Tetrahydroquinolizinium ylides: Prepation and 1,3-dipolar cycloaddition

Article abstract of DOI:10.1021/jo001162g

By the Cu(II)-catalyzed reaction of 2-(4-diazo-3-oxoalkyl)pyridines (2), 4-alkoxycarbonyl (or 4-acyl)-3-oxo-l,2,3,4-tetrahydroquinolizinium ylides (3) were obtained in high yields. From the cycloaddition reaction of 3 with acetylenic esters (propynoates or acetylenedicarboxylates) the labile [2 + 3] cycloadducts, 3-oxo-3H-2a,4,5,8a-tetrahydropyrrolo[2,1,5-de]quinolizine-2a-carboxylates (8 or 12), were identified, which further reacted with DMAD (dimethyl acetylenedicarboxylate) to afford azocine derivatives (15 or 16) and produced pyrrolodihydroquinolizines (9 or 20) by dealkoxycarbonylation.

Full text of DOI:10.1021/jo001162g

1638
J . Org. Chem. 2001, 66, 1638-1646
Tetr a h yd r oqu in olizin iu m Ylid es: P r ep a r a tion a n d 1,3-Dip ola r
Cycloa d d ition †
Elena I. Kostik,‡ Atsushi Abiko,‡ and Akira Oku*,§
Venture Laboratory and Department of Chemistry and Materials Technology, Kyoto Institute of
Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585 J apan
oku@ipc.kit.ac.jp
Received J uly 31, 2000
By the Cu(II)-catalyzed reaction of 2-(4-diazo-3-oxoalkyl)pyridines (2), 4-alkoxycarbonyl (or 4-acyl)-
3-oxo-1,2,3,4-tetrahydroquinolizinium ylides (3) were obtained in high yields. From the cycloaddition
reaction of 3 with acetylenic esters (propynoates or acetylenedicarboxylates) the labile [2 + 3]
cycloadducts, 3-oxo-3H-2a,4,5,8a-tetrahydropyrrolo[2,1,5-de]quinolizine-2a-carboxylates (8 or 12),
were identified, which further reacted with DMAD (dimethyl acetylenedicarboxylate) to afford
azocine derivatives (15 or 16) and produced pyrrolodihydroquinolizines (9 or 20) by dealkoxycar-
bonylation.
Sch em e 1
In tr od u ction
Iminium ylides have attracted much attention because
of the possible application to the synthesis of a wide
variety of novel heterocyclic systems.1 The 1,3-dipolar
cycloaddition reaction of iminium ylides leading to pyr-
rolidine derivatives has been explored intensively. Re-
cently many efforts are driven to the synthesis of the aza-
acenaphthylene ring system ([3,3,2]-cyclazine) by dipolar
cycloaddition, especially after the discovery of a new
family of coccinellid alkaloids having an aza-acenaph-
thylene moiety.2 These tricyclic systems could be acces-
sible from the bicyclic iminium ylides, possessing a
nitrogen atom at the ring juncture position, via a 1,3-
dipolar cycloaddition reaction (Scheme 1).
The prototype of these bicyclic iminium ylides, 3-oxo-
quinolizinium betaine, was isolated from the correspond-
ing salt in 19653 and was used later as a dipole in the
synthesis of [2.2.3]cyclazines.4 Recently, the synthesis
and decarboxylation reaction of stable substituted dihy-
dro-1-oxoquinolizinium ylides were reported.5 However,
only little is known about the chemical and physical
properties of iminium ylides having a partially saturated
quinolizinium structure, presumably because of limited
availability of the precursor, 3-oxotetrahydroquinoliz-
inium salts.
pyridinium ylides, derived from isoquinolines or pyridines
and carbenes with electron-withdrawing substituents,
have been synthesized and extensively studied. In the
last 10 years, such an approach was successfully applied
to the intramolecular reaction of carbenes and nitrogen
atoms to generate ammonium and iminium cyclic ylides.7,8
Padwa et al. demonstrated the ability of a variety of
R-diazocarbonyl compounds possessing imine moiety to
produce bicyclic iminium ylides by the action of rhodium-
(II) catalysts.8a So far, such iminium ylides have been
generated in the presence of dipolarophiles and only
characterized as 1,3-dipolar cycloadducts.
In this article, we would like to report syntheses of a
series of tetrahydroquinolizinium ylides as stable ylides
by the Cu(II)-catalyzed cyclization of 2-(4-diazo-3-oxoalkyl)-
pyridines. Investigation of the physical and chemical
properties of these quinolizinium ylides, including a
detailed study on the 1,3-dipolar cycloaddition reaction
of these ylides, is described.
Among the synthetic approaches toward iminium
ylides, the reaction of carbenes (or carbenoids) with
imines seems to be particularly interesting from its
diversity and generality.6 Stable isoquinolinium and
Resu lts a n d Discu ssion
Syn th esis of Tetr a h yd r oqu in olizin iu m Ylid e. The
diazocarbonyl-substituted pyridines, requisite for the
present study, were prepared by the alkylation of the
dianion of 1,3-dicarbonyl compounds with 2-(R-chloro-
alkyl)pyridines, followed by the reaction with arenesulfo-
nyl azides (Scheme 2). Using this simple protocol a
variety of diazo pyridines 2 were prepared conveniently.
† Part 1 of “The Studies on Tetrahydroquinolizinium Ylides”.
‡ Venture Laboratory.
§ Department of Chemistry and Materials Technology.
(1) (a) Tsuge, O.; Kanemasa, S. Adv. Heterocycl. Chem. 1989, 45,
231-349. (b) Claus, P. K. In Houben-Weyl, Methoden der Organischen
Chemie; Klamann, D., Hagemann, H., Eds.; Thieme: Stuttgart, 1990;
E14b, 2, pp 1-221. (c) Beall, L. S.; Padwa, A. In Advances in Nitrogen
Heterocycles; Moody, C. J ., Ed.; J ai Press Inc.: Greenwich, CT, 1998;
Vol. 3, pp 117-158.
(6) (a) Surpateanu, G.; Catteau, J . P.; Karafiloglou, P.; Lablashe-
Combier, A. Tetrahedron 1976, 32, 2647. (b) Padwa, A.; Hornbuckle,
S. Chem. Rev. 1991, 91, 263.
(7) Naidu, B. N.; West, F. G. Tetrahedron 1997, 53, 16565.
(8) (a) Padwa, A.; Austin, D. J .; Precedo, L.; Zhi, L. J . Org. Chem.
1993, 58, 1144. (b) Padwa, A.; Dean, D. C.; Osterhout, M. H.; Precedo,
L.; Semones, M. A. J . Org. Chem. 1994, 59, 5347.
(2) King, A. G.; Meinwald, J . Chem. Rev. 1996, 96, 1105.
(3) Duke, P. A.; Fozard, A.; J ones, G. J . Org. Chem. 1965, 30, 526.
(4) Farquhar, D.; Gough, T. T.; Leaver, D.; Miller, J . F.; Dick, J .
W.; J essep, M. A. J . Chem. Soc., Perkin Trans. 1 1984, 2553.
(5) Matsuda, Y.; Katou, K.; Nishiyori, T.; Uemura, T.; Urakami, M.
Heterocycles 1997, 45, 2197.
10.1021/jo001162g CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/08/2001

Tetrahydroquinolizinium Ylides
J . Org. Chem., Vol. 66, No. 5, 2001 1639
Sch em e 2
In the survey of the reaction conditions of the transition-
metal-catalyzed decomposition of 2, copper(II) bis(tri-
fluoroacetylacetonate) was found to be superior to rhod-
ium(II) acetate. Thus, stirring a mixture of 2 and the
copper catalyst (2.5 mol %) in dry benzene at 80 °C for
25 min afforded 3-oxo-1,2,3,4-tetrahydroquinolizinium-
4-ides (3) in high yields.
obtained in 70% yield by the treatment of 3b with 40%
HClO4.9 Bromide 7 was identical in all respects to the
reported specimen.3,10 Thus, the structures of 4a and 3a
were unambiguously established.
In the 1H NMR spectra of compounds 3a -j, four
aromatic protons (H6-9, see Scheme 3) appeared at
lower fields in comparison with those of pyridine precur-
sors 2, the H6 proton being observed around δ 9.1, which
were similar to those5 reported for 1,4-dihydroquinoliz-
inium ylides. 13C NMR spectra of 4-alkoxycarbonyl-3-oxo-
1,2,3,4-tetrahydroquinolizinium ylides (3a -c, 3e-h , 3j)
showed the signal of C-4 ylidic carbon around δ 106-
109, while those of 4-acyl-3-oxo-l,2,3,4- tetrahydroquino-
lizinium ylides (3d and 3i) and quinolizinium-3-olates (4a
and 4b) appeared around δ 118-123. The IR spectra of
the ylides showed carbonyl absorptions at lower frequen-
cies: a 3-carbonyl absorption maximum at 1677 cm-1 for
tert-butyl ester 3b , at 1656-30 cm-1 for other esters
3a , c and 3e-h , and at 1620 cm-1 for acyl ylide 3d . The
differences in both the 13C NMR chemical shift of C-4 and
the 3-carbonyl IR absorptions suggest that alkoxycarbo-
nyl-substituted ylides (3a -c, 3e-h , 3j) mainly exist in
a keto form, i.e., canonical structure A (Scheme 4),
whereas acyl-substituted (3d , 3i) and dehydrogenated
ylides (4a , 4b) do in enolate forms, i.e., canonical struc-
tures B and C (Scheme 4).
Sch em e 3
Sch em e 4
1,3-Dip ola r Cycloa d d ition of Tetr a h yd r oqu in o-
lizin iu m Ylid es. Dipolar reactivity of quinolizinium
ylides has been reported.4,8a Quinolizinium-3-olate re-
acted with acetylenic dipolarophiles to afford cyclazines
via 1,3-dipolar cycloaddition followed by oxidation. The
similar transformation, accompanied by the deacylative
cleavage of a carbon-carbon bond, was also reported for
the reaction of acetyl-substituted ylide with DMAD.8a The
1,3-dipolar cycloaddition of isoquinolinium dimethoxy-
carbonylmethylides with DMAD was explored exten-
sively, and sometimes relatively stable adducts were
isolated without oxidation,6a whereas it was also reported
that the 1,5-dipolar cycloaddition of isoquinolinium di-
ethoxycarbonylmethylides with DMAD produced
oxazepines.8a
Most of 3 could be isolated as stable crystals and
characterized spectroscopically as well as by elemental
analyses. Ylides 3a and 3b were readily converted to
quinolizinium-3-olates 4a and 4b in 70% and 89% yields,
respectively, by the oxidation with DDQ followed by
neutralization of the resulting DDQH salt (Scheme 3 (1)).
Treatment of 3a , e, f and 4a in 48% aqueous HBr at 110
°C for 2 h afforded the corresponding decarboxylated salts
6a , e, f (Scheme 3 (2)) and 7 (Scheme 3 (3)), respectively,
in high yields. Similarly, the perchlorate salt 6a ′ was
(9) Kro¨hnke, F. Chem. Ber. 1939, 72, 83.
(10) Schrtifstitter, E. Angew. Chem. 1962, 74, 874.

1640 J . Org. Chem., Vol. 66, No. 5, 2001
Kostik et al.
Sch em e 5
Sch em e 8
Sch em e 6
Sch em e 9
Sch em e 7
d6 at 75 °C for 10 min, formation of the primary
cycloadduct 8 was confirmed by NMR. When the reaction
mixture was heated longer (75 °C, 45 min) in DMSO, 9a
(30%) and 10 (14%) were isolated. It should be noted that
t-BuOH (about 30%) was also detected in the NMR
spectra of the reaction mixture (Scheme 5).
Reactions of acyl-substituted ylides 3d ,i with methyl
propynoate in DMSO at 75 °C afforded cyclazine 9a in
68% and 40% yield, respectively (Scheme 6). The forma-
tion of 1 equiv (vs 9a ) of acid (acetic or benzoic acid,
respectively) was confirmed by the NMR analysis of the
reaction mixture.
The same type of primary cycloadduct 12 could be
detected in the reaction of quinolizinium ylide 4b with
methyl propynoate in DMSO at 75 °C, and 12 was
converted to cyclazine 134 in 60% yield within 40 min of
stirring (Scheme 7).
It should be mentioned that the reactions of ylides 3d ,
i and 4a , b with acetylenic esters proceeded significantly
slower than that of 3b , presumably as a result of the
enolate structure of the former (vide supra). However,
the reactions were accelerated in polar solvents and by
using an excess amount of dipolarophile.
In this regard we were interested in examining the
reaction behavior of tetrahydroquinolizinium ylides (3)
in dipolar cycloadditions. The 1,3-dipolar cycloadducts of
ylides 3 should have higher stability toward oxidative
transformation to indolizines, because the oxidative
aromatization had to proceed through C-C bond cleavage
and elimination of alkoxycarbonyl group. Thus, we
expected it would be possible to investigate the reaction
course in detail by isolating the primary cycloadducts.
Tetrahydroquinolizinium ylides 3 were inert toward
ethylenic dipolarophiles but reacted readily with acety-
lenic esters.11 For example, ylide 3b in acetone-d6 at 55
°C reacted with methyl propynoate within 15 min to
furnish 1,3-dipolar cycloadduct 8 as a sole product.
Adduct 8 was not stable enough to be isolated, and the
structure was assigned on the basis of NMR spectra of
the reaction mixture. When the reaction mixture was
heated longer in acetone or treated with silica gel, initial
monoadduct 8 was transformed into two isolable prod-
ucts, i.e., aromatic cyclazine 9a and indolizinepropionic
acid 10, with concomitant considerable decomposition.
The reaction proceeded more smoothly in DMSO.12 Thus,
in the reaction of 3b with methyl propynoate in DMSO-
Reaction of ylide 3b with dimethyl acetylenedicarboxy-
late (DMAD) proceeded differently from that with pro-
pynoates. The cycloaddition reaction in acetone at 55 °C
(11) Ylides 3a and 3b showed similar reactivities in the cycloaddition
reactions.
(12) This may be attributed to the nucleophilic attack of DMSO to
facilitate the oxidative decarboxylation (or decarbonylation).
(13) The structure of the pentamethyl ester analogue of 15 was
determined by X-ray analysis. We thank Prof. Toshiro Harada, Kyoto
Institute of Technology, for the analysis.

Tetrahydroquinolizinium Ylides
J . Org. Chem., Vol. 66, No. 5, 2001 1641
Sch em e 10
20 (15%). Apparently 19 was formed from the Diels-
Alder addition of a second molecule of DMAD to the diene
moiety of the primary monoadduct, followed by aroma-
tization through a retro-Diels-Alder reaction. Product
19 was isolated as an oil, which upon treatment with
KOH/MeOH solution afforded two stable products, 21
and 22, quantitatively (Scheme 11). It should be noted
that the reaction proceeded rather slowly compared to
the reaction of 3b with DMAD. This may be because the
introduction of additional unsaturation in 4b caused
reduction in the reactivity of primary monoadduct 23 as
an enamine to 18 more significantly than as a diene to
19.
Tetrahydroquinolizinium salts 6a and 6e with methyl
propynoate in acetonitrile at 60 °C rapidly formed cycla-
zines 9a and 9e, respectively, in the presence of (i-
Pr)2NEt. Mechanism of the cycloaddition may be stepwise
rather than concerted, because when the reaction of 6a
was carried out in chloroform, acrylate betaine 24a was
isolated as a byproduct in 15-20% yield together with
40% of 9a . Betaine 24a was also formed exclusively from
6a in methanol in the presence of potassium carbonate.
The TLC analysis of the reaction in acetonitrile showed
that 24a was detected in the beginning, but it was
gradually converted to 9 (Scheme 12).
In conclusion, a variety of tetrahydroquinolizinium
ylides were synthesized in high yields by the Cu-
catalyzed reaction of diazo pyridines. The labile primary
cycloadducts 8 and 12 formed between tetrahydroquino-
lizinium (or quinolizinium) ylides and methyl propynoate
were identified spectroscopically. From the primary ad-
ducts 8, two more types of transformation were charac-
terized: (1) Michael type addition of the enamine moiety
of 8 to an acetylenic ester leading to azocine derivatives
and (2) facile decarbonylative oxidation leading to oxodi-
hydropyrroloquinolizines ([2,3,3]-cyclazines) by the aid
of a nucleophilic species such as DMSO.
did not stop at the stage of monocycloadduct (14) but
furnished the bisadduct, azocine 15, in 50% yield.13 It
should be noted that the bisadducts of this type were not
detected in the reaction with excess methyl propynoate.
Furthermore, the addition of an additional 1 equiv of
methyl propynoate to the reaction mixture containing
monoadduct 8 and heating at 55 °C caused complete
decomposition of 8, more rapidly than the control reaction
of 8 without additional dipolarophile under the same
conditions. In contrast, the reaction of monoadduct 8 with
DMAD gave the bisadduct, azocine 16, in 75% yield
(Schemes 8 and 9).
The striking difference between the reactions with
DMAD and propynoate can be explained by the difference
in the stability and reactivity of the initial Michael type
addition intermediate 17 (Scheme 10).
The reaction of quinolizinium ylide 4b with DMAD in
chloroform afforded azocine 18 (21%) as well as another
type of bisadduct 19 (19%) along with aromatic cyclazine
Sch em e 11

1642 J . Org. Chem., Vol. 66, No. 5, 2001
Kostik et al.
(1H, d, J ) 5.0 Hz; H6′); 13C NMR δ 31.4, 41.5, 49.2, 52.3,
121.3, 123.2, 136.3, 149.1, 159.8, 167.6, 202.0.
Sch em e 12
Meth yl 2-Diazo-3-oxo-5-(2-pyr idyl)pen tan oate (2a). Yield
90%; thick pale yellow oil; IR (KBr) 2139, 1724, 1656, 1593
cm-1; 1H NMR δ 3.14 (2H, t, J ) 7.2 Hz; H4), 3.50 (2H, t, J )
7.2 Hz; H5), 3.83 (3H, s; MeO), 7.10 (1H, t, J ) 7.8 Hz; H5′),
7.22 (1H, d, J ) 7.8 Hz; H3′), 7.58 (1H, dt, J ) 1.7, 7.8 and 7.8
Hz; H4′), 8.51 (1H, m; H6′); 13C NMR δ 31.9, 39.4, 52.1, 75.0,
121.1, 123.0, 136.2, 149.1, 160.2, 161.7. 191.6.
4-Meth oxyca r bon yl-3-oxo-1,2,3,4-tetr a h yd r oqu in oliz-
in iu m -4-id e (3a ). Yield 86%; yellow crystal; mp 151-152 °C;
1
IR (KBr) 1639, 1614, 1589 cm-1; H NMR δ 2.53 (2H, t, J )
6.8 Hz; H2), 3.13 (2H, t, J ) 6.8 Hz; H1), 3.87 (3H, s; MeO),
7.50 (1H, t, J ) 7 Hz; H7), 7.51 (1H, d, J ) 8.2 Hz; H9), 7.73
(1H, dd, J ) 7 and 8.2 Hz; H8), 9.12 (1H, d, J ) 6.8 Hz; H6);
13C NMR δ 28.4 (C1), 33.7 (C2), 51.0 (OMe), 108.0 (C4), 123.0
(C7), 124.5 (C9), 136.1 (C8), 142.0 (C6), 150.1 (C9a), 165.0
(CO2), 181.9 (C3). Anal. Calcd for C11H11NO3: C, 64.38; H, 5.40;
N, 6.82. Found: C, 64.08; H, 5.39; N, 6.81. HRMS calcd for
C
11H11NO3 205.0739, found 205.0739. UV λ (log ꢀ) nm: 245
Exp er im en ta l Section
(4.49), 274.5 (3.29), 386 (3.32).
ter t-Bu tyl 3-Oxo-5-(2-p yr id yl)p en ta n oa te (1b). Yield
72%; yellow oil; H NMR δ 1.45 (9H, s), 3.04 (1H, dd, J ) 6.9
Melting points are uncorrected. Mass spectra were deter-
1
1
mined at an ionizing voltage of 70 eV. H (500 MHz) and 13C
and 2.1 Hz), 3.05 (1H, brd, J ) 6.9 Hz), 3.09 (1H, brd, J ) 6.9
Hz), 3.11 (1H, dd, J ) 6.9 and 2.1 Hz), 3.40 (2H, s), 7.10 (1H,
dd, J ) 7.6 and 5.1 Hz), 7.19 (1H, d, J ) 7.6 Hz), 7.58 (1H, t,
J ) 7.6 Hz), 8.49 (1H, d, J ) 5.1 Hz); 13C NMR δ 27.9, 31.4,
41.6, 50.7, 81.8, 121.2, 123.2, 136.3, 149.1, 160.0, 166.4, 202.6.
ter t-Bu tyl 2-Dia zo-3-oxo-5-(2-p yr id yl)p en ta n oa te (2b).
(126 MHz) NMR spectra were measured in CDCl3, unless
otherwise noted, and assignment was done on the basis of CH-
COSY, HMBC, and NOE procedures. All reactions were
performed in oven-dried glassware under nitrogen atmosphere.
Solutions were evaporated under reduced pressure with a
rotary evaporator, and the residue was chromatographed on
a silica gel column using ethyl acetate-hexane mixture as an
eluent unless specified otherwise.
Gen er a l P r oced u r e for th e P r ep a r a tion of 4-Alk oxy-
ca r bon yl (or 4-Acyl)-3-oxo-1,2,3,4-t et r a h yd r oqu in oliz-
in iu m -4-id es. To a solution of the dianion R1C(O-Li+)dCHC-
(O-Na+)dCHR2 in THF (100 mL), prepared from the parent
1,3-dicarbonyl compound R1C(O)CH2C(O)CH2R2 (40 mmol)
according to the described procedure,14 2-(R-chloroalkyl)pyri-
dine in 8 mL of THF was added at 0 °C. The 2-(R-chloroalkyl)-
pyridine, in turn, was prepared from its hydrochloride (45
mmol) by the treatment with saturated sodium bicarbonate
solution, extraction with methylene chloride, drying over
magnesium sulfate, and evaporation of the solvent under
reduced pressure. The reaction mixture was allowed to warm
slowly to room temperature, stirred for 30 min, and quenched
with 6.8 mL of hydrochloric acid in 20 mL of water (pH 7-8).
The aqueous layer was further extracted with 2 × 40 mL of
ether. The extracts were combined, washed with water and
brine, dried over anhydrous magnesium sulfate, and concen-
trated under reduced pressure. The resulting residue was
subjected to flash column chromatography to give 1.
1
Yield 95%; thick yellow oil; H NMR δ 1.52 (9H, s), 3.13 (2H,
t, J ) 7.3 Hz), 3.32 (2H, t, J ) 7.3 Hz), 7.09 (1H, dd, J ) 7.3
and 5.0 Hz), 7.21 (1H, d, J ) 7.3 Hz), 7.58 (lH, t, J ) 7.3 Hz),
8.51 (1H, d, J ) 5.0 Hz); 13C NMR δ 28.2, 32.0, 39.5, 76.6,
83.1, 121.1, 123.0, 131.8, 136.3, 149.2, 160.5, 192.2.
4-ter t-Bu toxyca r bon yl-3-oxo-1,2,3,4-tetr a h yd r oqu in o-
lizin iu m -4-id e (3b). The cooled reaction mixture was filtered
through a glass filter to remove the tiny powder of catalyst,
and approximately half of the solvent was removed under
reduced pressure to afford 3b (82%) as yellow crystals: mp
134-135 °C; IR (KBr) 1678, 1645, 1541 cm-1; 1H NMR δ 1.59
(9H, s; C(Me)3), 2.47 (2H, t, J ) 6.9 Hz; H2); 3.11 (2H, t, J )
6.9 Hz; H1), 7.46 (1H, t, J ) 7.1 Hz; H7), 7.48 (1H, d, J ) 7.6
Hz; H9), 7.68 (1H, dd, J ) 7.1 and 7.6 Hz; H8), 9.0 (1H, d, J
) 7.1 Hz; H6); 13C NMR δ 28.5 (C1), 28.7 (Me), 33.8 (C2), 79.6
(C(Me)3), 109.4 (C4), 122.8 (C7), 124.5 (C9), 135.3 (C8), 145.7
(C6), 149.8 (C9a), 164.1 (CO2), 181.1 (C3). Anal. Calcd for
C
14H17NO3: C, 68.00; H, 6.93; N, 5.66. Found: C, 67.89; H,
6.88; N, 5.43.
Ben zyl 3-Oxo-5-(2-p yr id yl)p en ta n oa te (1c). Yield 50%;
1
yellow oil; H NMR δ 3.03 (1H, dt, J ) 2.0, 6.3 and 6.3 Hz;
To a mixture containing 10 mmol of 1,3-dicarbonyl com-
pound 1 and 11 mmol of mesitylenesulfonyl azide in 2.9 mL
of acetonitrile was added 3.5 mL of triethylamine. The reaction
was stirred for 30 min and concentrated under reduced
pressure. The resulting residue was refluxed with 45 mL of
hexane for 15 min and filtered still warm. The procedure was
repeated two more times. The cooled combined hexane solution
was once more filtered, and after removal of the solvent and
flash column chromatography of the resulting residue, 2 were
obtained.
A solution containing 7.9 mmol of 2 and 56 mg (2.5 mol %)
of copper(II) trifluoroacetylacetonate in 81 mL of dry benzene
was stirred at 80 °C for 20-25 min until no more nitrogen
was evolved. The reaction mixture with precipitated ylide was
cooled at 10 °C. Filtration and washing with dry ether gave
ylides 3 (in some cases partial removal of benzene and addition
of pentane was necessary for precipitation to occur).
H4), 3.04 (1H, d, J ) 6.3 Hz; H4), 3.08 (1H, d, J ) 6.3 Hz;
H5), 3.09 (1H, dt, J ) 2.0, 6.3 and 6.3 Hz; H5), 3.56 (2H, s;
H2), 5.16 (2H, s; CH2Ph), 7.09 (1H, dd, J ) 4.7 and 7.6 Hz;
H5′), 7.16 (1H, d, J ) 7.6 Hz; H3′), 7.30∼7.40 (5H, m; Ph),
7.56 (1H, t, J ) 7.6 Hz; H4′), 8.47 (1H, d, J ) 4.7 Hz; H6′); 13
C
NMR δ 31.4, 41.5, 49.3, 67.0, 121.3, 123.1, 128.3, 128.4, 128.5,
135.3, 136.3, 149.1, 159.7, 167.0, 201.9.
4-Ben zyloxyca r b on yl-3-oxo-1,2,3,4-t et r a h yd r oq u in o-
lizin iu m -4-id e (3c). Yield 75% (2 steps); yellow crystal; mp
135-136 °C; IR (KBr) 1641, 1618, 1589 cm-1; 1H NMR δ 2.50
(2H, brt, J ) 6.7 Hz; H2), 3.10 (2H, brt, J ) 6.7 Hz; H1), 5.36
(2H, s; CH2Ph), 7.24 (1H, t, J ) 7.4 Hz; Ph-p-H), 7.34 (2H, t,
J ) 7.4 Hz; Ph-m-H), 7.45 (1H, t, J ) 7.1 Hz; H7), 7.47 (1H,
d, J ) 7.1 Hz; H9), 7.54 (2H, d, J ) 7.4 Hz; Ph-o-H), 7.68 (1H,
t, J ) 7.1 Hz; H8), 9.07 (1H, d, J ) 7.1 Hz; H6); 13C NMR δ
28.4 (C1), 33.8 (C2), 65.0 (CH2Ph), 108.0 (C4), 123.0 (C7), 124.6
(C9), 127.1 (Ph-p-C), 127.2 (Ph-o-C), 128.2 (Ph-m-C), 136.0 (Ph-
ipso-C), 137.5 (C8), 141.8 (C6), 150.0 (C9a), 164.3 (CO2), 181.9
(C3). Anal. Calcd for C17H15NO3: C, 72.58; H, 5.38; N, 4.98.
Found: C, 72.29; H, 5.40; N, 4.86.
Meth yl 3-Oxo-5-(2-p yr id yl)p en ta n oa te (1a ). Yield 88%;
pale yellow oil; IR (KBr) 1747, 1716, 1592 cm-1 1H NMR δ
;
3.05 (2H, m; H4), 3.11 (2H, m; H5), 3.57 (2H, s; H2), 3.72 (3H,
s; MeO), 7.11 (1H, dd, J ) 7.3 and 5.0 Hz; H5′), 7.19 (1H, d, J
) 7.6 Hz; H3′), 7.58 (1H, dd, J ) 7.6 and 7.3 Hz; H4′), 8.48
3-Dia zo-6-(2-p yr id yl)h exa n e-2,4-d ion e (2d ). Yield 60%
(2 steps); yellow oil; 1H NMR δ 2.44 (3H, s), 3.17 (1H, m), 3.18
(1H, d, J ) 5.1 Hz), 3.20 (1H, d, J ) 5.1 Hz), 3.21 (1H, m),
7.12 (1H, dd, J ) 7.6 and 5.1 Hz), 7.21 (1H, d, J ) 7.6 Hz),
(14) Huckin, S. N.; Weiler, L. J . Am. Chem. Soc. 1974, 96, 1082.

Tetrahydroquinolizinium Ylides
J . Org. Chem., Vol. 66, No. 5, 2001 1643
7.59 (1H, t, J ) 7.6 Hz), 8.50 (1H, d, J ) 5.1 Hz); 13C NMR δ
28.7, 31.7, 39.0, 84.4, 121.3, 123.1, 136.3, 149.2, 159.6, 189.8.
4-Acet yl-3-oxo-1,2,3,4-t et r a h yd r oq u in olizin iu m -4-id e
(3d ). The cooled reaction mixture was filtered through a glass
filter to remove the tiny powder of catalyst, and pentane was
added to the solution until precipitation started to afford yellow
crystals: yield 82%; mp 150-152 °C; IR (KBr) 1620, 1585, 1537
d, J ) 6.2 Hz), 3.15 (2H, m), 3.55 (1H, A of ABq, J AB ) 15.7
Hz), 3.60 (1H, B of ABq, J AB ) 15.7 Hz), 3.75 (3H, s), 7.13
(1H, d, J ) 7.6 Hz), 7.14 (1H, dd, J ) 7.6 and 4.6 Hz), 7.61
(1H, t, 7.6 Hz), 8.56 (1H, d, J ) 4.6 Hz); 13C NMR δ 15.4, 19.1,
44.2, 49.1, 51.5, 52.3, 121.6, 122.9, 136.5, 149.4, 163.3, 167.6,
206.4.
Meth yl 2-Dia zo-4-m eth yl-3-oxo-5-(2-p yr id yl)h exa n oa te
(2g). Yield 79%; colorless needle (hexane); mp 75-77 °C; IR
cm-1 1H NMR δ 2.52 (2H, t, J ) 6.8 Hz; H2), 2.60 (3H, s;
;
1
COMe), 3.12 (2H, t, J ) 6.8 Hz; H1), 7.51 (1H, dd, J ) 6.4 and
7.7 Hz; H7), 7.53 (1H, d, J ) 7.7 Hz; H9), 7.80 (1H, t, J ) 7.7
Hz; H8), 9.24 (1H, d, J ) 6.4 Hz; H6); 13C NMR δ 28.2 (C1),
29.6 (COMe), 33.7 (C2), 119.6 (C4), 122.7 (C7), 124.5 (C9),
137.1 (C8), 143.2 (C6), 149.9 (C9a), 183.0 (COMe), 184.6 (C3).
Anal. Calcd for C11H11NO2: C, 69.87; H, 5.86; N, 7.40. Found:
C, 69.71; H, 5.92; N, 7.26.
Met h yl 4-Met h yl-3-oxo-5-(2-p yr id yl)p en t a n oa t e (1e).
Yield 80%; yellow oil; 1H NMR δ 1.16 (3H, d, J ) 6.9 Hz), 2.81
(1H, dd, J ) 14.3 and 6.2 Hz), 3.23 (1H, dd, J ) 14.3 and 7.7
Hz), 3.30 (1H, m), 3.54 (1H, A of ABq, J AB ) 15.6 Hz), 3.59
(1H, B of ABq, J AB ) 15.6 Hz), 3.70 (3H, s), 7.11 (1H, dd, J )
7.6 and 4.7 Hz), 7.13 (1H, d, J ) 7.6 Hz), 7.58 (1H, t, J ) 7.6
Hz), 8.50 (1H, d, J ) 4.7 Hz); 13C NMR δ 16.3, 40.7, 45.8, 48.1,
52.2, 121.4, 123.6, 136.3, 149.2, 158.9, 167.7, 205.9.
Meth yl 2-Diazo-4-m eth yl-3-oxo-5-(2-pyr idyl)pen tan oate
(2e). Yield 95%; yellow oil; 1H NMR δ 1.16 (3H, d, J ) 6.9
Hz), 2.81 (1H, dd, J ) 13.9, and 7.0 Hz), 3.28 (1H, dd, J )
13.9 and 7.4 Hz), 3.83 (3H, s), 4.08 (1H, m), 7.09 (1H, dd, J )
4.7 and 7.7 Hz), 7.20 (1H, d, J ) 7.7 Hz), 7.57 (1H, t, J ) 7.7
Hz), 8.50 (1H, d, J ) 4.7 Hz); 13C NMR δ 16.8, 40.9, 42.1, 52.2,
75.6, 121.2, 123.6, 136.2, 149.2, 159.5, 161.5, 195.7.
(KBr) 2144, 1720, 1647 cm-1; H NMR δ 0.88 (3H, d, J ) 6.9
Hz), 1.27 (3H, d, J ) 6.8 Hz), 3.25 (1H, dq, J ) 9.7 and 6.8
Hz), 3.86 (3H, s), 4.05 (1H, dq, J ) 9.7 and 6.9 Hz), 7.12 (1H,
dd, J ) 7.3 and 4.5 Hz), 7.16 (1H, d, J ) 7.7 Hz), 7.60 (1H, dd,
J ) 7.3 and 7.7 Hz), 8.57 (1H, d, J ) 4.5 Hz); 13C NMR δ 16.0,
19.2, 44.7, 46.8, 52.2, 76.3, 121.4, 122.7, 136.2, 149.4, 161.5,
163.7, 196.2. Anal. Calcd for C13H15N3O3: C, 59.76; H, 5.79;
N, 16.08. Found: C, 59.58; H, 5.70; N, 15.79.
4-Meth oxyca r bon yl-1,2-d im eth yl-3-oxo-1,2,3,4-tetr a h y-
d r oqu in olizin iu m -4-id e (3g). Yield 80% from 2g as a
mixture with 20% of the stereoisomer 3g′; yellow solid; IR
1
(KBr) 1630, 1610, 1585 cm-1; H NMR δ 0.90 (3H, br; 2-Me),
1.37 (3H, br; 1-Me), 2.53 (1H, br; H2), 3.29 (1H, br; H1), 3.87
(3H, s; OMe), 7.49 (1H, dd, J ) 6.4 and 7.7 Hz; H7), 7.50 (1H,
d, J ) 7.7 Hz; H9), 7.76 (1H, t, J ) 7.7 Hz; H8), 9.12 (1H, d,
J ) 6.4 Hz; H6); 13C NMR δ 14.6 (1-Me), 15.0 (2-Me), 39.4 (C1),
43.7 (C2), 51.1 (OMe), 106.3 (C4), 122.9 (C7), 124.3 (C9), 135.9
(C8), 141.5 (C6), 152.3 (C9a), 165.5 (CO2), 183.4 (C3). Anal.
Calcd for C13H15NO3: C, 66.94; H, 6.48; N, 6.01. Found: C,
67.03; H, 6.51; N, 5.85.
Meth yl 4-Meth yl-3-oxo-5-(2-p yr id yl)h exa n oa te (1g′, di-
astereomer of 1g). Yield 29% (isolated from a mixture with
1
4-Meth oxyca r bon yl-2-m eth yl-3-oxo-1,2,3,4-tetr a h yd r o-
qu in olizin iu m -4-id e (3e). The cooled reaction mixture was
filtered through a glass filter to remove the tiny powder of
catalyst, and pentane was added to a solution until precipita-
tion started to afford yellow crystals: yield 83%; mp 126-127
°C (134-136 °C, crystallosovate, benzene); IR (KBr) 1657, 1552
1g); yellow oil; H NMR δ 1.17 (3H, d, J ) 6.4 Hz), 1.28 (3H,
d, J ) 6.5 Hz), 3.25 (2H, overlapped), 3.38 (1H, A of ABq, J AB
) 15.7 Hz,), 3.47 (1H, B of ABq, J AB ) 15.7 Hz,), 3.66 (3H, s),
7.10 (1H, dd, J ) 4.7 and 6.9 Hz), 7.14 (1H, d, J ) 7.7 Hz),
7.59 (1H, dd, J ) 6.9 and 7.7 Hz), 8.49 (1H, d, J ) 4.7 Hz); 13
C
NMR δ 13.8, 17.5, 43.5, 48.7, 50.7, 52.1, 121.4, 122.7, 136.5,
1
cm-1; H NMR δ 1.15 (3H, d, J ) 7.1 Hz; Me), 2.44 (1H, ddq,
148.9, 163.9, 167.7, 206.6.
J ) 10.5, 4.2 and 7.1 Hz; H2), 2.87 (1H, dd, J ) 15.3 and 10.5
Hz; H1), 3.15 (1H, dd, J ) 15.4 and 4.2 Hz; H1), 3.85 (3H, s;
OMe), 7.48 (1H, dd, J ) 6.4 and 7.1 Hz; H7), 7.50 (1H, d, J )
7.8 Hz; H9), 7.72 (1H, dd, J ) 7.1 and 7.8 Hz; H8), 9.13 (1H,
d, J ) 6.4 Hz; H6); 13C NMR δ 14.5 (Me), 35.6 (C1), 36.7 (C2),
51.0 (OMe), 107.1 (C4), 123.0 (C7), 124.9 (C9), 135.5 (C8), 141.5
(C6), 149.1 (C9a), 165.4 (CO2), 184.1 (C3). Anal. Calcd for
Meth yl 2-Dia zo-4-m eth yl-3-oxo-5-(2-p yr id yl)h exa n oa te
(2g′, diastereomer of 2g). Yield 84% from 1g′; colorless needle
(hexane); 56-57 °C; IR (KBr) 2141, 1724, 1655, 1591 cm-1
;
1H NMR δ 1.19 (3H, d, J ) 7.0 Hz), 1.29 (3H, d, J ) 7.1 Hz),
3.33 (1H, dq, J ) 8.3 and 7.0 Hz), 3.83 (3H, s), 4.08 (1H, dq, J
) 8.3 and 7.1 Hz), 7.06 (1H, dd, J ) 7.4 and 4.7 Hz), 7.22 (1H,
d, J ) 7.8 Hz), 7.56 (1H, dd, J ) 7.4 and 7.8 Hz), 8.48 (1H, d,
J ) 4.7 Hz); 13C NMR δ 14.2, 17.3, 43.2, 46.5, 52.1, 75.5, 121.1,
122.6, 136.2, 148.9, 161.5, 164.6, 196.0. Anal. Calcd for
C
12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: C, 65.93; H,
5.96; N, 6.32. Anal. Calcd for (C12H13NO3C6H6): C, 72.71; H,
6.44; N, 4.71. Found: C, 72.30; H, 6.39; N, 4.76.
C
13H15N3O3: C, 59.76; H, 5.79; N, 16.08. Found: C, 59.72; H,
Met h yl 3-Oxo-5-(2-p yr id yl)h exa n oa t e (1f). Yield 65%;
yellow oil; 1H NMR δ 1.30 (3H, d, J ) 6.8 Hz), 2.80 (1H, dd, J
) 17.2 and 6.2 Hz), 3.21 (1H, dd, J ) 17.2 and 7.7 Hz), 3.42
(1H, A of ABq, J AB ) 15.6 Hz), 3.48 (1H, B of ABq, J AB ) 15.6
Hz), 3.50 (1H, m), 3.71 (3H, s), 7.10 (1H, dd, J ) 7.6 and 5.0
Hz), 7.20 (1H, d, J ) 7.6 Hz), 7.60 (1H, t, J ) 7.6 Hz), 8.49
(1H, d, J ) 5.0 Hz); 13C NMR δ 21.0, 36.8, 48.7, 49.5, 52.2,
121.4, 122.3, 136.5, 149.0, 164.1, 167.6, 201.8.
Meth yl 2-Dia zo-3-oxo-5-(2-p yr id yl)h exa n oa te (2f). Yield
94%; yellow oil; 1H NMR δ 1.33 (3H, d, J ) 6.8 Hz), 3.12 (1H,
m), 3.50 (1H, m), 3.52 (1H, m), 3.83 (3H, s), 7.09 (1H, dd, J )
7.6 and 4.8 Hz), 7.23 (1H, d, J ) 7.6 Hz), 7.50 (1H, t, J ) 7.6
Hz), 8.51 (1H, d, J ) 4.8 Hz); 13C NMR δ 20.9, 37.3, 46.4, 52.2,
76.1, 121.2, 122.0, 136.3, 149.1, 161.8, 164.7, 191.4.
5.59; N, 16.00.
4-Meth oxyca r bon yl-1,2-d im eth yl-3-oxo-1,2,3,4-tetr a h y-
d r oqu in olizin iu m -4-id e (3g′, diastereomer of 3g). Yield 78%
from 2g′; yellow crystal; mp 131-133 °C; IR (KBr) 1630, 1610,
1585 cm-1 1H NMR δ 1.08 (3H, d, J ) 7.2 Hz; 2-Me), 1.42
;
(3H, d, J ) 7.1 Hz; 1-Me), 2.28 (1H, dq, J ) 6.9 and 7.2 Hz;
H2), 2.93 (1H, dq, J ) 6.9 and 7.1 Hz; H1), 3.86 (3H, s; OMe),
7.50 (1H, dd, J ) 6.5 and 7.6 Hz; H7), 7.53 (1H, d, J ) 7.6 Hz;
H9), 7.77 (1H, t, J ) 7.6 Hz; H8), 9.14 (1H, d, J ) 6.5 Hz; H6);
13C NMR δ 14.7 (1-Me), 15.0 (2-Me), 39.4 (C1), 43.7 (C2), 51.0
(OMe), 106.7 (C4), 122.7 (C7), 124.2 (C9), 135.8 (C8), 141.7
(C6), 153.0 (C9a), 165.4 (CO2), 183.4 (C3). Anal. Calcd for
C
13H15NO3: C, 66.94; H, 6.48; N, 6.01. Found: C, 66.80; H,
6.54; N, 5.83.
4-Meth oxyca r bon yl-l-m eth yl-3-oxo-1,2,3,4-tetr a h yd r o-
qu in olizin iu m -4-id e (3f). Yield 92%; yellow crystal; mp 163-
165 °C; IR (KBr) 1637, 1612, 1589 cm-1; 1H NMR δ 1.46 (3H,
d, J ) 6.9 Hz; Me), 2.35 (1H, dd, J ) 15.8 and 10.9 Hz; H2),
2.56 (1H, dd, J ) 15.8 and 4.3 Hz; H2), 3.24 (1H, m; H1), 3.86
(3H, s; MeO), 7.51 (1H, dd, J ) 6.5 and 7.3 Hz; H7), 7.53 (1H,
d, J ) 8.6 Hz; H9), 7.81 (1H, dd, J ) 7.3 and 8.6 Hz; H8), 9.10
(1H, d, J ) 6.5 Hz; H6); 13C NMR δ 15.7 (Me), 32.6 (C1), 42.0
(C2), 51.1 (OMe), 107.9 (C4), 122.4 (C7), 122.8 (C9), 136.4 (C8),
142.2 (C6), 153.8 (C9a), 165.1 (CO2), 181.1 (C3). Anal. Calcd
for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found: C, 65.46;
H, 5.95; N, 6.14.
Eth yl 2-Dia zo-3-oxo-5-(2-p yr id yl)p en ta n oa te (2h ). Yield
73% (2 steps); yellow oil; H NMR δ 1.34 (3H, t, J ) 7.0 Hz),
2.46 (2H, t, J ) 7 Hz), 3.09 (2H, t, J ) 7 Hz), 4.28 (2H, q, J )
7.0 Hz), 7.45 (1H, t, J ) 7 Hz), 7.48 (1H, d, J ) 7.6 Hz) 7.70
(1H, dd, J ) 7.1 and 7.6 Hz), 9.04 (1H, d, J ) 6.8 Hz); 13C
NMR δ 14.2, 32.0, 39.5, 61.3, 75.9, 121.1, 123.0, 136.2, 149.1,
160.3, 161.3, 191.7.
1
4-Eth oxyca r bon yl-3-oxo-1,2,3,4-tetr a h yd r oqu in olizin -
iu m -4-id e (3h ). Yield 90%; yellow crystal; mp 144-145 °C;
1
IR (KBr) 1637, 1610, 1591 cm-1; H NMR δ 1.40 (3H, t, J )
7.1 Hz; CH3CH2O), 2.50 (2H, brt, J ) 6.9 Hz; H2), 3.13 (2H,
brt, J ) 6.7 Hz; Hi), 4.32 (2H, q, J ) 7.1 Hz; OCH2CH3), 7.49
(1H, dd, J ) 6.4 and 7.7 Hz; H7), 7.53 (1H, d, J ) 7.7 Hz; H9),
Meth yl 4-Meth yl-3-oxo-5-(2-pyr idyl)h exan oate (1g). Yield
34%; yellow oil; 1H NMR δ 0.91 (3H, d, J ) 6.3 Hz), 1.28 (3H,
7.74 (1H, t, J ) 7.7 Hz; H8), 9.09 (1H, d, J ) 6.4 Hz; H6); 13
C

1644 J . Org. Chem., Vol. 66, No. 5, 2001
Kostik et al.
NMR δ 14.6 (CH3CH2O), 28.4 (C1), 33.7 (C2), 59.6 (OCH2CH3),
108.2 (C4), 123.0 (C7), 124.5 (C9), 135.9 (C8), 142.0 (C6), 150.0
(C9a), 164.7 (CO2), 181.7 (C3). Anal. Calcd for C12H13NO3: C,
65.74; H, 5.98; N, 6.39. Found: C, 65.54; H, 5.89; N, 6.32.
1-P h en yl-5-(2-p yr id yl)p en ta n e-1,3-d ion e (1i). Yield 40%;
yellow oil; 1H NMR (major enol isomer) δ 2.94 (2H, t, J ) 7.6
Hz), 3.18 (2H, t, J ) 7.6 Hz), 6.19 (1H, s), 7.12 (1H, dd, J )
7.1 and 4.9 Hz; H5′), 7.21 (1H, d, J ) 7.7 Hz; H3′), 7.44 (2H,
t, J ) 7.3 Hz, Ph-m-H), 7.50 (1H, t, J ) 7.3 Hz, Ph-p-H), 7.60
(1H, dd, J ) 7.1 and 7.7 Hz; H4′), 7.84 (2H, d, J ) 7.3 Hz;
Ph-o-H), 8.54 (1H, brd, J ) 4.9 Hz; H6′); 13C NMR δ 33.5, 38.7,
96.4, 121.4, 123.1, 126.9, 128.6, 132.2, 134.7, 136.5, 149.3,
160.1, 182.3, 196.4.
2-Dia zo-1-p h en yl-5-(2-p yr id yl)p en ta n e-1,3-d ion e (2i).
Yield 84%; yellow oil; 1H NMR δ 3.20 (2H, t, J ) 7.2 Hz), 3.45
(2H, t, J ) 7.2 Hz), 7.11 (1H, dd, J ) 7.2 and 5.0 Hz), 7.24
(1H, d, J ) 7.8 Hz), 7.48 (2H, t, J ) 7.6 Hz), 7.57 (1H, t, J )
7.6 Hz), 7.59 (1H, dd, J ) 7.6 and 7.8 Hz), 7.63 (2H, d, J ) 7.6
Hz), 8.51 (1H, d, J ) 5.0 Hz); 13C NMR δ 32.2, 40.4, 83.2, 121.2,
123.1, 127.3, 128.8, 132.6, 136.3, 137.4, 149.2, 160.2, 185.1,
192.4.
4-P h en a cyl-3-oxo-1,2,3,4-t et r a h yd r oq u in olizin iu m -4-
id e (3i). Yield 85%; yellow crystal; mp 132-133 °C; IR (KBr)
1633, 1608, 1531 cm-1; 1H NMR (DMSO-d6) δ 2.29 (2H, t, J )
7.0 Hz; H2), 3.22 (2H, t, J ) 7.0 Hz; H1), 7.28 (3H, m; Ph),
7.38 (2H, d, J ) 6.9 Hz; Ph), 7.72 (1H, dd, J ) 6.4 and 7.7 Hz;
H7), 7.87 (1H, d, J ) 7.7 Hz; H9), 8.05 (1H, t, J ) 7.7 Hz; H8),
9.31 (1H, d, J ) 6.4 Hz; H6); 13C NMR δ 28.2 (C1), 30.8 (C2),
118.6 (C4), 123.1 (C7), 124.9 (C9), 127.3, 127.5 (Ph-o-C and
Ph-m-C), 128.2 (Ph-ipso-C), 128.9 (Ph-p-C), 137.3 (C8), 142.8
(C6), 150.1 (C9a), 182.2 (COPh), 183.4 (C3).
121.0, 124.4, 127.7, 129.0, 130.1, 130.8, 131.1, 132.9, 134.6,
151.7, 158.7, 162.7. Anal. Calcd for C19H11Cl2N3O5: C, 52.80;
H, 2.56; N, 9.72. Found: C, 52.66; H, 2.65; N, 9.67.
4-Meth oxyca r bon ylqu in olizin iu m -3-ola te (4a ). Com-
pound 5a (1.96 g, 4.5 mmol) was treated with ammonia-water,
and the resulting yellow solution was extracted three times
with chloroform. Combined extracts were washed with brine
and dried over anhydrous magnesium sulfate. Removal of the
solvent under reduced pressure gave 0.69 g of 4a (76%) as a
yellow oil, which gradually solidified upon standing.
4-Meth oxyca r bon yl-qu in olizin iu m -3-ola te (4a ). Yellow
needles (ether); mp 112-113 °C; IR (KBr) 1720, 1608, 1520
cm-1; 1H NMR δ 4.40 (3H, s; MeO), 7.36 (1H, dd, J ) 6.7 and
7.2 Hz; H7), 7.38 (1H, dd, J ) 7.2 and 7.9 Hz; H8), 7.50 (1H,
d, J ) 9.7 Hz; H2), 7.55 (1H, d, J ) 9.7 Hz; H1), 7.67 (1H, d,
J ) 7.9 Hz; H9), 8.95 (1H, d, J ) 6.7 Hz; H6); 13C NMR δ 52.7
(MeO), 119.8 (C4), 122.4 (C7), 125.9 (C8), 126.7 (C1), 127.1
(C9), 129.3 (C6), 132.0 (C9a), 139.5 (C2), 165.5 (CO2), 167.9
(C3); MS m/z (relative intensity) 203 (M+, 100), 175 (53), 172
(16), 144 (68), 128 (26), 117 (91), 89 (31), 69 (19), 63 (12), 57
(10); HRMS calcd for C11H9NO3, 203.0583, found 203.0568.
4-Met h oxyca r bon yl-3-oxyq u in olizin iu m P er ch lor a t e
(HClO4 sa lt of 4a ). Colorless crystal (i-PrOH); mp 147-147.5
°C; IR (KBr) 1730, 1630 cm-1. Anal. Calcd for C11H10ClNO7:
C, 43.51; H, 3.32; N, 4.61. Found: C, 43.29; H, 3.30; N, 4.53.
Analogously, 4b was obtained in 86% yield via 4-tert-
butoxycarbonyl-3-oxyquinolizinium 2,3-dichloro-5,6-dicyano-
4-oxy-phenyloxide (5b) from 3b.
4-ter t-Bu toxyca r bon yl-qu in olizin iu m -3-ola te (4b). Yel-
low needles (ether); mp 167-167.5 °C; IR (KBr) 1697, 1604,
1
1518 cm-1; H NMR δ 1.68 (9H, s; t-BuO), 7.26 (1H, dd, J )
ter t-Bu tyl 3-Oxo-5-(2-p yr id yl)h exa n oa te (1j). Yield 52%;
8.2 and 7.1 Hz; H8), 7.31 (1H, dd, J ) 6.9 and 7.1 Hz; H7),
7.46 (1H, d, J ) 9.6 Hz; H2), 7.54 (1H, d, J ) 9.6 Hz; H1),
1
yellow oil; H NMR δ 1.31 (3H, d, J ) 7.0 Hz), 1.45 (9H, s),
2.81 (1H, dd, J ) 17.3 and 6.4 Hz), 3.19 (1H, dd, J ) 17.3 and
7.4 Hz), 3.31 (1H, A of ABq, J AB ) 15.2 Hz), 3.37 (1H, B of
ABq, J AB ) 15.2 Hz), 3.49 (1H, m), 7.09 (1H, dd, J ) 7.3 and
4.9 Hz), 7.20 (1H, d, J ) 7.8 Hz), 7.58 (1H, dd, J ) 7.3 and 7.8
Hz), 8.50 (1H, d, J ) 4.9 Hz); 13C NMR δ 20.9, 27.8, 36.6, 48.8,
50.9, 81.6, 121.2, 122.1, 136.3, 148.9, 164.3, 166.3, 202.3.
ter t-Bu t yl 2-Dia zo-3-oxo-5-(2-p yr id yl)h exa n oa t e (2j).
Yield 80%; yellow oil; 1H NMR δ 1.35 (3H, d, J ) 6.8 Hz), 1.52
(9H, s), 3.12 (1H, dd, J ) 16.8 and 6.0 Hz), 3.46 (1H, dd, J )
17.0 and 7.6 Hz), 3.50 (1H, m), 7.08 (1H, dd, J ) 7.3 and 4.9
Hz), 7.22 (1H, d, J ) 7.9 Hz), 7.59 (1H, dd, J ) 7.3 and 7.9
Hz), 8.51 (1H, d, J ) 4.9 Hz); 13C NMR δ 21.0, 28.3, 37.2, 46.4,
76.9, 83.0, 121.2, 122.1, 136.3, 149.1, 160.5, 164.9, 191.9.
4-ter t-Bu toxyca r bon yl-1-m eth yl-3-oxo-1,2,3,4-tetr a h y-
d r oqu in olizin iu m -3-id e (3j). Yield 81%; yellow oil; 1H NMR
δ 1.46 (3H, d, J ) 6.9 Hz; Me), 1.59 (9H, s; C(Me)3), 2.30 (1H,
dd, J ) 15.8 and 11.6 Hz; H2), 2.53 (1H, dd, J ) 15.8 and 4.4
Hz; H2), 3.23 (1H, m; H1), 7.44 (1H, dd, J ) 6.4 and 7.6 Hz;
H7), 7.48 (1H, d, J ) 7.8 Hz; H9), 7.73 (1H, dd, J ) 7.6 and
7.8 Hz; H8), 8.99 (1H, d, J ) 6.4 Hz; H6); 13C NMR δ 15.8
(1-Me), 28.8 (Me3), 32.6 (C1), 41.7 (C2), 79.7 (C(Me)3), 109.3
(C4), 122.2 (C7), 122.6 (C9), 135.7 (C8), 142.2 (C6), 153.7 (C9a),
164.1 (CO2), 180.6 (C3).
Oxid a tion of Ylid es 3. P r ep a r a tion of 4-Meth oxyca r -
b on yl-3-oxyq u in olizin iu m 2,3-Dich lor o-5,6-d icya n o-4-
oxy-ph en yloxide (5a) an d 4-Meth oxycar bon yl- an d 4-ter t-
Bu toxycar bon ylqu in olizin iu m -3-olate (4a, 4b). To a stirred
solution of 3a (1.01 g, 4.9 mmol) in methylene chloride (96 mL)
was added a warm solution of DDQ (1.12 g, 4.9 mmol) in
methylene chloride (193 mL). The dark-purple reaction mix-
ture gradually became light with a brownish precipitate. Big
particles of solid were ground, and the stirring was continued
until the precipitate became homogeneous. The precipitate was
separated by filtration and washed with methylene chloride
to give 1.96 g (92%) of 5a .
7.64 (1H, d, J ) 8.2 Hz; H9), 8.43 (1H, d, J ) 6.9 Hz; H6); 13
C
NMR δ 28.2 (Me3), 83.6 (CMe3), 122.2 (C7), 123.1 (C4), 124.0
(C8), 126.5 (C1), 126.7 (C9), 127.1 (C6), 130.2 (C9a), 138.8 (C2),
163.9 (CO2), 166.8 (C3). Anal. Calcd for C14H15NO3: C, 68.56;
H, 6.16; N, 5.71. Found: C, 68.08; H, 6.13; N, 5.40.
Deca r boxyla tion of Ylid es 3, a n d 4a . P r ep a r a tion of
Tetr a h yd r oqu in olizin iu m Br om id es (6a , 6a ′, 6e a n d 6f)
a n d Qu in olizin iu m Br om id e 7. Ylide 3a (1.01 g, 4.9 mmol)
was refluxed in 47% HBr for 2.5 h. After removal of water
under reduced pressure the residue was triturated with ether
to give 6a (0.96 g, 4.2 mmol).
3-Oxo-1,2,3,4-tetr a h yd r oqu in olizin iu m Br om id e (6a ).
Yield 89% from 3a ; colorless crystals (ethanol-ethyl acetate);
mp 238-239 °C; IR (KBr) 1734, 1637, 1583, 1510 cm-1 1H
;
NMR (DMSO-d6) δ 2.69 (2H, t, J ) 6.5 Hz; H2), 3.60 (2H, t, J
) 6.5 Hz; H1), 5.32 (2H, s; H4), 8.04 (1H, dd, J ) 6.1 and 7.5
Hz; H7), 8.17 (1H, d, J ) 7.9 Hz; H9), 8.57 (1H, dd, J ) 7.5
and 7.9 Hz; H8), 8.94 (1H, d, J ) 6.1 Hz; H6); 13C NMR
(DMSO-d6) δ 26.7 (C1), 32.4 (C2), 63.8 (C4), 125.8, 127.7, 145.1,
145.8, 154.9, 201.3 (C3). Anal. Calcd for C9H10BrNO: C, 47.39;
H, 4.42; N, 6.14. Found: C, 47.06; H, 4.38; N, 5.93.
2-Meth yl-3-oxo-1,2,3,4-tetr a h yd r oqu in olizin iu m Br o-
m id e (6e). Yield 85% from 3e; colorless needles (ethanol); mp
218-219 °C; IR (KBr) 1732, 1635, 1581 cm-1; 1H NMR (DMSO-
d6) δ 1.16 (3H, d, J ) 6.8 Hz; Me), 2.77 (1H, ddq, J ) 12.5, 4.9
and 6.8 Hz; H2), 3.45 (1H, dd, J ) 16.0 and 12.5 Hz; H1), 3.67
(1H, dd, J ) 16.0 and 4.9 Hz; H1), 5.41 (1H, A of ABq, J AB
)
18.1 Hz; H4), 5.47 (1H, B of ABq, J AB ) 18.1 Hz; H4), 8.06
(1H, dd, J ) 6.0 and 7.4 Hz), 8.18 (1H, d, J ) 7.8 Hz), 8.58
(1H, dd, J ) 7.8 and 7.4 Hz), 9.02 (1H, d, J ) 6.0 Hz); 13C
NMR (DMSO-d6) δ 13.6, 33.5, 37.0, 63.3, 125.7, 127.6, 144.9,
145.7, 154.5, 203.0. Anal. Calcd for C10H12BrNO: C, 49.61; H,
4.99; N, 5.79. Found: C, 49.41; H, 4.95; N, 5.55.
1-Meth yl-3-oxo-1,2,3,4-tetr a h yd r oqu in olizin iu m Br o-
m id e (6f). Yield 75% from 3f; colorless needles (ethanol); mp
1
4-Meth oxyca r bon yl-3-oxyqu in olizin iu m 2,3-Dich lor o-
5,6-d icya n o-4-oxy-p h en yloxid e (5a ). Needles (MeOH); mp
201-202 °C; IR (KBr) 1732, 1626, 1574, 1508 cm-1; H NMR
(DMSO-d6) δ 1.47 (3H, d, J ) 6.9 Hz; Me), 2.53 (1H, dd, J )
17.6 and 9.4 Hz; H2), 2.87 (1H, dd, J ) 17.6 and 4.9 Hz; H2),
3.89 (ddq, 1H, J ) 9.4, 4.9 and 6.9 Hz; H1), 5.42 (1H, A of
ABq, J AB ) 18.1 Hz; H4), 5.53 (1H, B of ABq, J AB ) 18.1 Hz;
H4), 8.09 (1H, dd, J ) 6.1 and 7.5 Hz), 8.19 (1H, d, J ) 8.0
Hz), 8.64 (1H, dd, J ) 7.5 and 8.0 Hz), 9.04 (1H, d, J ) 6.1
1
195-196 °C; IR (KBr) 2231, 1722, 1606, 1514 cm-1; H NMR
(DMSO-d6) δ 4.00 (3H, s), 7.73 (1H, d, J ) 9.6 Hz; H1), 7.80
(1H, dd J ) 6.9 and 7.7 Hz), 7.9 (1H, dd, J ) 7.7 and 8.3 Hz),
8.25 (1H, d, J ) 9.6 Hz; H2), 8.32 (1H, d, J ) 8.3 Hz), 8.85
(1H, d, J ) 6.9 Hz); 13C NMR (DMSO-d6) δ 53.5, 99.5, 115.5,

Tetrahydroquinolizinium Ylides
J . Org. Chem., Vol. 66, No. 5, 2001 1645
Hz); 13C NMR (DMSO-d6) δ 16.7, 31.6, 40.0, 63.7, 125.7, 127.7,
145.2, 146.1, 157.8, 200.9. Anal. Calcd for C10H12BrNO: C,
49.61; H, 4.99; N, 5.79. Found: C, 49.65; H, 5.03; N, 5.75.
3-Hyd r oxyqu in olizin iu m Br om id e (7).3,10 Yield 89% from
4a ; colorless needles (ethanol); mp 255-256 °C; IR (KBr) 1655,
1633, 1518 cm-1; 1H NMR (DMSO-d6) δ 7.99 (1H, dd, J ) 6.7
and 7.4 Hz), 8.04 (1H, d, J ) 9.4 Hz), 8.14 (1H, dd, J ) 7.4
and 9.4 Hz), 8.47 (2H, ABq, J AB ) 13.5 Hz; H1 and H2), 8.85
(1H, s; H4), 9.26 (1H, d, J ) 6.7 Hz), 11.89 (1H, s; HO); 13C
NMR (DMSO-d6) δ 121.1, 124.0, 127.0, 128.2, 130.0, 133.4,
135.3, 137.6, 154.0. UV λ (log ꢀ) nm: 228 (4.40), 243 (4.36),
263 (3.72), 271 (3.90), 341 (3.90). Anal. Calcd for C9H8BrNO:
C, 47.82; H, 3.56; N, 6.20. Found: C, 47.91; H, 3.56; N, 6.13.
3-Oxo-1,2,3,4-t et r a h yd r oq u in olizin iu m P er ch lor a t e
(6a ′). Compound 3b (0.3 g, 1.2 mmol) was treated with 40%
HClO4 solution (2 mL) at room temperature, followed by the
treatment with dry ether to afford 0.21 g (70%) of precipitate
of 6a ′: Colorless crystals (MeOH); mp 203-205 °C; IR (KBr)
d, J ) 7 Hz; H6), 7.27 (1H, t, J ) 7 Hz; H7), 7.88 (1H, s; H2),
8.31 (1H, d, J ) 7 Hz; H8); 13C NMR δ 28.2, 29.4, 30.6, 51.2,
81.6, 104.5, 115.0, 118.0, 119.2, 125.7, 126.5, 140.3, 141.1,
160.4, 164.6, 177.4; MS m/z (relative intensity) 347 (M+, 18),
291 (100), 247 (20), 228 (21), 200 (13), 142 (9), 126 (6), 69 (9),
57 (4); HRMS calcd for C16H19NO4 347.1369, found 347.1377.
Analogously, 9a was prepared from the reactions of 3d and
3i with methyl propynoate (1.5 equiv) in DMSO in 68% and
40% yield, respectively.
ter t-Bu tyl 1-Meth oxyca r bon yl-3-oxo-3H-2a ,8a -d ih yd r o-
p yr r olo[2,1,5-d e]qu in olizin e-2a -ca r boxyla te (12). A solu-
tion of ylide 4b (29 mg, 0.12 mmol) and methyl propynoate
(0.033 mL, 0.36 mmol) in CDCl3 (0.5 mL) was kept at 60 °C
for 45 min. 1H NMR showed a formation of 12 as a sole
product, which decomposed upon attempted isolation: 1H NMR
δ 1.45 (9H, s; t-BuO), 3.83 (3H, s; MeO), 5.42 (1H, d, J ) 6.0
Hz; H6), 5.63 (1H, q, J ) 2.5 Hz; H8a), 5.99 (1H, dd, J ) 10.0
and 2.5 Hz; H8), 6.16 (1H, d, J ) 9.8 Hz; H4), 6.18 (1H, ddd,
J ) 10.0, 6.0 and 2.5 Hz; H7), 7.10 (1H, d, J ) 2.5 Hz; H2),
7.24 (1H, d, J ) 9.8 Hz; H5); 13C NMR δ 27.0 ((Me)3C), 51.5
(MeO), 64.4 (C8a), 81.9 (C2a), 83.6 (C(Me)3), 103.7 (C6), 116.8
(C8), 121.0 (C4), 123.7 (C7), 134.9, 137.0 (C5), 139.6, 141.2 (C8),
163.1 (CO2), 165.8 (CO2), 184.6 (C3).
1
1734, 1637 cm-1; H NMR (DMSO-d6) δ 2.69 (2H, t, J ) 6.5
Hz), 3.59 (2H, t, J ) 6.5 Hz), 5.29 (s, 2H), 8.03 (1H, dd, J )
6.1 and 7.3 Hz), 8.16 (1H, d, J ) 7.9 Hz), 8.56 (1H, dd, J ) 7.3
and 7.9 Hz), 8.9 (1H, d, J ) 6.1 Hz); 13C NMR (DMSO-d6) δ
26.5, 32.3, 63.6, 125.7, 127.6, 144.9, 145.7, 154.8, 201.2. Anal.
Calcd for C9H10ClNO5: C, 43.65; H, 4.07; N, 5.66. Found: C,
43.38; H, 3.99; N, 5.52.
Analogously, 12 was generated from 4b in DMSO-d6 at 75
°C within 30 min.
Met h yl 3-Oxo-3H -p yr r olo[2,1,5-d e]q u in olizin e-1-ca r -
boxyla te (13).4 A solution of ylide 4b (0.5 g, 2 mmol) and
methyl propynoate (0.275 mL, 3 mmol) in DMSO (15 mL) was
stirred at 75 °C for 1 h. Compound 13 (0.27 g, 1.2 mmol) was
isolated from the reaction mixture as described above for 9:
Rea ction s of Ylid es 3b, 4b w ith Meth yl P r op yn oa te.
A solution of 3b (30 mg, 0.12 mmol) and methyl propynoate
(0.011 mL, 0.12 mmol) in acetone-d6 (0.5 mL) was kept at 55
°C for 12 min15 to afford 8 as a sole product. Attempted
isolation of 8 caused decomposition.
1
yellow needles (benzene); mp 207-208 °C; H NMR (DMSO-
ter t-Bu tyl 1-Meth oxyca r bon yl-3-oxo-3H-2a ,4,5,8a -tet-
r a h yd r op yr r olo[2,1,5-d e]qu in olizin e-2a -ca r boxyla te (8).
1H NMR δ 1.51 (9H, s; t-BuO), 2.23 (1H, ddd, J ) 19.0, 12.8
and 6.4 Hz; H4), 2.47 (1H, ddd, J ) 13.6, 6.4 and 1.2 Hz; H5),
2.67 (1H, ddd, J ) 13.6, 12.8 and 6.4 Hz; H5), 2.81 (1H, ddd,
J ) 19.0, 6.4 and 1.2 Hz; H4), 3.82 (3H, s; MeO), 4.74 (1H, d,
J ) 5.9 Hz; H6), 5.28 (1H, dd, J ) 9.2 and 2.5 Hz; H8), 5.76
(1H, q, J ) 2.5 Hz; H8a), 5.86 (1H, ddd, J ) 9.2, 5.9 and 2.5
Hz; H7), 6.95 (1H, d, J ) 2.5 Hz; H2); 13C NMR δ 26.7 (C5),
27.8 ((Me)3C), 35.9 (C4), 52.3 (MeO), 66.2 (C8a), 84.4 and 84.9
(C2a and C(Me)3), 93.1 (C6), 109.2 (C8), 125.0 (C7), 136.9 (C2),
139.8 (C1), 140.5 (C5), 163.5 and 167.9 (CO2), 201.2 (C3); MS
m/z (relative intensity) 331 (M+, 16), 275 (26), 230 (93), 198
(100), 188 (40), 172 (35), 142 (24), 141 (20), 57 (26); HRMS
calcd for C18H21NO5 331.1420, found 331.1430.
Meth yl 4,5-Dih yd r o-3-oxo-3H-p yr r olo[2,1,5-d e]qu in o-
lizin e-1-ca r boxyla te (9a ). A solution of 3b (0.50 g, 2 mmol)
and methyl propynoate (0.185 mL, 2 mmol) in DMSO (15 mL)
was stirred at 80 °C for 45 min and then poured into water.
The solution was basified with ammonia water and extracted
with ether. Combined ether extracts were washed with water
and brine and dried over anhydrous magnesium sulfate. After
removal of the solvent, the residue was purified on silica gel
to give 9a (0.14 g, 30%). The water layer was washed with
methylene chloride, acidified with diluted HCl, and extracted
with diethyl ether. Combined ether extracts were dried over
anhydrous magnesium sulfate. Removal of the solvent gave
10.
Da ta for 9a . Colorless needles (i-PrOH); mp 147-148 °C;
IR (KBr) 1700, 1645 cm-1; 1H NMR δ 2.82 (2H, t, J ) 7.6 Hz;
H4), 3.42 (2H, t, J ) 7.6 Hz; H5), 3.92 (3H, s; MeO), 6.88 (1H,
d, J ) 6.9 Hz; H6), 7.30 (1H, dd, J ) 9.0 and 6.9 Hz; H7), 7.97
(1H, s; H2), 8.16 (1H, d, J ) 9.0 Hz; H8); 13C NMR δ 26.5 (C5),
33.5 (C4), 51.3 (MeO), 107.5 (C5a), 112.1 (C6), 117.8 (C8), 120.4
(C2), 122.9, 127.0 (C7), 134.6, 137.6, 164.6 (CO2), 184.7 (C3).
Anal. Calcd for C13H11NO3: C, 68.11; H, 4.84; N, 6.11. Found:
C, 67.72; H, 4.82; N, 6.08.
3-(ter t-Bu toxycar bon yl)-1-(m eth oxycar bon yl)-5-in doliz-
in ep r op ion ic Acid (10). Yield 71 mg (14%); dark oil; 1H NMR
δ 1.60 (9H, s; t-BuO), 2.70 (2H, t, J ) 7.5 Hz; CH2CO2), 3.55
(2H, t, J ) 7.5 Hz; CH2CH2CO2), 3.91 (3H, s; MeO), 6.82 (1H,
d6) δ 3.93 (3H, s), 7.29 (1H, d, J ) 9.9 Hz), 8.00 (1H, dd, J )
8.4 and 7.4 Hz), 8.15 (1H, s), 8.19 (1H, d, J ) 7.4 Hz), 8.33
(1H, d, J ) 9.9 Hz), 8.70 (1H, d, J ) 8.4 Hz); 13C NMR δ 51.8,
112.7, 119.3, 121.7, 122.3, 125.6, 127.1, 128.7, 130.4, 134.7,
135.2, 164.1, 172.7. Anal. Calcd for C13H9NO3: C, 68.72; H,
3.99; N, 6.17. Found: C, 69.08; H, 4.18; N, 5.83.
Rea ction of Ylid e 3b w ith DMAD. A mixture of 3b
(0.500g, 2 mmol) and DMAD (0.522 mL, 4.2 mmol) in acetone
(30 mL) was kept at 55 °C for 20 min without stirring. Removal
of the solvent under reduced pressure followed by silica gel
chromatography gave azocine 15.
ter t-Bu tyl (2a a ,10a a )-3-Oxo-1,2,6,7-tetr a m eth oxyca r -
bon yl-2a ,4,5,10a -tetr a h yd r o-3H-a zocin o[2,1,8-cd ]-in d oliz-
in e-2a -ca r boxyla te (15). Yield 0.54 g (50%); yellow prisms
(MeOH); mp 164.5-165.5 °C; IR (KBr) 1763, 1745, 1737, 1716,
1
1699 cm-1; H NMR δ 1.48 (9H, s; t-BuO), 2.41 (1H, m; H4),
2.53 (1H, m; H5), 2.64 (1H, brd, J ) 16.5 Hz; H4), 3.47, 3.75,
3.78, 3.87 (each 3H, s; MeO), 4.62 (1H, brd, J ) 18 Hz; H5),
5.95 (1H, t, J ) 8 Hz; H10), 6.12 (1H, d, J ) 7.8 Hz; H10a),
6.72 (1H, dd, J ) 8 and 2.3 Hz; H9), 7.21 (1H, d, J ) 2.3 Hz;
H8); 13C NMR δ 24.5, 27.4, 34.2, 51.3, 52.1, 52.6, 52.7, 65.3,
82.8, 84.9, 100.8, 131.3, 133.9, 134.1, 135.1, 137.2, 138.2, 152.5,
161.7, 162.2, 164.6, 167.5, 167.9, 201.2. Anal. Calcd for C26H29
-
NO11: C, 58.75; H, 5.50; N, 2.64. Found: C, 58.74; H, 5.51; N,
2.58.
St ep w ise R ea ct ion of Ylid e 3b w it h Met h yl P r o-
p yn oa te a n d DMAD. A mixture of 3b (0.500 g, 2 mmol) and
methyl propynoate (0.356 mL, 2 mmol) in acetone (30 mL) was
kept without stirring at 55 °C for 12 min, and then DMAD
(0.249 mL, 2 mmol) was added. The reaction mixture was kept
for 15 min at the same conditions. Removal of the solvent
under reduced pressure followed by silica gel chromatography
afforded 16.
ter t-Bu tyl (2a a ,10a a )-3-Oxo-2a ,4,5,10a -tetr a h yd r o-1,6,7-
tr im eth oxyca r bon yl-3H-a zocin o[2,1,8-cd ]-in d olizin e-2a -
ca r boxyla te (16). Yield 0.67 g (70%); light yellow prisms
(MeOH); mp 164.5-165.5 °C; IR (KBr) 1755, 1724, 1716, 1708,
1
1691 cm-1; H NMR δ 1.46 (9H, s; t-BuO), 2.44 (2H, m; H4,
H5), 2.60 (1H, brd, J ) 18 Hz), 3.58, 3.75, 3.77 (each 3H, s;
MeO), 4.65 (1H, brd, J ) 18.0 Hz), 5.79 (1H, dd, J ) 10.0 and
7.4 Hz; H10), 6.05 (1H, d, J ) 7.4 Hz; H10a), 6.70 (1H, dd, J
) 10.0 and 3.0 Hz; H9), 6.88 (1H, d, J ) 2.0 Hz; H2), 7.25
(1H, d, J ) 3.0 Hz; H8); 13C NMR δ 24.8 (C5), 27.6 ((Me)3C),
34.7 (C4), 51.3, 52.1, 52.2 (MeO), 64.8 (C10a), 83.6 (C(Me)3),
(15) Preparations of cycloadducts were performed without stirring
unless otherwise mentioned.

1646 J . Org. Chem., Vol. 66, No. 5, 2001
Kostik et al.
85.1 (C2a), 100.3 (C7a), 132.1, 134.0, 134.1, 134.9, 136.8, 138.8,
153.7 (C6a), 162.2, 165.0, 167.7, 168.2 (CO2), 201.8 (C3). Anal.
Calcd for C24H27NO9: C, 60.88; H, 5.75; N, 2.96. Found: C,
60.65; H, 5.82; N, 2.92.
Rea ction of Qu in olizin iu m -ola te 4b w ith DMAD. A
solution of 4b (1.00 g, 4 mmol) and DMAD (1.51 mL, 12 mmol)
in chloroform (50 ml) was refluxed for 5 h. The reaction
mixture was concentrated under reduced pressure and sub-
jected to silica gel chromatography. The first fraction was
identified as 18. The second fraction was isolated as a pale
yellow oil and assigned as 19. The third fraction was identified
as 20.
ter t-Bu tyl (2a a ,10a a )-2a ,10a -Dih yd r o-3-oxo-1,2,6,7-tet-
r a m et h oxyca r b on yl-3H -a zocin o[2,1,8-cd ]in d olizin e-2a -
ca r boxyla te (18). Yield 0.44 g (21%); orange prisms (MeOH);
mp 160.5-161.5 °C; IR (KBr) 1759, 1738, 1724, 1703, 1687
cm-1; 1H NMR δ 1.43 (9H, s; t-BuO), 3.65, 3.76, 3.78, 3.90 (each
3H, s; MeO), 5.94 (1H, dd, J ) 9.9 and 7.8 Hz; H10), 6.01 (1H,
d, J ) 7.8 Hz; H10a), 6.21 (1H, d, J ) 10.6 Hz; H5), 6.70 (1H,
dd, J ) 9.9 and 2.8 Hz; H9), 7.35 (1H, d, J ) 2.8 Hz; H8), 8.64
(1H, d, J ) 10.6 Hz; H4); 13C NMR δ 27.4, 52.1, 52.2, 52.6,
52.7, 66.8, 81.4, 84.6, 111.4 126.2, 130.3, 133.7, 134.0, 136.7,
137.0, 138.4, 141.0, 143.2, 161.7, 162.8, 165.3, 166.2, 166.5,
188.4; MS m/z (relative intensity) 529 (M+, 1.2), 498 (0.5), 470
(1), 429 (21), 397 (100), 365 (35), 338 (41), 306 (7), 278 (13),
7.47 (1H, t, J ) 7.8 Hz; Ph-H5), 7.66 (1H, d, J ) 7.8 Hz; Ph-
H6), 7.94 (1H, d, J ) 7.8 Hz; Ph-H4); 13C NMR δ 51.5, 52.6,
52.7, 123.0, 128.2, 128.7, 129.7, 133.2, 133.9, 134.0, 140.2,
165.5, 166.1, 168.8; MS m/z (relative intensity) 278 (M+, 2),
263 (0.5), 247 (15), 231 (5), 219 (100), 203 (4), 187 (6), 173 (6),
157 (9), 129 (5), 94 (6), 75 (5), 57(5); HRMS calcd for C14H14O6
278.0790, found 278.0780.
ter t-Bu tyl 3,4-Di(m eth oxyca r bon yl)p yr r ol-2-ca r boxy-
1
la te (21). Yield 0.198 g (97%); colorless oil; H NMR δ 1.55
(9H, s; t-BuO), 3.82, 3.94 (each 3H, s; MeO), 7.44 (1H, d, J )
2.7 Hz; H5), 9.98 (1H, brs; H1); 13C NMR δ 28.1, 51.6, 52.6,
82.8, 115.7, 122.3, 122.5, 125.7, 159.2, 163.2, 165.9; MS m/z
(relative intensity) 283 (M+, 12), 247 (7), 227 (61), 219 (50)
196 (100), 178 (49), 152 (36), 93 (15), 57 (15); HRMS calcd for
C13H17NO6 283.1056, found 283.1034.
Rea ction s of 3-Oxo-1,2,3,4-tetr a h yd r oqu in olizin iu m
Br om id es 6 w ith Meth yl P r op yn oa te. To a stirred suspen-
sion of salt 6a (0.50 g, 2.2 mmol) in acetonitrile (20 mL) were
added ethyldiisopropylamine (0.42 mL, 2.4 mmol) and methyl
propynoate (0.4 mL, 4.4 mmol). The reaction mixture was
stirred at 60 °C for 0.5 h and then concentrated under reduced
pressure. The residue was distributed between methylene
chloride and water, and water layer was extracted with
methylene chloride. Combined methylene chloride solutions
were washed with brine and dried over anhydrous magnesium
sulfate. The residue after removal of the solvent was purified
by silica gel chromatography to give 9a (0.30 g, 65%). Further
elution with 6% water-ethanol mixture gave a second fraction
as an orange oil, which was identified as 24a (90 mg, 20%).
4-(2-Met h oxyca r b on ylet h en yl)-3-oxo-1,2,3,4-t et r a h y-
d r oqu in olizin iu m -4-id e (24a ). 1H NMR δ 2.51 (2H, t, J )
7.2 Hz), 3.12 (2H, t, J ) 7.2 Hz), 3.73 (3H, s), 6.67 (1H, d, J )
15.0 Hz), 7.43 (1H, d, J ) 7.6 Hz), 7.47 (1H, dd, J ) 6.4 and
7.2 Hz), 7.55 (1H, dd, J ) 7.2 and 7.6 Hz), 7.72 (1H, d, J )
15.0 Hz), 8.34 (1H, d, J ) 6.4 Hz); 13C NMR δ 28.3, 31.5, 51.0,
103.2, 115.0, 124.8, 125.3, 132.7, 134.1, 134.7, 146.4, 171.1,
181.0.
254 (6), 220 (6), 193 (6), 57 (15). Anal. Calcd for C26H27NO11
:
C, 58.98; H, 5.14; N, 2.65. Found: C, 58.92; H, 5.08; N, 2.52.
ter t-Bu tyl 3,4-Di(m eth oxyca r bon yl)-2-[2,3-d i(m eth oxy-
ca r bon yl)cin n a m oyl]p yr r ol-2-ca r boxyla te (19). Yield 0.39
1
g (19%); H NMR δ 1.55 (9H, s; t-BuO), 3.78, 3.88, 3.89, 3.93
(each 3H, s; MeO), 6.46 (1H, d, J ) 12.2 Hz; CHdCHCO), 7.34
(1H, d, J ) 12.2 Hz; CHdCHCO), 7.42 (1H, t, J ) 7.8 Hz; Ph-
H5), 7.60 (1H, s; H5), 7.65 (1H, d, J ) 7.8 Hz; Ph-H6), 7.90
(1H, d, J ) 7.8 Hz; Ph-H4); 13C NMR δ 27.6, 51.6, 52.2, 52.4,
52.6, 83.2, 115.6, 123.2, 124.2, 125.3, 127.7, 128.5, 129.3, 130.3,
132.5, 132.8, 133.5, 142.2, 158.2, 161.8, 163.0, 163.6, 165.6,
168.1; MS (CI+) m/z (relative intensity) 530 (M+, 25), 474 (100),
428 (10), 284 (12), 228 (83), 196 (8); HRMS calcd for C26H27
-
NO11 (M+ + 1) 530.1662, found 530.1636.
Similarly, 9e was obtained from 6e.
Dim et h yl 3-Oxo-3H -p yr r olo[2,1,5-d e]q u in olizin e-1,2-
d ica r boxyla te (20). Yield 0.114 g (10%); 1H NMR δ 3.97 (3H,
s), 4.08 (3H, s), 7.29 (1H, d, J ) 10 Hz), 7.81 (2H, m), 7.92
(1H, d, J ) 10 Hz), 8.75 (1H, dd, J ) 1.8 and 7.6 Hz); 13C NMR
δ 55.2, 53.4, 109.3, 119.9, 122.3, 123.9, 126.5, 128.4, 128.9,
130.6, 134.0, 134.9, 163.1, 165.2, 172.1.
Met h yl 4,5-Dih yd r o-4-m et h yl-3-oxo-3H-p yr r olo[2,1,5-
d e]qu in olizin e-1-ca r boxyla te (9e). Light yellow needles (i-
1
PrOH); mp 127-128 °C; IR (KBr) 1701, 1643 cm-1; H NMR
δ 1.30 (3H, d, J ) 6.3 Hz; Me), 2.84 (1H, m; H4), 3.14 (1H, dd,
J ) 16.3 and 11.1 Hz; H5), 3.44 (1H, dd, J ) 16.3, and 5.7 Hz;
H5), 3.91 (3H, s; MeO), 6.88 (1H, d, J ) 6.9 Hz; H6), 7.32 (1H,
dd, J ) 6.9 and 8.9 Hz; H7), 7.96 (1H, brs; H2), 8.16 (1H, d, J
) 8.9 Hz; H8); 13C NMR δ 14.9 (Me), 34.2 (C5), 37.6 (C4), 51.3
(MeO), 107.5 (C5a), 112.2 (C6), 117.8 (C8), 120.5 (C2), 122.2,
126.8 (C7), 134.4, 137.2, 164.6 (CO2), 187.5 (C3). Anal. Calcd
for C14H13NO3: C, 69.12; H, 5.38; N, 5.76. Found: C, 69.05;
H, 5.40; N, 5.64.
Hyd r olysis of 19. A mixture of 19 (0.39 g, 0.74 mmol) and
0.01 mL of 10% KOH/MeOH in 15 mL of methanol was stirred
at room temperature for 30 min. After removal of the solvent
under reduced pressure, the residue was acidified with 1% HCl
and extracted with methylene chloride. Combined extracts
were washed with brine and dried over anhydrous magnesium
sulfate; the residue after removal of solvent was subjected to
silica gel chromatography. The first fraction, a clear oil, 0.195
g (95%), was identified as 22. The second fraction was
identified as 21.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of 3a -i, 4a ,b, 5a , 6a -c, 9a ,e, 12, 13, 15, 16,and 18-
22. This material is available free of charge via the Internet
at http://pubs.acs.org.
Meth yl 2′,3′-Di(m eth oxyca r bon yl)cin n a m a te (22). 1H
NMR δ 3.63 (3H, s; MeO), 3.90 (6H, s; 2MeO), 6.10 (1H, d, J
) 12.6 Hz; CHdCHCO), 7.11 (1H, d, J ) 12.6 Hz; CHdCHCO),
J O001162G