Metal-catalyzed reaction of indoline diazoamides possessing a C-2 CH2X substituent: Site-selectivity, diastereoselectivity, and chemoselectivity

Full text of DOI:10.1021/jo951320h

J . Org. Chem. 1996, 61, 2897-2900
2897
Sch em e 1
Meta l-Ca ta lyzed Rea ction Of In d olin e
Dia zoa m id es P ossessin g a C-2 CH2X
Su bstitu en t: Site-Selectivity,
Dia ster eoselectivity, a n d Ch em oselectivity
Andrew G. H. Wee* and J . Slobodian
Department of Chemistry, University of Regina,
Regina, Saskatchewan, S4S 0A2, Canada
Received J uly 20, 1995 (Revised Manuscript Received February
12, 1996 )
Recently we reported1 that the rhodium(II)-acetate
catalyzed C-H insertion in indoline diazoamides, such
as 1 (eq 1), resulted in the preferential formation of
tetrahydropyrrolo[1,2-a]indole derivatives, 2 and 3, in
high yields. This process represents a useful and mild
method for the construction of the pyrrolo[1,2-a]indole
ring system.2 Herein we report the results from our
investigation into the intramolecular metallocarbenoid
C-H insertion reaction of indoline diazoamides, typified
by 9 and 10, that possess a CH2X substituent (where X
) “heteroatom group”) at the C-2 position of the indoline
nucleus.
diastereomeric products, exo-trans (EX-t)-, exo-cis (EX-
c)-, and endo-trans (EN-t)-11 (Chart 1)5 were obtained,
which resulted from metallocarbenoid insertion into the
methylene C-H of the CH2X moiety. Aromatic substitu-
tion products were not detected in all the reactions
studied, even in cases (entries 3-5, 10-12) where an
electron-donating methoxy group was located ortho to the
aromatic C-H bond. The formation of the diastereomer
EN-t-11 was unexpected when compared to the results
obtained for 1 (eq 1).1 The absence of the EN-t- and EN-
c-type diastereomers in the reaction of 1 suggests that
the transition states that led to these diastereomers were
destabilized by an unfavorable syn Me/Me interaction
(see A, R ) Me, Chart 1) between the C-3 methyl group
and the methyl moiety of the ethyl group. This desta-
bilizing interaction is not present in the reactions of 9
and 10 (A, R ) H) and, as a result, the EN-t and EN-c
diasteromers were formed. The present results, and
especially the data from the reaction of 9c and 10c
(entries 6, 13), support this reasoning.
Resu lts
The diazoamides 9 and 10 were prepared from the
indoline alcohols 5-7, which were readily obtained from
the known3 2-indolecarboxylates 4 (R ) H or OMe)
(Scheme 1). Alcohols 5-7 were converted via standard
functional group manipulations (supporting information)
to yield the indoline derivatives 8a -g. Acylation1 of
compounds 8 with either R-(carbomethoxy)acetic acid or
R-(phenylsulfonyl)acetic acid gave the corresponding
indoline amides, which were diazotized1 (MsN3, DBU) to
yield the diazoamides 9 and 10. We were unable to
obtain 10d in satisfactory yields because it was unstable
and readily decomposed under the diazotization condi-
tions. Therefore, the metal-catalyzed reaction of 10d was
not examined.
EN-t-11a , the diastereomers 11b and 11h were un-
stable and decomposed during chromatographic purifica-
tion. Therefore, they were characterized as the pyrro-
The metal-catalyzed reaction of diazoamides 9a -e and
4
10 a -e was conducted in refluxing dry CH2Cl2 and the
results are summarized in Table 1. In general, three
(1) Wee, A. G. H.; Liu, B.-S.; Zhang, L. J . Org. Chem. 1992, 57, 4404.
(2) Some recent approaches, see for example: (a) Cotterill, A. S.;
Hartopp, P.; J ones, G. B.; Moody, C. J .; Norton, C. L.; O’Sullivan, N.
O.; Swann, E. Tetrahedron 1994, 50, 7657. (b) Ziegler, F. E.; Belema,
M. J . Org. Chem. 1994, 59, 7962. (c) Michael, J . P.; Chang, S.-F.;
Wilson, C. F. Tetrahedron Lett. 1993, 34, 8365. (d) Vedejs, E.;
Piotrowski, D. W. J . Org. Chem. 1993, 58, 1341. (e) Shiue, J .-S.; Fang,
J .-M. J . Chem. Soc., Chem. Commun. 1993, 1277. Review of earlier
approaches see: Verboom, W.; Reinhoudt, D. N. Recl. Trav. Chim.
Pays-Bas 1986, 105, 199.
(4) We found that reaction temperature (rt vs reflux) had no
influence on the diastereoselectivity and the chemoselectivity (C-H
insertion versus O-interception) of the reaction.
(5) (a) Exo and endo refers to the orientation of X with respect to
the convex side of tricyclic ring: exo ) â-orietation and endo )
R-orientation; cis and trans refer to the relative stereochemistry of X
and R′ at C-1 and C-2 (pyrrolo[1,2-a]indole numbering), respectively.
We thank a referee for bringing this designation to our attention. (b)
The assignment of the relative stereochemistries at C-1, C-2, and C-9a
was based on results obtained from difference NOE experiments
performed on EX-t, EX-c, and EN-t-12a ,b.
(3) Knittel, D. Synthesis 1985, 186.
0022-3263/96/1961-2897$12.00/0 © 1996 American Chemical Society

2898 J . Org. Chem., Vol. 61, No. 8, 1996
Ta ble 1. Meta l-Ca ta lyzed Rea ction of In d olin e Dia zoa m id es 9a -e a n d 10a -e in Reflu xin g CH2Cl2
Notes
entry
diazoamide
catalystg
diastereomers
interceptionf
1
2
3
4
5
6
7
8
9
10
11
12
13
14
9a
9a
9b
9b
9b
9c
9d
10a
10a
10b
10b
10b
10c
10e
A
C
A
B
C
A
A
A
C
A
B
C
A
A
EX-t/EX-c-11a a (48%; 4.6:1b), EN-t-11a (38%)
EX-t/EX-c-11a a (28%; 4.6:1b), EN-t-11a (4.1%)
EX-t/EX-c-11ba (47%; 3.7:1b), EN-t-11b (43%)
EX-t/EX-c-11ba (33%; 2.7:1b), EN-t-11b (18%)
EX-t/EX-c-11ba (34%; 2.7:1b), EN-t-11b (16.8%)
EX-t/EX-c-11ea (83%; 8.0:1c), EN-t/EN-c-11ea (12%; 7.3:1c)
EX-t-11g (56%), EX-c/EN-t-11ga (25%; 1:10c)
n.d.h
13a (39%)
n.d.
n.d.
13b (10%)
EX-t/EX-c/EN-t-11ca (67%; 9:1:2.5c,d
EX-t/EX-c/EN-t-11ca (80%; 5:1.5:4c,d
)
)
n.d.
n.d.
n.d.
n.d.
n.d.
EX-t/EX-c/EN-t-11d a (84%; 8.7:1:1.4c,d
)
EX-t/EX-c/EN-t-11d a (60%; 19:1:1.4c,d
)
EX-t/EX-c/EN-t-11d a (76%; 1.5:0:1c,d
)
EX-t/EX-c/EN-t-11fa (77%; 9:1.1:1c,d
EX-t/EX-c/EN-t-11h a (72%)e
)
n.d.
a
b
Obtained as an inseparable mixture of diastereomers. Ratio is based on the integration of H-9a (major) and H-1 (minor). c Ratio is
based on the integration of H-2. Ratio is approximate due to overlap of the H-2/H-9a resonances; integration for H-2 is taken as 1/2 total
d
integration of the H-2/H-9a. e Ratio was not determined due to instability of product. f Heteroatom interception product. A ) Rh2(OAc)4,
g
h
B ) Rh2(Oct)4, C ) Cu(hfacac)2. n.d. ) Not detected.
Ch a r t 1
loindoles 12; EN-t-11a and diastereomers 11b were
decarboxylated6 to give 12a 7 and 12b, respectively. The
diastereomers 11h were treated with DBU in refluxing
benzene to give the pyrroloindole 12c.
The copper-catalyzed reaction of 9a ,b and 10a ,b proved
interesting. It is well established that copper carbenoids
are highly electrophilic,8 but show diminished reactivity
toward C-H insertion.9,10 In addition, it was recently
shown11 that, unlike rhodium carbenoids, copper car-
benoids react more efficiently with heteroatoms. The
diazoamides 9a ,b furnished both C-H insertion and
O-interception products (Table 1: entries 2,5); the latter
products, 13a ,b, were generated with poor stereoselec-
tivity. Thus 13a ,b were obtained as a 1:1 and 2:1
mixture of diastereomers, respectively. The data also
indicated that 13a ,b were formed at the expense (in the
yields) of the C-H insertion products, especially those
of EN-t-11a ,b. Unlike 9a ,b, the diazoamides 10a ,b gave
only C-H insertion products (entries 9, 12); in the case
of 10b, the minor diastereomer, EX-c-11d , was not
detected.
The interception of the Rh(II)-carbenoid by the X
moiety was found to be the primary reaction pathway in
the Rh2(OAc)4-catalyzed reaction of the diazoamides 9f,g
and 10f,g. Thus, 9f and 10f gave only the interception
product 14 (Chart 1). These results were surprising
because the azide group was recently shown12 to be
effective in activating adjacent C-H bonds to metallo-
carbenoid insertion. To the best of our knowledge this
is the first example of an interception of the Rh(II)-
carbenoid by an azide group.13 We found the yield of 14a
was dependent on the reaction temperature; in refluxing
CH2Cl2, a yield of 55% was obtained (20% 9f was also
recovered), whereas in refluxing benzene a 76% yield was
(6) Krapcho, A. P. Synthesis 1982, 893.
(7) (a) Cliff, G. R.; J ones, G.; Woollard, J . McK. 1973, 2401. (b)
Franck, R. W.; Auerbach, J . J . Org. Chem. 1971, 36, 31.
(8) Doyle, M. P.; Tamblyn, W. H.; Bagheri, V. J . Org. Chem. 1981,
46, 5094.
(9) (a) Taber, D. F.; Ruckle, R. E., J r. J . Am. Chem. Soc. 1986, 108,
7686. (b) Taber, D. F.; Saleh, S. A.; Korsmeyer, R. W. J . Org. Chem.
1980, 45, 4699. For a review on copper-catalyzed reactions: Burke, S.
D.; Grieco, P. A. Org. React. (N.Y.) 1979, 26, 361. See also Ye, T.;
McKervey, M. A. Chem Rev. 1994, 94, 1091.
(10) Recently, Lim and Sulikowski showed that copper carbenoids
efficiently partake in C-H insertion reactions in R-(2-pyrrolidinophen-
yl)-R-diazoacetates wherein the carbenoid carbon and the C-H inser-
tion site are held in close proximity. Sulikowski, G.; Lim, H.-J . J . Org.
Chem. 1995, 60, 2326.
(12) (a) Wang, P.; Adams, J . J . Am. Chem. Soc. 1994, 116, 3296 and
references cited.
(11) (a) Clark, J . S.; Krowiak, S. A.; Street, L. J . Tetrahedron Lett.
1993, 34, 4385. (b) West, F. G.; Naidu, B. N.; Tester, R. W. J . Org.
Chem. 1994, 59, 6892.
(13) For an example of an interception of a carbene, generated under
phase transfer reaction conditions, by an azide group see: Szonyi, F.;
Cambon, A. Tetrahedron Lett. 1992, 33, 2339.

Notes
J . Org. Chem., Vol. 61, No. 8, 1996 2899
Ta ble 2. NOE Resu lts
irradiate
observed NOE (%)
irradiate
H-1
observed NOE (%)
EX-t-11a
H-1
H-2
H-1
H-1
H-9a
H-1
H-2 (3.2%), trans
H-9a (4.8%), syn
H-2 (11%), cis
H-9a (12%), cis
H-2 (4.4%), syn
H-2 (16%), cis
H-9a (2.8%), trans
EX-c-11a
EN-t-11a
EX-t-11c
EX-c-11c
H-2
H-1
H-1
H-1 (3.8%), trans
H-2 (4%), trans
H-9a (3.5%), trans
[133.89], 138.80, 163.99, [167.06], 168.70. EIMS (m/ z, rel inten-
sity): 362 (M + 1, 100), 304 (M - t-Bu+, 35), 230 (M + 1 -
t-BuMe2SiOH, 41). See Table 2 for NOE results. Anal. Calcd
for C19H27NO4Si: C, 63.13; H, 7.53; N, 3.88. Found: C, 63.41;
H, 7.73; N, 3.91.
realized. On the other hand, the reaction of 10f in
refluxing CH2Cl2 resulted in complete conversion to the
unstable 14b. The structure of 14b was assigned based
on the 1H NMR of the crude product, which showed a
spectrum similar to that of 14a . The characteristic
1-(t er t -Bu t yld im e t h ylsiloxy)-2-ca r b om e t h oxy-3-oxo-
1,2,9,9a -tetr a h yd r op yr r olo[1,2-a ]in d ole (EN-t-11a ). Pale
yellow oil; yield 37.7%. IR υmax (neat): 2953, 2856, 1737, 1707,
1
features in the H NMR are the double doublet centered
at δ 3.74 due to H-1, the multiplet between δ 4.25 and
4.47 due to H-10a, and the double doublet centered at δ
4.67 attributed to H-1′.
1606 cm-1 1H NMR δ: 0.10 (s, 6H), 0.82 (s, 9H), 2.80 (dd, 1H,
.
J ) 14.5, 8.6 Hz), 3.38 (dd, 1H, J ) 14.5, 9.6 Hz), 3.53 (s, 1H),
3.76 (s, 3H), 4.68 (d, 1H, J ) 3.7 Hz), 4.96 (dt, 1H, J ) 8.6, 3.7
Hz), 7.00 (dt, 1H, J ) 7.7, 1.3 Hz), 7.10-7.25 (m, 2H), 7.58 (dd,
1H, J ) 7.7, 1.3 Hz). 13C NMR δ: -5.15, -4.95, 17.96, 25.50,
27.27, 52.66, 64.23, 67.14, 71.33, 114.86, 124.58, 125.21, 127.40,
134.21, 138.60, 164.81, 167.39. It was further characterized as
12a . See Table 2 for NOE results.
The reaction of 9g gave, in high yields (95%), a 12:1
ratio of the [2,3]-Wittig rearrangement14 product 15a and
11i (relative stereochemistry at C-1/C-2 is unknown) as
an inseparable mixture. The presence of 11i was based
on the observation of the characteristic H-5 doublet
centered at δ 7.53. On the other hand, the reaction of
10g resulted in a 3:1 ratio of 15b to EX-t-11j, which was
also obtained as an inseparable mixture. The presence
of the latter compound was evidenced by the presence of
the characteristic H-9a double triplet and H-2 doublet
centered at δ 4.40 and 4.47, respectively.
In summary, the metal-catalyzed reaction of indoline
diazoamides 9 and 10, where X ) OTBDMS, phthalimide
(NPhth), and OAc, gave tetrahydropyrrolo[1,2-a]indole
derivatives in good overall yields. However, O-intercep-
tion products 13a ,b were also obtained in the copper-
catalyzed reaction of 9a ,b. In diazoamides where X )
N3 and SCH2CHdCH2, the major products were derived
from the interception of the metallocarbenoid by the X
group.
1-(ter t-Bu tyldim eth ylsiloxy)-2-car bom eth oxy-6-m eth oxy-
3-oxo-1,2,9,9a -tetr a h yd r op yr r olo[1,2-a ]in d ole (EX-t-/EX-c-
11b). Pale yellow oil. Obtained as an inseparable mixture, ratio
3.7:1. Combined yield: 46.8%. IR υmax (neat): 2954, 2856, 1746,
1713, 1616, 1593 cm-1 1H NMR δ: 0.04 (s, 3H); 0.10 (s, 3H);
.
0.88 (s, 9H); [2.86, dd, J ) 14.1, 10 Hz] and 2.94 (dd, J ) 15.7,
9.6 Hz) (1H); [3.15, dd, J ) 14.1, 8.7 Hz] and 3.17 (dd, J ) 15.7,
8.8 Hz) (1H); [3.74] and 3.75 (s, 3H); [3.76] and 3.78 (s, 3H);
[3.72, d, J ) 7.9 Hz] and 3.82 (d, J ) 9.4 Hz) (1H); 4.37 (dt, J )
9.8, 8.8, 7.6 Hz) and 4.69-4.80 (m) (1H); [4.52, t, J ) 7.9 Hz]
and 4.75 (dd, J ) 9.4, 7.6 Hz) (1H), 6.57 (dd, 1H, J ) 8.3, 2.5
Hz); [7.02, d, J ) 8.3 Hz] and 7.03 (d, J ) 8.3 Hz) (1H); 7.12 (d,
J ) 2.5 Hz) and [7.15, d, J ) 2.5 Hz] (1H). 13C NMR δ: -5.10,
-4.29, 18.32, 26.07, [33.37], 33.48, [52.83], 53.15, 56.13, [61.08],
62.01, 68.26, [68.97], [76.29], 78.58, 101.81, 111.53, 125.27,
[125.58], 126.19, 140.46, 160.32, [164.52], [167.74], 169.17. Due
to the instability of this mixture, it was further characterized
as compound 12b.
1-(ter t-Bu tyldim eth ylsiloxy)-2-car bom eth oxy-6-m eth oxy-
3-oxo-1,2,9,9a -tetr a h yd r op yr r olo[1,2-a ]in d ole (EN-t-11b).
Pale yellow oil; yield 43%. IR υmax (neat): 2954, 2856, 1747,
Exp er im en ta l Section
Gen er a l. See reference 5 for general experimental proce-
dures.
1711, 1661, 1601 cm-1 1H NMR δ: 0.09 (s, 6H), 0.84 (s, 9H),
.
Meta l-Ca ta lyzed Rea ction of In d olin e Dia zoa m id es.
The appropriate indoline diazoamide 9 or 10 (1 mmol) was
dissolved in dry CH2Cl2 (or PhH) under Ar. The metal catalyst
(5 mol % Rh2(OAc)4 or Rh2(Oct)4 or 10 mol % Cu(hfacac)2) was
added, under Ar, to the solution, and the mixture was stirred
either at rt or immediately immersed in an oil-bath set at 50 °C
(90 °C when PhH was used). There was evolution of N2 gas
before the mixture started refluxing, and the color of the mixture
changed from yellow to green (sometimes brown). The mixture
was refluxed for 3-4 h and then cooled to rt, filtered, and
evaporated. The residue was flash chromatographed to give 11.
Unless otherwise indicated, the ratio of diastereomeric mixtures
is that observed for the Rh2(OAc)4-catalyzed reaction.
1-(t er t -Bu t yld im e t h ylsiloxy)-2-ca r b om e t h oxy-3-oxo-
1,2,9,9a -tetr a h yd r op yr r olo[1,2-a ]in d ole (EX-t-/EX-c-11a ).
Off-white solid. Inseparable mixture, ratio 4.6:1. Yield: 48.6%.
2.74 (dd, 1H, J ) 15.1, 9.1 Hz), 3.31 (dd, 1H, J ) 15.1, 9.9 Hz),
3.54 (s, 1H), 3.78 (s, 6H), 4.67 (d, 1H, J ) 4.2 Hz), 4.97 (dt, 1H,
J ) 9.6, 4.2 Hz), 6.58 (dd, 1H, J ) 8.2, 2.4 Hz), 7.05 (d, 1H, J )
8.2 Hz), 7.20 (d, 1H, J ) 2.4 Hz). 13C NMR δ: -5.11, -4.85,
18.07, 25.60, 26.64, 52.79, 55.54, 64.36, 68.06, 71.45, 100.89,
110.96, 125.56, 125.87, 139.60, 159.52, 164.88, 167.49. Due to
the instability of this compound, it was further characterized
as compound 12b.
1-(ter t-Bu t yld im et h ylsiloxy)-2-(p h en ylsu lfon yl)-3-oxo-
1,2,9,9a -tetr a h yd r op yr r olo[1,2-a ]in d ole (EX-t-/EX-c-/EN-t-
11c). Off-white solid. Obtained as an inseparable mixture, ratio
9:1:2.5. Combined yield: 67%. IR υmax (Nujol): 1712, 1687,
1604, 1323, 1155 cm-1
.
1H NMR δ: [0.01], [0.14], [0.20], 0.26
and 0.30 (s, 6H); [0.85], 0.95 and [0.98] (s, 9H); 2.60-3.50 (m,
2H); [3.95, s], [4.12, d, J ) 7.4 Hz] and 4.37 (d, J ) 7.9 Hz),
4.32-4.44 (m), [4.77, t, J ) 7.7 Hz], [4.87, t, J ) 8.9 Hz], [4.97-
5.10, m], 5.07 (dd, J ) 7.7, 6.0 Hz) and [5.14, d, J ) 4.5 Hz]
(3H), 7.00-7.25 (m, 3H), 7.55-7.75 (m, 4H), 7.90-8.10 (m, 2H).
See Table 2 for NOE results.
mp: 89-100 °C. IR υmax (Nujol): 1756, 1737, 1712, 1605 cm-1
.
1H NMR δ: 0.05, 0.10, and 0.12 (s, 6H); 0.90 (s, 9H); [2.94, J )
15.7, 10 Hz] and 3.03 (dd, J ) 15.7, 9.8 Hz) (1H); 3.24 (dd, J )
15.7, 8.6 Hz) and [3.26, dd, J ) 15.7, 8.6 Hz] (1H); [3.72, d, J )
8 Hz] and 3.83 (d, J ) 9.5 Hz) (1H); [3.75] and 3.79 (s, 3H); 4.37
(dt, J ) 9.3, 8.1 Hz) and [4.70-4.82, m] (1H); [4,54, t, J ) 7.8
Hz] and 4.77 (dd, J ) 10, 7.2 Hz) (1H); 6.98-7.09 (m, 1H); 7.13-
7.25 (m, 2H); 7.49-7.60 (m, 1H). 13C NMR δ: -4.78, [0.61],
17.83, 25.56, [30.00], 33.69, [52.21], 52.64, [60.49], 61.49, 66.96,
[67.87], [75.85], 78.12, 115.42, 124.80, 125.39, 127.96, 133.23,
1-(ter t-Bu tyld im eth ylsiloxy)-6-m eth oxy-2-(p h en ylsu lfo-
n yl)-3-oxo-1,2,9,9a -tetr a h yd r op yr r olo[1,2-a ]in d ole (EX-t-/
EX-c-/EN-t-11d ). White solid. Obtained as an inseparable
mixture, ratio 6.7:1:1.3. Combined yield: 84%. Mp: 185-192
°C. IR υmax (Nujol): 1698, 1614, 1588 cm-1 1H NMR δ: [0.10,
.
0.12, 0.19], 0.22 and 0.30 (s, 6H); [0.85], 0.93 and [0.95] (s, 9H);
2.65-3.40 (m, 2H); 3.73, [3.75] and [3.78] (s, 3H); [3.96, s], [4.18,
d, J ) 7.7 Hz], 4.37 (d, J ) 8.2 Hz), 4.32-4.45 (m), [4.76, t, J
)8.2 Hz], [4.86, t, J ) 8.5 Hz], [5.00-5.15, m] and 5.08 (dd, J )
7.7, 6.2 Hz) (3H); 6.55-6.64 (m, 1H); 7.00-7.18 (m, 2H); 7.50-
(14) (a) For a review: Padwa, A.; Hornbuckle, S. F. 1991, 91, 263.
(b) A review of earlier work on [2,3]-Wittig rearrangement of sulfonium
ylides see: Ando, W. Acc. Chem. Res. 1977, 10, 179.

2900 J . Org. Chem., Vol. 61, No. 8, 1996
Notes
7.71 (m, 3H); 7.93-8.07 (m, 2H). Anal. Calcd for C24H31NO5-
SSi: C, 60.87; H, 6.60; N, 2.96. Found: C, 60.50; H, 6.64; N,
2.70.
and 2.94 (dd, 1H, J ) 12.3, 4.1 Hz); 3.13 and [3.19] (dd, 1H, J )
12.3, 8.2 Hz); [3.82] and 3.87 (s, 3H); 4.27-4.73 (m, 3H, H-1);
[4.84] and 4.93 (s, 1H); 7.05-7.15 (m, 1H); 7.19-7.30 (m, 2H);
7.95-8.08 (m, 1H). Anal. Calcd for C13H13NO4: C, 63.15; H,
5.30; N, 5.66. Found: C, 63.06; H, 5.12; N, 5.43.
1-Ca r b om e t h oxy-2-m e t h yl-3-oxo-1,2,9,9a -t e t r a h yd r o-
p yr r olo[1,2-a ]in d ole (EX-t-/EXc-11e). Off-white solid. Ob-
tained as a mixture, ratio 8:1. Combined yield: 83%. Mp: 111-
3-Car bom eth oxy-6-m eth oxy-4-oxo-3,4,10,10a-tetr ah ydr o-
1H-[1,4]oxa zin o[4,3-a ]in d ole (13b). Crystalline, orange solid.
Obtained as an inseparable, 2:1 mixture of diastereomers; yield
10%. Mp: 138-143 °C. IR υmax (film): 1743, 1667, 1612, 1596,
115 °C. IR υmax (Nujol): 1738, 1694, 1604 cm-1
.
1H NMR δ:
[1.19] and 1.25 (d, 3H, J ) 7.4 Hz); [2.57-2.92, m] and 2.95 (dd,
J ) 15.4, 9.7 Hz) (2H); [3.18] and 3.21 (dd, 1H, J ) 15.4, 8.7
Hz); 3.52 (J ) 11.4 Hz) and [3.63, J ) 8.5 Hz] (d, 1H); [3.77]
and 3.81 (s, 3H); [4.12, J ) 7.2 Hz] and 4.18 (J ) 8.7 Hz) (“q”);
6.98-7.09 (m, 1H); 7.14-7.27 (m, 2H); 7.52-7.62 (m, 1H). 13C
NMR δ: [12.73], 15.63, 33.79, [41.69], 42.87, [52.10], 52.44,
[59.23], 60.09, 66.65, [67.64], 114.78, [114.94], 124.44, [124.52],
125.30, 127.64, 133.61, [134.35], 138.90, 166.15, 168.84. EIMS
(m/ z, rel intensity): 246 (M+ + 1, 27), 245 (M+, 100), 186 (M -
CO2Me, 43). Anal. Calcd for C14H15NO3: C, 68.54; H, 6.17; N,
5.71. Found: C, 68.81; H, 6.17; N, 5.47.
1532 cm-1 1H NMR δ: [2.73] and 2.80 (dd, 1H, J ) 11, 4 Hz);
.
3.00 and [3.08] (t, 1H, J ) 8.8 Hz); 3.75, 3.77 and 3.82 (s, 6H);
4.19-4.69 (m, 3H); [4.79] and 4.87 (s, 1H); 6.61 (dd, 1H, J )
8.2, 2.1 Hz); 7.06 (d, 1H, J ) 8.2 Hz); [7.61] and 7.64 (d, 1H, J
)2.1 Hz). Anal. Calcd for C14H15NO5: C, 60.64; H, 5.45; N, 5.05.
Found: C, 60.52; H, 5.46; N, 4.99.
3-Ca r b om et h oxy-1,4,10,10a -t et r a h yd r o-4-oxop yr a zin o-
[1,2-a ]in d ole (14a ). Bright yellow solid; yield 55% (CH2Cl2);
76% (PhH). Mp: 119.2-120.4 °C. IR υmax (Nujol): 1732, 1666,
1-Ca r b om e t h oxy-2-m e t h yl-3-oxo-1,2,9,9a -t e t r a h yd r o-
p yr r olo[1,2-a ]in d ole (EN-t-/EN-c-11e). Pale yellow oil. Ob-
tained as a mixture, ratio 7.3:1. Combined yield: 12%. IR υmax
1633, 1599 cm-1 1H NMR, δ: 2.97 (dd, 1H, J ) 16, 10.3), 3.37
.
(dd, 1H, J ) 16, 8.7 Hz), 3.65 (dd, 1H, J ) 17.1, 13.2 Hz), 3.96
(s, 3H), 4.34 (d sept, 1H, J ) 13.2, 10.3, 8.7, 4.2 Hz), 4.53 (dd,
1H, J ) 17.1, 4.2 Hz), 7.14 (dt, 1H, J ) 7.5, 1.4 Hz), 7.23-7.33
(m, 2H), 8.08 (br d, 1H, J ) 7.5 Hz). 13C NMR δ: 33.13, 52.98,
53.63, 55.37, 116.52, 124.88, 125.43, 128.10, 129.37, 140.37,
150.78, 157.55, 163.34. Anal. Calcd for C13H12N2O3: C, 63.91;
H, 4.95; N, 11.47. Found: C, 63.98; H, 4.74; N, 11.47.
(film): 1732, 1698, 1604 cm-1 1H NMR δ: [1.05] and 1.15 (d,
.
3H, J ) 7.3 Hz); 2.80-3.22 (m, 3H); 3.32 (s) and [4.02, d, J )
6.7 Hz] (1H); [3.78] and 3.81 (s, 3H); [4.74] and 5.04 (J ) 9.2,
5.9 Hz); 6.99-7.10 (m, 1H); 7.15-7.30 (m, 2H); 7.58-7.69 (m,
1H). 13C NMR δ: [11.32], 15.55, 28.58, [28.70], 35.38, [35.64],
52.73, [57.23], 62.47, [63.32], 64.59, [114.59], 114.90, [124.34],
124.67, 125.44, 127.72, 134.20, 138.43, 165.21, 169.27. EIMS
(m/ z, rel intensity): 246 (M+ + 1, 22), 245 (M+, 100), 186 (M -
CO2Me, 45). Anal. Calcd for C14H15NO3: C, 68.54; H, 6.17; N,
5.71. Found: C, 68.71; H, 6.17; N, 5.39.
4-Oxo-3-(p h en ylsu lfon yl)-1,4,10,10a -tetr a h yd r opyr a zin o-
[1,2-a ]in d ole (14b). This compound was the only product
formed as judged by TLC, but is highly unstable; attempted
chromatographic purification resulted in complete decomposi-
tion. The crude product on storage slowly decomposes. The data
obtained is for the unpurified material. IR υmax (Nujol): 1674,
1-Met h yl-3-oxo-2-(p h en ylsu lfon yl)-1,2,9,9a -t et r a h yd r o-
pyr r olo[1,2-a ]in dole (EX-t-/EX-c-/EN-t-11f). Crystalline solid.
Obtained as a mixture, ratio 8.9:1.1:1. Combined yield: 77%.
1633, 1599, 1583 cm-1 1H NMR δ: 2.92 (dd, 1H, J ) 15.4, 10.8
.
Mp: 228-231 °C. IR υmax (Nujol): 1694, 1604 cm-1 1H NMR
.
Hz), 3.35 (dd, 1H, J ) 15.7, 7.7 Hz), 3.74 (dd, 1H, J ) 16.9, 13.7
Hz), 4.25-4.47 (m, 1H), 4.67 (dd, 1H, J ) 16.9, 4.3 Hz), 7.00-
7.32 (m, 3H), 7.45-7.86 (m, 3H), 8.00-8.20 (m, 3H).
δ: [1.20], 1.51 and [1.70] (d, 1H, J ) 7 Hz); 2.83-3.60 (m, 3H);
[3.73, s], [4.01, d, J ) 7.7 Hz] and 4.08 (d, J ) 10.2 Hz) (1H);
4.12 (“q”, J ) 8.5 Hz), [4.85, “q”, J ) 9 Hz] and [5.12, br t, J )
7.7 Hz] (1H); 6.90-7.25 (m, 3H); 7.32-7.80 (m, 4H); 7.85-8.10
(m, 2H). Anal. Calcd for C18H17NO3S: C, 66.04; H, 5.23; N, 4.28.
Found: C, 66.24; H, 5.26; N, 4.31.
3-Allyl-3-ca r bom eth oxy-4-oxo-3,4,10,10a -tetr a h yd r o-1H-
[1,4]th ia zin o[4,3-a ]in d ole (15a ) a n d 11i. Pale yellow oil; yield
95%. Obtained as an inseparable mixture consisting of a
diastereomeric mixture of 15a and 11i. IR υmax (neat): 3077,
2952, 2847, 1741, 1650, 1599 cm-1 1H NMR: For 15a : δ: 2.64-
.
2-Ca r bom eth oxy-3-oxo-1-p h th a lim id o-1,2,9,9a -tetr a h y-
d r op yr r olo[1,2-a ]in d ole (EX-t-11g). Off-white solid; yield
55.7%. Mp: 196.3-197.6 °C. IR υmax (Nujol): 1773, 1745, 1715,
3.57 (m, 6H), 3.75 (s, 3H), 4.33-4.52 and 4.52-4.71 (m, 1H),
5.06-5.10 (m, 2H), 5.75-6.01 (m, 1H), 7.00-7.30 (m, 3H), 8.14
and 8.22 (d, 1H, J ) 8 Hz). Discernible signal for 11i: δ 7.53
(d, J ) 8 Hz). Anal. Calcd for C16H17NO3S: C, 63.35; H, 5.65;
N, 4.62. Found: C, 63.07; H, 5.65; N, 4.68.
1604 cm-1 1H NMR δ: 3.19 (d, 2H, J ) 8.9 Hz), 3.77 (s, 3H),
.
5.01 (d, 1H, J ) 11.1 Hz), 5.03 (q, 1H, J ) 8.9 Hz), 5.39 (dd, 1H,
J ) 11.1, 8.9 Hz), 7.07 (dt, 1H, J ) 7.8, 1.1 Hz), 7.19 (br d, 1H,
J ) 7.8 Hz), 7.24 (br t, 1H, J ) 7.8 Hz), 7.59 (br d, 1H, J ) 7.8
Hz), 7.72-7.43 (m, 4H). 13C NMR δ: 33.73, 52.83, 53.56, 54.86,
61.43, 115.22, 123.62, 124.94, 125.33, 127.84, 131.30, 132.89,
134.47, 138.64, 163.39, 167.44, 167.52. EIMS (m/ z, rel inten-
sity): 376 (M+, 19), 229 (M - HNPhth, 93). Anal. Calcd for
3-Allyl-4-oxo-3-(p h en ylsu lfon yl)-3,4,10,10a -t et r a h yd r o-
1H-[1,4]th ia zin o[4,3-a ]in d ole (15b) a n d EX-t-11j. Pale yel-
low solid. Obtained as an inseparable mixture. Yield: 92%. IR
υ
max (Nujol): 1710, 1651, 1600 cm-1 1H NMR: For 15b: δ: 2.55
.
(dd, J )12.8, 7.7 Hz), 2.80-3.45 (m), 3.65-4.05 (m), 4.61 (d
quint, J ) 10.2, 7.7, 2.5 Hz), 4.95 (dq, J ) 8.9, 3.8 Hz) 5.10-
5.45 (m) and 5.60-6.00 (m) (10H), 7.00-7.30 (m, 3H), 7.45-
8.12 (m, 6H). Discernible resonance for EX-t-11j: δ 4.40 (dt, J
C
21H16N2O5: C, 67.00; H, 4.29; N, 7.45. Found: C, 66.72; H,
4.09; N, 7.28.
2-Ca r bom eth oxy-3-oxo-1-p h th a lim id o-1,2,9,9a -tetr a h y-
d r op yr r olo[1,2-a ]in d ole (EX-c-/EN-t-11g). Crystalline prod-
uct; obtained as an inseparable mixture, ratio 1:11. Combined
yield: 25.3%. Mp: 188.5-190.0 °C. IR υmax (Nujol): 1770, 1727,
) 10.2, 8.2 Hz) and 4.47 (d, J ) 8.9 Hz). Anal. Calcd for C20H19
-
NO3S2: C, 62.31; H, 4.97; N, 3.63. Found: C, 62.41; H, 5.00; N,
3.55.
1714, 1607 cm-1 1H NMR δ: 2.76 (dd, 1H, J ) 16.1, 10.1 Hz);
.
2.99 (dd, 1H, J ) 16.1, 10.1Hz); [3.59] and 3.82 (s, 3H); 3.85 (s)
and [4.24, d, J ) 7.3 Hz] (1H); [5.07, J ) 9.7, 6 Hz] and 5.26 (J
) 9.7, 7.3 Hz) (dt, 1H); 5.46 (dd, J ) 7, 1.7 Hz) and [5.48, t, J )
7 Hz] (1H); 7.03 (dt, 1H, J ) 7.2 Hz); 7.15 (br d, 1H, J ) 7.2
Hz); 7.23 (br t, 1H, J ) 7.2 Hz); 7.56 (br d, 1H, J ) 7.2 Hz); 7.72
-7.86 (m, 4H). Anal. Calcd for C21H16N2O5.1/4H2O: C, 66.21;
H, 4.36; N, 7.36. Found: C, 66.39; H, 4.03; N, 7.15.
Ack n ow led gm en t. We are grateful to the Natural
Science and Engineering Research Council, Canada, and
the University of Regina for financial support. We also
thank Professor P. Smith, University of Saskatchewan,
for obtaining mass spectra, and Mr. K. Marat and T.
Wolowiec, Regional High Field NMR Center, Winnipeg,
Manitoba, for conducting the NOE experiments.
1-Acetoxy-2-(p h en ylsu lfon yl)-3-oxo-1,2,9,9a -tetr a h yd r o-
p yr r olo[1,2-a ]in d ole (EX-t-/EX-c-/EN-t-11h ). Unstable, pale
yellow solid; yield 72%. 1H NMR δ (CDCl3/MeCN-d3): [2.02],
[2.06] and 2.14 (s, 3H); 2.90-3.70 (m, 2H); [4.30, s], [4.50, d, J
) 6.4 Hz], 4.75 (dt, J ) 10.2, 3.8 Hz), 4.85 (d, J ) 5.4 Hz), [5.14,
dt, J ) 10.2, 5.1 Hz], [5.57, t, J ) 8.7 Hz], [5.68, dd, J ) 8.7, 7.2
Hz], [5.90, d, J ) 5.1 Hz] and 6.18 (t, J ) 5.1 Hz) (3H); 7.00-
7.30 (m, 3H); 7.50-7.80 (m, 4H); 7.90-8.20 (m, 2H). This
mixture was unstable and was characterized as compound 12c.
3-Ca r bom eth oxy-4-oxo-3,4,10,10a -tetr a h yd r o-1H-[1,4]ox-
a zin o[4,3-a ]in d ole (13a ). Crystalline, colorless solid. Ob-
tained as an inseparable, 1:1 mixture of diastereomers; yield
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic and
1
analytical data for diazoamides 9a -g and 10a -g, 12a -c, H
NMR spectra of 14b, table listing multiplicity and δ for H-1
and H-2 in 11a -d , and a chart illustrating the synthesis of
8a -g (9 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
39%. IR υmax (film): 1749, 1666, 1601 cm-1
.
1H NMR δ: [2.89]
J O951320H