Cu(ii)-catalyzed domino reaction of 2H-azirines with diazotetramic and diazotetronic acids. Synthesis of 2-substituted 2H-1,2,3-triazoles

Article abstract of DOI:10.1039/c3ob40708j

The Cu(ii)-catalyzed addition of two molecules of a 3-aryl-2H-azirine to diazotetramic or diazotetronic acids proceeds as a domino reaction with the formation of 1,2,3-triazole derivatives with ortho-fused (pyrrolo[3,4-b]pyrrol or furo[3,4-b]pyrrol) and spiro-cyclic (1-oxa-4,7-diazaspiro[4.4]nonane or 1,7-dioxa-4-azaspiro[4.4]nonane) substituents at the N2 position. The disclosed reaction is a new type of formation of a 1,2,3-triazole ring from (N-N) and (C-C-N) building blocks. The Royal Society of Chemistry.

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ARTICLE TYPE
Cu(II)-Catalyzed domino reaction of 2H-azirines with diazotetramic and
diazotetronic acids. Synthesis of 2-substituted 2H-1,2,3-triazoles
Nikolai V. Rostovskii,a , Mikhail S. Novikov*a, Alexander F. Khlebnikov a, Sergei M. Korneev a and
Dmitry S. Yufit b
5
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
The Cu(II)-catalyzed addition of two molecules of a 3-aryl-2H-azirine to diazotetramic or diazotetronic
acids proceeds as a domino reaction with the formation of 1,2,3-triazole derivatives with ortho-fused
(pyrrolo[3,4-b]pyrrol or furo[3,4-b]pyrrol systems) and spiro-cyclic (1-oxa-4,7-diazaspiro[4.4]nonane or 1,7-
10 dioxa-4-azaspiro[4.4]nonane systems) substituents at the N2 position. The disclosed reaction is a new
type of formation of a 1,2,3-triazole ring from (N-N) and (C-C-N) building blocks.
procedures for the preparation of azete,12 2H-1,4-oxazine10 and
5,7-dioxa-1-azabicyclo[4.4.1]undecane15
derivatives were
Introduction
developed (Scheme 1). In the course of our investigations of
50 reactions of diazo compounds with azirines, we tested some
cyclic α-diazodicarbonyl substrates and found an unusual
reactivity of these compounds under catalytic conditions.
1,2,3-Triazoles have found a wide use in different industrial
applications and serve as important structural elements in many
15 biologically active products. In contrast to 1-substituted 1,2,3-
triazoles, which are considered to be synthetically available
compounds, there are no general methods for the preparation of
the 2-substituted isomers. All known approaches, such as
alkylation of NH-1,2,3-triazoles,1 cyclization of bishydrazones or
20 bissemicarbazones,2 Pd(0)-Cu(I)-catalyzed three-component
reactions between alkyne, allyl carbonate and trimethylsilyl
azide3 as well as the Cu(I)-catalyzed three-component reaction
between alkyne, formaldehyde and sodium azide4 are valid for
the introduction of only specific types of substituent at N2. The
25 structural diversification of 2-substituted 1,2,3-triazoles for
medicinal, industrial and synthetic needs provides a challenge for
the search for new methods for their preparation. 2H-Azirines are
widely used as building blocks for the synthesis of various
heterocyclic nitrogen-containing compounds, such as pyrrole,5
30 isoxazole,6 indole,6,7 pyridine, 8 pyrazine,9 2H-1,4-oxazine,10 1,3-
diazepine,11 azete12 derivatives and others.13 The majority of
these compounds are formed via cleavage of one of the carbon-
nitrogen bonds of the three-membered ring, which could occur
with heating or by the action of various nucleophiles
35 (carboxylates, nitrogen ylides, enols, enolates), carbenes,
carbenoids or transition metal compounds. Thus, nucleophilic
reagents break the C=N bond of the azirine ring, providing good
access to five-membered heterocycles (Scheme 1).5,14 In contrast,
dihalocarbene- or rhodium carbenoid-mediated azirine ring
40 opening occurs exclusively via a NC2 bond cleavage to give 2-
azabuta-1,3-diene derivatives or 46-membered heterocycles.
The reactions of azirines with metallocarbenoids, which can be
generated from readily available and structurally diverse
diazocarbonyl compounds, are of special interest. Until now, the
45 activities of only acyclic α-diazodicarbonyl compounds towards
azirines under catalysis and thermolysis were studied and
55 Scheme 1 Ring opening pathways of 2H-azirines.
In the present work a new catalytic domino reaction of 2H-
azirines with diazotetramic and diazotetronic acids is reported.
This reaction proceeds without nitrogen extrusion and leads to the
formation of three heterocyclic systems, 2-substituted 1,2,3-
60 triazole, pyrroline and oxazoline cycles, in one synthetic
operation.
Results and Discussion
Our initial studies focused on attempts to involve Rh(II)-
carbenoid,16 derived from the cyclic α-diazo amide, diazotetramic
65 acid 1a, in reaction with azirines. No products were detected after
a mixture of 1a, azirine 2a and catalytic amounts of Rh2(OAc)4
was heated in 1,2-dichloroethane (DCE). However, if the
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rhodium catalyst was replaced by copper acetylacetonate the 1:2
adduct 3a was formed (Scheme 2). When the reaction was carried
out at 100 C using 3 equivalents of azirine 2a, the compound 3a
was isolated after chromatographic separation in 16% yield (32%
based on recovered 1a). Its structure was verified by standard
spectral methods and confirmed by X-ray analysis (Fig. 1).
5
The compound 3a arises from the addition of two molecules of
azirine to diazotetramic acid, one of which adds to the nitrogen-
nitrogen bond of the diazo function of 1a and the second to the
10 C3C4 bond of the pyrrolidine ring. As a result two heterocyclic
units, 1,2,3-triazole and pyrroline, are formed. The formation of a
triazole cycle can in principle be the result of the azirine ring
opening of either the NC2 or the NC3 bonds, whereas the
pyrroline fragment unequivocally arises from the breaking of the
15 azirine NC2 bond.
Fig. 1 X-ray structure of the solvate 3aEtOAc.
20
In spite of the fact that a significant amount of 1a was
recovered from the reaction, we failed to improve the yield of 3a
by changing the temperature or increasing either the quantity of
the azirine or the catalyst in the reaction mixture. We assumed
25 that this is due to secondary processes involving the lactamic
NH bond, both in the starting compound and in the product. To
examine this hypothesis N-acyldiazotetramic acid 1b was
prepared by the action of acetic anhydride on diazotetramic acid
1a in the presence of DMAP. When 1b was reacted with azirine
30 2a under the above conditions the ortho-fused pyrroline 3b was
isolated as the main product and a 2:1 mixture of diastereomeric
spiro-oxazolines 4b as minor product (Scheme 3, Table 1). The
structure of 3b was confirmed by X-ray analysis (Supp. Inf., Fig.
2). The dimer of the azirine, imidazole 5, was also isolated in
35 trace amounts. The formation of imidazole-type dimers of 2H-
azirines was reported by Auricchio et al. for the FeCl2-catalyzed
decomposition of 3-aryl-2H-azirines.17a The spiro-compound 4b
is a structural isomer of 3b and is the result of the formal addition
of azirine 2a to the keto group of 1b. This spiro compound was
40 isolated as an equilibrium mixture of two diastereomers.
Scheme 2 Cu(acac)2-catalyzed reaction of 1a with 2a.
45
Scheme 3 Cu(acac)2-catalyzed reaction of 1bd with 2ac.
50
2
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Table 1 Yields of compounds 3bf, 4bfa
Diazo compound
1
R
Azirine 2
Ar
Yield 3, (%)
Yield 4, (%)
(5RS,9RS)-4/
(5RS,9SR)-4
ratiob
1b
1b
1b
1c
1d
Ac
2a
2b
2c
2a
2a
4-MeC6H4
Ph
34c (3b)
28 (3c)
27 (3d)
43d (3e)
23 (3f)
17c (4b)
20 (4c)
12 (4d)
12d (4e)
7 (4f)e
1.5 : 1
1.6 : 1
1.8 : 1
1.8 : 1
Ac
Ac
4-MeOC6H4
4-MeC6H4
4-MeC6H4
Boc
4-MeOC6H4CH2
a Reaction conditions: 100 C, concentration of 1 0.128 м, 57 eq. of 2, 5 mol% Cu(acac)2. b Diastereomeric ratio was determined by 1H NMR. c When the
concentration of 1b is 2.0 м the product yields are: 24% (3b) and 13% (4b). d When the concentration of 1c is 0.4 м the product yields are: 35% (3e) and
5 14% (4e). e Only one diastereomer is formed.
It is noticeable that all the tested Cu(II)-compounds catalyzed
the reaction, even at room temperature, but the process proceeded
40 very slowly. Moreover it took 25 h of heating at 80 C in 1,2-
dichloroethane to consume all the starting diazo compound 1b in
the presence of 4 equivalents of azirine 2a. In a tightly screwed
tube at 100 C the reaction time was reduced to 1.5 h. It was also
found that the increase of the concentration of 1b above 0.2 м led
45 to the formation of byproducts and decreased yields of adducts 3
and 4.
It is known that compounds of various transition metals, such as
Cu(II),5b Fe(II),17 Rh(II),18,19 Ru(II),19 Ni(II)20 or Pd(II)21 catalyze
10 intra- and intermolecular transformations of 2H-azirines to give
ring-expansion products. The influence of the catalysts, the
concentration of the reagents and the temperature on the output of
the reaction of 1b with 2a was studied to optimize the yields of
the triazole derivatives 3 and 4 (Table 2). The Cu(II)-compounds
15 (Entries 28), providing adducts 3 and 4 in total yields of up to
53%, proved to be the catalysts of choice. The reaction of 1b with
2a in the presence of Co(acac)3, Fe(acac)3, Cd(acac)2 or CuCl did
not lead to even trace amounts of the desired products, while
Mg(acac)2 catalyzed the reaction to give both products in low
20 yields (Entry 9). In contrast to Cu(II)-catalysis, it is notable that
Ni(acac)2 (Entry 10) and Rh2(OAc)4 (Entry 11), having only a
weak catalytic activity in this reaction, gave spiro-adduct 4 as the
major product. Addition of the acidic catalyst ZnCl2 to the
reaction mixture led to a fast decomposition of azirine 2a, even at
25 room temperature, but without formation of the desired products.
The action of catalytic amounts of AgNO3 or Pd(PPh3)4 resulted
in the complete consumption of the diazo compound without
formation of any identifiable products.
The optimal conditions for the preparation of 1,2,3-triazole
derivatives 3 and 4 were found to be the following: heating at
100110 C of a 1:3 mixture of diazotetramic acid 1 (0.10.2 м)
50 and azirine 2 in dry DCE under catalysis of 5% (on diazo
compound) Cu(II)-chelates or salts, followed by addition of the
amount of azirine necessary for complete consumption of the
diazo compound. By using these conditions the compounds 3ce
and 4ce were also prepared, starting from N-acetyl- and N-Boc-
55 protected diazotetramic acid and azirines 2a,b (Scheme 3, Table
1). In all cases the spiro-regioisomer was formed as a mixture of
two diastereomers in 1.72.0:1 ratio in favour of the (5RS,9RS)-
isomer. From N-alkylated diazotetramic acid 1d and azirine 2a
both ortho-fused adduct 3f and spiro-adduct 4f were also
60 obtained. It is notable that the latter in this case was detected as a
sole diastereomer. It was found that 3-(p-nitrophenyl)-2Н-
azirine does not react with diazo compound 1b even at 110 C.
The Boc-protecting group in 3e and 4e could be effectively
removed by treatment with a dichloromethane solution of
65 trifluoroacetic acid at 0 C (Scheme 4). The N-unsubstituted
ortho-fused adduct 3a was isolated from the reaction of
diazotetramic acid 1a with 3-tolyl-2H-azirine 2a in low yield
(Scheme 2). It could be prepared more effectively by the use of
the Boc-protected analogue 1c, followed by deprotection. A two-
70 stage procedure must be employed for the preparation of the
spiro-adduct 4a.
30
Table 2 Optimization of the reaction conditions of the reaction of diazo
compound 1b with azirine 2a (4 eq.)
Entry
Catalysta
Concentration Time Yield b
Yield b
4b, (%)
0c
10
14
13
10
12
1b, (м)
0.064
0.064
0.032
0.064
0.128
0.064
(h)
2
1.25
3
1.5
0.75
25
3b, (%)
1
2
3
4
5
6
none
CuCl2
0c
34
38
40
40
Cu(acac)2
Cu(acac)2
Cu(acac)2
Cu(acac)2,
80 C
Cu(tfacac)2
Cu(hfacac)2 0.064
Mg(acac)2
Ni(acac)2
Rh2(OAc)4
33
It was found that the diastereomer (5RS,9RS)-4a, isolated by
column chromatography in pure form, was slowly transformed to
the diastereomeric mixture (5RS,9RS)- and (5RS,9SR)-4a in a
75 CDCl3 solution at room temperature.
7
8
9
10
11
0.064
1.5
1.5
13
16
10
37
41
14
traces
0
11
12
8
0.064
0.064
0.064
6
4d
a 5 mol% catalyst used, temperature 100 C. b Yields were determined by
1H NMR spectra using acenaphthene as an internal standard; (5RS,9RS)-
35 4/(5RS,9SR)-4 ratio in reaction mixtures is 1.82.1. c 97% of diazo
compound was recovered. d 26% of diazo compound was recovered.
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Table 3 Yields of compounds 6ad and 7ad
Azirine
Ar
Yield 6,
(%)
Yield 7,
(%)
(5RS,9SR)-7/
(5RS,9RS)-7
ratioa
2a
2b
2c
2d
4-MeC6H4
Ph
4-MeOC6H4 18 (6c)
4-BrC6H4 6 (6d)
25 (6a)
16 (6b)
24 (7a)
11 (7b)
5 (7c)
1.7:1
2:1
1.8:1
1.9:1
3 (7d)
a Diastereomeric ratio was determined by 1H NMR.
Scheme 4 Boc-deprotection of compounds 3e and 4e.
The known transition metal-catalyzed reactions of
diazotetronic acid 1e are limited to the Rh(II)-catalytic insertions
into the alcoholic OH22 and aromatic CH23 bonds. Otherwise,
three examples of the Wolf rearrangement of 1e, resulting in ring
contraction products, are also known.24 All the reactions proceed
with extrusion of nitrogen. The reaction of diazotetronic acid 1e
with azirines 2ad in the presence of Cu(acac)2 is the first
5
30
Fig. 2 X-ray structure of compound (5RS,9SR)-7a.
10 example of a transformation of this compound with retention of
the N2 moiety. This reaction gives rise to the oxygen analogues of
adducts 3 and 4, that is triazole derivatives 6ad and 7ad
(Scheme 5, Table 3). The structures of these compounds were
verified by standard spectral methods. The chemical shift of the
15 5-H proton of the triazole cycle in the 1H NMR spectra of
diastereomers 7bd, as well as diastereomers 4ad, were used for
their structural assignment. The signal of the triazolic 5-H proton
in stereoisomers 7bd (or 4ad), with trans-oriented N-
substituents in the tetrahydrofuran ring in 7 or the pyrrolidine ring
20 in 4, is shifted downfield by ca. 0.1 ppm compared to that of the
cis-isomer. The molecular structures of the compounds 6a and
(5RS,9SR)-7a were confirmed by X-ray analysis (Fig. 2 and
Supp. Inf., Fig. 3).
The most probable pathway for the formation of compounds 3, 4,
6 and 7 is outlined in Scheme 6. According to the structures of
the final products, at least one of the new cycles is formed via an
35 opening of the NC2 bond of the azirine ring. It has been
generally assumed that this process can occur either under
heating via nitrene formation,25 or under catalysis via vinyl
nitrene metal complex formation.19,20,26 The intermediate
formation of vinyl nitrene rhodium complex was assumed by
40 Padwa and Stengel in the solvolytic 2-vinylazirine ring opening
using Wilkinson’s catalyst.19 The formation of a nitrene copper
complex was reported for the Cu(II)-catalyzed decomposition of
2-pyridinesulfonyl azides.26 We assumed that the coordination of
azirine with a Cu(II)-catalyst (structure 8) would lead to the vinyl
45 nitrene complex 9, which is trapped by the diazo compound,
followed by ring closure into the 1,2,3-triazole 10. The latter can
attack a second nitrene complex molecule to provide, after
cyclization, the fused adducts 3 and 6 (attack by C3-atom of 10)
or spiro-adducts 4 and 7 (attack by hydroxyl oxygen of 10).
50
25
Scheme 5 Cu(acac)2-catalyzed reaction of 1e with 2ad.
4
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Scheme 6 Probable reaction mechanism.
During careful TLC- and 1H NMR-monitoring of the slow
addition either of the azirine to a mixture of diazotetramic acid and
catalyst or vice versa it was not possible to detect any
intermediates, e.g. enol 10. To verify the reaction mechanism and
to check the feasibility of the formation of adducts 3, 4, 6 and 7 via
the intermediate triazolyl-substituted enol 10, we synthesized its p-
5
10 methoxyphenyl analogue 11 (Scheme 7). This compound was
prepared in 82% yield, according to a known procedure,27 from
diazo compound 1b and anisole in the presence of dirhodium
tetraacetate. Heating the enol 11 with 3-tolyl-2H-azirine 2a in the
presence of Cu(acac)2 in DCE at 100 C gave the desired bicycle 12
15 in 55% yield. It is notable that in this case the spiro-isomer of type
4 is not formed. From this it follows that the nature of the
substituent at C3 of enol 10 dramatically affects the regiochemistry
of the enol addition to the vinyl nitrene complex. At the same time
the modification of the fragment X of enol 10 has insignificant
20 influence on the ortho-fused adduct/spiro-adduct ratio (3:1 for 1b
1
and 2.3:1 for 1e according to H NMR). The successful annelation
Scheme 7 Synthesis of enol 11 and its Cu(II)-catalyzed reaction with azirine
30 2a.
of a pyrrole ring to the cyclic enol 11, by the action of azirine 2a
and the catalysis of this reaction with Cu(acac)2 confirm the
suggested mechanism, which involves a nitrene copper complex-
25 mediated consecutive formation of the 1,2,3-triazole and the
pyrroline/oxazoline systems.
Conclusions
The Cu(II)-catalyzed reaction of 3-aryl-2H-azirines with
diazotetramic and diazotetronic acids provides a new approach to
1,2,3-triazole derivatives having heterocyclic substituents in the N2
35 position. The most probable mechanism of the reaction involves the
catalytic ring opening of the azirine N-C2 bond to generate a vinyl
nitrene copper complex, which is then trapped by the diazo group
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of the diazo compound to form derivatives of 1,2,3-triazol-2-yl- tetrahydropyrrolo[3,4-b]pyrrole-4(3Н)-one (3a): Following the
tetramic/tetronic acid. The addition of a second nitrene copper general procedure (reaction time 30 min) diazo compound 1a (125 mg,
complex molecule then gives the bicyclic or spirocyclic system. N- 1 mmol) and azirine 2b (393 mg, 3 mmol) were reacted in DCE (0.5
Boc-protected diazotetramic acid can be used in the reaction to60 mL). Column chromatography (petroleum ether/EtOAc = 2:1) gave
form, after deprotection, NH-analogues of the final adducts. The unreacted 1a (62 mg, 50%) and the solvate of triazole 3aEtOAc as
disclosed reaction is a new type of formation of a 1,2,3-triazole ring a colourless solid. The solvate was twice dissolved in DCM and
5
from (N-N) and (C-C-N) building blocks.
dried during 1 h under vacuum (0.1 torr) at room temperature.
Triazole 3a (41 mg, 16%) is a colourless solid, mp 194200 С
65 (dec.). (Found С, 65.75; H, 6.17; N, 14.82. C22H21N5O2C4H8O2
requires С, 65.67; H, 6.15; N, 14.73%); max (KBr)/cm−1 3410,
3214, 3121 (О-Н, N-H), 2970, 2922, 1727, 1606, 1568, 1488, 1424,
1393, 1343, 1303, 1223, 1163, 1117, 980, 955, 904, 815; H (300
Experimental
10 General methods
Melting points were determined on a hot stage microscope and are MHz; DMSO-d6; Me4Si) 2.34 (3 H, s, CH3), 2.39 (3 H, s, CH3),
uncorrected. 1H (300 MHz), 13C (75 MHz) NMR spectra were70 3.683.75 (3 Н, m, 3-Н, 2 6-Н), 4.50 (1 Н, d, J 17.8 Hz, 3-Н), 6.47
measured in CDCl3 or DMSO-d6 on
a Bruker DPX 300 (1 Н, s, ОН), 7.29 (2 Н, d, J 8.0 Hz, ArH), 7.34 (2 Н, d, J 8.0 Hz,
spectrometer and 1H (400 MHz), 13C (100 MHz) NMR spectra were ArH), 7.77 (2 Н, d, J 8.0 Hz, ArH), 7.91 (2 Н, d, J 8.0 Hz, ArH),
15 measured in CDCl3 or DMSO-d6 on a Bruker Avance-400 8.32 (1 Н, s, N=СН), 8.53 (1 Н, br. s, NH). C (75 MHz, DMSO-d6;
spectrometer. Chemical shifts (δ) are reported in ppm downfield Me4Si) 20.9 (CH3), 21.1 (CH3), 40.7 (C-3), 51.2 (C-6), 74.8 (C-3а),
from tetramethylsilane. Electrospray ionization mass spectra were75 103.3 (С-6а), 125.6, 127.1, 128.1, 129.3, 129.5, 130.0, 131.5,
measured on a Bruker micrOTOF mass spectrometer. Elemental 137.9, 141.9, 146.9, 171.2, 171.5. Crystal data: C26H29N5O4, M
analysis was performed on a Hewlett-Packard 185B CHN-analyser. =475.54, triclinic, a = 10.9436(5), b = 11.0673(6) , c = 11.6719(5)
20 IR spectra were recorded on a Bruker TENSOR 27 spectrometer as Å, α = 94.869(4), β = 113.495(4), γ = 104.707(4)°, V = 1226.08(10)
solutions in CCl4, CHCl3 or as tablets in KBr. Single crystal X-ray Å3, space group P-1, Z = 2, μ(Mo Kα) = 0.089, 15824 reflections
data were collected at 120.0K on a Bruker SMART 600080 measured, 6486 unique (Rint = 0.0292) which were used in all
(compounds 3b, 6a and 7a) and an Agilent Gemini S-Ultra calculations. The final R1 is 0.0458 (5298 >2σ(I)) and wR2 is
diffractometers (3a) (graphite monochromated λMoKα radiation, λ 0.1232 (all data).
25 = 0.71073Å) equipped with Cryostream (Oxford Cryosystems)
Preparation from 3e: Trifluoroacetic acid (2 mL) was slowly
open flow nitrogen cryostates. The structure was solved by direct added to a cooled (0 C) solution of Boc-protected lactam 3e (70
method and refined by full-matrix least squares on F2 for all data85 mg, 0.144 mmol) in dichloromethane (10 mL). The mixture was
using SHELX28 and OLEX229 software. All non-disordered non- then stirred at 0 C for 2 h before being evaporated to dryness,
hydrogen atoms were refined with anisotropic displacement dissolved in DCM (30 mL) and washed with an aqueous saturated
30 parameters, non-disordered H-atoms were located on the difference NaHCO3 solution (230 mL). The organic layer was dried over
map and refined isotropically. Disordered solvent atoms in the MgSO4, filtered, and evaporated to dryness to give 50 mg (90%) of
structure 3b were refined isotropically with fixed SOF=0.5, the90 triazole 3a as a beige solid.
disordered hydrogen atoms were placed in calculated positions and
refined in "riding" mode. Crystallographic data for the structures
3-(4-Methylphenyl)-9-[4-(4-methylphenyl)-2Н-1,2,3-trazol-2-
35 have been deposited with the Cambridge Crystallographic Data yl]-1-oxa-4,7-diazaspiro[4.4]non-3-en-8-one (4a): Following the
Centre as supplementary publication CCDC-924896924899. Thin- procedure reported for preparation of compound 3a from 3e, Boc-
layer chromatography (TLC) was conducted on aluminum sheets95 protected lactam 4e (31 mg, 0.064 mmol) was treated with
precoated with SiO2 ALUGRAM SIL G/UV254. Diazo compounds trifluoroacetic acid (0.9 mL). The obtained mixture of
1c,30 1d31 and 1e23 and azirines 2ad32 were synthesized according diastereomers 4a was separated by column chromatography
40 to published procedures.
(petroleum ether/EtOAc = 2:1) to give 13 mg of pure isomer
(5RS,9RS)-4a and 9 mg of an unseparated diastereomeric mixture
100 4a (overall yield 89%). Isomer (5RS,9RS)-4a. Colourless solid, mp
107111 С (from Et2O). H (300 MHz; CDCl3; Me4Si) 2.38 (3 Н,
s, CH3), 2.43 (3 Н, s, CH3), 3.89 and 3.94 (2 Н, AB-q, J 10.4 Hz, 6-
Н), 4.47 (1 Н, d, J 13.7 Hz, 2-Н), 4.99 (1 Н, d, J 13.7 Hz, 2-Н),
5.45 (1 Н, s, 9-Н), 6.55 (1 Н, br. s, NH), 7.22 (2 Н, d, J 8.1 Hz,
105 ArH), 7.27 (2 Н, d, J 8.1 Hz, ArH), 7.62 (2 Н, d, J 8.1 Hz, ArH),
7.66 (2 Н, d, J 8.1 Hz, ArH), 7.94 (1 Н, s, N=СН). C (75 MHz;
CDCl3; Me4Si) 21.3 (CH3), 21.6 (CH3), 51.3 (C-6), 69.2 (C-9), 75.2
(C-2), 112.0 (С-5), 126.1, 127.0, 127.3, 128.1, 129.4, 129.6, 132.2,
138.5, 143.0, 148.8, 168.5, 169.8. HRMS (ESI) [M + H+] calcd. for
С22Н22N5O2 388.1768, found 388.1756. Isomer (5RS,9SR)-4a (not
separated from (5RS,9RS)-isomer). H (300 MHz; CDCl3; Me4Si)
2.34 (3 Н, s, CH3), 2.37 (3 Н,s, CH3), 3.83 and 3.88 (2 Н, AB-q, J
10.4 Hz, 6-Н), 4.95 and 5.09 (2 Н, AB-q, J 13.7 Hz, 2-Н), 5.62 (1
Н, s, 9-Н), 7.12 (2 Н, d, J 8.1 Hz, ArH), 7.19 (2 Н, d, J 8.1 Hz,
General procedure for preparation of triazoles 3,4,6,7 and
compound 12
A screw cap ampoule containing diazo compound 1ae (1 eq),
45 azirine 2ad (3 eq), Cu(acac)2 (5 mol% on diazo compound) and
anhyd 1,2-dichloroethane (DCE) was closed and heated at 100 C
until the azirine was completely consumed (the reaction was
monitored by TLC, petroleum ether/EtOAc, 2:1). Azirine 2ad
was then added and the reaction mixture heated at the same
50 temperature until the azirine was consumed. The solvent was
removed under vacuum and the residue was purified by colum1n10
chromatography on silica gel to give, after crystallization, triazoles
3 and 4 (or 6 and 7).
55
(3аRS,6aRS)-6а-Hydroxy-2-(4-methyphenyl)-3а-[4-(4-
methyphenyl)-2Н-1,2,3-triazol-2-yl]-3a,5,6,6а-
6
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Organic & Biomolecular Chemistry
ArH), 7.42 (2 Н, d, J 8.2 Hz, ArH), 7.59 (2 Н, d, J 8.2 Hz, Ar), 7.81 general procedure (reaction time 4 h) diazo compound 1b (70 mg, 0.42
(1 Н, s, N=СН).
60 mmol) and azirine 2b (246 mg, 2.1 mmol) were reacted in DCE (3.2
mL). Column chromatography (benzene/EtOAc = 15:1) followed
by recrystallization gave triazole 3c (47 mg, 28%) and triazole 4c
(3аRS,6aRS)-5-Acetyl-6а-hydroxy-2-(4-methylphenyl)-3а-[4-(4-
methylphenyl)-2Н-1,2,3-triazol-2-yl]-3a,5,6,6а-
5
tetrahydropyrrolo[3,4-b]pyrrol-4(3Н)-one (3b) and 7-acetyl-3-(4- (34 mg, 20%) as a mixture of diastereomers (5RS,9RS)-4c and
methylphenyl)-9-[4-(4-methylphenyl)-2Н-1,2,3-triazol-2-yl]-1-
(5RS,9SR)-4c in 1.6:1 ratio. Compound 3c. Colourless solid, mp
oxa-4,7-diazaspiro[4.4]non-3-en-8-one (4b): Following the65 185191 С (from Et2O, dec.). max (KBr)/cm−1 3125 (О-Н), 2951,
general procedure (reaction time 3 h) diazo compound 1b (50 mg, 0.3 2852, 1755, 1702, 1606, 1577, 1461, 1426, 1394, 1371, 1293, 1221,
mmol) and azirine 2a (197 mg, 1.5 mmol) were reacted in DCE (2.3 1191, 1161, 1112, 1087, 976, 955, 763, 690. H (300 MHz; CDCl3;
10 mL). Column chromatography (benzene/EtOAc = 15:1) followed M`e4Si) 2.57 (3 H, s, CH3), 3.91 (1 Н, d, J 18.2 Hz, 3-Н), 4.10 (1
by recrystallization from EtOAc gave solvate of triazole Н, d, J 12.2 Hz, 6-Н), 4.52 (1 Н, d, J 12.2 Hz, 6-Н), 4.69 (1 Н, d, J
3b1/2EtOAc and triazole 4b (22 mg, 17%) as a mixture of70 18.2 Hz, 3-Н), 4.85 (1 Н, br. s, ОН), 7.367.51 (5 Н, m, ArH),
diastereomers (5RS,9RS)-4b and (5RS,9SR)-4b in 1.5:1 ratio. The 7.557.62 (1 Н, m, ArH), 7.777.86 (4 Н, m, ArH), 8.01 (1 Н, s,
solvate 3b1/2EtOAc was dissolved twice in DCM and dried under N=СН). C (75 MHz; CDCl3; Me4Si) 25.5 (CH3), 42.7 (C-3), 54.5
15 vacuum (0.1 torr) at room temperature for 1 h to give triazole 3b (С-6), 77.1 (C-3а), 100.3 (С-6а), 126.2, 128.5, 128.9, 129.0, 129.6,
(44 mg, 34%) as a colourless solid. Mp 188193 С (dec.). (Found 131.6, 132.4, 132.8, 148.8, 170.0, 170.6, 174.6. HRMS (ESI) [M +
С 65.83, H 5.56, N, 14.99. C24H23N5O30.5C4H8O2 requires С,
Na+] calcd. for С22Н19N5O3Na 424.1380, found 424.1371.
7
5
65.95; H, 5.75; N, 14.79%); max (KBr)/cm−1 3310 (О-Н), 2919, Compound 4c (diastereomeric mixture). Light pink solid, mp
2861, 1752, 1710, 1603, 1566, 1488, 1460, 1423, 1373, 1339, 1284, 5968 С. max (KBr)/cm−1 3126, 3061, 3037, 2926, 2856, 1760,
20 1216, 1181, 1148, 1043, 978, 959, 822 cm-1. H (300 MHz; CDCl3; 1709, 1663, 1627, 1579, 1451, 1354, 1287, 1120, 1095, 1058, 1039,
Me4Si) 2.42 (3 H, s, CH3), 2.44 (3 H, s, CH3), 2.56 (3H, s, CH3), 1015, 976, 917, 809, 768, 692. HRMS (ESI-TOF): calcd. for
3.88 (1 Н, d, J 18.2 Hz, 3-Н), 4.10 (1 Н, d, J 12.1 Hz, 6-Н), 4.50 (180 С22Н19N5O3Na [M+Na+] 424.1380; found 424.1377. Isomer
Н, d, J 12.1 Hz, 6-Н), 4.66 (1 Н, d, J 18.2 Hz, 3-Н), 5.19 (1 Н, br. (5RS,9RS)-4c. H (300 MHz; CDCl3; Me4Si) 2.71 (3 Н, s, CH3),
s, ОН), 7.25 (2 Н, d, J 8.1 Hz, ArH), 7.26 (2 Н, d, J 8.1 Hz, ArH), 4.29 (2 Н, s, 6-H), 4.50 (1 Н, d, J 14.1 Hz, 2-Н), 5.06 (1 Н, d, J
25 7.69 (2 Н, d, J 8.1 Hz, ArH), 7.71 (2 Н, d, J 8.1 Hz, ArH), 7.97 (1 14.1 Hz, 2-Н), 5.78 (1 Н, s, Н-9), 7.307.79 (10 Н, m, ArH), 7.98
Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 21.3 (CH3), 21.6 (CH3), (1 Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 25.4 (СH3), 53.1 (C-
25.6 (CH3), 42.6 (C-3), 54.6 (С-6), 77.0 (C-3а), 100.1 (С-6а),85 6), 71.3 (C-9), 75.3 (C-2), 108.9 (С-5), 126.2, 128.2, 128.7132.7
126.1, 126.8, 128.6, 128.9, 129.5, 129.6, 132.2, 138.9, 143.6, 148.8, (7 signals), 149.1, 166.2, 170.6, 171.0. Isomer (5RS,9SR)-4c. H
170.2, 170.7, 174.4. Crystal data: C24H23N5O30.5C4H8O2, M = (300 MHz; CDCl3; Me4Si) 2.72 (3 Н, s, CH3), 4.07 (1 Н, d, J 11.9
30 473.53, monoclinic, a = 22.883(2), b = 17.0326(17), c = Hz, 6-Н), 4.33 (1 Н, d, J 11.9 Hz, 6-Н), 4.92 (1 Н, d, J 14.1 Hz, 2-
14.7571(15) Å, β = 124.209(2)°, V = 4756.6(8) Å3, space group Н), 5.14 (1 Н, d, J 14.1 Hz, 2-Н), 5.84 (1 Н, s, Н-9), 7.307.79 (10
C2/c, Z = 8, μ(MoKα) = 0.091, 22209 reflections measured, 603190 Н, m, ArH), 7.86 (1 Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 25.5
unique (Rint = 0.0571) which were used in all calculations. The final (СH3), 52.5 (C-6), 72.9 (C-9), 74.9 (C-2), 109.7 (С-5), 126.2,
R1 is 0.0564 (3598>2σ(I)) and wR2 is 0.1688 (all data). Compound 128.1, 128.7132.4 (7 signals), 148.9, 165.8, 170.6, 170.7.
35 4b (diastereomeric mixture). Pink semi-solid. IR (CCl4):  = 3034,
2924, 2864, 1760, 1716, 1626, 1373, 1281 cm-1. HRMS (ESI) [M + (3аRS,6aRS)-5-Acetyl-6а-hydroxy-2-(4-methoxyphenyl)-3а-[4-(4-
H+] calcd. for С24Н24N5O3 430.1874, found 430.1871. Isomer95 methoxyphenyl)-2Н-1,2,3-triazol-2-yl]-3a,5,6,6а-
(5RS,9RS)-4b. H (300 MHz; CDCl3; Me4Si) 2.38 (3 Н, s, CH3), tetrahydropyrrolo[3,4-b]pyrrol-4(3Н)-one (3d) and 7-acetyl-3-(4-
2.42 (3 Н, s, CH3), 2.69 (3 Н, s, CH3), 4.27 (2 Н, s, 6-Н), 4.45 (1 Н, methoxyphenyl)-9-[4-(4-methoxyphenyl)-2Н-1,2,3-triazol-2-yl]-
40 d, J 14.0 Hz, 2-Н), 5.02 (1 Н, d, J 14.0 Hz, 2-Н), 5.77 (1 Н, s, 9-Н), 1-oxa-4,7-diazaspiro[4.4]non-3-en-8-one (4d): Following the
7.177.27 (4 Н, m, ArH), 7.577.68 (4 Н, m, ArH), 7.93 (1 Н, s, general procedure (reaction time 1.5 h) diazo compound 1b (167 mg, 1
N=СН). C (75 MHz; CDCl3; Me4Si) 21.2 (CH3), 21.6 (CH3), 25.400 mmol) and azirine 2c (735 mg, 5 mmol) were reacted in DCE (7.8
1
(CH3), 53.0 (C-6), 71.1 (C-9), 75.2 (C-2), 108.7 (С-5), 126.0, mL). Column chromatography (benzene/EtOAc = 10:1) followed
126.6, 126.8, 128.0, 129.4, 129.5, 132.4, 138.7, 143.1, 149.0, 166.2, by recrystallization gave triazole 3d (124 mg, 27%) and triazole 4d
45 170.4, 170.8. Isomer (5RS,9SR)-4b. H (300 MHz; CDCl3; Me4Si) (57 mg, 12%) as a mixture of diastereomers (5RS,9RS)-4d and
2.35 (3 Н, s, CH3), 2.38 (3 Н, s, CH3), 2.70 (3 Н, s, CH3), 4.04 (1 (5RS,9SR)-4d in 1.8:1 ratio. Compound 3d. Colourless solid. Mp
Н, d, J 12.0 Hz, 6-Н), 4.30 (1 Н, d, J 12.0 Hz, 6-Н), 4.88 (1 Н, d, J
05 193208 С (from acetone, dec.). HRMS (ESI) [M + H+] calcd. for
1
13.8 Hz, 2-Н), 5.10 (1 Н, d, J 13.8 Hz, 2-Н), 5.83 (1 Н, s, 9-Н), С24Н24N5O5 462.1772, found 462.1774. H (400 MHz; DMSO-d6;
7.127.22 (4 Н, m, ArH), 7.45 (2 Н, d, J 8.0 Hz, ArH), 7.60 (2 Н, Me4Si) 2.48 (3 H, s, CH3), 3.81 (3 H, s, CH3), 3.85 (3H, s, CH3),
50 d, J 8.0 Hz, ArH), 7.82 (1 Н, s, N=СН). C (75 MHz; CDCl3; 3.91 (1 Н, d, J 17.9 Hz, 3-Н), 3.93 (1 Н, d, J 11.6 Hz, 6-Н), 4.25 (1
Me4Si) 21.2 (CH3), 21.5 (CH3), 25.5 (CH3), 52.4 (C-6), 72.7 (C-9), Н, d, J 11.6 Hz, 6-Н), 4.61 (1 Н, d, J 17.9 Hz, 3-Н), 6.72 (1 Н,
74.8 (C-2), 109.6 (С-5), 126.0, 126.7, 126.9, 128.0, 129.3, 129.4,10 ОН), 7.05 (2 Н, d, J 8.8 Hz, ArH), 7.07 (2 Н, d, J 8.8 Hz, ArH),
1
132.1, 138.5, 142.8, 148.8, 165.9, 170.55, 170.59.
7.81 (2 Н, d, J 8.8 Hz, ArH), 8.00 (2 Н, d, J 8.8 Hz, ArH), 8.35 (1
Н, s, N=СН). C (100 MHz; DMSO-d6; Me4Si) 25.2 (CH3), 41.7
(C-3), 54.2 (С-6), 55.2 (CH3), 55.4 (CH3), 77.5 (C-3а), 99.5 (С-6а),
55
(3аRS,6aRS)-5-Acetyl-6а-hydroxy-2-phenyl-3а-(4-phenyl-2Н-
1,2,3-triazol-2-yl)-3a,5,6,6а-tetrahydropyrrolo[3,4-b]pyrrol-4(3Н)- 114.1, 114.4, 122.0, 124.9, 127.2, 130.2, 131.8, 147.2, 159.6, 162.3,
one (3c) and 7-acetyl-3-phenyl-9-(4-phenyl-2Н-1,2,3-triazol-2-yl)15 170.5, 170.6, 171.3. Compound 4d (diastereomeric mixture). Beige
1-oxa-4,7-diazaspiro[4.4]non-3-en-8-one (4c): Following the semi-solid. HRMS (ESI) [M + H+] calcd. for С24Н24N5O5 462.1772,
1-
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found 462.1772. Isomer (5RS,9RS)-4d. H (400 MHz; CDCl3; 148.9, 149.4, 164.5, 170.6. Isomer (5RS,9SR)-4d. H (300 MHz;
Me4Si) 2.67 (3 Н, s, CH3), 3.82 (3 Н, s, CH3), 3.84 (3 Н, s, CH3),60 CDCl3; Me4Si) 1.60 (9 Н, s, 3 CH3), 2.35 (3 Н, s, CH3), 2.38 (3 Н,
4.24 (2 Н, s, 6-Н), 4.42 (1 Н, d, J 13.8 Hz, 2-Н), 4.99 (1 Н, d, J s, CH3), 4.06 (1 Н, d, J 11.4 Hz, 6-Н), 4.24 (1 Н, d, J 11.4 Hz, 6-
13.8 Hz, 2-Н), 5.76 (1 Н, s, 9-Н), 6.92 (2 Н, d, J 8.8 Hz, ArH), 6.93 Н), 4.89 (1 Н, d, J 14.1 Hz, 2-Н), 5.10 (1 Н, d, J 14.1 Hz, 2-Н),
(2 Н, d, J 8.8 Hz, ArH), 7.64 (2 Н, d, J 8.8 Hz, ArH), 7.67 (2 Н, d, 5.73 (1 Н, s, 9-Н), 7.14 (2 Н, d, J 8.1 Hz, ArH), 7.18 (2 Н, d, J 8.1
J 8.8 Hz, ArH), 7.88 (1 Н, s, N=СН). C (100 MHz; CDCl3; Me4Si) Hz, ArH), 7.44 (2 Н, d, J 8.1 Hz, ArH), 7.59 (2 Н, d, J 8.1 Hz,
25.4 (CH3), 53.0 (C-6), 55.2 (CH3), 55.4 (CH3), 71.1 (C-9), 75.065 ArH), 7.80 (1 Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 21.3
(C-2), 108.7 (С-5), 114.1, 114.2, 122.0, 122.3, 127.4, 129.9, 132.1, (CH3), 21.5 (CH3), 28.0 (3 CH3), 53.7 (C-6), 72.6 (C-9), 74.7 (C-2),
148.7, 160.0, 162.9, 166.3, 170.1, 170.6. Isomer (5RS,9SR)-4d. H 84.1 (C(CH3)3), 109.6 (С-5), 126.1, 126.8129.6 (5 signals) 132.1,
5
10 (400 MHz; CDCl3; Me4Si) 2.68 (3 Н, s, CH3), 3.79 (3 Н, s, CH3), 138.4, 142.8, 148.7, 149.4, 164.1, 170.4.
3.82 (3 Н, s, CH3), 4.02 (1 Н, d, J 12.0 Hz, 6-Н), 4.28 (1 Н, d, J
12.0 Hz, 6-Н), 4.85 (1 Н, d, J 13.7 Hz, 2-Н), 5.05 (1 Н, d, J 13.770 (3аRS,6aRS)-6a-hydroxy-5-(4-methoxybenzyl)-2-(4-
Hz, 2-Н), 5.79 (1 Н, s, 9-Н), 6.81 (2 Н, d, J 8.7 Hz, ArH), 6.90 (2 methylphenyl)-3a-[4-(4-methylphenyl)-2H-1,2,3-triazol-2-yl]-
Н, d, J 8.7 Hz, ArH), 7.50 (2 Н, d, J 8.7 Hz, ArH), 7.62 (2 Н, d, J 3a,5,6,6a-tetrahydropyrrolo[3,4-b]pyrrol-4(3H)-one (3f) and 7-
15 8.7 Hz, ArH), 7.77 (1 Н, s, N=СН). C (100 MHz; CDCl3; Me4Si) (4-methoxybenzyl)-3-(4-methylphenyl)-9-[(4-methylphenyl)-2H-
25.5 (CH3), 52.4 (C-6), 55.2 (CH3), 55.3 (CH3), 72.7 (C-9), 74.6 1,2,3-triazol-2-yl]-1-oxa-4,7-diazaspiro[4.4]non-3-en-8-one (4f):
(C-2), 109.5 (С-5), 114.0, 114.1, 122.1, 122.4, 127.4, 129.9, 131.8,75 Following the general procedure (reaction time 10 h) diazo compound
148.5, 159.9, 162.7, 166.0, 169.7, 170.6.
1d (100 mg, 0.41 mmol) and azirine 2a (380 mg, 2.9 mmol) were
reacted in DCE (3.2 mL). Column chromatography (hexane/EtOAc
20
tert-Butyl (3аRS,6aRS)-6а-hydroxy-2-(4-methylphenyl)-3а- = 3:1) followed by recrystallization gave triazole 3f (48 mg, 23%)
[4-(4-methylphenyl)-2Н-1,2,3-triazol-2-yl]-4-oxo-3a,4,6,6а- and triazole 4f (15 mg, 7%) as a sole diastereomer. Compound 3f.
tetrahydropyrrolo[3,4-b]pyrrole-5(3Н)-carboxylate (3e) and80 Colourless solid. Mp 181182 С (from acetone). HRMS (ESI) [M
tert-butyl 3-(4-methylphenyl)-9-[4-(4-methylphenyl)-2Н-1,2,3- + H+] calcd. for С30Н30N5O3 508.2343, found 508.2337. H (400
triazol-2-yl]-8-oxo-1-oxa-4,7-diazaspiro[4.4]non-3-ene-7-
MHz; DMSO-d6; Me4Si) 2.36 (3 H, s, CH3), 2.39 (3 H, s, CH3),
25 carboxylate (4e): Following the general procedure (reaction time 2 3.68 and 3.71 (2 Н, AB-q, J 10.5 Hz, CН2), 3.78 (3H, s, CH3), 3.79
h) diazo compound 1c (132 mg, 0.59 mmol) and azirine 2a (386 mg, (1 Н, d, J 17.9 Hz, 3-Н), 4.23 (1 Н, d, J 14.8 Hz, 6-Н), 4.54 (1 Н, d,
2.95 mmol) were reacted in DCE (4.5 mL).
Column85 J 17.9 Hz, 3-Н), 4.80 (1 Н, d, J 14.8 Hz, 6-Н), 6.56 (1 Н, br. s,
chromatography (petroleum ether/Et2O 1:1) followed by ОН), 6.93 (2 Н, d, J 8.5 Hz, ArH), 7.247.40 (6 Н, m, ArH), 7.75
=
recrystallization gave triazole 3e (123 mg, 43%) and triazole 4e (36 (2 Н, d, J 8.0 Hz, ArH), 7.91 (2 Н, d, J 8.0 Hz, ArH), 8.33 (1 Н, s,
30 mg, 12%) as a mixture of diastereomers (5RS,9RS)-4e and N=СН). C (100 MHz; DMSO-d6; Me4Si) 20.9 (CH3), 21.1 (CH3),
(5RS,9SR)-4e
in
1.8:1
ratio
and
2-methyl-2,4-bis(4- 40.7 (C-3), 45.2 (CH2), 55.0 (CH3), 55.6 (С-6), 75.6 (C-3а), 101.2
methylphenyl)imidazole 5 (8 mg, 1% based on azirine). Partial90 (С-6а), 113.9, 125.6, 127.0, 127.7, 128.2, 129.1, 129.3, 129.5,
deprotection of both 3e and 4e occurred when a petroleum 130.0, 131.2, 138.1, 142.0, 147.3, 158.7, 169.0, 171.7.
ether/EtOAc mixture was used as eluent. Compound 3e. Colourless Compound 4f. Yellowish semi-solid. HRMS (ESI) [M + H+] calcd.
35 solid, mp 179185 С (from Et2O/hexane, dec.). (Found С, 66.50; for С30Н30N5O3 508.2343, found 508.2344. H (400 MHz; CDCl3;
H, 6.01; N, 14.31. C27H29N5O4 requires С, 66.51; H, 6.00; N, Me4Si) 2.39 (3 Н, s, CH3), 2.42 (3 Н, s, CH3), 3.67 and 3.75 (2 Н,
14.36%); max (KBr)/cm−1 3300 (О-Н), 2987, 2933, 2865, 1793,95 AB-q, J 10.5 Hz, CH2), 3.85 (3 Н, s, CH3O), 4.51 (1 Н, d, J 13.9
1763, 1723, 1601, 1566, 1489, 1474, 1426, 1392, 1368, 1341, 1309, Hz, 2-Н), 4.56 (1 Н, d, J 14.7 Hz, 6-Н), 4.87 (2 Н, d, J 14.7 Hz, 6-
1260, 1221, 1150, 948, 854, 819. H (300 MHz; CDCl3; Me4Si) Н), 4.92 (1 Н, d, J 13.9 Hz, 2-Н), 5.44 (1 Н, s, 9-Н), 6.94 (2 Н, d, J
40 1.54 (9 H, s, CH3), 2.42 (3 H, s, CH3), 2.45 (3 H, s, CH3), 3.86 (1 8.6 Hz, ArH), 7.22 (2 Н, d, J 8.1 Hz, ArH), 7.26 (2 Н, d, J 8.1 Hz,
Н, d, J 18.4 Hz, 3-H), 4.17 (1 Н, d, J 11.4 Hz, 6-H), 4.35 (1 Н, d, J ArH), 7.38 (2 Н, d, J 8.6 Hz, ArH), 7.59 (2 Н, d, J 8.1 Hz, ArH),
11.4 Hz, 6-H), 4.52 (1 Н, d, J 18.4 Hz, 3-H), 5.63 (1 Н, s, ОН),00 7.66 (2 Н, d, J 8.1 Hz, ArH), 7.93 (1 Н, s, N=СН). C (100 MHz;
1
7.23 (2 Н, d, J 8.1 Hz, ArH), 7.27 (2 Н, d, J 8.1 Hz, ArH), 7.61 (2 CDCl3; Me4Si) 21.3 (CH3), 21.6 (CH3), 46.4 (CH2), 55.3, 55.4
Н, d, J 8.1 Hz, ArH), 7.71 (2 Н, d, J 8.1 Hz, ArH), 7.98 (1 Н, s, (CH3O, C-6), 70.5, 75.1 (C-9, C-2), 109.8 (С-5), 114.2, 126.1,
45 N=СН). C (75 MHz; CDCl3; Me4Si) 21.3 (CH3), 21.7 (CH3), 27.9 127.0, 127.2, 127.3, 128.0, 129.4, 129.59, 129.64, 132.0, 138.4,
(3 CH3), 42.6 (C-3), 55.6 (C-6), 76.1 (C-3а), 84.3 (C(CH3)3), 100.1 142.9, 148.7, 159.3, 166.0, 169.4.
(С-6а), 126.1, 126.9, 128.5, 128.6, 129.49, 129.53, 132.2, 138.7
105
,
143.5, 148.4, 149.0, 168.7, 174.9. Compound 4e (diastereomeric (3аRS,6aSR)-6a-Hydroxy-2-(4-methylphenyl)-3a-[4-(4-
mixture). Yellowish semi-solid. HRMS (ESI) [M + Na+] calcd. for methylphenyl)-1,2,3-triazol-2-yl]-6,6a-dihydro-3H-furo[3,4-
50 С27Н29N5O4Na 510.2112, found 510.2123. Isomer (5RS,9RS)-4e. H b]pyrrol-4(3aH)-one (6a) and 3-(4-methylphenyl)-9-[4-(4-
(300 MHz; CDCl3; Me4Si) 1.60 (9 Н, s, 3 CH3), 2.38 (3 Н, s, CH3), methylphenyl)-1,2,3-triazol-2-yl]-1,7-dioxa-4-azaspiro[4.4]non-
2.42 (3 Н, s, CH3), 4.21 and 4.26 (2 Н, AB-q, J 11.5 Hz, 6-Н), 4.4210 3-en-8-one (7a): Following the general procedure (reaction time 12
1
(1 Н, d, J 13.9 Hz, 2-Н), 5.02 (1 Н, d, J 13.9 Hz, 2-Н), 5.67 (1 Н, s, h) diazo compound 1e (90 mg, 0.71 mmol) and azirine 2a (372 mg,
9-Н), 7.21 (2 Н, d, J 8.1 Hz, ArH), 7.25 (2 Н, d, J 8.1 Hz, ArH), 2.84 mmol) were reacted in DCE (22 mL). Column
55 7.59 (2 Н, d, J 8.1 Hz, ArH), 7.65 (2 Н, d, J 8.1 Hz, ArH), 7.91 (1 chromatography (petroleum ether/EtOAc = 10:13:1) followed by
Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 21.3 (CH3), 21.6 (CH3), recrystallization gave triazole 6a (69 mg, 25%) and triazole 7a (66
28.0 (3 CH3), 54.3 (C-6), 70.9 (C-9), 75.2 (C-2), 84.1 (C(CH3)3)
1
,15 mg, 24%) as a mixture of diastereomers (5RS,9SR)-7a and
108.7 (С-5), 126.1, 126.8129.6 (5 signals) 132.3, 138.6, 143.1, (5RS,9RS)-7a in 1.7:1 ratio. Isomer (5RS,9SR)-7a (39 mg, 14%)
8
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Organic & Biomolecular Chemistry
was separated from the mixture by fractional crystallization. 129.0, 129.1, 129.3, 132.0, 132.4, 132.7, 147.7, 172.5, 172.9.
Compound 6a: Colourless solid, mp 203204 С (from EtOH). H60 Compound 7b (diastereomeric mixture). Light green semi-solid.
(300 MHz; CDCl3; Me4Si) 2.34 (3 Н, s, CH3), 2.39 (3 Н, s, CH3), max (CCl4)/cm−1 3068, 3039, 2963, 2928, 2864, 1811 (С=О), 1743,
3.94 (1 Н, d, J 18.2 Hz, 3-Н), 4.62 (1 Н, d, J 9.4 Hz, 6-Н), 4.67 (1 1627, 1580, 1477, 1460, 1451, 1261, 1234, 1171. HRMS (ESI) [M
Н, d, J 18.2 Hz, 3-Н), 4.78 (1 Н, d, J 9.4 Hz, 6-Н), 7.01 (1 Н, s, + Na+] calcd. for С20Н16N4O3Na 383.1115, found 383.1116. Isomer
ОН), 7.30 (2 Н, d, J 8.0 Hz, ArH), 7.35 (2 Н, d, J 8.0 Hz, ArH), (5RS,9SR)-7b. H (300 MHz; CDCl3; Me4Si) 4.53 (1 Н, d, J = 14.2
7.79 (2 Н, d, J 8.0 Hz, ArH), 7.94 (2 Н, d, J 8.0 Hz, ArH), 8.44 (165 Hz, 2-Н), 4.71 and 4.81 (2 Н, AB-q, J 9.8 Hz, 6-Н), 5.06 (1 Н, d, J
Н, s, N=СН). C (75 MHz; DMSO-d6; Me4Si)) 20.9 (CH3), 21.2 14.2 Hz, 2-Н), 5.72 (1 Н, s, 9-Н), 7.337.79 (10 Н, m, ArH), 7.98
(CH3), 41.8 (C-3), 73.4 (C-3а), 75.3 (C-6), 103.5 (С-6а), 125.8, (1 Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 67.2 (C-9), 74.2 (C-
5
10 126.6, 128.4, 129.4, 129.6, 132.4, 138.4, 142.5, 147.7, 172.3, 173.0. 6), 75.6 (C-2), 111.8 (С-5), 126.1129.6 (7 signals), 132.7, 132.8,
HRMS (ESI) [M + H+] calcd. for С22Н21N4O3 389.1608, found 149.2, 167.9, 171.2. Isomer (5RS,9RS)-7b. H (300 MHz; CDCl3;
389.1598. Crystal data: C22H20N4O3, M=388.42, monoclinic, a =70 Me4Si) 4.63 (1 Н, d, J 9.8 Hz, 6-Н), 4.75 (1 Н, d, J 9.8 Hz, 6-Н),
11.2557(3), b = 7.9016(2), c = 21.4436(6) Å, β = 100.571(10)°, V = 5.00 and 5.16 (2 Н, AB-q, J 14.0 Hz, 2-Н), 5.74 (1 Н, s, 9-Н),
1874.78(9) Å3, space group P21/n, Z = 4, μ(Mo-Kα) = 0.094, 20470 7.337.79 (10 Н, m, ArH), 7.88 (1 Н, s, N=СН). C (75 MHz;
15 reflections measured, 5197 unique (Rint = 0.0344) which were used CDCl3; Me4Si) 69.1 (C-9), 73.6 (C-6), 75.0 (C-2), 112.5 (С-5),
in all calculations. The final R1 is 0.0659 (3865>2σ(I)) and wR2 is 126.1129.7 (7 signals), 132.5, 132.5, 149.0, 167.6, 171.4.
0.1358 (all data). Isomer (5RS,9SR)-7a. Colorless needles, mp75
138140 С (from hexane/СН2Сl2). H (300 MHz; CDCl3; Me4Si) (3аRS,6aSR)-6a-Hydroxy-2-(4-methoxyphenyl)-3a-[4-(4-
2.39 (3 Н, s, CH3), 2.43 (3 Н, s, CH3), 4.49 (1 Н, d, J 14.2 Hz, 2- methoxyphenyl)-1,2,3-triazol-2-yl]-6,6a-dihydro-3H-furo[3,4-
20 Н), 4.69 and 4.79 (2 Н, AB-q, J 9.8 Hz, 6-Н), 5.03 (1 Н, d, J 14.2 b]pyrrol-4(3aH)-one (6c) and 3-(4-methoxyphenyl)-9-[(4-
Hz, 2-Н), 5.69 (1 Н, s, 9-Н), 7.22 (2 Н, d, J 8.1 Hz, ArH), 7.26 (2 methoxyphenyl)-1,2,3-triazol-2-yl]-1,7-dioxa-4-azaspiro[4.4]non-
Н, d, J 8.1 Hz, ArH), 7.61 (2 Н, d, J 8.1 Hz, ArH), 7.66 (2 Н, d, J80 3-en-8-one (7c): Following the general procedure (reaction time 8 h)
8.1 Hz, ArH), 7.94 (1 Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) diazo compound 1e (80 mg, 0.635 mmol) and azirine 2c (374 mg, 2.54
21.3 (CH3), 21.7 (CH3), 67.2 (C-9), 74.3, 75.5, 111.7 (С-5), 126.1, mmol) were reacted in DCE (5 mL). Column chromatography
25 126.5, 126.8, 128.1, 129.5, 129.7, 132.6, 138.8, 143.4, 149.2, 168.0, (petroleum ether/EtOAc = 10:13:1) followed by recrystallization
171.0. HRMS (ESI) [M + Na+] calcd. for C22H20N4O3Na 411.1428, gave triazole 6c (49 mg, 18%) and triazole 7c (14 mg, 5%) as a
found 411.1416. Crystal data: C22H20N4O3, M=388.42, Monoclinic, mixture of diastereomers (5RS,9SR)-7c and (5RS,9RS)-7c in 1.8:1
8
5
a = 26.8700(9), b = 14.9778(5), c = 10.1263(4) Å, β = 102.53(2)°, ratio.
V = 3978.3(2) Å3, space group C2/c, Z = 8, μ(Mo-Kα) = 0.089, Compound 6c. Colourless solid, mp 182187 С (from
30 21597 reflections measured, 5041 unique (Rint = 0.0610) which EtOAc/hexane, dec.). max (CHCl3)/cm−1 3308 (О-Н), 2964, 2940,
were used in all calculations. The final R1 is 0.0553 (3352>2σ(I)) 2840, 1790 (С=О), 1604, 1516, 1488, 1464, 1422, 1392, 1342,
and wR2 is 0.1551 (all data). Isomer (5RS,9RS)-7a. H (300 MHz;90 1252, 1174, 1114, 1034, 1020, 834. H (300 MHz; DMSO-d6;
CDCl3; Me4Si) 2.36 (3 Н, s, CH3), 2.39 (3 Н, s, CH3), 4.61 (1 Н, d, Me4Si) 3.81 (3 Н, s, CH3), 3.85 (3 Н, s, CH3), 3.92 (1 Н, d, J 18.0
J 9.7 Hz, 6-Н), 4.74 (1 Н, d, J 9.7 Hz, 6-Н), 4.97 and 5.13 (2 Н, Hz, 3-Н), 4.59 (d, J 9.5 Hz, 1 Н, 6-Н), 4.61 (1 Н, d, J 18.0 Hz, 3-
35 AB-q, J 14.0 Hz, 2-Н), 5.72 (1 Н, s, 9-Н), 7.15 (2 Н, d, J 8.1 Hz, Н), 4.75 (1 Н, d, J 9.5 Hz, 6-Н), 6.94 (1 Н, s, ОН), 7.05 (2 Н, d, J
ArH), 7.21 (2 Н, d, J 8.1 Hz, ArH), 7.45 (2 Н, d, J 8.1 Hz, ArH), 8.7 Hz, ArH), 7.08 (2 Н, d, J 8.7 Hz, ArH), 7.82 (2 Н, d, J 8.7 Hz,
7.61 (2 Н, d, J 8.1 Hz, ArH), 7.84 (1 Н, s, N=СН).
95 ArH), 8.01 (2 Н, d, J 8.7 Hz, ArH), 8.39 (1 Н, s, N=СН). C (75
MHz; CDCl3; Me4Si) 41.6 (C-3), 55.2 (CH3), 55.5 (CH3), 73.4 (C-
(3аRS,6aSR)-6a-Hydroxy-2-phenyl-3a-(4-phenyl-1,2,3-triazol-2- 3а), 75.2 (C-6), 103.4 (С-6а), 114.2, 114.4, 121.9, 124.6, 127.3,
40 yl)-6,6a-dihydro-3H-furo[3,4-b]pyrrol-4(3aH)-one (6b) and 3- 130.3, 132.0, 147.6, 159.7, 162.5, 171.7, 173.1. HRMS (ESI) [M +
phenyl-9-(4-phenyl-1,2,3-triazol-2-yl)-1,7-dioxa-4-
azaspiro[4.4]non-3-en-8-one (7b): Following the genera
H+] calcd. for С22Н21N4O5 421.1506, found 421.1505. Compound
l
00 7c (diastereomeric mixture). Yellow semi-solid. max (CHCl3)/cm−1
1
procedure (reaction time 6 h) diazo compound 1e (60 mg, 0.476 mmol) 3052, 3004, 2960, 2928, 2856, 1800 (С=О), 1738 (С=О), 1608,
and azirine 2b (208 mg, 1.78 mmol) were reacted in DCE (5 mL). 1518, 1488, 1396, 1258, 1178, 1032, 1016. HRMS (ESI) [M + H+]
45 Column chromatography (benzene/EtOAc = 15:1) followed by calcd. for С22Н21N4O5 421.1506, found 421.1507. Isomer
recrystallization gave triazole 6b (27 mg, 16%) and triazole 7b (18 (5RS,9SR)-7c. H (300 MHz; CDCl3; Me4Si) 3.85 (3 Н, s, CH3),
mg, 11%) as a mixture of diastereomers (5RS,9SR)-7b and05 3.88 (3 Н, s, CH3), 4.47 (1 Н, d, J 14.2 Hz, 2-Н), 4.68 and 4.78 (2
1
(5RS,9RS)-7b in 2:1 ratio. Compound 6b: Colourless solid, mp Н, AB-q, J 9.8 Hz, 6-Н), 5.01 (1 Н, d, J 14.2 Hz, 2-Н), 5.68 (1 Н, s,
206210 С (from EtOAc, dec.) (Found С, 66.85; H, 4.27; N, 9-Н), 6.93 (2 Н, d, J 8.8 Hz, ArH), 6.95 (2 Н, d, J 8.8 Hz, ArH),
50 15.70. C20H16N4O3 requires С, 66.66; H, 4.48; N, 15.55). max 7.67 (2 Н, d, J 8.8 Hz, ArH), 7.70 (2 Н, d, J 8.8 Hz, ArH), 7.90 (1
(KBr)/cm−1 3299 (О-Н), 2975, 2938, 1786, 1609, 1574, 1449, 1421, Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 55.3 (CH3), 55.5 (CH3),
1393, 1363, 1343, 1247, 1162, 1125, 1041, 1018, 978, 958, 901,10 67.3 (C-9), 74.3 (C-6), 75.4 (C-2), 111.7 (С-5), 114.2, 114.3, 121.9,
1
870, 773, 692. H (300 MHz; DMSO-d6; Me4Si) 3.98 (1 Н, d, J 122.3, 127.5, 130.0, 132.3, 149.0, 160.1, 163.0, 168.1, 170.3.
18.2 Hz, 3-Н), 4.62 (1 Н, d, J 9.5 Hz, 6-Н), 4.69 (1 Н, d, J 18.2 Hz, Isomer (5RS,9RS)-7c. H (300 MHz; CDCl3; Me4Si) 3.82 (3 Н, s,
55 3-Н), 4.79 (1 Н, d, J 9.5 Hz, 6-Н), 7.05 (1 Н, s, ОН), 7.387.67 (6 CH3), 3.85 (3 Н, s, CH3), 4.60 (1 Н, d, J 9.7 Hz, 6-Н), 4.74 (1 Н, d,
Н, m, ArH), 7.90 (2 Н, d, J 7.2 Hz, ArH), 8.06 (2 Н, d, J 7.2 Hz, J 9.7 Hz, 6-Н), 4.95 and 5.11 (2 Н, AB-q, J 13.8 Hz, 2-Н), 5.69 (1
ArH), 8.50 (1 Н, s, N=СН). C (75 MHz; DMSO-d6; Me4Si) 41.
1
915 Н, s, 9-Н), 6.83 (2 Н, d, J 8.8 Hz, ArH), 6.93 (2 Н, d, J 8.8 Hz,
(C-3), 73.4 (C-3а), 75.3 (C-6), 103.6 (С-6а), 125.9, 128.4, 128.9, ArH), 7.51 (2 Н, d, J 8.8 Hz, ArH), 7.65 (2 Н, d, J 8.8 Hz, ArH),
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7.80 (1 Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 55.3 (CH3), 55.4 J 8.0 Hz, ArH). C (75 MHz; CDCl3; Me4Si) 21.6 (CH3), 25.4
(CH3), 69.0 (C-9), 73.7 (C-6), 74.8 (C-2), 112.4 (С-5), 114.1 (CH3), 45.4 (C-3), 54.9 (С-6), 55.3 (CH3), 61.9 (C-3а), 101.3 (С-
6,0
122.0, 122.4, 127.5, 130.0, 132.0, 148.8, 160.0, 162.9, 167.8, 170.5. 6а), 114.1, 126.8, 128.5, 128.9, 129.3, 129.4, 143.1, 159.2, 170.8,
175.5, 176.3. HRMS (ESI) [M + H+] calcd. for С22Н23N2O4
5
(3аRS,6aSR)-2-(4-Bromophenyl)-3а-[4-(4-bromophenyl)-1,2,3-
triazole-2-yl]-6а-hydroxy--6,6a-dihydro-3H-furo[3,4-b]pyrrol-
4(3aH)-one (6d) and 3-(4-bromophenyl)-9-[(4-bromophenyl)-1,2,3-
379.1652, found 379.1641.
triazol-2-yl]-1,7-dioxa-4-azaspiro[4.4]non-3-en-8-one
Following the general procedure (reaction time 20 min) diazo
(7d):
65 Acknowledgements
We gratefully acknowledge the financial support of the Russian Foundation
for Basic Research (grant No. 11-03-00186) and Saint Petersburg State
University (grant No. 12.38.78.2012). This research used resources of the
Centre for Magnetic Resonance and the Centre for chemical analysis and
10 compound 1e (126 mg, 1.0 mmol) and azirine 2d (980 mg, 5 mmol)
were reacted in DCE (1.0 mL). Column chromatography
(petroleum ether/EtOAc = 6:1) followed by recrystallization gave
triazole 6d (32 mg, 6%) and triazole 7d (16 mg, 3%) as a mixture70 material research of Saint Petersburg State University.
of diastereomers (3RS,4SR)-7d and (3RS,4RS)-7d in 1.9:1 ratio.
15 Compound 6d: Colourless solid, mp 204211 С (from EtOAc,
dec.). max (KBr)/cm−1 3298 (О-Н), 2963, 2921, 2851, 1796, 1607,
1588, 1561, 1474, 1424, 1396, 1364, 1333, 1259, 1188, 1159, 1123,
1097, 1068, 1042, 1008, 977, 822, 801. H (300 MHz; DMSO-d6
Me4Si) 3.97 (1 Н, d, J 18.3 Hz, 3-Н), 4.60 (1 Н, d, J 9.6 Hz, 6-Н),
20 4.67 (1 Н, d, J 18.3 Hz, 3-Н), 4.78 (1 Н, d, J 9.6 Hz, 6-Н), 7.12 (1
H, s, ОН), 7.70 (2 Н, d, J 8.5 Hz, ArH), 7.75 (2 Н, d, J 8.5 Hz,
ArH), 7.85 (2 Н, d, J 8.5 Hz, ArH), 7.98 (2 Н, d, J 8.5 Hz, ArH),
8.53 (1 Н, s, N=СН).  (75 MHz; DMSO-d ; Me Si) 41.9 (C-3),
Notes and references
a Department of Chemistry, Saint-Petersburg State University,
Universitetskii pr. 26, 198504 St. Petersburg, Russia Fax: +7 812-428-
6939; Tel: +7 812-428-4021; E-mail: m.s.novikov@chem.spbu.ru
75 b Department of Chemistry, Durham University, Durham, South Rd., DH1
3LE, UK.
† Electronic Supplementary Information (ESI) available: : spectroscopic
data of all new compounds and experimental procedures for preparation of
compounds 1ac, 11. See DOI: 10.1039/b000000x/
80 ‡ CCDC 924896 (for 3a), 924897 (for 3b), 924898 (for 6a), and 924899
(for (5RS,9SR)-7a) contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
C
6
4
73.6, 75.3 (C-3а, C-6), 103.9 (С-6а), 122.2, 126.3, 127.9, 128.6,
25 130.4, 131.2, 132.0, 132.1, 132.9, 146.8, 171.8, 172.7. HRMS
(ESI) [M + H+] calcd. for C20H15Br2N4O3 516.9505, found
516.9505. Compound 7d (diastereomeric mixture). Yellow semi-
85
1
(a) A. C. Tome in Science of Synthesis ed. R. C. Storr and T. L.
Gilchrist, Thieme, Stuttgart, New York, 2004, vol. 13, p. 415;
(b) X.-j. Wang, L. Zhang, D. Krishnamurthy, C. H. Senanayake
and P. Wipf, Org. Lett., 2010, 12, 46324635.
(a) V. P. Krivopalov and O. P. Shkurko, Russ. Chem. Rev., 2005,
74, 339379; (b) S. Kamijo, T. Jin, Z. Huo and Y. Yamamoto,
Tetrahedron Lett., 2002, 43, 97079710; (c) S. Kamijo, T. Jin,
Z. Huo and Y. Yamamoto, J. Am. Chem. Soc., 2003, 25,
77867787.
(a) S. Kamijo,; T. Jin, Z. Huo and Y. Yamamoto, Tetrahedron
Lett., 2002, 43, 97079710; (b) S. Kamijo, T. Jin, Z. Huo and Y.
Yamamoto, J. Am. Chem. Soc., 2003, 125, 77867787.
J. Kalisiak and K. B. Sharpless, V. V. Fokin, Org. Lett., 2008,
10, 31713174.
(a) A. F. Khlebnikov, M. V. Golovkina, M. S. Novikov and D.
S. Yufit. Org. Lett., 2012, 14, 37683771. (b) S. Chiba, Y.-F.
Wang, G. Lapointe and K. Narasaka, Org. Lett., 2008, 10,
313316; (c) E. P. J. Ng, Y.-F. Wang, B. W.-Q. Hui, G. Lapointe
and S. Chiba, Tetrahedron, 2011, 67, 77287737.
X. Li, Y. Du, Z. Liang, X. Li, Y. Pan and K. Zhao, Org. Lett.,
2009, 11, 26432646.
solid. max (CCl4)/cm−1 2928, 1810 (С=О), 1739, 1626, 1593, 1489,
1474, 1404, 1260, 1234, 1170. HRMS (ESI) [M + Na+] calcd.
30 С20Н14N4O3Br2Na 538.9325, found 538.9300. Isomer (5RS,9SR)-
7d. H (300 MHz; CDCl3; Me4Si) 4.49 (1 Н, d, J 14.2 Hz, 2-Н),
2
90
4.69 and 4.79 (2 Н, AB-q, J 9.8 Hz, 6-Н), 5.02 (1 Н, d, J 14.2 Hz,
2-Н), 5.69 (1 Н, s, 9-Н), 7.537.66 (8 Н, m, ArH), 7.96 (1 Н, s,
N=СН). C (75 MHz; CDCl3; Me4Si) 67.2 (C-9), 74.1 (C-6), 75.4
35 (C-2), 111.9 (С-5), 123.0, 127.6, 128.0, 128.5, 129.6, 132.1, 132.4,
3
95
132.7, 148.3, 167.6, 170.3. Isomer (5RS,9RS)-7d. H (300 MHz;
CDCl3; Me4Si) 4.62 and 4.72 (2 Н, AB-q, J 9.7 Hz, 6-Н), 4.96 and
5.12 (2 Н, AB-q, J 14.1 Hz, 2-Н), 5.73 (1 Н, s, 9-Н), 7.417.66 (8
Н, m, ArH), 7.85 (1 Н, s, N=СН). C (75 MHz; CDCl3; Me4Si) 69.1
4
5
100
40 (C-9), 73.4 (C-6), 74.9 (C-2), 112.6 (С-5), 122.9, 127.5, 127.6,
128.5, 129.5, 132.0, 132.2, 132.4, 148.1, 167.2, 170.5.
6
7
(3аRS,6aSR)-5-Acetyl-6а-hydroxy-2-(4-methylphenyl)-3а-(4-
methoxyphenyl)-3a,5,6,6а-tetahydropyrrolo[3,4-b]pyrrol-4(3Н)-one105
45 (12): A solution of enol 11 (40 mg, 0.16 mmol), azirine 2a (31 mg,
0.24 mmol), Cu(acac)2 (5 mol% on enol) in anhydrous DCE (1 mL)
was heated at 100 С in screw cap ampoule for 5 min. The solvent
(a) D. F. Taber and W. Tian, J. Am. Chem. Soc., 2006, 128,
10581059; (b) H. Inui and S. Murata, J. Am. Chem. Soc., 2005,
127, 26282636.
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10921101.
8
110
was removed under vacuum, and the residue was purified by
column chromatography on silica gel (petroleum ether/EtOAc =
50 4:1) to give, after crystallization, triazole 12 (33 mg, 55%) as a
colourless solid, mp 192197 С (dec.) (Et2O). max (KBr)/cm−1
9
F. Palacios, A. M. Ochoa de Retana, J. I. Gil and R. L. de
Munain, Org. Lett., 2002, 4, 24052408.
115
10 (a) V. A. Khlebnikov, M. S. Novikov, A. F. Khlebnikov and N.
V. Rostovskii, Tetrahedron Lett., 2009, 50, 65096511; (b) N.
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42924301.
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3074 (О-Н), 2957, 2901, 2840, 1736, 1708, 1604, 1515, 1440,
1375, 1357, 1341, 1282, 1256, 1214, 1181, 1153, 1106, 1038. H
(300 MHz; CDCl3; Me4Si) 2.44 (s, 3 H, CH3), 2.47 (3 H, s, CH3),
55 3.52 (1 Н, d, J 17.8 Hz, 3-Н), 3.85 (3 H, s, CH3), 3.86 (1 Н, d, J
17.8 Hz, 3-Н), 3.94 (1 Н, d, J 12.4 Hz, 6-Н), 4.48 (1 Н, d, J 12.1420
Hz, 6-Н), 5.37 (1 Н, br. s, ОН), 6.97 (2 Н, d, J 8.7 Hz, ArH), 7.23
(2 Н, d, J 8.0 Hz, ArH), 7.32 (2 Н, d, J 8.7 Hz, ArH), 7.73 (2 Н, d,
12 (a) M. S. Novikov, I. A. Smetanin, A. F. Khlebnikov, N. V.
Rostovskii and D. S. Yufit, Tetrahedron Lett., 2012, 53,
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