2,3,7-Triazabicyclo[3.3.0]octenes prepared by tandem cascade reaction of allyl azides and olefinic dipolarophiles

Article abstract of DOI:10.1002/jccs.200200016

Tandem cascade reactions of allyl azides and olefinic dipolarophiles to give cis-fused 2,3,7-triazabicyclo[3.3.0]octenes (5,6 or 7) are reported. Therein, an intermolecular dipolar cycloaddition of azide and alkene gave a triazoline which was followed by isomerization of the triazoline to a diazo ester (4) and then an intramolecular dipolar cycloaddition from the diazo functional group and the double bond in 4 to give 5. Compound 5 may furthermore undergo a Michael addition to give 7-substituted-2,3,7-triazabicyclo[3.3.0]oct- 2-ene (6) or a tautomerization to give 2,3,7-triazabicyclo[3.3.0]oct-3-ene (7). The reaction may be manipulated to stop at a particular stage by adopting a suitable solvent or an appropriate temperature.

Full text of DOI:10.1002/jccs.200200016

JournaloftheChineseChemicalSociety, 2002, 49, 95-102
95
2,3,7-Triazabicyclo[3.3.0]octenesPreparedbyTandemCascadeReaction
of Allyl Azides and Olefinic Dipolarophiles
Chia-Hsi Yanga* (
), Huang-Jang Shena (
) and Ju-Chun Wangb (
),
Ruey-Hsuan Wanga (
)
aDepartmentofChemistry,Chung-YuanChristianUniversity,Taoyuan,Taiwan,R.O.C.
bDepartmentofChemistry,SoochowUniversity,Taipei,Taiwan,R.O.C.
Tan dem cas cade re ac tions of allyl azides and olefinic dipolarophiles to give cis-fused 2,3,7- t riazabicy-
clo[3.3.0]octenes(5, 6 or 7) are re ported. Therein, an intermolecular dipolar cycloaddition of azide and alkene
gave a triazoline which was fol lowed by isomerization of the triazoline to a diazo es ter (4) and then an intra-
molecular dipolar cycloaddition from the diazo func tional group and the dou ble bond in 4 to give 5. Com-
pound 5mayfurthermoreundergoaMichaeladditiontogive7-substituted-2,3,7-triazabicyclo[3.3.0]oct-2-
ene( 6) or a tautomerization to give 2,3,7-triazabicyclo[3.3.0]oct-3-ene (7).Thereactionmaybemanipulated
tostopataparticularstagebyadoptingasuitablesolventoranappropriatetemperat ure.
INTRODUCTION
Tandemcascadereactions,alsoknownasdominoreac-
tions, are ef fi cient pro cesses to pre pare or ganic com pounds.
Manysynthesesbasedonthisconsiderationhavebeendevel-
oped.1-6
For the pur pose of study ing the gen er al ity of the re ac-
tion,moreexperimentswerecarriedoutwithvariousolefinic
dipolarophiles, sev eral sub sti tuted allyl azides and dif fer ent
sol vents. The prod uct ob tained could be 3, a 2-triazoline
(en tries 1 and 5), 5, an 7-unsubstituted 2,3,7- triazabicyclo-
[3.3.0] oct- 2-ene (for ex am ple, en tries 2, 6 and 11),6, a 7-
substituted-2,3,7-triazabicyclo[3.3.0]oct-2-ene (for ex am-
ple, en tries 4 and 7) or a 7-unsubstituted 2,3,7-triazabicyclo-
[3.3.0]oct-3-ene(7), a tau to mer of5 (en try 12). The re sults
are given in Ta ble 1.
The re ac tion of acrylate with alkyl or aryl azide was
found to be a tan dem cas cade re ac tion.7 Therein, a se quence
of intermolecular dipolar cycloaddition, isomerization and
an other intermolecular dipolar cycloaddition gave a 2-pyra-
zoline. Re placing alkyl azide with allyl azide, we have found
that 2,3,7-triazabicyclo[3.3.0]oct-2-enes (5 and 6) were ob-
tained by a different tandem cascade reaction sequence;
intermolecular dipolar cycloaddition, isomerization, fol-
lowed by an intramolecular dipolar cycloaddition. This pa per
de scribes the full de tails of our in ves ti ga tion on this tan dem
cascadereactionandthepossibilitiestopreparemorederiva-
tives of5 and 6. Some of these re sults have been re ported as a
preliminarycommunication.8
All these re sults could be ac counted for by Scheme I.
Therein, an intermolecular dipolar cycloaddition of allyl
azide and acrylate gave a 2-triazoline (3). 3 underwentan
isomerization to give a diazo es ter (4)9 which sub se quently
gave 5 by an intramolecular dipolar cycloaddition.10 In ad di-
Table 1. Reaction of Allyl Azides and Olefinic Dipolarophiles
Entry
Reactants
Solvent
Product (yield)
1
2
3
4
5
6
7
8
1a + 2u
CHCl3 (7 h)
CHCl3 (4 days)
DMSO/n-hexane
THF
CHCl3
THF
DMSO
CHCl3
THF
THF
3au (53)
5au (70)
5au (75)
6au (84)
3av (85)
5av (91)
6av (88)
6aw (81)
6aw (87)
6ax (66)
5bv (40)
7cu (82)
6du (51)
RESULTSANDDISCUSSION
1a + 2v
1a + 2w
A mix ture of one equiv a lent of allyl azide (1a) and 2
equivalentsofmethylacrylate( 2u) dis solved in THF at room
tem per a ture was stirred for two days to give a 7- sub stituted-
2,3,7-triazabicyclo[3.3.0]oct-2-ene(6au) as the sole prod uct
in an iso lated yield of 84%. This is a very ef fi cient one pot re-
ac tion to pre pare a com pound hav ing a skel e ton like 6 from
simplereactants.
9
10
11
12
13
1a + 2x
1b + 2v
1c + 2u
1d + 2u
THF
THF
THF

96 J. Chin. Chem. Soc., Vol. 49, No. 1, 2002
Yang et al.
Scheme I
Z
R3
R2
R3
R2
R1
N3
+
N
Z
N
N
2
1
R1
3
1a: R1 = H, R3 = H
2u: R2 = H, Z = C(O)OCH3
2v: R2 = H, Z = CN
8
HN
1b: R1 = H, R3 = CH3
1c: R1 = C6H5, R3 = H
7
6
N
N
3
2
1
5
2w: R2 = H, Z= C(O)CH3
2x: R2 = H, Z = C(O)NH2
Z
2y: R2 = CH3, Z=C(O)OC2H5
2z: R2 = C6H5, Z = C(O)OCH3
4
R
3
4
R2
Z
R2
Z
H
N
N
N
N
R N
4
R N
4
R3
R3
R1
R1
7 R4 = H
8 R4 = R5
5 R4 = H
6 R4 = R5
**R1,R3,R4 subsituents are omitted in 4 for clarity
tion, Mi chael ad di tion of acrylate to 5 would give 6. 5 may
give 7 by tautomerization of N=N-CH to NH-N=C.
6 and 7. In addition, it is known that 7av is cis-fused
2,3,7-triazabicyclo[3.3.0]oct-3-ene. Since tautomerization
of 5av to 7av involvingonlyN 2, N3 and C 4, no change in con-
figurationsofringfusioncarbons,C1 and C 5, was sup posed to
oc cur, there fore com pounds 5 and 6 should be cis-fused
2,3,7-triazabicyclo[3.3.0]oct-2-enes. Husigen11 pointed out
Inanappropriatecondition, someoftheseintermedi-
ates could be iso lated and the re ac tion could be con trolled to
bestepwise.Forinstance,inchloroform,thereactionofallyl
azide and acrylonitrile stopped at the 2-triazoline (3) stage
to give 3av.Isolated3avin a more po lar sol vent or at a higher
temperaturewasconvertedto5av.Similarly,isolated5av, in
anevenmorepolarsolvent, DMSO, andthepresenceofmore
acrylonitrileunderwentMichaeladditiontogive6av.
At a higher tem per a ture or in the pres ence of acid or
base, com pound 5 could be con verted to its tau to mer 7. For
instance, 5au and 5av were tautomerized to 7au and 7av, re-
spec tively, in the pres ence of acid or base.
The as sign ment of the struc tures of3, 5, 6 and 7 were
based on NMR spec tra. To fur ther sub stan ti ate these as sign-
ments and to study the stereochemistry of the re ac tion, a sin-
glecrystalX-raydiffractionstudyoncompound7av was car-
ried out. The re sult con firms our as sign ment of the struc ture
of 7av(Fig.1)andsupportsourassignmentofstructuresof5,
Fig. 1. ORTEP of 7av.

PreparationbyTandemCascadeReaction
J. Chin. Chem. Soc., Vol. 49, No. 1, 2002 97
that there was an ori en ta tion com plex pre ced ing the tran si-
tion state for dipolar cycloaddition. In or der to ful fill this re-
quirementintramolecularly,C6-N7-C8 link age must be in one
side of the plane formed by C1, N3, C 4 and C 5 (4 in Scheme I),
there fore both Z and R3 must be in the other side. Con se-
quently, the re ac tion gives a cis-fused bicyclo[3.3.0]oct- 2-
ene as the prod uct in this intramolecular cycloaddition step.
Since 5au and 5av, 2,3,7-triazabicyclo[3.3.0]oct-2-
enes with out substituent at 7-position are avail able, it is pos-
si ble to pre pare the cor re spond ing 7-substituted 2,3,7- tria-
zabicyclo[3.3.0]oct-2-enes (6) by Mi chael ad di tion or nu-
cleophilic sub sti tu tion (Scheme II). Sev eral 7-unsubstituted
or 7-substituted 2,3,7-triaza- bicyclo[3.3.0]oct-3-enes (7)
were also pre pared by tautomerization of5 and6. The re sults
are given in Ta ble 2. The yields of these re ac tions are gen er-
allygoodtoexcellent.
ByMichaeladdition,nucleophilicsubstitutionortautomeriza-
tion, many 2,3,7-triazabicyclo[3.3.0]octene de riv a tives can
beprepared.
EXPERIMENTAL SECTION
Re agents and Gen eral Pro ce dure
Melting points were determined on a Yanagimoto
micromeltingpointapparatusandarereporteduncorrected.
1
The H, 13C and 2D NMR spectra were obtained by an
Ace-300MHzFT-NMRspectrometer.Themassspectrawere
ob tained on a JEOL JMS-SX/SX 102A spec trom e ter op er at-
ingat12eV.Theelementalcompositionsofcompoundswere
de ter mined by a JOEL JMS-SX/Sx 102A high res o lu tion
mass spectrometer. Infrared spectra were obtained on a
BIORAD-FTSFT-IRspectrometer.
Allyl azides 12 (1a) were pre pared by the fol low ing pro-
ce dure; to 1 equiv a lent of allyl bro mide dis solved in a mix-
ture of DMSO and wa ter, 1.2 equiv a lents of so dium azide
were added. Af ter stir ring for 3 hours, 50 mL sat u rated brine
wasaddedtothemixture.Theorganiclayerafterdryingwith
magnesiumsulfatewasseparatedandthesolventwasevapo-
rated to ob tain allyl azide.
Scheme II
Z
Z
N
N
Z1
N
N
+
N
HN
Z1
Z
5
N
2-Methyl-2-propenyl azide ( 1b) was ob tained in a yield
of 75%. 1H NMR (CDCl3) 1.76 (s, 3H), 3.76 (s, 2H), 4.95 (s,
2H). 13C NMR (CDCl3): 20.1 (CH3), 57.1 (CH2), 114.1 (CH2),
139.5 (C), IR: max (cm-1) 2100.
N
R
N
+
RX
E-3-Phenyl-2-propenyl azide (1c ) was ob tained in a
yield of 83%. 1H NMR (CDCl3) 3.82 (d, 2H, J = 6.6 Hz), 6.14
(td, 1H, J = 15.8, 6.6 Hz), 6.55 (d, 1H, J = 15.8 Hz), 7.1-7.4
(m, 5H). 13C NMR (CDCl3): 48.1 (CH2), 127.1 (CH), 128.1
(CH), 128.5 (CH), 129.1 (CH), 132.3 (CH), 144.1 (C), IR:
max (cm-1) 2120.
In con clu sion, allyl azides and olefinic dipolarophiles
un dergo a tan dem cas cade re ac tion to give cis-fused 2,3,7-
triazabicyclo[3.3.0]octenes in good yields. The re ac tion can
bestoppedatdifferentstagesbyselectingasuitablesolvent.
Table 2. Preparations of Derivatives
E-2-Butenyl azide (1d) was ob tained in a yield of 70%.
1H NMR (CDCl3) 1.71 (d, 3H, J = 6.2 Hz), 3.65 (d, 2H,J = 6.4
Hz), 5.2-5.6 (m, 1H), 5.7-5.8 (m, 1H). 13C NMR (CDCl3):
Product
Z
R
procedure yield
6au-1
6au-2
6au-3
6au-4
6av-1
6av-2
6av-3
7au
COOCH3
COOCH3
COOCH3
COOCH3
CN
CN
CN
COOCH3
COOCH3
COOCH3
CN
CH2CH2COCH3
CH2CH2COCH2CH3
CH2CH2CH2CH3
C6H5CH2
CH2CH2CH3
CH2CH=CH2
propagyl
CH2CH2CO2CH3
CH2CH2COCH3
C6H5CH2
M*
M
S*
S
93
85
88
71
74
77
61
90
85
87
81
18.1 (CH3), 54.1 (CH2), 122.1 (CH), 124.5 (CH), IR:
(cm-1) 2110.
max
S
S
Pro ce dure A: Gen eral pro ce dure for the re ac tion of
allyl azide and alkene carrying electron-withdrawing
group
S
I*
I
7au-1
7au-2
7av
To allyl azide (50 mmol) in 40 mL sol vent, olefinic
dipolarophile (51 mmol or 102 mmol) dis solved in 10 mL sol-
vent was added dropwise at room tem per a ture. The mix ture
was stirred for sev eral hours or a few days. The sol vent and
I
I
H
* M: Michael addition, S: substitution, I: isomerization.

98 J. Chin. Chem. Soc., Vol. 49, No. 1, 2002
Yang et al.
theunreactedstartingmaterialswereremovedbyrotatory
evap o ra tor to give the crude prod uct. The prod uct could be
furtherpurifiedbycolumnchromatography.
(CH2), 94.1 (C), 116.7 (CN); EIMS m/z (%) 136 (M, 1), 107
(64), 93 (100), 80 (42). HRMS: Calcd. for C6H8N4: 136.0748,
Found: 136.0750.
2
1-Allyl-4-methoxycarbonyl- -1,2,3-triazaoline (3au)
7-(2-Methoxycarbonylethyl)-1-Methoxycarbonyl-2,3,7-
triazabicyclo[3.3.0]oct-2-ene (6au)
Fol low ing pro ce dure A us ing chlo ro form as the sol-
vent, the re ac tion of allyl azide and methyl acrylate at 0 C
gave 3au in a re ac tion time of 7 hours. 3au is a yel low oil
(53%). 1H NMR (CDCl3) 3.23 (d, 2H, J = 12 Hz), 3.72 (s,
3H), 4.07, 4.21 (d of AB, 2H, J = 21.0, 15.0, 6.4 Hz), 4.87 (t,
1H, J = 12 Hz), 5.1-5.3 (m, 2H), 5.6-5.9 (m, 1H). 13C NMR
(CDCl3): 46.8 (CH), 52.9 (CH3), 53.1 (CH2), 78.2 (CH2),
119.3 (CH2), 132.2 (CH), 168.9 (CO); CIMS m/z (%) 170
(M+1, 20), 142 (20), 110 (4), 55 (100).
6au was pre pared in a yield of 84% by the re ac tion of
allyl azide and methyl acrylate (mo lar ra tio = 1:2) fol low ing
procedureAusingTHFasthesolvent. 6au is a yel low oil.1H
NMR (CDCl3): 2.38 (dd, 1H, J = 9.5, 6.5 Hz), 2.39 (t, 2H, J =
7.5 Hz), 2.66 (t, 2H,J = 7.5 Hz), 2.63-2.70 (m, 2H), 2.73, 3.43
(AX, 2H, J = 10.0 Hz), 3.60 (s, 3H), 3.75 (s, 3H), 4.45, 4.75
(AB part of ABX, 2H, JAB = 18.5 Hz, JAX = 9.0 Hz, JBX = 3.5
Hz). 13C NMR (CDCl3): 33.2 (CH2), 37.8 (CH), 49.1 (CH2),
51.3 (CH3), 52.6 (CH3), 58.7 (CH2), 60.0 (CH2), 85.9 (CH2),
104.9 (C), 169.0 (CO), 172.2 (CO); EIMS m/z (%) 255 (M,
15), 227 (10), 196 (12), 168 (21), 154 (100). HRMS: Calcd.
for C11H17N3O4: 255.1215, Found: 255.1214.
1-Allyl-4-cyano- 2-1,2,3-triazaoline (3av)
The re ac tion of allyl azide and acrylonitrile us ing chlo-
roformasthesolventgave3av in 2 days. 3avwas ob tained as
a yel low oil in a yield of 85%. 1H NMR (CDCl3): 3.9-4.15 (m,
2H), 4.2-4.4 (m, 1H), 4.5-4.7 (m, 2H), 5.2-5.4 (m, 2H), 5.7-
6.0 (m, 1H).13C NMR (CDCl3): 45.8 (CH), 52.0 (CH2), 70.1
(CH2), 118.5 (CN), 120.2 (CH2), 131.2 (CH); EIMS m/z (%)
136 (M, 12), 108 (32).
7-(2-Cyanoethyl)-1-Cyano-2,3,7-triazabicyclo[3.3.0]oct-2-
ene (6av)
Thereactionofallylazideandacrylonitrile(molarratio
= 1:2) us ing DMSO as the sol vent gave 6av in a yield of 88%
yield in 2 days. 6avis a yel low oil.1H NMR (CDCl3): 2.42 (t,
2H, J = 6.6 Hz), 2.56 (dd, 1H,J = 10.0, 6.0 Hz), 2.64-2.80 (m,
2H), 2.76 (d, 1H, J = 10.4 Hz), 2.81 (d, 1H, J = 10.0 Hz),
2.8-2.9 (m, 1H), 3.62 (d, 1H, J = 10.4 Hz), 4.59 (dd, 1H, J =
19.0, J = 3.6 Hz), 4.91 (dd, 1H, J = 19.0 Hz, J = 9.0 Hz). 13C
NMR (CDCl3): 17.0 (CH2), 39.6 (CH), 48.2 (CH2), 59.4
(CH2), 60.3 (CH2), 87.3 (CH2), 90.9 (C), 116.4 (CN), 117.9
(CN).
1-Methoxycarbonyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene
(5au)
5au(in a yield of 70%) was pre pared from the re ac tion
of allyl azide and methyl acrylate in 4 days by pro ce dure A
usingchloroformasthesolvent.Inaddition,amixedsolvent
of dimethyl sulfoxide (DMSO) and n-hexane (1:1) also give
5au in a yield of 75%. 5au is a yel low oil.1H NMR (CDCl3):
2.67-2.76 (m, 2H), 3.01 (dd, 1H,J = 12.2, 7.1 Hz), 3.31, 3.58
(AB, 2H, J = 12.7 Hz), 3.75 (s, 3H), 4.44, 4.69 (AB part of
ABX, 2H,JAB = 18.6 Hz,JAX = 8.7 Hz, JBX = 3.0 Hz). 13C NMR
(CDCl3): 40.5 (CH), 52.8 (CH3), 54.9 (CH2), 55.7 (CH2), 85.4
(CH2), 108.1 (C), 169.6 (CO); CIMS m/z (%) 170 (M+1, 28),
141 (2), 110 (11), 82 (100). HRMS: Calcd for C7H11N3O2:
169.0849, Found: 169.0860.
7-(3-Oxo-n-butyl)-1-acetyl-2,3,7-triazabicyclo[3.3.0]oct-2-
ene (6aw)
The re ac tion of allyl azide and methyl vi nyl ketone
(mo lar ra tio = 1:2) us ing chlo ro form or THF as the sol vent
followingprocedureAgave6aw in a yield of 81% and 87%,
respectively, in2days. 6awis a yel low oil. 1H NMR (CDCl3):
2.03 (s, 3H), 2.28 (dd, 1H, J = 9.6, 6.0 Hz), 2.31 (s, 3H), 2.41
(d, 1H, J = 10 Hz), 2.43-2.47 (m, 2H), 2.58 (t, 2H, J = 6.8
HZ), 2.62 (d, 1H, J = 9.6 Hz), 2.66 (m, 1H), 3.40 (d, 1H, J =
10.0 Hz), 4.34, 4.66 (AB part of ABX, 2H,JAB = 18.6. Hz, JAX
= 9.4 Hz, JBX = 3.8 Hz). 13C NMR (CDCl3): 28.3 (CH3), 29.8
(CH3), 35.4 (CH), 42.3 (CH2), 48.3 (CH2), 59.6 (CH2), 60.6
(CH2), 85.6 (CH2), 112.5 (C), 202.4 (C=O), 207.2 (C=O);
EIMS m/z (%) 223 (M, 17), 195 (54), 180 (56), 152 (42), 138
1-Cyano-2,3,7-triazabicyclo[3.3.0]oct-2-ene (5av)
Using THF as the sol vent, 5av was pre pared in a yield
of91%followingprocedureAin14days. 5avis a yel low oil.
1H NMR (CDCl3): 2.85-2.95 (m, 2H), 3.07 (m, X part of
ABX, 1H), 3.27, 3.78 (AB, 2H, J = 12.0 Hz), 4.59, 4.91 (AB
part of ABX, 2H,JAB = 19 Hz, JAX = 9.0 Hz, JBX = 2.8 Hz), 13C
NMR (CDCl3): 41.8 (CH), 55.4 (CH2), 56.9 (CH2), 86.8

PreparationbyTandemCascadeReaction
(62).
J. Chin. Chem. Soc., Vol. 49, No. 1, 2002 99
2-methyl-2-propenyl azide and acrylotrile fol low ing pro ce-
dure A us ing THF as the sol vent. 5bv is a yel low solid, mp.
108-109 C. 1H NMR (CDCl3): 1.37 (s, 3H), 2.70 (d, 1H, J =
11.8 Hz), 3.00 (d, 1H,J = 11.8 Hz), 3.25 (d, 1H, J = 12.4 Hz),
3.75 (d, 1H, J = 12.4 Hz), 4.51, 4.68 (AB, 2H, J = 19.0 Hz).
13C NMR (CDCl3): 20.5 (CH3), 47.7 (C), 57.3 (CH2), 62.3
(CH2), 92.9 (CH2), 97.8 (C), 115.1 (CN). EIMS m/z (%) 15
(M, 1), 121 (31), 93 (100).
1-Aminocarbonyl-7-(2-aminocarbonylethyl)-2,3,7-
triazabicyclo[3.3.0]oct-2-ene (6ax)
The re ac tion of allyl azide and acrylamide (mo lar ra tio
= 1:2) in THF gave 6axin a yield of 66% in 2 days fol low ing
procedureA.6ax is a white solid, mp.: 172-174 C. 1H NMR
(CDCl3): 1.84 (t, 2H, J = 6.8 Hz), 1.99 (dd, 1H, J = 8.8, 6.4
Hz), 2.19 (dd, 1H, J = 8.8, 5.2 Hz), 2.22 (t, 2H, J = 6.8 Hz),
2.30-2.37 (m, 1H), 2.35 (d, 1H, J = 10.0 Hz), 3.07 (d, 1H, J =
10.0 Hz), 3.94 (dd, 1H, J = 18.8, 3.6 Hz), 4.32 (dd, 1H, J =
18.8, 9.6 Hz), 5.87 (s, 1H), 6.57 (s, 1H), 6.76 (s, 2H). 13C
NMR (CDCl3): 34.6 (CH2), 36.8 (CH), 50.2 (CH2), 60.4
(CH2), 60.7 (CH2), 85.5 (CH2), 106.3 (C), 170.1 (C=O), 173.3
(C=O); EIMS m/z (%) 197 (M-28, 30), 182 (9), 114 (100).
1-Cyano-2,3,7-triazabicyclo[3.3.0]oct-3-ene (7av)
5avdis solved in THF is heated to 50 C for 4 hours; af-
ter evap o ra tion of the sol vent, 7av was ob tained quan ti ta-
1
tively. 7av is a white solid, m.p. 120-121 C. H NMR
(CDCl3): 2.08 (s, 1H), 3.04 (d, 1H, J = 12.5 Hz), 3.09 (dd, 1H,
J = 12.6, 7.6 Hz), 3.23 (dd, 1H, J = 12.6, 2.0 Hz), 3.42 (d, 1H,
J = 12.5 Hz), 3.99 (ddd, 1H,J = 7.6, 2.2, 2.0 HZ), 6.14 (s, 1H),
6.66 (d, 1H,J = 2.2 Hz),13C NMR (CDCl3): 53.1 (CH2), 61.2
(CH2), 62.0 (CH), 65.4 (C), 119.5 (C), 144.0 (CH); EIMS m/z
(%) 137 (M+1, 17), 93 (80). HRMS: Calcd. for C6H8N4:
136.0748, Found: 136.0757.
1-Methoxycarbonyl-4-phenyl-2,3,7-triazabicyclo[3.3.0]oct-
3-ene (7cu)
7cu was pre pared by the re ac tion ofE-3-phenylallyl
azideandmethylacrylatefollowingprocedureAinayieldof
82%. 7cu is a white solid, mp. 180-182 C; 1H NMR (CDCl3):
3.17 (d, 1H, J = 12.0 Hz), 3.2-3.40 (m, 2H), 3.31 (d, 1H, J =
12.0 Hz), 3.80 (s, 3H), 4.8 (dd, 1H, J = 5.4, 3.4 Hz), 6.54 (b,
1H), 7.30-7.37 (m, 3H), 7.56-7.61 (m, 2H). 13C NMR (CDCl3):
52.9 (CH3), 54.3 (CH2), 58.2 (CH2), 61.1 (CH2), 81.1 (C),
126.1 (CH), 128.1 (CH), 129.0 (CH), 131.2 (C), 153.2 (C),
173.9 (C=O). EIMS m/z (%) 245 (M, 8), 203 (74), 186 (5),
171 (100). HRMS: Calcd. for C 13H15N3O2: 245.1161, Found:
245.1160.
Crys tal data for 7av:Colorlesssinglecrystal, 0.3 0.3
0.4 mm, rhombohedral, space group P3221, unit cell di men-
sions: a = 6.0988(5) Å, c = 31.485(4) Å; V = 1014.2(3) Å3;
dcalcd = 1.338 g/cm3 (Z 6); ra di a tion Mo-K ; limits(max)
23.3º, to tal re flec tion scanned 3907, 976 unique re flec tions,
968 ob served re flec tions with F > 2 (F); R = 0.045; Rw =
0.052; 123 re fined pa ram e ters. List of po si tional and aniso-
tropicthermalparametersofnon-hydrogenatoms,positional
andthermalparametersofhydrogenatoms,bonddistances
and bond an gles are avail able upon re quest.
1-Methoxycarbonyl-7-(2-methoxycarbonylethyl)-4-methyl-
2,3,7-triazabicyclo[3.3.0]oct-2-ene (6du)
Pro ce dure B: Gen eral pro ce dure for the Mi chael
addition of 5 to alkenes
6du was pre pared by the re ac tion of 2-butenyl azide
andmethylacrylatefollowingprocedureAinayieldof51%.
6du is a yel low liq uid;1H NMR (CDCl3): 1.34 (d, 3H, J = 7.2
Hz), 2.27 (dd, 1H, J = 6.3, 3.3 Hz), 2.39 (dd, 1H, J = 9.0, 6.6
Hz), 2.42 (t, 2H, J = 6.9 Hz), 2.69 (t, 2H, J = 6.9 Hz), 2.70 (d,
1H, J = 10.2 Hz), 2.77 (d, 1H, J = 9.0 Hz), 3.47 (d, 1H, J =
10.2 Hz), 3.64 (s, 3H), 3.78 (s, 3H), 4.60 (dq, 1H, J = 7.2, 3.9
Hz). 13C NMR (CDCl3): 18.7 (CH3), 33.4 (CH2), 45.4 (CH2),
49.3 (CH2),51.6 (CH3), 52.9 (CH3), 58.8 (CH), 59.7 (CH2),
94.4 (CH), 105.0 (C), 169.4 (C=O), 172.4 (C=O). MS
(EIMS) m/z (%) 269 (M, 3), 241 (8), 226 (29), 168 (100).
HRMS: Calcd. for C12H19N3O4: 269.1371, Found: 269.1374.
To a so lu tion of one equiv a lent of 5 dis solved in THF,
one equiv a lent of alkene is added slowly. The so lu tion is
stirred for one day. The crude is ob tained af ter the sol vent is
rotatoryevaporated.Ayellowoilisobtainedbycolumnchro-
ma tog ra phy us ing sil ica gel as the pack ing ma te rial and the
mixed sol vent of ethyl ac e tate and n-hexane (3:1) as the
eluent.
7-(3-Oxo-n-butyl)-1-Methoxycarbonyl-2,3,7-triazabicyclo-
[3.3.0]oct-2-ene (6au-1)
6au-1 was pre pared in a yield of 93% by the re ac tion of
5au andmethylvinylketonefollowingprocedureB.6au-1 is
a yel low liq uid, 1H NMR (CDCl3): 2.01 (s, 3H), 2.32, 2.64
(AM part of AMX, 2H,JAM = 9.2 Hz,JAX =6.5 Hz,JMX = 0 Hz),
1-Cyano-5-methyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene (5bv)
5bv was pre pared in a yield of 40% by the re ac tion of

100 J. Chin. Chem. Soc., Vol. 49, No. 1, 2002
Yang et al.
2.45 (t, 2H, J = 6.3 Hz), 2.58 (t, 2H,J = 6.3 Hz), 2.57 (d, 1H, J
= 10.4 Hz), 2.67 (m, 1H), 3.35 (d, 1H, J = 10,4 Hz), 3.68 (s,
3H), 4.39, 4.65 (AB part of ABX, 2H, JAB = 18.4 Hz, JAX = 9.1
Hz, JBX = 3.5 Hz). 13C NMR (CDCl3): 29.8 (CH3), 37.9 (CH),
42.2 (CH2), 48.4 (CH2), 52.7 (CH3), 59.0 (CH2), 60.4 (CH2),
86.0 (CH2), 104.8 (C), 170.0 (CO), 207.1 (CO); CIMS m/z
(%) 240 (M+1, 100), 239 (63), 212 (22). HRMS: Calcd. for
C11H17N3O3: 239.1266, Found: 239.1270.
Hz). 13C NMR (CDCl3): 13.9 (CH3), 20.4 (CH2), 30.4 (CH2),
38.0 (CH), 52.7 (CH3), 54.2 (CH2), 59.4 (CH2), 60.7 (CH2),
86.0 (CH2), 105.2 (C), 169.4 (CO); EIMS m/z (%) 225 (M+,
19), 196 (5), 154 (100). HRMS: Calcd. for C11H19N3O2:
225.1373, Found: 225.1483.
7-Benzyl-1-Methoxycarbonyl-2,3,7-triazabicyclo[3.3.0]oct-
2-ene (6au-4)
6au-4 was pre pared in a yield of 71% by the re ac tion of
5au and benzyl chlo ride fol low ing pro ce dure C. 6au-4 is a
7-(2-Ethoxycarbonylethyl)-1-Methoxycarbonyl-2,3,7-
triazabicyclo[3.3.0]oct-2-ene (6au-2)
1
yel low liq uid, H NMR (CDCl3): 2.38, 2.59 (AM part of
6au-2 was pre pared in a yield of 83% by the re ac tion of
5au andethylacrylatefollowingprocedureB. 6au-2 is a yel-
low liq uid,1H NMR (CDCl3): 1.14 (t, 3H,J = 7.1 Hz), 2.33 (t,
2H, J = 7.1 Hz), 2.35, 2.67 (AM part of AMX, 2H, JA M = 9.4
Hz, JAX = 6.2 Hz,JMX = 0 Hz), 2.62 (t, 2H,J = 7.1 Hz), 2.63 (d,
1H, J = 10.3 Hz), 2.68 (m, 1H), 3.42 (d, 1H,J = 10.3 Hz), 3.73
(s, 3H), 4.04 (q, 2H, J = 7.1 Hz), 4.40, 4.74 (AB part of ABX,
2H, JAB = 18.3 Hz, JAX = 9.1 Hz, JBX = 3.5 Hz). 13C NMR
(CDCl3): 14.1 (CH3), 33.6 (CH2), 38.0 (CH), 49.4 (CH2), 52.8
(CH3), 59.0 (CH2), 60.2 (CH2), 60.4 (CH2), 86.0 (CH2), 104.9
(C), 169.1 (CO), 171.9 (CO); EIMS m/z (%) 269 (M, 63), 241
(40), 153 (100). HRMS: Calcd. for C12H19N3O2: 269.1371,
Found: 269.1378.
AMX, 2H, JAM = 9.2 Hz, JAX = 6.40 Hz, JMX = 0 Hz), 2.75 (d,
1H, J = 10.4 Hz), 2.70-2.80 (m, 1H), 3.44 (d, 1H, J = 10.4
Hz), 3.51, 3.55 (AB, 2H,J = 13.1 Hz), 3.74 (s, 3H), 4.48, 4.76
(AB part of ABX, 2H, JAB = 18.3 Hz, JAX = 9.0 Hz, JBX = 3.6
Hz), 7.17-7.28 (m, 5H). 13C NMR (CDCl3): 38.1 (CH), 52.7
(CH3), 58.2 (CH2), 59.0 (CH2), 60.1 (CH2), 86.0 (CH2), 105.2
(C), 127.1 (CH), 128.2 (CH), 128.3 (CH), 138.0 (C), 169.3
(CO); EIMS m/z (%) 259 (M+, 5), 232 (2), 91 (100). HRMS:
Calcd. for C14H17N3O2: 259.1317, Found: 259.1318.
1-Cyano-7-propyl-2,3,7-triazabicyclo[3.3.0]oct-2-ene
(6av-1)
6av-1was pre pared in a yield of 74% by the re ac tion of
5av and propyl bro mide fol low ing pro ce dure C.6av-1 is a
yellowliquid,1H NMR (CDCl3): 0.75 (t,J = 7.5 Hz, 3H), 1.32
(q, J = 7.5 Hz, 2H), 2.25 (t, J = 7.5 Hz, 2H), 2.34, 3.49 (AM
part of AMX, 2H, JAM = 10.3 Hz, JAX =5.9 Hz, JMX = 0 Hz),
2.53 (d, 1H, J = 10.3 Hz), 2.71-2.78 (dddd, 1H, J = 9.3, 5.9,
3.4, 0 Hz), 3.49 (d, 1H, J = 10.3 Hz), 4.50, 4.86 (AB part of
ABX, 2H,JAB = 18.7 Hz,JAX = 9.3 Hz,JBX = 3.4 Hz).13C NMR
(CDCl3): 11.4 (CH3), 21.1 (CH2), 39.5 (CH), 55.2 (CH2), 59.7
(CH2), 60.7 (CH2), 87.1 (CH2), 91.1 (C), 116.8 (CN); EIMS
m/z (%) 179 (M+1, 100), 151 (74), 121 (43). HRMS: Calcd
for C9H14N4: 178.1216, Found: 178.1219.
Procedure C: General procedure for the substitution
reactionof 5 to alkyl halide
A pre cip i tate is ob tained from the mix ture of equal
moles of5 andalkylhalidedissolvedinTHFstirringforthree
days. The pre cip i tate is sep a rated from the sol vent and neu-
tral ized us ing a 5% NaHCO3 so lu tion. The crude prod uct is
obtainedafterextractionwithchloroformandtheremovalof
the sol vent by ro ta tory evap o ra tion. A brown oil is ob tained
bycolumnchromatographyusingsilicagelasthestationary
phase and the mix ture of chlo ro form and n-hexane (3:1) as
the eluent.
7-Allyl-1-cyano-2,3,7-triazabicyclo[3.3.0]oct-2-ene (6av-2)
6av-2was pre pared in a yield of 77% by the re ac tion of
5av andallylbromidefollowingprocedureC.6av-2 is a yel-
low liq uid,1H NMR (CDCl3): 2.40, 2.68 (AM part of AMX,
2H, JAM = 9.6 Hz, JAX =5.9 Hz, JMX = 0 Hz), 2.59 (d, 1H, J =
10.3 Hz), 2.77 (dddd, 1H, J = 9.3, 5.9, 3.4, 0 Hz), 2.97 (d, J =
6.4 Hz, 2H), 3.52 (d, 1H, J = 10.3 Hz), 4.55, 4.93 (AB part of
ABX, 2H, JAB = 18.7 Hz, JAX = 9.3 Hz, JBX = 3.4 Hz). 5.07-
5.15 (m, 2H), 5.62-5.74 (m, 1H). 13C NMR (CDCl3): 39.7
(CH), 56.2 (CH2), 59.6 (CH2), 60.5 (CH2), 87.2 (CH2), 91.3
(C), 116.8 (CN), 117.9 (CH), 134.0 (CH2); CIMSm/z (%) 177
7-Butyl-1-Methoxycarbonyl-2,3,7-triazabicyclo[3.3.0]oct-
2-ene (6au-3)
6au-3 was pre pared in a yield of 88% by the re ac tion of
5au andbutylbromidefollowingprocedureC.6au-3is a yel-
1
low liq uid, H NMR (CDCl3): 0.82 (t, J = 7.4Hz, 3H),
1.16-1.37 (m, 4H) 2.30 (t, J = 6.9 Hz, 2H), 2.27, 2.66 (AM
part of AMX, 2H, JA M = 9.4 Hz, JAX = 6.3 Hz, JMX = 0 Hz),
2.60 (d, 1H, J = 10.2 Hz), 2.65 (dddd, 1H, J = 10.6, 6.2, 3.7,
0.1 Hz), 3.40 (d, 1H, J = 10.2 Hz), 3.73 (s, 3H), 3.46, 4.74
(AB part of ABX, 2H, JAB = 18.3 Hz, JAX = 9.0 Hz, JBX = 3.5

PreparationbyTandemCascadeReaction
J. Chin. Chem. Soc., Vol. 49, No. 1, 2002 101
(M+1, 100), 149 (61), 99 (65), 84 (70). HRMS: Calcd. for
C9H12N4: 176.1060, Found: 176.1068.
207.4 (C=O); CIMS m/z (%) 240 (M+1, 77), 182 (35), 113
(100). HRMS: Calcd. for C11H17N3O3: 239.1266, Found:
239.1260.
1-Cyano-7-(2-propynyl)-2,3,7-triazabicyclo[3.3.0]oct-2-ene
(6av-3)
1-(Methoxycarbonyl)-7-benzyl-2,3,7-triazabicyclo[3.3.0]-
oct-3-ene (7au-2)
6av-3was pre pared in a yield of 71% by the re ac tion of
5av and2-propynylbromidefollowingprocedureC.6av-3 is
a yel low liq uid,1H NMR (CDCl3): 2.24 (t, J = 2.3 Hz, 1H),
2.51, 2.65 (AM part of AMX, 2H, JAM = 9.6 Hz, JAX =5.8 Hz,
JMX = 0 Hz), 2.76 (dddd, 1H,J = 9.3, 5.9, 3.4, 0 Hz), 2.86, 3.36
(AB, 2H, J = 10.8 Hz), 3.28 (d, J = 2.4 Hz, 2H), 4.51, 4.85
(AB part of ABX, 2H, JAB = 18.7 Hz, JAX = 9.0 Hz, JBX = 3.3
Hz). 13C NMR (CDCl3): 39.3 (CH), 40.2 (CH2), 57.6 (CH2),
58.4 (CH2), 74.2 (CH), 76.3 (C), 87.0 (CH2), 91.0 (C), 116.4
(CN); CIMS m/z (%) 175 (M+1, 100), 147 (76), 82 (95).
HRMS: Calcd. for C9H10N4: 174.0904, Found: 174.0914.
The isomerization of 6au-4 to 7au-2 fol lowed the same
procedureasthatforthepreparationof7au-1. The yield was
1
87%. 7au-2is a yel low liq uid, H NMR (CDCl3): 2.54, 2.90
(AM part of AMX, 2H, JA M = 9.1 Hz, JAX = 7.5 Hz, JMX = 0
Hz), 2.70, 3.02 (AB, 2H, J = 9.6 Hz), 3.53, 3.65 (AB, 2H, J =
13.1 Hz), 3.71 (s, 3H, OCH3), 3.78 (m, 1H), 6.16 (s, 1H), 6.17
(s, 1H), 7.14-7.26 (m, 5H). 13C NMR (CDCl3): 52.7 (CH3),
56.7 (CH2), 57.0 (CH2), 58.5 (CH), 65.1 (CH2), 74.2 (C),
126.9 (CH), 128.1 (CH), 128.4 (CH), 137.8 (C), 144.4 (CH),
173.0 (C=O); EIMS m/z (%) 260 (M+1, 100), 91 (25).
HRMS: Calcd. for C14H17N3O2: 259.1317, Found: 259.1302.
1-Methoxycarbonyl-7-(2-methoxycarbonylethyl)-2,3,7-
triazabicyclo[3.3.0]oct-3-ene (7au)
Supplementary Materials
Ta bles of crys tal data for7av includingtablesofhydro-
gen co or di nates, U val ues, bond lengths, bond an gles, aniso-
tropicparameters,anddatacollectionparameters.
To 1 g of 6au dis solved in 5 mL of meth a nol kept at 0
C, a so lu tion of 2 mL con cen trated hy dro chlo ric acid in 15
mL meth a nol was added dropwise. The mix ture was stirred
foronehour.Thesolventwasrotatoryevaporatedandtheres-
iduewasneutralizedbya5%NaHCO3 solution.Theaqueous
so lu tion was then ex tracted with THF. Af ter evap o ra tion of
THF, 7au could be ob tained as an or ange oil in a yield of
90%. 7au is a yel low liq uid, 1H NMR (CDCl3): 2.64 (t, 2H, J
= 7.4 Hz), 2.66 (d, 1H, J = 8.2 Hz), 2.78 (d, 1H, J = 9.4 Hz),
2.80 (t, 2H, J = 7.4 Hz), 2.88 (m, 1H), 3.04 (dd, 1H, J = 9.4,
2.1 Hz), 3.10 ( , 1H, J = 9.5 Hz), 3.67 (s, 3H), 3.78 (s, 3H),
6.15 (bs. 1H), 6.61 (d, 1H, J = 1.2 Hz), 13C NMR (CDCl3):
33.2 (CH2), 49.7 (CH2), 51.5 (CH3), 55.8 (CH3), 56.6 (CH),
57.3 (CH2), 65.1 (CH2), 74.2 (C), 144.2 (CH), 172.3 (C=O),
172.9 (C=O); MS (EIMS) m/z (%) 255 (M, 4), 240 (6), 224
(33), 196 (100). HRMS: Calcd. for C11H17N3O4: 255.1223,
Found: 255.1215.
Received July 23, 2001.
Key Words
Allyl azide; Cycloaddition; Diazo compounds;
Isomerization; Bicyclic heterocyclic com pounds;
Tandem cascade reaction; One-pot reaction.
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1-(Methoxycarbonyl)-7-(3-oxo-1-butyl)-2,3,7-triazabicyclo-
[3.3.0]oct-3-ene (7au-1)
The isomerization of 6au-1 to7au-1 fol lowed the same
pro ce dure as that for the prep a ra tion of 7au. 7au-1 could be
ob tained as a yel low oil in a yield of 85%,1H NMR (CDCl3):
2.11 (s, 3H), 2.51, 2.80 (AM part of AMX, 2H,JAM = 9.2 Hz,
JAX = 6.4 Hz, JMX = 0 Hz), 2.65 (t, J = 7.4 Hz, 2H), 2.68, 3.02
(AB, 2H, J = 9.6 Hz), 2.76 (t, J = 7.4 Hz, 2H), 2.96 (m, 1H),
3.76 (s, 3H), 6.22 (s, 1H), 6.25 (s, 1H). 13C NMR (CDCl3):
30.1 (CH3), 42.6 (CH2), 48.9 (CH2), 52.9 (CH3), 56.8 (CH2),
57.7 (CH2), 65.5 (CH2), 74.4 (C), 144.5 (CH), 173.1 (C=O),

102 J. Chin. Chem. Soc., Vol. 49, No. 1, 2002
Yang et al.
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