A Ruthenium Complex-Catalyzed Cyclotrimerization of Halodiynes with Nitriles. Synthesis of 2- and 3-Halopyridines

Article abstract of DOI:10.1002/adsc.201600127

Monohalo- and dihalodiynes efficiently undergo [2+2+2] cyclotrimerization with nitriles in the presence of a catalytic amount of the ruthenium complex Cp*RuCl(cod) (10 mol%) to afford the corresponding halopyridines under ambient conditions in good isolated yields (up to 90%). The halopyridines are formed as two separable regioisomers. This is the first example of a direct synthesis of halopyridines from haloalkynes and nitriles. (Figure presented.) .

Full text of DOI:10.1002/adsc.201600127

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DOI: 10.1002/adsc.201600127
A Ruthenium Complex-Catalyzed Cyclotrimerization of Halo-
diynes with Nitriles. Synthesis of 2- and 3-Halopyridines
a,b
b
b,
a,
ˇ
Eva Bednµrovµ, Evelina Colacino, FrØdØric Lamaty, * and Martin Kotora *
a
Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Albertov 6, 128 43 Praha 2,Czech
Republic
Fax: (+420)-221-951-326; phone: (+420)-221-951-058; e-mail: martin.kotora@natur.cuni.cz
Institut des BiomolØcules Max Mousseron (IBMM), UMR 5247, CNRS-UniversitØ Montpellier-ENSCM, UniversitØ de
b
Montpellier, Campus Triolet, Place Eug›ne Bataillon, 34095 Montpellier Cedex 5, France
Fax: (+33)-(0)4 6714-4866; phone: (+33)-(0)4-6714-3847; e-mail: frederic.lamaty@umontpellier.fr
Received: January 29, 2016; Revised: April 1, 2016; Published online: May 24, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600127.
Abstract: Monohalo- and dihalodiynes efficiently
undergo [2+2+2]cyclotrimerization with nitriles in
the presence of a catalytic amount of the ruthenium
complex Cp*RuCl(cod) (10 mol%) to afford the
corresponding halopyridines under ambient condi-
tions in good isolated yields (up to 90%). The halo-
pyridines are formed as two separable regioisomers.
This is the first example of a direct synthesis of
halopyridines from haloalkynes and nitriles.
give the corresponding halobenzenes. These processes
include: (i) Ru- or Co-catalyzed reactions of monoio-
dodiynes and diiododiynes[4] with alkynes to iodoben-
zenes that were further functionalized by cross-cou-
pling reactions;[5] (ii) Ru- or Rh-catalyzed cyclotrime-
rization of monobromodiynes with alkynes as a route
to new potentially selective inhibitors of tyrosine
kinase 2;[6] (iii) Ru-catalyzed cyclotrimerization of
a highly substituted chlorodiyne and alkyne during
the course of the sporolide B synthesis.[7] Although,
a Ru-complex catalyzed cycloaddition of haloalkynes
with nitrile oxides and organic azides has been recent-
ly described,[8] their cyclotrimerization with nitriles
providing halopyridines, interestingly, has not been re-
ported so far (to the best of our knowledge). Our in-
terest in cyclotrimerization of the halodiynes with the
Keywords: alkynes; cyclotrimerization; homogene-
ous catalysis; nitrogen heterocycles; ruthenium
Pyridines and their more complex derivatives are an nitriles stemmed for the fact that this procedure could
important class of heteroaromatic compounds. Sub- be used as an important step in syntheses of pyridines
stances possessing the pyridine framework are found and derivatives thereof. They can be used in numer-
in numerous branches of chemistry.[1] Out of many ous homogeneous catalytic racemic or enantioselec-
synthetic methods used for their preparation,[2] per- tive processes as ancillary ligands and their deriva-
haps the simplest and the most efficient, is catalytic tives (e.g., N-oxides, etc.) as Lewis basic organocata-
cyclotrimerization of alkynes with nitriles by using lysts.[1b,c,9] One such an example is Bolmꢀs ligand,
transition metal compounds.[3]
which has the bipyridine scaffold.[10] Therefore, it
Although a number of catalytic protocols have would be thus desirable to develop the cyclotrimeriza-
been developed, there is still a considerable space to tion of halodiynes with alkynes to substituted halopyr-
explore cyclotrimerization for hitherto untried combi- idines, because they could serve as convenient inter-
nations of alkynes and nitriles. In this respect, it mediates for synthesis of bipyridines and other types
would be desirable to develop a procedure allowing of pyridine based ligands.
synthesis of pyridines possessing a reactive functional
At the outset, the cyclotrimerization of iododiyne
group on the pyridine scaffold that would allow fur- 1a with ethyl cyanoformate 2a as model compounds
ther transformations. It would be synthetically inter- was screened under different conditions, to explore
esting if a cyclotrimerization would allow formation a possibility for the preparation of iodopyridines
of halopyridines by a catalytic reaction of haloalkynes (Table 1). The reaction was carried out in dichloro-
with nitriles.
ethane (DCE) in the presence of a large excess of cy-
As far as the cyclotrimerization of chloro-, bromo- anoformate (20 equiv.) to ensure high conversion by
and iodoalkynes is concerned, they can efficiently using the previously reported conditions for Ru-cata-
react with alkynes in cyclotrimerization processes to lyzed cyclotrimerization of iodoalkynes with alkynes
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Table 1. Catalytic cyclotrimerization of 1a with 2a under different conditions.
Entry
2a (equiv.)
Catalyst[a]
(mol%)
Time [h]
Solvent[b]
Yield [%][c]
3aa
4aa
5aa
Combined
1
2
3
4
5
6
7
8
20
1
2
5
10
2
2
2
2
2
Ru
Ru
Ru
Ru
Ru
Ru
Ru
Ru
Ru
Ru
Ru
Ru
Co[e]
Rh[f]
6
5
5
5
5
2
5
10
10
10
10
10
5
88
27
27
27
27
136
136
37
39
39
39
39
82
36
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
THF
23
33
3
59
18[d]
32[d]
26[d]
16[d]
9
19[d]
39[d]
28[d]
21[d]
7
3[d]
5[d]
2[d]
2[d]
1
40[d]
76[d]
56[d]
39[d]
17
19
29
27
27
35
34
nr
traces
28
45
38
45
47
49
nr
traces
3
5
5
5
7
5
–
–
50
79
70
77
89
88
–
–
9
10
11
12
13
14
2
2
5
2
CHCl3
CPME
toluene
DCE
2.5
[a]
Ru=Cp*RuCl(cod); Co=CpCo[P(OEt)3]diethylfumarate; Rh=[Rh(cod)]BF4, (R)-BINAP. Reactions were run at 208C
unless otherwise noted.
[b]
[c]
[d]
[e]
[f]
DCE=1,2-dichloroethane, DCM=dichloromethane, CPME=cyclopentyl methyl ether.
Isolated yields unless otherwise noted; nr=no reaction.
1
Yields determined by H NMR.
The reaction was run at 1008C.
The reaction was run at 208C (20 h) and then at 508C (16 h).
[Cp*RuCl(cod) at 208C]. Gratifyingly, the cyclotrime- (entries 13 and 14). Although speculative, their inac-
rization took place and provided three products 3aa, tivity may arise from a competitive oxidative addition
À
4aa, and 5aa in 23, 33, and 3% isolated yields (59% of the reactive spC halogen bond that might oxida-
combined yield) (entry 1). Compounds 3aa and 4aa tively add to these compounds providing catalytically
were regioisomers formed by different insertion path- inactive species.[11] With respect to the above de-
ways into the intermediate ruthenacycle, whereas 5aa scribed results, the following conclusions could be
possessed chlorine instead of iodine. The formation of made on the optimal reaction conditions: (i) 2/1 ni-
this compound was a bit puzzling, but subsequent in- trile/alkyne ratio, (ii) 10 mol% of Cp*RuCl(cod), (iii)
vestigation could reveal the origin of its formation chlorinated solvents as the reaction medium, (iv) re-
(vide infra). Then, the effects of the nitrile/alkyne action temperature of 208C. The structure of the re-
ratio, catalyst load and solvent on the course of the gioisomers was unequivocally confirmed by single
reaction were explored. The obtained results (en- crystal X-ray analyses of 3aa and 4aa (Figure 1 and
tries 2–5) indicated the 2/1 nitrile/diyne ratio to be op- Figure 2).
timal giving products in 76% combined yield. Using
Then the efficacy of the Ru-catalyzed cyclotrimeri-
10 mol% of the catalyst seemed to be optimal for zation of bromo- 1b and chlorodiynes 1c with cyano-
high yields of the products (entries 6–8). As far as the acetate 2a was examined for comparison under the
reaction medium is concerned, cyclotrimerization pro- optimized conditions (Table 2). The reaction with bro-
ceeded to give high isolated yields of the products modiyne 1b proceeded with full conversion of the
(77–89%) in dichloromethane, tetrahydrofuran, starting material and provided a mixture of 3ba, 4ba,
chloroform, and cyclopentyl methyl ether (entries 9– and 5aa in a combined 91% isolated yield (entry 2).
12). Attempts to induce the cyclotrimerization with The use of the chlorodiyne 1c furnished 3ca and 4ca
Co or Rh catalysts were not successful, despite the in a lower yield of 72% (entry 3). Obviously, the use
fact that these catalysts were shown to catalyze the of the bromo derivative 1b was advantageous with re-
cyclotrimerization of iodoalkynes with alkynes.[4e,5] In spect to yields of products. Attempts to increase the
both cases the reaction did not take place; moreover, reaction rate of cyclotrimerization of 1b by using
slight decomposition of iodoalkyne 1a was observed AgOTf to generate a cationic complex[12] or to sup-
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press formation of 5aa by addition of Bu4NBr did not
meet with success. The former resulted in the forma-
tion of a complex reaction mixture, in which only
traces of the desired products were detected (entry 4).
The latter had only a marginal if any effect on the
product distribution (entry 5).
In order to elucidate the formation of the chloro
derivatives, the following experiments were carried
out, Firstly, 3aa (containing approximately 12% of
5aa) was mixed with an equimolar amount of
Cp*RuCl(cod) in deuterated dichloromethane and
1
stirred at 208C. According to the H NMR analysis of
the reaction mixture (thanks to characteristic signals
of 3aa and 5aa) already 50% of 3aa was converted to
5aa after 10 h while after 10 days the conversion was
80% (see Figure SI-1 and Figure SI-2 in the Support-
ing Information).
Figure 1. ORTEP drawing of 3aa with 30% thermal ellip-
soids.
A halogen exchange reaction is a synthetically in-
teresting reaction proceeding in the presence of vari-
ous transition metal compounds, including ruthenium
complexes.[13] The Ru-catalyzed halogen exchange has
been observed with triflates ([Cp*Ru(MeCN)3]OTf
and LiBr)[14] and acyl halides (CpRuCl(PPh3)2 with
Me(CO)X, X=Cl, Br, I).[15] As for the reaction mech-
anism of the Ru-catalyzed halide exchange, two hy-
potheses have been proposed. The first one assumes
the halogen exchange to proceed via oxidative addi-
tion forming a cationic Ru(IV) 18 electron complex
followed by ligand exchange (TfOÀ for XÀ) and sub-
sequently undergoing reductive elimination. The
second one, based on experimental results and DFT
calculations, proposes the course of the reaction to
proceed via a radical pathway. Since thermochemical
À
data clearly show that in 2-chloropyridine the C Cl
bond [BDE (C Cl)=90.5 kcalmolÀ1][16] is much stron-
À
Figure 2. ORTEP drawing of 4aa with 30% thermal ellip-
soids.
À
À
ger than the C I bond in 2-iodopyridine [BDE (C
I)=63.1 kcalmolÀ1].[17] We assume this difference in
Table 2. Ru-catalyzed cyclotrimerization of diynes 1 with nitrile 2a.
Entry
1 (equiv.)
Time [h]
Additives
Yield [%][a]
4
3
5aa[b]
Combined
1
2
3
4
5
1a
1b
1c
1b
1b
37
21
21
39
20
–
–
–
3aa
3ba
3ca
3ba
3ba
29
40
36
traces
31
4aa
4ba
4ca
4ba
4ba
45
48
36
traces
39
5
3
–
79
91
72
–
[b]
AgOTf
Bu4NBr
traces
2
72
[a]
Isolated yields.
The compound’s structure is the same as that of 3ca.
[b]
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bond strength to be the driving force of the reac- various nitriles 2 with 1b was undertaken (Table 3).
tion.[18] To verify this assumption 2-iodopyridine was Although the reaction with cyanoformate 2a proceed-
stirred with Cp*RuCl(cod) in deuterated dichlorome- ed to give high yields of products (Table 2, entry 2),
thane. The exchange proceeded in the same fashion, the reactions with other nitriles gave variable yields.
but the reaction rate was much faster: 50% conver- Thus the reaction with cyanoacetate 2b at 20 or 508C
sion to 2-chloropyridine was observed already after 5 did not yield the desired products. On the other hand,
hours and 90% conversion after 48 h (see Figure SI-3 the use of highly electron-deficient malononitrile 2c
and Figure SI-4 in the Supporting Information). How- at 208C provided a mixture of 3bc (59%) and 4bc
ever, attempts to carry out the iodine-chlorine ex- (13%) yield along with minor amount of 5ac (2%)
change under catalytic conditions [10 mol% (entry 1). A possible product of the double cyclotri-
Cp*RuCl(cod)] in the presence of LiCl (THF, MeOH, merization was not observed. A reaction of 1b with
DMF) or Me4NCl (DCE/MeOH) in various solvents benzonitrile 2d and 4-chlorobenzonitrile 2e did not
were not met with success and only traces (~1–2%) provide the expected products at 20 or 508C. Interest-
of the desired 2-chloropyridine were observed after ingly, reaction with 3,5-difluorobenzonitrile 2f and
prolonged reaction time (1 week) even if the temper- 2,4,6-trifluorobenzonitrile 2g gave opposite results.
ature was increased to 508C.
The former gave rise to 3bf and 5af in 16% and 3%
Having elucidated the formation of the chloro de- isolated yields, respectively (entry 2), whereas 4bf was
rivatives, we decided to proceed with an assessment formed just in traces (~1%). Gratifyingly, the use of
of the reaction scope and the cyclotrimerization of highly electron-deficient nitrile 2h at 20 or 508C pro-
Table 3. Ru-catalyzed cyclotrimerization of various nitriles 2 with 1b.
Entry
2
R=
Temp. [8C]
Time [h]
13
Yield [%][a]
3
4
5
Combined
74
1
2
2c
2f
20
20
3bc
3bf
59
16
4bc
4bf
13
5ac
2
3
143
traces
5af
5ah
5ai
19
35
48
3
4
2h
2i
20
20
40
69
3bh
3bi
30
31
4bh
4bi
nd[b]
5
5
12
5
6
2j
2l
50
20
10
11
3bj
3bl
31
48
4bj
4bl
8
5aj
5al
5
1
44[c]
82
33
7
2m
2n
20
20
15
12
3bm
3bn
32
51
4bm
4bn
11
13
5am
5an
2
3
45
67
8
[a]
Isolated yields.
[b]
[c]
nd=not detected.
An inseparable mixture of regioisomers. The ratio was determined from 1H NMR.
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vided 3bh in 30% yield, along with a minor amount combined yields of 36, 55, and 87% (entries 1–3). It is
of 5ah (5%) (entry 3). Interestingly, formation of re- worth noting that the reaction with 1d provided only
gioisomer 4bh was not detected. The use of electron- regioisomer 3da, the other one – 4da – was not de-
deficient nitriles such as 3,5-bis(trifluoromethyl)ben- tected in the reaction mixture and the reaction had to
zonitrile 2i and 4-nitrobenzonitrile 2j resulted in the be carried at 508C. Interestingly, a reaction with 1-
formation of both regiosiomers. The former furnished bromo-1’-cyclopropyl dipropargyl ether 1g did not
3bi and 4bi in 31% and 12% isolated yields along proceed at 20 or at 508C (entry 4). The discrepancy in
with 5ai (5%) (entry 4). The latter furnished 3bj and reactivity of 1f and 1g cannot be simply rationalized
4bj in 27% and 5% isolated yields along with 5aj in terms of steric hindrance, because according to the
(6%). Carrying out the reaction at 508C had only Charton parameters,[19] the trimethylsilyl group (n=
marginal effect on the overall yields of products and 1.40) should exert larger steric hindrance than the cy-
provided 3bj, 4bj, and 5aj in 31, 8, and 5% yields, re- clopropyl group (n=1.06). In addition, a complex re-
spectively (entry 5). Interestingly, the reaction with action mixture was obtained in the reaction with 1g
1
1,4-dicyanobenzene 2k gave rise only to traces of the and, according to its H NMR analysis, the presence
expected products. Then our attention turned to acyl of other compounds possessing the cyclopropane ring
cyanides such as acetyl cyanide 2l, pivaloyl cyanide was not noticed. Hence side-reactions involving cleav-
2m and benzoyl cyanide 2n. In all cases the reaction age of the cyclopropane ring might hamper the over-
proceeded at 208C to give mixtures of both re- all outcome of the cyclotrimerization. The use 1-
gioisomers in good isolated yields (entries 6, 7, and 8). bromo-1,6-heptadiyne 1h did not provide the expect-
Formation of chloro derivatives 5al–5an was observed ed pyridine derivatives 3ha and 4ha (entry 5); prefer-
in the usual extent (1–3%). The above mentioned re- ential homocyclotrimerization to a bromobenzene SI-
sults indicate that only strongly electron-deficient ni- 1 was observed instead. A similar result was observed
triles enter this type of cyclotrimerization reaction. It in cyclotrimerization of diethyl 2-(3-bromoprop-2-
should be also noted that somewhat better results, ynyl)-2-(prop-2-ynyl)malonate 1i in which homocyclo-
that is, up to 15% higher yields, were obtained with trimerization to SI-2 was the major reaction pathway.
new batches of the catalyst, indicating that the course In spite of that, 3ia was isolated in low yield of 12%
of the reaction with respect to conversions and yields and only traces of 4ia were detected (entry 6). On the
could be affected by the catalyst quality.
other hand, cyclotrimerization of diethyl 2-(3-bromo-
The scope of the reaction with respect to diynes prop-2-ynyl)-2-(but-2-ynyl)malonate 1j with 2a pro-
was tested afterwards (Table 4). Cyclotrimerizations ceeded to give 3ja and 4ja in 31 and 38% yields, re-
were carried out with 1-bromo- 1d, 1-bromo-1’- spectively (entry 7). Cyclotrimerizations of 1-bromo-
phenyl- 1e, and 1-bromo-1’-trimethylsilyl- 1f dipro- 1,7-octadiyne 1k with 2a did not give the desired
pargyl ethers giving rise to the corresponding mix- products (entry 8). These results are not so much sur-
tures of regioisomers 3da–3fa and 4da–4fa in good prising since a similar phenomenon had been ob-
Table 4. Ru-catalyzed cyclotrimerization of various diynes 1 with 2a.
Entry
1
X
R=
Temp. [8C]
Time [h]
Yield [%][a]
3
4
5
Combined
1
2
3
4
5
6
7
8
1d
1e
1f
1g
1h
1i
O
O
O
O
H
50
20
20
50
20
20
20
50
24
22
13
47
66
82
18
24
3da
3ea
3fa
3ga
3ha
3ia
32
32
44
traces
nr[b]
12
31
traces
4da
4ea
4fa
4ga
4ha
4ia
nd[b]
17
36
traces
nr[b]
traces
38
5da
5ea
5fa
5ga
5ha
5ia
4
6
7
36
55
87[c]
–
Ph
TMS
c-Pr
H
H
Me
H
traces
[d]
CH2
–
2
2
–
–
C(COOEt)2
C(COOEt)2
(CH2)2
14[d]
71
1j
1k
3ja
3ka
4ja
4ka
5ja
5ka
[d]
traces
–
[a]
Isolated yields.
nd=not detected, nr=no reaction.
An inseparable mixture of regioisomers. The ratio was determined from H NMR.
Homocyclotrimerization of the starting diyne was observed.
[b]
[c]
[d]
1
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Scheme 1. Cyclotrimerizations of dibromodiynes 1l–1n with 2a.
served in Ru-[4e] as well as in Rh-catalyzed[20] cyclotri- with 3,5-dimethylphenylboronic acid 6 and vinylbor-
merizations of halodiynes previously. It should be onic acid pinacol ester 7 was briefly screened
noted that in cases of cyclotrimerization of diynes (Scheme 2). Thus reaction of 3ba with 6 and 7 under
possessing the terminal triple bond (1h, 1i, and 1k) the recently reported Suzuki coupling conditions[21]
homocyclotrimerization of diynes was observed as an [Pd(PPh3)2Cl2 (10 mol%), CsF, dioxane, H2O, 958C]
undesirable side reaction (in case of 1k only traces of provided the expected phenylated and vinylated prod-
1
the benzene product were detected by H NMR anal- ucts 8 and 9 in very good 92 and 79% isolated yields,
ysis of the reaction mixture).
respectively. Analogously proceeded the reactions
Finally cyclotrimerization of 2a with 1,1’-dibromo- with 4ba that gave rise to phenylated and vinylated
diynes was screened (Scheme 1). In the case of dibro- products 10 and 11 in nice 89 and 83% isolated yields,
modiynes 1l–1n cyclotrimerization proceeded un- respectively.
eventfully and furnished the desired products 6la–6na
In summary, (i) 1-halo- and 1,7-dibromoheptadiynes
in high isolated yields of 83, 81, and 77%, respective- could be successfully cyclotrimerized with electron-
ly. In all cases also chloro derivatives 5la–5na were deficient nitriles to the corresponding halopyridines
formed as minor by-products (2–6%). As expected on under catalysis of the Ru-complex (10 mol% of the
the base of previous results (entry 8, Table 4) cyclotri- catalyst is required); (ii) the optimal nitrile/alkyne
merization of 1,8-dibromo-1,7-octadiyne 1o did not ratio is 2/1; (iii) the optimal reaction temperature is
give the desired product either at 20 or at 508C.
208C, in the case of less reactive alkynes/nitriles,
Last but not least, utilization of the prepared bro- 508C could be used, (iv) the reaction can be run in
mopyridines 3ba and 4ba in cross-coupling reactions different solvents such as chloroalkanes or ethers, (v)
for the reactions of 1a, 1b, and 1j with 2a a slight pref-
erence for 3-halopyridine is observed, whereas for
other cases a slight preference for the formation of 2-
halopyridines was observed. A brief study regarding
cross-coupling reactions of the regioisomeric products
was undertaken: both regioisomers reacted almost
quantitatively providing basic proof of concept for
further functionalization.
Experimental Section
Ethyl 4-Iodo-7-methyl-1,3-dihydrofuro[3,4-c]pyridine-
6-carboxylate (3aa), Ethyl 7-Iodo-4-methyl-1,3-dihy-
drofuro[3,4-c]pyridine-6-carboxylate (4aa), and Ethyl
4-Chloro-7-methyl-1,3-dihydrofuro[3,4-c]pyridine-6-
carboxylate (5aa)
Into
a dried flask containing Cp*RuCl(cod) (7.6 mg,
0.02 mmol) under an argon atmosphere, DCE (1 mL) and
nitrile 2a (40 mg, 0.4 mmol) were slowly added. Then diyne
1a (47 mg, 0.2 mmol) dissolved in DCE (1.2 mL) was added
during the course of 15 min and the reaction mixture was
stirred at 208C. After the full consumption of the starting
diyne (disappearance of the respective spot from TLC anal-
ysis), volatiles were evaporated under reduced pressure.
Column chromatography of the residue on silica gel (gradi-
Scheme 2. Cross-coupling of 3ba and 4ba with boronic acid
derivatives 6 and 7 under Suzuki conditions.
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ent 10/1!5/1 hexanes/EtOAc) furnished 22 mg of an insepa-
rable mixture of 3aa and 5aa (yields: 29% and 5% deter-
mined from H NMR) and 30 mg (yield: 45%) of 4aa as col-
Domínguez, J. PØrez-Castells, Chem. Soc. Rev. 2011, 40,
3430–3444; e) D. L. J. Broere, E. Ruijter, Synthesis
2012, 2639–2672. For applications of the metal-cata-
lyzed [2+2+2]cycloaddition reaction in natural product
synthesis, see: f) B. Witulski, J. Grand, in: Application
to the Synthesis of Natural Products, in: Transition-
Metal-Mediated Aromatic Ring Construction, (Ed.: K.
Tanaka), John Wiley & Sons, Hoboken, NJ, USA, 2013,
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1
ourless solids. The combined yield is 79%.
3aa: mp 1688C (for a mixture containing 5aa); H NMR
1
(600 MHz, CDCl3): d=5.24 (t, J=2.4 Hz, 2H, CH2), 5.05 (t,
J=2.4 Hz, 2H, CH2), 4.44 (q, J=7.1 Hz, 2H, CH2), 2.36 (s,
3H, CH3), 1.42 (t, J=7.1 Hz, 3H, CH3); 13C NMR
(150 MHz, CDCl3): d=165.23, 150.24, 148.83, 143.74, 128.30,
106.17, 76.44, 74.52, 62.18, 15.76, 14.37; IR (3aa+5aa; drift
KBr): nmax =2977, 1709, 1467, 1413, 1380, 1281, 1183, 1063,
1099, 905 cmÀ1; HR-MS (EI-TOF): m/z=332.9861, calculat-
ed for C11H12NO3I (M): 332.9862; Rf (5/1 hexanes/EtOAc)=
0.31 (the same value for 3aa and 5aa).
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1
3ca: mp 112.48C; H NMR (600 MHz, CDCl3): d=5.18 (s,
4H, 2”CH2), 4.44 (q, J=7.1 Hz, 2H, CH2), 2.41 (s, 3H,
CH3), 1.42 (t, J=7.1 Hz, 3H, CH3); 13C NMR (150 MHz,
CDCl3): d=165.21, 153.15, 147.58, 141.41, 136.33, 128.08,
74.08, 73.18, 62.20, 15.88, 14.38; IR (drift KBr): nmax =1715,
1470, 1416, 1311, 1290, 1260, 1186, 1066, 1039, 905 cmÀ1
;
HR-MS
(EI-TOF):
m/z=241.0503,
calculated
for
C11H12NO3Cl (M): 241.0506.
1
4aa: mp 1138C; H NMR (600 MHz, CDCl3): d=5.26 (t,
J=2.1 Hz, 2H, CH2), 5.06 (t, J=2.1 Hz, 2H, CH2), 4.47 (q,
J=7.1 Hz, 2H, CH2), 2.44 (s, 3H, CH3), 1.44 (t, J=7.1 Hz,
3H, CH3); 13C NMR (150 MHz, CDCl3): d=166.17, 155.36,
151.49, 151.02, 135.65, 80.69, 78.74, 73.78, 62.53, 21.70, 14.31;
IR (drift KBr): nmax =1730, 1419, 1377, 1335, 1308, 1204,
1159, 1060, 905, 854 cmÀ1; HRMS (EI-TOF): m/z=332.9864,
calculated for C11H12NO3I (M): 332.9862; Rf (5/1 hexanes/
EtOAc)=0.16.
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Acknowledgements
This work was supported by a grant from the Czech Science
Foundation (P207/11/0587). The authors would like to thank
ˇ
Dr. Ivana Císarovµ (Department of Inorganic Chemistry,
Charles University in Prague) for the X-ray structure deter-
minations. Financial support from the French Embassy in
Prague is acknowledged.
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Adv. Synth. Catal. 2016, 358, 1916 – 1923
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