Combination of hydrazine polyanion strategy and ring-closing metathesis in the synthesis of heterocycles

Article abstract of DOI:10.1016/j.tet.2011.11.091

An efficient method for the synthesis of cyclic hydrazine derivatives starting from disubstituted hydrazines is reported. The method is based on the selective alkylation of hydrazine dianions with bromoalkenes and subsequent cyclization using Grubbs' cata

Full text of DOI:10.1016/j.tet.2011.11.091

Tetrahedron 68 (2012) 1011e1016
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Combination of hydrazine polyanion strategy and ring-closing metathesis in the
synthesis of heterocycles
*
ꢀ
€
Svetlana Tsupova, Oleg Lebedev, Uno Maeorg
Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient method for the synthesis of cyclic hydrazine derivatives starting from disubstituted hydra-
zines is reported. The method is based on the selective alkylation of hydrazine dianions with bro-
moalkenes and subsequent cyclization using Grubbs’ catalysts. The described method provides fast and
easy access to the substrates for ring-closing metathesis and the corresponding heterocycles containing
a hydrazine moiety. The scope and limitations of the new method are also demonstrated.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 22 September 2011
Received in revised form 5 November 2011
Accepted 28 November 2011
Available online 6 December 2011
Keywords:
Hydrazines
Heterocycles
Alkylation
Dianion
Ring-closing metathesis
1. Introduction
alkene-bearing hydrazines was not solved, which still hampers the
development of effective hydrazine-based RCM platform.
Hydrazine derivatives are well-known compounds used as
pesticides, dyes, drugs and building blocks in organic synthesis.
Currently known hydrazine-based drugs are used for the treatment
of tuberculosis, hypertension and Parkinson’s disease.1 Some hy-
drazines demonstrate neuroprotective properties and are used as
antidepressants.2 Also, hydrazine-based peptidomimetics were
shown to be potent agents against hepatitis3 and AIDS.4 In recent
years, great interest in the synthesis of heterocyclic hydrazine de-
rivatives has emerged since certain compounds were proven to
show remarkable biological activities.5e7
A number of methods for the synthesis of heterocycles con-
taining endocyclic NeN bond have been developed. Mainly these
compounds are prepared by direct alkylation of hydrazines with
dihalides,8e10 however, DielseAlder11,12 and Mitsunobu13 trans-
formations are also utilized. These methods are good for the syn-
thesis of particular molecules, but the scope is limited to five-, six-
and seven-membered rings. The scope may be significantly ex-
panded by applying a ring-closing metathesis (RCM) strategy,
however, it requires efficient methods for the synthesis of the
corresponding dienes, which is an additional challenge. Synthesis
of cyclic hydrazines by the RCM reaction was first mentioned by
Tae.14,15 At the same time, the problem of efficient synthesis of
In our current work we provide an efficient one-pot method for
the synthesis of the corresponding dienes based on a hydrazine
polyanion strategy, the advantages of which have been shown in
our previous works.16e19 The dienes were further converted to the
corresponding heterocycles via the RCM reaction.
2. Results and discussion
We started with symmetrical dialkylation of dianions with
bromoalkenes (Scheme 1). The dianions from PhNHNHBoc,
EtNHNHBoc and BocNHNHBoc were generated by treatment with
2 equiv of BuLi in THF at ꢀ78 ꢁC with subsequent addition of the
alkylating agent. The reaction progress was monitored by TLC. The
addition of 2 equiv of allyl bromide to the dianions lead to the rapid
formation of the monoalkylated products (1 h) and the slow for-
mation of the dialkylated products (1e3 days) even at 40 ꢁC. At
room temperature the reactions were incomplete. Unfortunately,
we failed to introduce the alkenyl groups with longer chain in the
similar manner obtaining the monoalkylated products with a small
amount of the dialkylated species. We propose the different rea-
sons for the alkylation reactions with 4-bromobutene and 5-
bromopentene. The dianion being also a strong base may pro-
mote elimination of 4-bromobutene with formation of butadiene.
We suppose the dialkylation with 5-bromopentene was incomplete
because of steric problems as similar behaviour has been previously
observed.16
* Corresponding author. Tel.: þ372 7375243; fax: þ372 7375264; e-mail address:
€
uno@chem.ut.ee (U. Maeorg).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.091

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S. Tsupova et al. / Tetrahedron 68 (2012) 1011e1016
Table 2
R1
Boc
R1
Boc
H
2 equiv BuLi
Products of mono- and double alkylation
N
N
N
N
Ph
N
Boc
m
H
1 equiv
Br
n
n
N
R2
R2
1a-f
n
1 equiv
Br
R
THF
R1 = Ph, Et, Boc; R2 = H, Me;
n = 1-3
R
n
m
Conditions
Yield, %
2a16
2b
2c
1d
1g
1h
1i
1j
1k
1k
1
2
3
2
1
1
1
2
2
2
AllBr, ꢀ78 ꢁC, 1 h;
90
80
75
CH2]CH(CH2)2Br, ꢀ78 ꢁC, 1 h
CH2]CH(CH2)3Br, ꢀ78 ꢁC, 1 h
1 equiv AllBr, rt, 1day
Scheme 1. Direct dialkylation of dianions.
81a
93a
91a
61a
71a
79a
65b
Considering these limitations next we tried the consecutive
one-pot monoalkylation of both nitrogens of the PhNHNHBoc
dianion to introduce the alkenyl groups with longer or branched
chain onto the Ph nitrogen and smaller allyl group onto the Boc
nitrogen (Scheme 1). The corresponding products were obtained in
good yields (Table 1). Again, the formation of the dialkylated
products took 1e2 days at 40 ꢁC.
H
H
H
Me
H
1
2
3
1
2
3
3
1 equiv CH2]CH(CH2)2Br, rt, 1 day
1 equiv CH2]CH(CH2)3Br, rt, 1 day
1 equiv CH2]C(CH3)CH2Br, rt, 1 day
2 equiv CH2]CH(CH2)2Br, rt, 2 days
1 equiv CH2]CH(CH2)3Br, rt, 1 day
1 equiv CH2]CH(CH2)2Br, ꢀ78 ꢁC, 1 h;
1 equiv CH2]CH(CH2)3Br, rt, 1 day
2 equiv CH2]CH(CH2)2Br, rt, 2 days
H
H
1l
H
3
2
71a
a
Table 1
Synthesized from the corresponding monoalkylated derivative.
One-pot synthesis starting from PhNHNHBoc.
b
Products of direct alkylation of dianions
R1
N
Boc
N
using 2 and 5 mol % of the catalyst the corresponding six-
membered ring 3a was obtained in 39% and 89% yields, re-
spectively. All other dienes containing unsubstituted double bonds
except 1b were cyclized under the same conditions (Table 3).
Compound 1b did not react at all in the presence of Grubbs’ first
generation catalyst, so, the corresponding cycle was obtained by
employing Grubbs’ second generation catalyst. A possible reason
for such behaviour is that 1b may also act as a ligand interacting
and deactivating the catalyst. The interaction with the second
generation catalyst must be much weaker because of higher elec-
tron density on the Ru atom and hence the ring-closed product 3b
may be obtained. Prochiral cycles 3f and 3i were also synthesized
utilizing Grubbs’ second generation catalyst.
n
R2
R1 R2
n
Conditions
Yield, %
1a16 Ph
1b Et
1c20 Boc
H
H
H
H
H
1
1
1
2
3
1
2 equiv of AllBr, ꢀ78 ꢁC to 40 ꢁC, 1 day
2 equiv of AllBr, ꢀ78 ꢁC to 40 ꢁC, 1 day
2 equiv of AllBr, ꢀ78 ꢁC to 40 ꢁC, 3 days
77
49
81
1d
1e
1f
Ph
Ph
CH2]CH(CH2)2Br, ꢀ78 ꢁC, 1 h; AllBr, 40 ꢁC, 2 days 60
CH2]CH(CH2)3Br, ꢀ78 ꢁC, 1 h; AllBr, 40 ꢁC, 2 days 81
CH2]C(CH3)CH2Br, ꢀ78 ꢁC, 1 h; AllBr, 40 ꢁC, 1 day 80
Ph Me
To synthesize the dienes containing substituents with a longer
chain on the Boc nitrogen we worked out another methodology. At
first we performed monoalkylation of the PhNHNHBoc dianion
with 1 equiv of the alkylating agent. The monoalkylated derivatives
formed within 1 h and were obtained in very good yields. Further
alkylation was performed under PTC conditions (K2CO3/NaOH/
TBAHS/toluene) at room temperature (Scheme 2).
Grubbs' 1st or 2nd
generation catalyst,
R1
R2
R1
R2
5 mol %
N
N
N N
DCM
m
n
n
m
R3
1a-l
R3
3a-l
R1, R2 = Ph, Et, Boc; R3 = H, Me;
n, m = 1-3
Br
m
R
Ph
N N
Ph
H
Boc
H
Boc
m
Ph
Boc
H
Scheme 3. Ring-closing metathesis of dienes.
2 equiv BuLi
1 equiv
N
N
N
N
PTC
Br
n
Table 3
Products of ring-closing metathesis
n
n
1 equiv
THF
R
1d, 1g-l
R1
N
R2
N
2a-c
R = H, Me;
n = 1-3; m = 1-3
n
m
Scheme 2. Monoalkylation of dianions and further alkylation under PTC conditions.
R3
Generally 1 equiv of the alkylating agent was used and the re-
action was complete after 1 day. However, in some cases (entries 1j
and 1l) 2 equiv of 4-bromobutene and longer reaction times were
required. The corresponding dienes were obtained in good or ex-
cellent yields (Table 2). As both alkylation reactions were very clean
we decided to make this approach easier and to perform the same
reaction sequence in a one-pot fashion without separation of the
monoalkylated product. We found that such way has the same ef-
ficiency and may be successfully used (entry 1k). To the best of our
knowledge, this one-pot method for the synthesis of alkene-
bearing hydrazines has not been previously reported.
R1
R2
R3
n
m
Conditions
Yield, %
3a
3b
3c21
3d
3e
3f
3g
3h
3i
Ph
Et
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Ph
H
H
H
H
H
Me
H
H
Me
H
1
1
1
2
3
1
1
1
1
2
2
3
1
1
1
1
1
1
2
3
1
2
3
2
GI, 5 mol %, rt, 30 mina
GII, 5 mol %, rt, 1 dayb
GI, 5 mol %, rt, 2 ha
89
71
87
88
94
80
86
81
82
77
54
51
Boc
Ph
Ph
Ph
Ph
Ph
Boc
Ph
Ph
Ph
GI, 5 mol %, rt, 1 daya
GI, 5 mol %, rt, 1 daya
GII, 5 mol %, rt, 1 dayb
GI, 5 mol %, rt, 1 daya
GI, 5 mol %, rt, 1 daya
GII, 5 mol %, rt, 1 dayb
GI, 5 mol %, rt, 2 ha
3j
3k
3l
Boc
Boc
Boc
H
H
GI, 5 mol %, rt, 1 daya
GI, 5 mol %, rt, 1 daya
RCM studies started with the cyclization of 1a using Grubbs’ first
generation catalyst (Scheme 3). We found that the use of 5 mol % of
the catalyst seemed to be optimal for the cyclization. For example,
a
GI¼Grubbs’ first generation catalyst.
b
GII¼Grubbs’ second generation catalyst.

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S. Tsupova et al. / Tetrahedron 68 (2012) 1011e1016
1013
All six-, seven- and eight-membered rings including prochiral
cycles were obtained in good to excellent yields. Some decrease of
yields for nine-membered heterocycles 3k and 3l was observed
even when lower substrate concentrations were used for more
efficient cyclization. The use of Grubbs’ second generation catalyst
did not improve the yields. We also noticed that the cyclization of
the substrates with identical alkenyl groups proceeded much
faster. To the best of our knowledge, RCM studies with different
alkene-bearing hydrazines and synthesis of the corresponding
prochiral heterocycles have not been previously described in the
literature.
obtained as yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.67; 1H
NMR (200 MHz, CDCl3):
d
¼7.19e7.27 (m, 2H, Ph), 6.82 (t, 1H,
J¼7.3 Hz, Ph), 6.68 (d, 2H, J¼8.0 Hz, Ph), 5.89e6.09 (m, 2H, CH]
CH2), 5.13e5.36 (m, 4H, CH]CH2), 3.92e4.39 (m, 4H, NCH2), 1.30/
1.48 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
d
¼155.5, 148.7,
135.0,134.1,129.0, 119.0,118.1,117.0,112.6, 81.0, 57.3, 53.0, 28.4. FTIR
(cmꢀ1): 3079, 2979, 2929, 1702, 1599, 1499, 1367, 1241, 1145, 921,
n
748, 693.
4.2.2. tert-Butyl 1,2-diallyl-2-ethylhydrazinecarboxylate (1b). The
reaction was carried out following the typical procedure in Section
4.2 to afford the title compound 1b (49% yield) as yellowish oil. Rf
(petroleum ether/EtOAc 5:1)¼0.65; 1H NMR (200 MHz, CDCl3):
3. Conclusion
d
¼5.67e5.91 (m, 2H, CH]CH2), 4.98e5.13 (m, 4H, CH]CH2), 3.78
In summary, we have demonstrated a fast and convenient
synthetic route to cyclic hydrazines. The key step of the method is
the efficient one-pot double alkylation of disubstituted hydrazines.
During the study heterocycles of different size and structure were
synthesized which demonstrates the wide scope of the method.
This approach can be easily utilized in the systematic synthesis of
hydrazine derivatives.
(br s, 2H, NCH2), 3.40 (br s, 2H, NCH2), 2.61e3.03 (m, 2H, CH2), 1.40
(s, 9H, C(CH3)3), 0.91e0.98 (m, 3H, CH3); 13C NMR (50 MHz, CDCl3):
d
¼155.6, 136.0, 135.2, 117.1, 116.5, 80.0, 58.8, 54.9, 48.6, 28.7, 13.5;
FTIR n
(cmꢀ1): 3081, 2975, 2932, 2868, 1694, 1374, 1366, 1244, 1170,
1142, 918; HRMS (ESI): m/z calcd for C13H25N2O2 (MHþ): 241.1911;
found: 241.1908.
4.2.3. Di-tert-butyl 1,2-diallylhydrazine-1,2-dicarboxylate (1c)20. The
reaction was carried out following the typical procedure in Section
4.2 to afford the title compound 1c (81% yield) as colourless liquid. Rf
(petroleum ether/EtOAc 5:1)¼0.68; 1H NMR (200 MHz, CDCl3):
4. Experimental section
4.1. General
d
¼5.77e5.97 (m, 2H, CH]CH2), 5.09e5.20 (m, 4H, CH]CH2),
All polyanion alkylation and ring-closing metathesis reactions
were performed under argon atmosphere in oven-dried glassware.
THF was freshly distilled from Na/benzophenone, DCM was freshly
distilled from calcium hydride. PhNHNHBoc, BocNHNHBoc and
EtNHNHBoc were prepared by known methods.18,22 All other re-
agents were obtained from commercial sources and used without
further purification. TLC was performed using MachereyeNagel
silica gel TLC plates, AlugramÒ SIL G/UV 254. Spots were visualized
by UV light at 254 nm or by w1% ethanolic solution of phospho-
molybdic acid with subsequent heating. Column chromatography
was carried out on a Merck Kieselgel 70e230 mesh. 1H and 13C
spectra were recorded at 200 MHz and 50 MHz, respectively, on
a AVANCE II 200 spectrometer (Spektrospin AG, Switzerland).
Deuteroform was used as a solvent. The chemical shifts are re-
ported in parts per million scale relative to the singlet (7.26 for 1H)
and triplet (77.0 for 13C). Coupling constants are reported in hertz.
IR spectra were measured on a PerkineElmer Spectrum BXII FTIR
spectrometer using ATR technique with ZnSe. Melting points were
determined on a Gallenkamp melting point apparatus. HRMS
spectra were measured on a Thermo Electron LTQ Orbitrap ESI
spectrometer. Compounds 3c, 3j, 3k and 3l are crystalline solids,
others are oils.
3.90e4.21 (m, 4H, NCH2), 1.44 (s, 18H, C(CH3)3); 13C NMR (50 MHz,
CDCl3):
¼155.5/154.8/154.4, 134.1/134.0/133.6, 118.2/117.9/117.3,
81.1/81.0/80.9, 54.8, 52.7, 28.3 (the product was isolated as a 2.9:1
d
ratio of rotamers); FTIR
1246, 1142.
n
(cmꢀ1): 3082, 2978, 2930,1709,1392,1367,
4.3. Typical procedure for selective one-pot dialkylation of
dianions (1eef)
4.3.1. tert-Butyl 1-allyl-2-(pent-4-enyl)-2-phenylhydrazinecarboxylate
(1e). An oven-dried flask was charged with PhNHNHBoc
(1.00 mmol, 208 mg), evacuated and backfilled with argon. There-
after THF (5 mL) was added to dissolve the solid. The reaction mix-
ture was cooled down to ꢀ78 ꢁC and 1.6 M n-BuLi solution in hexane
(2.10 mmol, 1.30 mL) was added dropwise. The reaction mixture was
allowed to warm up to ꢀ40 ꢁC for 15 min and 5-bromopentene
(1.00 mmol, 0.12 mL) was added. The reaction mixture was
allowed to warm up to room temperature for 1 h, then allyl bromide
(1.10 mmol, 0.10 mL) was added and the reaction mixture was heated
to 40 ꢁC and stirred overnight. The reaction progress was monitored
by TLC (petroleum ether/EtOAc 5:1). When the reaction was com-
plete the volatiles were removed under reduced pressure and the
residue was purified by column chromatography on silica (petro-
leum ether/EtOAc 5:1). The title compound 1e (256 mg, 81%) was
obtained as yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.70; 1H
4.2. Typical procedure for symmetrical diallylation of
dianions (1aec)
NMR (200 MHz, CDCl3):
d
¼7.18e7.26 (m, 2H, Ph), 6.75e6.82 (m, 1H,
4.2.1. tert-Butyl 1,2-diallyl-2-phenylhydrazinecarboxylate (1a)16. An
oven-dried flask was charged with PhNHNHBoc (1.00 mmol,
208 mg), evacuated and backfilled with argon. Thereafter THF
(5 mL) was added to dissolve the solid. The reaction mixture was
cooled down to ꢀ78 ꢁC and 1.6 M n-BuLi solution in hexane
(2.10 mmol, 1.30 mL) was added dropwise. The reaction mixture
was allowed to warm up to ꢀ40 ꢁC for 15 min and allyl bromide
(2.10 mmol, 0.185 mL) was added. The reaction mixture was
allowed to warm up to room temperature for 1 h, then heated to
40 ꢁC and stirred overnight. The reaction progress was monitored
by TLC (petroleum ether/EtOAc 5:1). When the reaction was com-
plete the volatiles were removed under reduced pressure and the
residue was purified by column chromatography on silica (petro-
leum ether/EtOAc 5:1). The title compound 1a (222 mg, 77%) was
Ph), 6.64 (d, 2H, J¼8.0 Hz, Ph), 5.75e6.08 (m, 2H, CH]CH2),
4.99e5.24 (m, 4H, CH]CH2), 3.30e4.35 (m, 4H, NCH2), 2.09e2.19
(m, 2H, CH2), 1.71e1.86 (m, 2H, CH2), 1.29/1.49 (s/s, 9H, C(CH3)3); 13
C
NMR (50 MHz, CDCl3):
115.1, 112.5, 80.9, 53.0, 31.4, 28.4, 27.2; FTIR
d
¼155.6, 148.7, 138.1, 134.2, 129.1, 118.7, 117.9,
n
(cmꢀ1): 3079, 2976,
2929, 1699, 1599, 1499, 1366, 1149, 914, 746, 692; HRMS (ESI): m/z
calcd for C19H29N2O2 (MHþ): 317.2224; found: 317.2226.
4.3.2. tert-Butyl 1-allyl-2-(2-methylallyl)-2-phenylhydrazinecarbox-
ylate (1f). The reaction was carried out following the typical pro-
cedure in Section 4.3 to afford the title compound 1f (80% yield) as
yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.74; 1H NMR
(200 MHz, CDCl3):
Ph), 6.69 (d, 2H, J¼8.0 Hz, Ph), 5.93e6.13 (m, 1H, CH]CH2),
d
¼7.21e7.29 (m, 2H, Ph), 6.85 (t, 1H, J¼7.3 Hz,

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S. Tsupova et al. / Tetrahedron 68 (2012) 1011e1016
1014
4.94e5.30 (m, 4H, CH]CH2), 3.78e4.37 (m, 4H, NCH2), 1.84 (s, 3H,
CH3), 1.32/1.51 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
ether/EtOAc 5:1). After 1 day the reaction was complete. H2O
(3 mL) was added and the mixture was extracted with diethyl
ether (3ꢂ3 mL). Combined diethyl ether solutions were evapo-
rated under reduced pressure and the residue was purified by
column chromatography on silica (petroleum ether/EtOAc 5:1).
The title compound 1d (140 mg, 81%) was obtained as a yellowish
oil. Rf (petroleum ether/EtOAc 5:1)¼0.70; 1H NMR (200 MHz,
d
¼155.5, 149.0,141.4,134.0,128.8,119.0,118.0,112.6,111.7, 81.0, 61.9,
52.7, 28.3, 20.5; FTIR
n
(cmꢀ1): 3064, 2975, 2937, 1701, 1600, 1499,
1366, 1235, 1147, 899, 748, 692; HRMS (ESI): m/z calcd for
C18H26N2NaO2 (MNaþ): 325.1887; found: 325.1887.
4.4. Typical procedure for monoalkylation of dianions (2aec)
CDCl3):
d
¼7.20e7.28 (m, 2H, Ph), 6.80 (t, 1H, J¼7.3 Hz, Ph), 6.65 (d,
2H, J¼8.2 Hz, Ph), 5.77e6.11 (m, 2H, CH]CH2), 5.05e5.26 (m, 4H,
CH]CH2), 3.30e4.37 (m, 4H, NCH2), 2.46 (q, 2H, J¼7.4 Hz, CH2),
4.4.1. tert-Butyl 2-allyl-2-phenylhydrazinecarboxylate (2a)16. An
oven-dried flask was charged with PhNHNHBoc (3.17 mmol,
660 mg), evacuated and backfilled with argon. Thereafter THF
(16 mL) was added to dissolve the solid. The reaction mixture was
cooled down to ꢀ78 ꢁC and 1.6 M n-BuLi solution in hexane
(6.34 mmol, 3.96 mL) was added dropwise. The reaction mixture
was allowed to warm up to ꢀ40 ꢁC for 15 min and allyl bromide
(3.20 mmol, 0.29 mL) was added. The reaction progress was
monitored by TLC (petroleum ether/EtOAc 5:1). After 1 h the re-
action was complete. The volatiles were removed under reduced
pressure and the residue was purified by column chromatography
on silica (petroleum ether/EtOAc 5:1). The title compound 2a
(704 mg, 90%) was obtained as colourless liquid. Rf (petroleum
1.29/1.48 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
d
¼155.8,
148.3, 135.8, 134.1, 129.1, 118.8, 118.1, 116.5, 112.3, 80.9, 53.2, 52.9,
32.5, 28.4; FTIR
n
(cmꢀ1): 3075, 2976, 2925, 1699, 1598, 1498, 1381,
1366, 1248, 1150, 915, 746, 692; HRMS (ESI): m/z calcd for
C18H27N2O2 (MHþ): 303.2067; found: 303.2063.
4 . 5 . 2 . t e r t - B u t y l 2 - a l l y l - 1 - ( b u t - 3 - e n y l ) - 2 -
phenylhydrazinecarboxylate (1g). The reaction was carried out fol-
lowing the typical procedure in Section 4.5 to afford the title com-
pound 1g (93% yield) as yellowish oil. Rf (petroleum ether/EtOAc
5:1)¼0.68; 1H NMR (200 MHz, CDCl3):
¼7.19e7.27 (m, 2H, Ph),
d
6.82 (t, 1H, J¼7.3 Hz, Ph), 6.68 (d, 2H, J¼8.2 Hz, Ph), 5.71e6.12 (m,
2H, CH]CH2), 5.03e5.37 (m, 4H, CH]CH2), 3.36e4.25 (m, 4H,
NCH2), 2.37e2.50 (m, 2H, CH2), 1.28/1.50 (s/s, 9H, C(CH3)3); 13C NMR
ether/EtOAc 5:1)¼0.52; 1H NMR (200 MHz, CDCl3):
¼7.25e7.33
d
(m, 2H, Ph), 6.85e6.92 (m, 3H, Ph), 6.55 (br s, 1H, NH), 5.87e6.07
(m, 1H, CH]CH2), 5.25e5.37 (m, 2H, CH]CH2), 4.14 (s, 2H, NCH2),
(50 MHz, CDCl3):
116.6, 112.5, 80.8, 58.0, 49.3, 32.9, 28.4; FTIR n
d
¼155.8, 148.8, 135.7, 135.0, 129.0, 119.0, 116.7,
1.53 (s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
133.0, 129.2, 119.5, 118.4, 113.1, 80.9, 55.8, 28.4; FTIR
d
¼155.2, 149.1,
(cmꢀ1): 3079, 2977,
n
(cmꢀ1):
2929, 1701, 1599, 1499, 1389, 1366, 1150, 916, 747, 692; HRMS (ESI):
3296, 3070, 2979, 2933, 1705, 1599, 1499, 1366, 1247, 1158, 746,
690.
m/z calcd for C18H27N2O2 (MHþ): 303.2067; found: 303.2062.
4 . 5 . 3 . t e r t - B u t y l 2 - a l l y l - 1 - ( p e n t - 4 - e n y l ) - 2 -
phenylhydrazinecarboxylate (1h). The reaction was carried out fol-
lowing the typical procedure in Section 4.5 to afford the title com-
pound 1h (91% yield) as yellowish oil. Rf (petroleum ether/EtOAc
4.4.2. tert-Butyl 2-(but-3-enyl)-2-phenylhydrazinecarboxylate
(2b). The reaction was carried out following the typical pro-
cedure in Section 4.4 to afford the title compound 2b (80% yield) as
yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.49; 1H NMR
5:1)¼0.74; 1H NMR (200 MHz, CDCl3):
¼7.19e7.27 (m, 2H, Ph),
d
(200 MHz, CDCl3):
d
¼7.25e7.33 (m, 2H, Ph), 6.84e6.88 (m, 3H, Ph),
6.82 (t, 1H, J¼7.3 Hz, Ph), 6.68 (d, 2H, J¼7.8 Hz, Ph), 5.72e6.11 (m,
2H, CH]CH2), 4.96e5.37 (m, 4H, CH]CH2), 3.31e4.26 (m, 4H,
NCH2), 2.04e2.15 (m, 2H, CH2), 1.71e1.86 (m, 2H, CH2), 1.29/1.49 (s/
6.33/6.50 (br s/s, 1H, NH), 5.86e6.00 (m, 1H, CH]CH2), 5.09e5.22
(m, 2H, CH]CH2), 3.58e3.61 (m, 2H, NCH2), 2.47 (q, 2H, J¼7.1 Hz,
CH2), 1.41/1.55 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
d
¼155.7, 148.8, 137.9,
d
¼155.2, 149.2, 136.0, 129.2, 119.2, 116.6, 112.8, 81.0, 52.0, 31.3, 28.4;
134.9, 129.0, 118.9, 116.7, 115.1, 112.4, 80.7, 57.9, 49.6, 31.3, 28.3, 27.7;
FTIR
n
(cmꢀ1): 3287, 3071, 2977, 2937, 1703, 1599, 1498, 1366, 1247,
FTIR n
(cmꢀ1): 3075, 2976, 2925, 1701, 1598, 1498, 1390, 1366, 1300,
1159, 911, 745, 690; HRMS (ESI): m/z calcd for C15H23N2O2 (MHþ):
1151, 913, 746, 692; HRMS (ESI): m/z calcd for C19H29N2O2 (MHþ):
263.1754; found: 263.1750.
317.2224; found: 317.2223.
4.4.3. tert-Butyl 2-(pent-4-enyl)-2-phenylhydrazinecarboxylate
(2c). The reaction was carried out following the typical procedure
in Section 4.4 to afford the title compound 2c (75% yield) as yel-
lowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.53; 1H NMR
4.5.4. tert-Butyl 2-allyl-1-(2-methylallyl)-2-phenylhydrazinecarbox-
ylate (1i). The reaction was carried out following the typical pro-
cedure in Section 4.5 to afford the title compound 1i (61% yield) as
yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.77; 1H NMR
(200 MHz, CDCl3):
d
¼7.25e7.33 (m, 2H, Ph), 6.83e6.88 (m, 3H, Ph),
(200 MHz, CDCl3):
d
¼7.22e7.30 (m, 2H, Ph), 6.85 (t,1H, J¼7.3 Hz, Ph),
6.22/6.42 (br s/s, 1H, NH), 5.82e5.96 (m, 1H, CH]CH2), 5.03e5.15
(m, 2H, CH]CH2), 3.48e3.55 (m, 2H, NCH2), 2.20 (q, 2H, J¼7.1 Hz,
CH2), 1.76e1.87 (m, 2H, CH2), 1.41/1.54 (s/s, 9H, C(CH3)3); 13C NMR
6.68 (d, 2H, J¼8.0 Hz, Ph), 5.92e6.11 (m,1H, CH]CH2), 4.94e5.37 (m,
4H, CH]CH2), 3.68e4.53 (m, 4H, NCH2),1.85 (s, 3H, CH3),1.35 (s, 9H,
C(CH3)3); 13C NMR (50 MHz, CDCl3):
d
¼156.0, 148.3, 141.8, 135.5,
(50 MHz, CDCl3):
81.0, 52.3, 31.3, 28.4, 26.0; FTIR
d
¼155.0, 149.5, 138.2, 129.2, 119.3, 115.2, 112.9,
129.0, 118.9, 116.4, 114.2, 112.5, 81.0, 58.0, 56.2, 28.3, 20.7; FTIR n
n
(cmꢀ1): 3295, 3071, 2977, 2929,
(cmꢀ1): 3075, 2973, 2929, 1702, 1599, 1499, 1366, 1234, 1165, 1140,
747, 692; HRMS (ESI): m/z calcd for C18H27N2O2 (MHþ): 303.2067;
found: 303.2062.
1702, 1599, 1498, 1366, 1249, 1158, 745, 690; HRMS (ESI): m/z calcd
for C16H25N2O2 (MHþ): 277.1911; found: 277.1905.
4.5. Typical procedure for alkylation of trisubstituted
hydrazines under PTC conditions (1d, gel)
4.5.5. tert-Butyl 1,2-di(but-3-enyl)-2-phenylhydrazinecarboxylate
(1j). The reaction was carried out following the typical pro-
cedure in Section 4.5 to afford the title compound 1j (71% yield) as
colourless oil. Rf (petroleum ether/EtOAc 5:1)¼0.73; 1H NMR
4.5.1. tert-Butyl 1-allyl-2-(but-3-enyl)-2-phenylhydrazinecarboxylate
(1d). Compound 2b (0.57 mmol, 150 mg) was dissolved in tolu-
ene (0.6 mL) and allyl bromide (0.60 mmol, 0.053 mL) was added.
The reaction was performed at room temperature under PTC
conditions by adding K2CO3 (1.14 mmol, 158 mg), NaOH
(1.99 mmol, 76 mg) and TBAHS (0.06 mmol, 20 mg) to the reaction
mixture. The reaction progress was monitored by TLC (petroleum
(200 MHz, CDCl3):
d
¼7.23e7.31 (m, 2H, Ph), 6.84 (t, 1H, J¼7.2 Hz,
Ph), 6.70 (d, 2H, J¼8.0 Hz, Ph), 5.74e6.01 (m, 2H, CH]CH2),
5.06e5.23 (m, 4H, CH]CH2), 3.34e3.82 (m, 4H, NCH2), 2.43e2.58
(m, 4H, CH2), 1.32/1.54 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz,
CDCl3):
d
¼155.8, 148.5, 135.6, 135.4, 129.0, 118.7, 116.5, 112.3, 80.7,
53.6, 49.4, 32.8, 32.5, 28.2; FTIR
n
(cmꢀ1): 3067, 2977, 2929, 1699,

ꢀ
S. Tsupova et al. / Tetrahedron 68 (2012) 1011e1016
1015
1598, 1498, 1366, 1151, 913, 746, 693; HRMS (ESI): m/z calcd for
residue was purified by column chromatography on silica (petro-
leum ether/EtOAc 5:1). The title compound 3a (80 mg, 89%) was
obtained as yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.41. 1H
C18H29N2O2 (MHþ): 317.2224; found: 317.2228.
4.5.6. tert-Butyl 2-(but-3-enyl)-1-(pent-4-enyl)-2-phenylhydrazinec-
arboxylate (1k). The reaction was carried out following the typi-
cal procedure in Section 4.5 to afford the title compound 1k (79%
yield) as yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.70; 1H
NMR (200 MHz, CDCl3):
d
¼7.19e7.27 (m, 2H, Ph), 6.79e6.84 (m, 3H,
Ph), 5.79e5.86 (m, 2H, CH]CH), 3.81e4.39 (m, 4H, NCH2), 1.38 (s,
9H, C(CH3)3). 13C NMR (50 MHz, CDCl3):
¼156.0, 148.3, 129.2, 125.1,
124.2, 119.5, 113.4, 81.0, 45.2, 43.1, 28.4. FTIR
(cmꢀ1): 3067, 2972,
d
n
NMR (200 MHz, CDCl3):
d
¼7.19e7.27 (m, 2H, Ph), 6.80 (t, 1H,
2929, 1697, 1599, 1497, 1366, 1250, 1228, 1162, 1142, 749, 690. HRMS
J¼7.3 Hz, Ph), 6.66 (d, 2H, J¼8.0 Hz, Ph), 5.70e5.98 (m, 2H, CH]
CH2), 4.95e5.19 (m, 4H, CH]CH2), 3.29e3.68 (m, 4H, NCH2), 2.47
(q, 1H, J¼7.3 Hz, CH2), 2.03e2.14 (m, 2H, CH2), 1.74e1.86 (m, 2H,
CH2), 1.27/1.50 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
(ESI): m/z calcd for C15H21N2O2 (MHþ): 261.1598; found: 261.1597.
4.6.2. tert-Butyl
2-ethyl-2,3-dihydropyridazine-1(6H)-carboxylate
(3b). The reaction was carried out following the typical procedure
in Section 4.7 using Grubbs’ second generation catalyst to afford the
title compound 3b (71% yield) as yellowish oil. Rf (petroleum ether/
d
¼156.0, 148.6, 137.9, 135.7, 129.1, 118.7, 116.6,115.2, 112.4, 80.7, 53.7,
49.8, 32.6, 31.4, 28.4, 27.8; FTIR
n
(cmꢀ1): 2970, 2929, 1702, 1599,
1498, 1392, 1367, 1163, 914, 748, 694; HRMS (ESI): m/z calcd for
EtOAc 5:1)¼0.53; 1H NMR (200 MHz, CDCl3):
¼5.70 (s, 2H, CH]
d
C20H31N2O2 (MHþ): 331.2380; found: 331.2372.
CH), 3.66 (br s, 4H, NCH2), 2.79 (s, 2H, CH2), 1.44 (s, 9H, C(CH3)3),
1.02 (t, 3H, J¼7.1 Hz, CH3); 13C NMR (50 MHz, CDCl3):
¼155.8,
d
4.5.7. tert-Butyl 1-(but-3-enyl)-2-(pent-4-enyl)-2-phenylhydrazine-
carboxylate (1l). The reaction was carried out following the typi-
cal procedure in Section 4.5 to afford the title compound 1l (71%
yield) as colourless oil. Rf (petroleum ether/EtOAc 5:1)¼0.72; 1H
122.9, 122.7, 79.9, 51.2, 46.9, 37.3, 28.5, 12.6; FTIR n
(cmꢀ1): 3039,
2974, 2932, 2848, 1687, 1408, 1377, 1364, 1232, 1174, 1123; HRMS
(ESI): m/z calcd for C11H21N2O2 (MHþ): 213.1598; found: 213.1598.
NMR (200 MHz, CDCl3):
d
¼7.22e7.30 (m, 2H, Ph), 6.83 (t, 1H,
4.6.3. Di-tert-butyl 1,2,3,6-tetrahydropyridazine-1,2-dicarboxylate
(3c)21. The reaction was carried out following the typical pro-
cedure in Section 4.7 to afford the title compound 3c (87% yield) as
a white solid. Rf (petroleum ether/EtOAc 5:1)¼0.41; mp¼67e69 ꢁC
J¼7.3 Hz, Ph), 6.69 (d, 2H, J¼8.0 Hz, Ph), 5.73e6.01 (m, 2H, CH]
CH2), 5.05e5.17 (m, 4H, CH]CH2), 3.32e3.80 (m, 4H, NCH2), 2.48
(q, 1H, J¼7.3 Hz, CH2), 2.15e2.25 (m, 2H, CH2), 1.78e1.94 (m, 2H,
CH2), 1.31/1.52 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
(lit.22 75 ꢁC); 1H NMR (200 MHz, CDCl3):
d
¼5.74 (s, 2H, CH]CH),
d
¼156.0, 148.8, 138.0, 135.6, 129.1, 118.7, 116.6, 115.3, 112.5, 80.8,
4.17e4.40 (m, 2H, NCH2), 3.62e3.79 (m, 2H, NCH2), 1.44 (s, 18H,
C(CH3)3); 13C NMR (50 MHz, CDCl3):
¼154.7, 124.0, 81.0, 43.3, 28.4;
FTIR
(cmꢀ1): 2980, 2935, 1695, 1388, 1367, 1226, 1166, 1142, 1120,
1074.
53.5, 49.5, 32.9, 31.4, 28.4, 27.3; FTIR
n
(cmꢀ1): 3075, 2976, 2929,
d
1700, 1598, 1499, 1366, 1163, 1132, 902, 745, 692; HRMS (ESI): m/z
n
calcd for C20H31N2O2 (MHþ): 331.2380; found: 317.2376.
4.5.8. Demonstrative procedure for one-pot dialkylation of di-
substituted hydrazines (1k). An oven-dried flask was charged with
PhNHNHBoc (1.5 mmol, 312 mg), evacuated and backfilled with
argon. Thereafter THF (7.5 mL) was added to dissolve the solid. The
reaction mixture was cooled down to ꢀ78 ꢁC and 1.6 M n-BuLi
solution in hexane (3.10 mmol, 1.90 mL) was added dropwise. The
reaction mixture was allowed to warm up to ꢀ40 ꢁC for 15 min and
4-bromobutene (1.50 mmol, 0.15 mL) was added. The reaction
progress was monitored by TLC (petroleum ether/EtOAc 5:1). After
1 h the reaction was complete. The volatiles were removed under
reduced pressure. The residue was dissolved in toluene (1.5 mL)
and 5-bromopentene (1.6 mmol, 0.19 mL) was added. The second
alkylation was performed at room temperature under PTC condi-
tions by adding K2CO3 (3 mmol, 414 mg), NaOH (5.25 mmol,
210 mg) and TBAHS (0.15 mmol, 49.5 mg) to the reaction mixture.
The reaction progress was monitored by TLC (petroleum ether/
EtOAc 5:1). After 1 day the reaction was complete. H2O (7.5 mL) was
added and the mixture was extracted with diethyl ether
(3ꢂ7.5 mL). Combined diethyl ether solutions were evaporated
under reduced pressure and the residue was purified by column
chromatography on silica (petroleum ether/EtOAc 5:1). Compound
1k (320 mg, 65%) was obtained as yellowish oil.
4.6.4. tert-Butyl 2-phenyl-2,3,4,7-tetrahydro-1H-1,2-diazepine-1-
carboxylate (3d). The reaction was carried out following the typi-
cal procedure in Section 4.7 to afford the title compound 3d (88%
yield) as yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.52; 1H
NMR (200 MHz, CDCl3):
d
¼7.25e7.33 (m, 2H, Ph), 6.70e6.87 (m, 3H,
Ph), 5.47e5.94 (m, 2H, CH]CH), 4.62e4.97/3.60e3.88 (m/m, 4H,
NCH2), 2.25e2.71 (m, 2H, CH2), 1.36/1.55 (s/s, 9H, C(CH3)3); 13C NMR
(50 MHz, CDCl3):
128.0, 127.4/126.2/125.4, 118.6/118.3, 111.6/111.2, 81.1/80.7, 50.7,
49.7/48.8, 28.4, 24.1/23.7 (the product was isolated as a 2.2:1 ratio
d
¼156.3/155.8, 148.2/147.8, 129.4/129.2, 128.3/
of rotamers); FTIR
n
(cmꢀ1): 3061, 2975, 2925, 1702, 1599, 1499,
1366, 1238, 1165, 1138, 747, 690; HRMS (ESI): m/z calcd for
C16H23N2O2 (MHþ): 275.1754; found: 275.1751.
4.6.5. tert-Butyl 2-phenyl-2,3,4,5-tetrahydro-1,2-diazocine-1(8H)-
carboxylate (3e). The reaction was carried out following the typical
procedure in Section 4.7 to afford the title compound 3e (94% yield)
as brownish oil. Rf (petroleum ether/EtOAc 5:1)¼0.53; 1H NMR
(200 MHz, CDCl3):
d
¼7.23e7.31 (m, 2H, Ph), 6.65e6.82 (m, 3H, Ph),
5.87e6.12 (m, 2H, CH]CH), 3.16e4.51 (m, 4H, NCH2), 2.05e2.47 (m,
2H, CH2CH2), 1.36/1.54 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
d
¼155.9, 147.3, 134.8, 129.4, 127.6, 117.5, 110.3, 80.5, 51.5, 43.2, 28.4,
27.3, 23.9; FTIR
n
(cmꢀ1): 3064, 2975, 2931, 1700, 1598, 1500, 1366,
4.6. Typical procedure for ring-closing metathesis for six-,
seven- and eight-membered rings (3aej)
1342, 1274, 1232, 1160, 1135, 745, 692; HRMS (ESI): m/z calcd for
C17H25N2O2 (MHþ): 289.1911; found: 289.1914.
4.6.1. tert-Butyl 2-phenyl-2,3-dihydropyridazine-1(6H)-carboxylate
(3a). An oven-dried flask was charged with 1a (0.35 mmol,
100 mg), evacuated and backfilled with argon. Thereafter freshly
distilled DCM (17 mL) was added. A solution of Grubbs’ first gen-
eration catalyst (0.05 equiv, 14.4 mg) in freshly distilled DCM (1 mL)
was added to the reaction mixture. The reaction was performed at
room temperature and the reaction progress was monitored by TLC
(petroleum ether/EtOAc 5:1). After 30 min the reaction was com-
plete. The volatiles were removed under reduced pressure and the
4.6.6. tert-Butyl 4-methyl-2-phenyl-2,3-dihydropyridazine-1(6H)-
carboxylate (3f). The reaction was carried out following the typical
procedure in Section 4.7 using Grubbs’ second generation catalyst
to afford the title compound 3f (80% yield) as yellowish oil. Rf (pe-
troleum ether/EtOAc 5:1)¼0.53; 1H NMR (200 MHz, CDCl3):
d
¼7.24e7.32 (m, 2H, Ph), 6.83e6.87 (m, 3H, Ph), 5.50 (s, 1H, C]CH),
3.68e4.39 (m, 4H, NCH2), 1.79 (s, 3H, CH3), 1.43e1.58 (m, 9H,
C(CH3)3); 13C NMR (50 MHz, CDCl3):
¼156.0, 148.1, 131.3, 129.2,
119.5, 118.7, 113.5, 81.0, 49.1, 42.2, 28.4, 20.5; FTIR
(cmꢀ1): 3066,
d
n

ꢀ
S. Tsupova et al. / Tetrahedron 68 (2012) 1011e1016
1016
2974, 2932, 1702, 1599, 1497, 1392, 1367, 1248, 1159, 1135, 748, 730,
690; HRMS (ESI): m/z calcd for C16H23N2O2 (MHþ): 275.1754;
found: 275.1752.
monitored by TLC (petroleum ether/EtOAc 5:1). After 1 day the re-
action was complete. The volatiles were removed under reduced
pressure and the residue was purified by column chromatography
on silica (petroleum ether/chloroform) to yield the title compound
3k (49 mg, 54%) as awhite solid. Mp¼82e83 ꢁC; Rf (petroleum ether/
4.6.7. tert-Butyl 2-phenyl-2,3,6,7-tetrahydro-1H-1,2-diazepine-1-
carboxylate (3g). The reaction was carried out following the typi-
cal procedure in Section 4.7 to afford the title compound 3g (86%
yield) as yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.47; 1H
EtOAc 5:1)¼0.63; 1H NMR (200 MHz, CDCl3):
¼7.18e7.26 (m, 2H,
d
Ph), 6.80 (t,1H, J¼7.3 Hz, Ph), 6.63 (d, 2H, J¼8.0 Hz, Ph),1.59e4.10 (m,
10H, NCH2, CH2), 1.22/1.50 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz,
NMR (200 MHz, CDCl3):
d
¼7.20e7.28 (m, 2H, Ph), 6.69e6.83 (m, 3H,
CDCl3):
d
¼157.2, 150.6, 129.8, 129.5, 129.2, 119.0, 112.4, 80.4, 53.9,
(cmꢀ1): 2972, 2913, 1701, 1598,
Ph), 5.63e5.84 (m, 2H, CH]CH), 3.50e4.38 (m, 4H, NCH2),
50.7, 28.4, 25.3, 24.4, 22.9; FTIR
n
2.07e2.56 (m, 2H, CH2), 1.33 (s, 9H, C(CH3)3); 13C NMR (50 MHz,
1498, 1392, 1366, 1324, 1281, 1162, 1141, 747, 725, 690; HRMS (ESI):
CDCl3):
47.9, 28.5, 25.1; FTIR
d
¼156.0, 148.8, 129.3, 127.9, 127.2, 118.8, 112.2, 80.6, 50.3,
(cmꢀ1): 3067, 2977, 2931, 1698, 1599, 1499,
m/z calcd for C18H27N2O2 (MHþ): 303.3067; found: 303.3068.
n
1366, 1241, 1226, 1168, 1141, 748, 691; HRMS (ESI): m/z calcd for
4.7.2. tert-Butyl 2-phenyl-2,3,4,5,8,9-hexahydro-1H-1,2-diazonine-
1-carboxylate (3l). The reaction was carried out following the
typical procedure in Section 4.7 to afford the title compound 3l (51%
yield) as a white solid. Mp¼81e83 ꢁC; Rf (petroleum ether/EtOAc
C16H23N2O2 (MHþ): 275.1754; found: 275.1750.
4.6.8. tert-Butyl 2-phenyl-2,3,7,8-tetrahydro-1,2-diazocine-1(6H)-
carboxylate (3h). The reaction was carried out following the typical
procedure in Section 4.7 to afford the title compound 3h (81% yield)
as yellowish oil. Rf (petroleum ether/EtOAc 5:1)¼0.56; 1H NMR
5:1)¼0.64; 1H NMR (200 MHz, CDCl3):
¼7.19e7.27 (m, 2H, Ph),
d
6.83 (t, 1H, J¼7.3 Hz, Ph), 6.64 (d, 2H, J¼7.8 Hz, Ph), 5.47e5.68 (m,
2H, CH]CH), 3.13e4.03 (m, 4H, NCH2), 1.52e2.92 (m, 6H, CH2), 1.19/
(200 MHz, CDCl3):
d
¼7.21e7.29 (m, 2H, Ph), 6.69e6.84 (m, 3H, Ph),
1.46 (s/s, 9H, C(CH3)3); 13C NMR (50 MHz, CDCl3):
d
¼156.6, 151.0/
5.91e6.04 (m, 2H, CH]CH), 3.84e4.10/2.36e2.90 (m/m, 4H, NCH2),
150.2, 130.5, 129.9/129.8, 129.3/129.1, 119.2, 112.6/112.4, 80.9/80.4,
56.0/55.6, 49.3/48.6, 28.6/28.3, 26.4/26.1, 24.4/23.8, 23.3/23.0 (the
2.08e2.36/1.52/1.39 (m/s/s, 13H, CH2CH2, C(CH3)3); 13C NMR
(50 MHz, CDCl3):
d
¼156.0/155.4, 147.5, 136.0/135.3, 129.3, 125.8/
product was isolated as a 4.1:1 ratio of rotamers); FTIR n
(cmꢀ1):
124.7, 118.7, 112.5/112.2, 80.1, 48.6/48.1, 46.1/45.6, 28.4, 27.1/25.7,
25.0/24.7 (the product was isolated as a 1:1 ratio of rotamers); FTIR
2977, 2925, 1698, 1600, 1497, 1358, 1165, 1138, 748, 730, 692; HRMS
(ESI): m/z calcd for C18H27N2O2 (MHþ): 303.3067; found: 303.3061.
n
(cmꢀ1): 3075, 2977, 2941, 1698, 1598, 1498, 1387, 1366, 1150, 917,
746, 692; HRMS (ESI): m/z calcd for C17H25N2O2 (MHþ): 289.1911;
Acknowledgements
found: 289.1904.
This study was supported by grant Nos. 8031 and 8794 from the
Estonian Science Foundation and from the project SF0182734s06 of
the Ministry of Education of Estonia.
4.6.9. tert-Butyl 5-methyl-2-phenyl-2,3-dihydropyridazine-1(6H)-
carboxylate (3i). The reaction was carried out following the typical
procedure in Section 4.7 using Grubbs’ second generation catalyst
to afford the title compound 3i (82% yield) as yellowish oil. Rf (pe-
troleum ether/EtOAc 5:1)¼0.58; 1H NMR (200 MHz, CDCl3):
Supplementary data
d
¼7.24e7.32 (m, 2H, Ph), 6.84e6.88 (m, 3H, Ph), 5.61 (s, 1H, C]CH),
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2011.11.091.
3.62e4.43 (m, 4H, NCH2), 1.69 (s, 3H, CH3), 1.44 (s, 9H, C(CH3)3); 13
NMR (50 MHz, CDCl3):
¼156.0, 148.3, 132.3, 129.2, 119.5, 117.9,
113.5, 81.0, 46.1, 45.1, 28.4, 20.1; FTIR
(cmꢀ1): 3064, 2974, 2930,
C
d
n
References and notes
1702, 1599, 1498, 1391, 1366, 1250, 1163, 1138, 751, 691; HRMS (ESI):
m/z calcd for C16H23N2O2 (MHþ): 275.1754; found: 275.1749.
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0.52; 1H NMR (200 MHz, CDCl3):
d¼7.23e7.31 (m, 2H, Ph),
6.67e6.90 (m, 3H, Ph), 5.75e5.98 (m, 2H, CH]CH), 2.92e4.37 (m,
4H, NCH2), 2.10e2.50 (m, 4H, CH2), 1.30/1.54 (s/s, 9H, C(CH3)3); 13
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C
d
¼156.9/154.4, 149.3/148.8, 130.5/130.2,
130.0/129.7, 129.4/129.2, 119.0/118.8, 112.0, 81.0/80.6, 51.2/51.0,
50.2/49.9, 28.6/28.4, 26.6/26.4, 25.7/25.5 (the product was isolated
as a 2.8:1 ratio of rotamers); FTIR n
(cmꢀ1): 3063, 2974, 2934, 1696,
1598, 1498, 1385, 1366, 1318, 1161, 1140, 747, 734, 690; HRMS (ESI):
m/z calcd for C17H25N2O2 (MHþ): 289.1911; found: 289.1912.
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€
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€
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18. Bredihhin, A.; Maeorg, U. Tetrahedron 2008, 64, 6788e6793.
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