24N2O: C, 82.07; H, 6.36; N, 7.36. Found: C, 81.95; H,
6.52; N, 7.28. The third fraction gave 422 mg (29%) of (+)-
(RR,3S,3aS,10bS)-1-(R-phenylethyl)-3-phenyl-1,3a,4,10b-tet-
rahydro-3H-isoxazolo[3′,4′:3,4]pyrrolo[1,2-a]indole (19b): mp
(28) The 1H NMR spectrum taken at the usual temperature showed
two sets of broadening signals, whose multiplicity was not always
definied. Complete coalescence was observed at 35 °C.
(27) Wovkulich, P. M.; Uskokovic, M. R. Tetrahedron 1985, 41, 3455.

Access to Pyrrolo- and Pyrido[1,2-a]indole Derivatives
J . Org. Chem., Vol. 65, No. 26, 2000 8931
71-72 °C (diisopropyl ether); [R]D ) +20.0 (c ) 0.10, CHCl3);
1H NMR (δ, CDCl3, 300 MHz) 1.63 (d, J ) 6.5 Hz, 3H), 3.73
(dddd, J ) 2.8, 7.6, 8.0, 8.8 Hz 1H), 3.98 (dd, J ) 7.6, 10.2 Hz,
1H), 4.08 (dd, J ) 2.8, 10.2 Hz, 1H), 4.13 (q, J ) 6.5 Hz, 1H),
4.73 (d, J ) 8.8 Hz, 1H), 4.83 (d, J ) 8.0 Hz, 1H), 5.08 (s, 1H),
6.96 (ddd, J ) 1.0, 7.5, 7.6 Hz, 1H), 7.05 (ddd, J ) 1.0, 7.1, 7.2
Hz, 1H), 7.10 (dd, J ) 7.9, 8.0 Hz, 1H), 7.26-7.49 (overlapping,
11H); 13C NMR (δ, CDCl3, 75 MHz) 22.03 (q), 46.82 (t), 59.92
(d), 68.23 (d), 85.44 (d), 95.89 (d), 110.13 (d), 120.10 (d), 121.69
(d), 127.37 (d), 128.72 (d), 129.25 (d), 132.78 (s), 133.65 (s),
142.89 (s); MS m/z 380 (M+). Anal. Calcd for C26H24N2O: C,
82.07; H, 6.36; N, 7.36. Found: C, 82.21; H, 6.48; N, 7.45.
The above mixture labeled A was newly chromatographed
on a silica gel column with light petroleum/diethyl ether (10/
1) as eluent. The first fraction contained 29 mg (2%) of (-)-
(RR,1R,4S,12R)-2-(R-phenyethyl)-12-phenyl-1,2,4,5-tetrahydro-
1,4-methanoindolo[2,1-d][1,2,5]oxadiazepine (18b ): mp 58-
(s), 133.48 (s), 143.67 (s); IR (Nujol) 3370 cm-1; MS m/z 187
(M+). Anal. Calcd for C12H13NO: C, 76.98; H, 7.00; N, 7.48.
Found: C, 76.93; H, 6.85; N, 7.60. The second fraction gave
23 mg (36%) of (-)-(2R,3S)-3-amino-2,3-dihydro-1H-pyrrolo-
[1,2-a]indolo-2-methanol (14a ): oil; [R]D ) -14.5 (c ) 0.15,
CHCl3).
A mixture of (-)-21a (12 mg, 0.064 mmol), Mosher’s (R)-
acid chloride (19 mg, 0.075 mmol), and pyridine (20µL) in CH2-
Cl2 (2 mL) was stirred at room temperature for 24 h. Evapo-
ration of the solvent gave the crude ester: 1H NMR (δ, CDCl3,
300 MHz) 2.76 (dd, J ) 5.8, 16.2 Hz, 1H), 3.12 (dd, J ) 8.3,
16.2 Hz, 1H), 3.30-3.39 (m, 1H), 3.50 (s, 3H), 3.77 (dd, J )
5.5, 10.3 Hz, 1H), 4.10 (dd, J ) 7.7, 10.3 Hz, 1H), 4.31 (dd, J
) 7.9, 11.0 Hz, 1H), 4.51 (dd, J ) 6.1, 11.0 Hz, 1H), 6.12 (s,
1H),6.99-7.15 (overlapping, 3H), 7.29-7.51 (overlapping, 6H);
ee >97%; MS m/z 403 (M+).
Hyd r ogen a tion of 20a w ith ou t HCl. According to the
procedure described in the preceding preparation, compound
20a (93 mg, 0.31 mmol) gave 8 mg (14%) of (+)-(2S)-2,3-
dihydro-1H-pyrrolo[1,2-a]indolo-2-methanol (21a ), [R]D ) +2.9
(c ) 0.12, CHCl3), and 28 mg (44%) of (+)-(2S,3R)-3-amino-
1
59 °C (diisopropyl ether); [R]D ) -59.7 (c ) 0.16, CHCl3); H
NMR (δ, CDCl3, 300 MHz) 1.41 (d, J ) 6.3 Hz, 3H), 3.42 (q, J
) 6.3 Hz, 1H), 3.62 (br s, 1H), 4.20 (dd, J ) 1.8, 11.8 Hz, 1H),
4.27 (br s, 1H), 4.45 (dd, J ) 2.2, 11.8 Hz, 1H), 4.93 (dd, J )
1.8, 2.2 Hz, 1H), 5.94 (s, 1H), 7.12-7.35 (overlapping, 10H),
7.41 (dd, J ) 7.0, 7.7 Hz, 2H), 7.60 (d, J ) 8.0 Hz, 1H), 7.62
(d, J ) 7.0 Hz, 1H); 13C NMR (δ, CDCl3, 75 MHz) 23.59 (q),
51.94 (t), 54.30 (d), 60.30 (d), 63.41 (d), 100.57 (d), 108.94 (d),
119.83 (d), 121.12 (d), 122.71 (d), 127.27 (d), 127.70 (d), 128.01
(d), 136.08 (s), 136.48 (s), 139.64 (s), 143.37 (s); MS m/z 380
(M+). Anal. Calcd for C26H24N2O: C, 82.07; H, 6.36; N, 7.36.
Found: C, 82.12; H, 6.19; N, 7.52. The second fraction
contained 115 mg (8%) of (+)-(RR,1S,4R,12S)-2-(R-phenyl-
ethyl)-12-phenyl-1,2,4,5-tetrahydro-1,4-methanoindolo[2,1-
d][1,2,5]oxadiazepine (17b): mp 88-89 °C (diisopropyl ether);
[R]D ) +132.8 (c ) 0.12, CHCl3); 1H NMR (δ, CDCl3, 300 MHz)
1.20 (d, J ) 6.5 Hz, 3H), 3.33 (q, J ) 6.5 Hz, 1H), 3.68 (br s,
1H), 4.08 (dd, J ) 1.8, 11.8 Hz, 1H), 4.31 (dd, J ) 2.0, 11.8
Hz, 1H), 4.59 (br s, 1H), 4.80 (br s, 1H), 6.42 (br s, 1H), 7.08-
7.24 (overlapping, 8H), 7.28 (dd, J ) 7.2, 7.5 Hz, 1H), 7.36
(dd, J ) 7.0, 7.5 Hz, 2H), 7.55 (d, J ) 7.2 Hz, 2H), 7.61 (d, J
) 7.7 Hz, 1H); 13C NMR (δ, CDCl3, 75 MHz) 22.35 (q), 51.81
(t), 54.26 (d), 60.71 (d), 63.15 (d), 76.34 (d), 99.99 (d), 109.18
(d), 120.06 (d), 120.77 (d), 121.92 (d), 126.72 (d), 126.99 (d),
127.36 (d), 127.98 (s), 128.42 (d), 133.65 (s), 136.92 (s), 139.62
(s), 144.76 (s); MS m/z 380 (M+). Anal. Calcd for C26H24N2O:
C, 82.07; H, 6.36; N, 7.36. Found: C, 81.90; H, 6.23; N, 7.50.
Hyd r ogen a tion of 17a . A mixture of 10% Pd/C (86 mg)
and 17a (100 mg, 0.33 mmol) in a 0.04 N solution of HCl in
MeOH (8 mL) was stirred under H2 for 24 h. After filtration
through Celite, the solvent was removed under reduced
pressure. The residue was treated with KOH and extracted
with CH2Cl2. After evaporation of the solvent the crude product
was chromatographed on silica gel. Elution with AcOEt/light
petroleum (1/1) gave 49 mg (79%) of (+)-(7R)-7-hydroxy-
6,7,8,9-tetrahydropyrido[1,2-a]indole (13): [R]D ) +18.0 (c )
0.10, CHCl3).
2,3-dihydro-1H-pyrrolo[1,2-a]indolo-2-methanol (14a ), [R]D
+13.9 (c ) 0.10, CHCl3).
)
Hyd r ogen a tion of 19a in th e P r esen ce of HCl. A
mixture of 10% Pd/C (87 mg) and 19a (107 mg, 0.35 mmol) in
a 0.04 N solution of HCl in MeOH (8 mL) was stirred under
H2 for 24 h. After filtration through Celite, the solvent was
removed under reduced pressure. The residue was treated with
KOH and extracted with CH2Cl2. After evaporation of the
solvent, the crude product was chromatographed on silica with
AcOEt as eluent. The first fraction gave 15 mg (23%) of (-)-
21a . The second fraction contained 10 mg (15%) of (+)-
(3aR,2R)-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]indolo-2-metha-
nol (22): oil; [R]D ) +47.9 (c ) 0.11, CHCl3); 1H NMR (δ,
CDCl3, 300 MHz) 1.13 (ddd, J ) 10.8, 10.8, 11.4 Hz, 1H), 1.68
(br s, 1H, missing after deuteriation), 2.00 (ddd, J ) 5.9, 6.1,
11.4 Hz, 1H), 2.50-2.64 (m, 1H), 2.88-2.99 (overlapping, 2H),
3.17 (dd, J ) 9.4, 16.1 Hz, 1H), 3.53 (d, J ) 6.7 Hz, 2H), 3.59
(dd, J ) 8.2, 10.8 Hz, 1H), 3.96-4.09 (m, 1H), 6.56 (d, J ) 7.7
Hz, 1H), 6.74 (dd, J ) 7.1, 7.7 Hz, 1H), 7.04-7.12 (overlapping,
2H); 13C NMR (δ, CDCl3, 75 MHz) 34.09 (t), 35.28 (t), 43.83
(d), 55.56 (t), 65.94 (d), 66.13 (t), 111.14 (d), 119.74 (d), 125.40
(d), 128.08 (d), 129.71 (s), 134.54 (s); IR (Nujol) 3340 cm-1; MS
m/z 189 (M+). Anal. Calcd for C12H15NO: C, 76.16; H, 7.99; N,
7.40. Found: C, 76.01; H, 8.12; N, 7.31. The third fraction gave
15 mg (21%) of (-)-14a .
Hyd r ogen a tion of 20a in th e P r esen ce of HCl. Accord-
ing to the procedure described in the preceding preparation,
compound 20a (108 mg, 0.35 mmol) gave 8 mg (12%) of (+)-
(2S)-(21a ), 14 mg (21%) of (-)-(3aS,2S)-2,3,3a,4-tetrahydro-
1H-pyrrolo[1,2-a]indolo-2-methanol (22), [R]D ) -46.2 (c )
0.10, CHCl3), and 15 mg (21%) of (+)-14a .
Hyd r ogen a tion of 19b. A mixture of 10% Pd(OH)2/C (70
mg) and 19b (100 mg, 0.26 mmol) in MeOH (10 mL) was
stirred under H2 for 24 h. After filtration through Celite, the
solvent was removed under reduced pressure and the crude
product was chromatographed on silica with AcOEt/light
petroleum (1/1) as eluent. The first fraction gave 10 mg (14%)
of (-)-(RS,2R)-2-(R-hydroxybenzyl)-2,3-dihydro-1H-pyrrolo[1,2-
Hyd r ogen a tion of 18a . According to the procedure de-
scribed in the preceding preparation, compound 18a (107 mg,
0.35 mmol) gave 52 mg (79%) of (-)-(7S)-7-hydroxy-6,7,8,9-
tetrahydropyrido[1,2-a]indole (13): [R]D ) -17.3 (c ) 0.14,
CHCl3).
1
Hyd r ogen a tion of 19a w ith ou t HCl. A mixture of 10%
Pd(OH)2/C (87 mg) and 19a (100 mg, 0.32 mmol) in MeOH
(10 mL) was stirred under H2 for 24 h. After filtration through
Celite, the solvent was removed under reduced pressure and
the crude product was chromatographed on silica gel with
AcOEt/light petroleum (1/3) as eluent. The first fraction gave
14 mg (24%) of (-)-(2R)-2,3-dihydro-1H-pyrrolo[1,2-a]indolo-
2-methanol (21a ): oil; [R]D ) -3.7 (c ) 0.15, CHCl3); 1H NMR
(δ, CDCl3, 300 MHz) 1.65 (br s, 1H, missing after deuteriation),
2.76-2.88 (m, 1H), 3.10-3.28 (overlapping, 2H), 3.71 (dd, J
) 7.2, 10.3 Hz, 1H), 3.80 (dd, J ) 6.0, 10.3 Hz, 1H), 3.93 (dd,
J ) 5.1, 10.2 Hz, 1H), 4.19 (dd, J ) 7.5, 10.2 Hz, 1H), 6.15 (s,
1H), 7.05 (ddd, J ) 1.0, 6.9, 7.6 Hz, 1H), 7.11 (ddd, J ) 1.0,
6.9, 7.9 Hz, 1H), 7.22 (d, J ) 7.9 Hz, 1H), 7.54 (d, J ) 7.6 Hz,
1H); 13C NMR (δ, CDCl3, 75 MHz) 27.76 (t), 44.70 (d), 46.72
(t), 65.48 (t), 93.20 (d), 109.74 (d), 119.60 (d), 120.68 (d), 133.14
a]indole (21b): oil; [R]D ) -19.5 (c ) 0.08, CHCl3); H NMR
(δ, CDCl3, 300 MHz) 2.01 (br s, 1H, missing after deuteria-
tion),3.11-3.28 (overlapping, 2H), 3.33-3.44 (m, 1H), 3.71 (dd,
J ) 6.9, 10.3 Hz, 1H), 3.89 (dd, J ) 8.1, 10.3 Hz, 1H), 4.73 (d,
J ) 8.3 Hz, 1H), 6.15 (s, 1H), 6.99-7.13 (overlapping, 3H),
7.32-7.42 (overlapping, 5H), 7.51 (dd, J ) 2.4, 6.7 Hz, 1H);
13C NMR (δ, CDCl3, 75 MHz) 27.9 (t), 46.1 (t), 49.6 (d), 76.7
(d), 92.7(d), 105.3 (s), 109.2 (d), 119.2 (d),120.1 (d), 120.3 (d),-
125.8 (s), 126.5 (d), 128.4 (d), 128.9 (d), 132.1 (s), 140.2(s); MS
m/z 263 (M+). Anal. Calcd for C18H17NO: C, 82.10; H, 6.51; N,
5.32. Found: C, 81.94; H, 6.39; N, 5.51. The second fraction
contained 31 mg (42%) of of (+)-(RS,2S,3S)-1-amino-2-(R-
hydroxybenzyl)-2,3-dihydro-1H-pirrolo[1,2-a]indolo (14b): oil;
[R]D ) +19.2 (c ) 0.16, CHCl3); ee >97%.
A mixture of (-)-21b (6 mg, 0.023 mmol), Mosher’s (R)-acid
chloride (7 mg, 0.028 mmol), and pyridine (10µL) in CH2Cl2 (1

8932 J . Org. Chem., Vol. 65, No. 26, 2000
Beccalli et al.
mL) was stirred at room temperature for 24 h. Evaporation of
the solvent gave the crude ester: 1H NMR (δ, CDCl3, 300 MHz)
3.12 (d, J ) 7.6 Hz, 2H),3.29-3.45 (m, 1H), 3.60 (s, 3H), 3.74
(dd, J ) 6.9, 10.2 Hz, 1H), 3.90 (dd, J ) 8.1, 10.2 Hz, 1H),4.76
(d, J ) 8.1 Hz, 1H), 6.13 (s, 1H),7.00-7.11 (overlapping, 3H),
7.31-7.51 (overlapping, 11H); ee >97%; MS m/z 479 (M+).
Hyd r ogen a tion of 20b. According to the procedure de-
scribed in the preceding preparation, compound 20b (100 mg,
0.26 mmol) gave 11 mg (15%) of (+)-(RR,2S)-2-(R-hydroxy-
benzyl)-2,3-dihydro-1H-pyrrolo[1,2-a]indole (21b), [R]D ) +18.1
(c ) 0.10, CHCl3), and 29 mg (40%) of of (-)-(RR,2R,3R)-1-
amino-2-(R-hydroxybenzyl)-2,3-dihydro-1H-pirrolo[1,2-a]indo-
lo (14b), [R]D ) -18.9 (c ) 0.10, CHCl3).
Ack n ow led gm en t. Thanks are due to MURST and
CNR for financial support.
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic data and copies of 1H and 13C NMR spectra for
compounds 3, 4, 9-14, and 17-22 as well as of two-
1
dimensional H-NOESY NMR spectra for compound 22.
J O000842G