Three-component reaction and organocatalysis in one: synthesis of densely substituted 4-aminochromanes

Article abstract of DOI:10.1016/j.tet.2016.10.019

Cyclocondensation of salicylaldehydes with alkyl acetoacetates and 2-aminobenzothiazoles or 2-amino-thiadiazole/thiazoles under L-proline catalysis gives 4-hetarylamino substituted chromanecarboxylate derivatives. The mechanism involving the Mannich/hemik

Full text of DOI:10.1016/j.tet.2016.10.019

Tetrahedron xxx (2016) 1e8
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Three-component reaction and organocatalysis in one: synthesis of
densely substituted 4-aminochromanes
,
c
d
Jan Svĕtlík a , Nad’a Pronayova , Vladimír Frecer , Dariusz Ciez
ꢀ b
_
*
ꢀ
a Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32
Bratislava, Slovakia
b Department of NMR Spectroscopy and Mass Spectrometry, Faculty of Chemical and Food Technology, Slovak University of Technology, 812 37
Bratislava, Slovakia
c Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University in Bratislava, Odbojarov 10, 832 32 Bratislava, Slovakia
d
ꢀ
Department of Organic Chemistry, Jagiellonian University, 30 060 Krakow, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 July 2016
Received in revised form 27 September 2016
Accepted 10 October 2016
Available online xxx
Cyclocondensation of salicylaldehydes with alkyl acetoacetates and 2-aminobenzothiazoles or 2-amino-
thiadiazole/thiazoles under L-proline catalysis gives 4-hetarylamino substituted chromanecarboxylate
derivatives. The mechanism involving the Mannich/hemiketalization cascade reaction and the observed
stereoselectivity of the three component process are discussed.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Organocatalysis
L-Proline
4-Aminochromane
Salicylaldehyde
1. Introduction
new promising cardioprotective agents for myocardial ischemia.5
Moreover, potassium channels have become attractive pharmaco-
The chromane skeleton represents a key structural unit found in
a plethora of natural products like flavans and isoflavans.1 This
privileged heterocyclic entity is also an essential feature of more
complex compounds including vitamin E, tocopherols and canna-
binoids.2 Among the numerous types of bioactive functionalized
chromanes,3 the 4-amino derivatives have received unusual in-
terest because of their ability to act as ATP-sensitive potassium
channel openers.4 Cromakalim (1, Fig. 1) being a lead compound of
KATP activators has had a pivotal influence in the development of
logical targets for novel therapeutic strategies in the treatment of
hypertension, asthma, urinary incontinence, epilepsy and certain
neurodegenerative diseases, glaucoma and diabetes.5
Most of synthetic approaches to the 4-aminochromane frame-
work involve reactions between o-hydroxybenzaldimines and
electron-rich cyclic or open-chain alkenes catalyzed by several
Lewis6 and Brønsted7 acids. An alternative route making use of
salicylaldehyde Schiff bases consists in their Sc(OTf)3 promoted
cyclization with 2,2-dimethoxypropane.8 Besides, an intra-
molecular etherification of bromo substituted
b-aminoalcohols
mediated by CuI/8-hydroxyquinoline constitutes an another pre-
parative protocol.9 Notably, an adaption of the established imine
method for chiral organocatalysts and complexes has permitted
development of an enantioselective entry to this molecular
architecture.10
O
N
OH
Me
Me
NC
Recently we have found11 that the cyclocondensation of salicy-
laldehydes 2 with alkyl acetoacetates 3 and 2-aminobenzothiazoles
4 or 2-amino-5-methylthiazole 5b under classical Biginelli reaction
conditions (concd HCl catalysis) gave hetarylamino substituted
spiroketals 6 (Fig. 2) instead of the expected pyrimidine12a,b or
oxygen-bridged pyrimidine scaffold.12a,c In one case we succeeded
O
Fig. 1. Pharmacologically valuable cromakalim 1.
in identifying
a minor chromane by-product (namely 7b,
* Corresponding author. E-mail address: svetlik@fpharm.uniba.sk (J. Svĕtlík).
http://dx.doi.org/10.1016/j.tet.2016.10.019
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Svĕtlík, J.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.10.019

2
J. Svĕtlík et al. / Tetrahedron xxx (2016) 1e8
Scheme 1).11 It was therefore of interest to study whether a modi-
fication of the above experimental procedure might affect the re-
action outcome. The widely used organocatalysis by -proline in
S
S
X
Het:
L
Y
diverse multicomponent processes13 prompted us to examine this
amino acid as a promoter for the previously studied transformation.
In pursuing our work on the conformationally restricted hetero-
cycles,11,12 we report here a practical one-pot synthesis of highly
substituted 4-aminochromanes. Generally, in this case construction
of these bicyclic molecules involves the formation of three new
bonds (one CeC, one CeN, and one CeO) and three consecutive
stereocenters in one synthetic step.
O
N
N
O
H
X
N
H
Het
Me
CO2R
6
Fig. 2. Spirobischromane product formed under Biginelli conditions.
Scheme 1. L-Proline catalyzed three-component reaction.
Please cite this article in press as: Svĕtlík, J.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.10.019

J. Svĕtlík et al. / Tetrahedron xxx (2016) 1e8
3
2. Results and discussion
to a database search 2-aminobenzothiazol-3-ium prolinate 8
proves to be the first isolated and characterized 1:1 proton-transfer
derivative in the proline family.
With the optimized conditions in hand, we first explored the
scope of the reaction with various acetoacetates. The isopropyl (3b),
tert-butyl (3c) and benzyl (3d) esters produced the corresponding
aminochromanes 7 and 70 in good yields (50e71%). The determined
diastereomeric ratio (dr) values (7b/70b 82:18, 7c/70c 84:16, 7d/70d
86:14) which are slightly higher than that for the methyl derivative
reflect the bulkiness of the alcohol moieties.
Next, the synthetic utility of the studied heterocyclization was
tested by modifying the amine component while the salicylalde-
hyde (2a) and tert-butyl 3-oxobutanoate (3c) input was fixed. As
shown in Scheme 1, we were successful in converting both selected
2-aminobenzothiazoles 4bed, two 2-aminothiazoles 5a,b as well
as 2-amino-5-methylthiadiazole 5c to the desired chromanes 7eej
in moderate to good yields (42e78%) with average drs of 80:20.
At the outset of our work, we reacted salicylaldehyde 2a, methyl
acetoacetate 3a and 2-aminobenzothiazole 4a as the model com-
pounds at the same molar ratio (2:1:1) used for the spiroketaliza-
tion mentioned above.11 Unfortunately, refluxing ethanolic solution
of the substrates in the presence of 15 mol % L-proline resulted in
substantial decomposition progressing with the time of heating.
However, when the mixture was stirred at ambient temperature for
a prolonged time period, a white solid could be isolated through
filtration. Its 1H NMR spectrum closely resembled to that of the
foregoing aminochromane 7b, and, hence, the product structure
must correspond to the methyl ester analogue 7a. In addition, el-
emental analysis data for the isolated substance showed satisfac-
tory agreement with the empirical formula of
C19H18N2O4S
corresponding to derivative 7a, thereby confirming equimolar ter-
nary adduct formation in this organocatalytic three-component
cyclization. A control experiment indicated that no cyclization
proceeded in the absence of the catalyst. To identify the optimal
conditions, several different solvents, catalyst loading and reaction
times were evaluated (Table 1). Taken together, the screening at-
Nevertheless,
the
cyclocondensation
with
2-amino-6-
methoxybenzothiazole 4d proceeded very slowly and a small
quantity of the unreacted intermediary azomethine 911 (Fig. 3) was
isolated even after 7 days.
tempts revealed that using 30 mol % charge of
L
-proline in ethanol
On the other hand, the employment of salicylaldehydes 2b,c
enabled us to install a substituent onto the benzene ring of the
chromane skeleton in the products 7k,l (Scheme 1).
for 45 h afforded the desired compound in an improved yield of
45%. According to the 1H NMR spectrum, particularly due to dif-
ferentiated doublets of H-3 (Dd 0.15 ppm), the obtained product
was a mixture of two diastereomers 7a and 70a in a 77:23 ratio
(Scheme 1). Regarding other reaction media, DMF and DMSO also
functioned well, although they showed certain drawbacks due to
slightly lower yields and a more complicated work-up procedure
(Table 1). Surprisingly, the same three-component condensation
reaction did not take place in acetonitrile, while a 1:1 proton-
transfer compound 8 of the catalyst and amine substrate 4a was
formed. Based on the 1H NMR spectrum, and in agreement with an
earlier experimental study on dissociation constants of substituted
2-aminobenzothiazoles,14 the protonation by the proline carboxylic
group is believed to occur on the ring nitrogen atom (Fig. 3). The
fact that an equimolar mixture of the two constituents alone un-
derwent conversion to prolinate 8 in essentially quantitative yield
(85%), may be seen as a proof of the observed transformation.
Moreover, a similar proton-transfer process between 2-amino-6-
methylbenzothiazole and dipicolinic acid has recently been de-
scribed.15 With regard to the proline behavior, our literature survey
revealed in this context only an article referring to in situ genera-
tion of triethylammonium prolinate.16 Curiously enough, according
As to the minor isomer 70, we suppose that it differs from 7 only
in the configuration at C-2 while their relative stereochemistry
between the C-3 and C-4 positions remained intact. This finding
relies on the similar vicinal coupling constants JH-3,H-4, the values of
which for the H-3 doublet signal amount to 12 Hz in 7 and to
9.6e10.5 Hz in 70, respectively. Since such JH,H magnitudes corre-
spond obviously to a trans-diaxial relationship of H-3 and H-4 in
both cases, the diastereomers 7 and 70 must possess an opposite
configuration at the stereogenic C-2 atom.
During the course of this work, we attempted to dehydrate the
crude 2-hydroxychromane 7b/70b by a treatment with p-TosOH
(25 mol %). Interestingly, instead of the expected water elimination
a conversion to single diastereomer 7b occurred (dr¼95:5) under
prolonged stirring of ethanolic or acetone solution at room tem-
perature. The isomerization has been successfully undertaken with
all diastereomeric mixtures, except for 7a/70a and 7i/70i. In most
cases chromanes 7 were isolated in good yields (80e90%) and high
purity (dr¼95:5).
A plausible mechanism for the studied multicomponent cycli-
zation is outlined in Scheme 2. The reaction pathway commences
with the -proline catalyzed formation of 2-hydroxybenzaldimine A
L
from salicylaldehyde 2 and heterocyclic amine 4 or 5. The con-
densation is apparently facilitated by activation of the aldehyde
carbonyl oxygen via intermolecular hydrogen bonding with the
acidic group of the catalyst, since this reaction does not take place
Table 1
Reaction optimization for the synthesis of 7/70a
Entry
Solvent
L-Proline [mol %]
Time [h]
Isolated yield [%]
in the absence of the L-proline. In contrast, the catalytic aldimine
1
2
3
4
5
6
7
8
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
DMF
15
25
30
30
30
30
30
30
25
25
25
30
35
45
45
45
26
31
34
38
42
45
32
35
generation represents a fast step because separation of the Schiff
base could be observed within a short time. A simultaneously oc-
curring dehydrative condensation between acetoacetate 3 and
proline gives
b-enamino ester B which then adds diaster-
eoselectively to the preformed imine A to produce intermediary
iminium ion C. Its sequential hydrolysis liberates syn-Mannich
DMSO
S
OMe
S
_
NH2
COO
N
.
N
+
N
H
H
N
OH
8
9
Fig. 3. Isolated by-products 8 and 9.
Please cite this article in press as: Svĕtlík, J.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.10.019

4
J. Svĕtlík et al. / Tetrahedron xxx (2016) 1e8
NHet
L-Pro
O
HetNH2
X
X
+
_
+
H2O
OH
OH
2
4
A
_
+
COO
HetHN
Me
HetHN
N
COOR
Me
H
COOR
COO
L-Pro
_
MeCOCH2COOR
Me
COOR
OH
_
X
H2O
X
N
3
N
OH
+
COOH
B
C
C'
_
H2O
L-Pro
O
HetHN
HetHN
HetHN
O
COOR
COOR
Me
Me
COOR
COOH
Me
X
X
_
X
O
N
OH
OH
E
D
D'
+
_
H
L-Pro
L-Pro
path "a"
HetHN
HetHN
H
COOR
X
path "b"
COOR
Me
X
7
H
+
O
_
+
H
Me
O
F
G
_
H-O-H
_
path "c"
H2O
Scheme 2. Plausible mechanisms leading to compound 7.
adduct D with concomitant release of the catalyst molecule. Finally,
the key precursor D undergoes intramolecular hemiketalization
reaction to yield the 4-aminochromane product diastereomers 7
and 70. Nevertheless, the stereochemistry observed for the major
isomer 7 with an axial hydroxyl group suggests a stereocontrol
arising as a consequence of the anomeric effect. This stereo-
electronic phenomenon thus favors the formation of the thermo-
skeleton E, followed by the generation of the cyclic oxocarbenium
ion F together with proline elimination. The resulting addition of
water to the postulated cationic species F then leads to the desired
anomeric lactols 7 and 70. In this case, the preferable formation of
isomer 7 can be explained by the axial nucleophilic attack of H2O on
the Si-face of the 3,4-dihydrochromenium C-2 center. On the other
hand, Re-approach to the transient ion F, adopting a sofa-like
conformation with the C-3 out of plane, would encounter a desta-
bilizing 1,2-diaxial interaction between the incoming water mole-
cule and H-3 atom (Scheme 2). However, in contrast to the recently
reported synthesis of 2-alkoxychromenes through trapping of the
heteroaromatic 1-benzopyrylium cation with alcohols,13g,k our at-
tempts to detect the potential 2-ethoxy-2-methylchromane de-
rivatives in the crude products by NMR spectroscopy failed. In the
light of the given facts the mechanistic rationale discussed here
appears therefore less probable.
Nevertheless, there is yet another possible pathway from E to
diastereoisomers 7 and 70. It consists in the acidic H-3 hydrogen
assisted elimination of proline leading to 4H-chromene G followed
by the final addition of water (Scheme 2). Unfortunately, such an
explanation when confronted with a reported competing formation
of 2-alkoxy- and hydroxychromenes via similar chromene inter-
mediate,13l seems to be rather debatable, too.
dynamically more stable
a-lactol form 7. As to the invoked
fundamental stabilizing interaction, its existence in the 2-hydroxy-
and 2-alkoxychromanes had long been recognized from NMR
conformational analysis of 3JHH coupling constants.17
The observed syn-selectivity can be rationalized in terms of the
HoukeList paradigm18 for the organocatalytic Mannich reaction. In
agreement with this concept we postulated a simple stereochem-
ical model that features the proton transfer from proline carboxyl to
imine nitrogen along with an additional hydrogen bonding be-
tween the phenolic hydroxyl and ester carbonyl oxygen (Fig. 4). The
above mentioned intervening non-covalent interactions thus
allowed organizing both (E)-configurated components into a 15-
membered cyclic transition state assembly through an Si, Si
approach.
An alternative plausible pathway can be envisaged to involve, at
first, a ring closure of the above intermediate C into chromane
Please cite this article in press as: Svĕtlík, J.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.10.019

J. Svĕtlík et al. / Tetrahedron xxx (2016) 1e8
5
hydroxyl in the hemiketal 7c is held in place by a hydrogen bond to
the proximal ester carbonyl oxygen (OH/O]CeO 2.03 A), thereby
O
O
ꢁ
N
N
increasing the stability of this anomer. The observed lower wave-
OH
OH
number of n
(C]O) at 1708 cmꢀ1 matches well with an ester car-
H
ROOC
Me
COOR
Me
bonyl group arrested by a hydrogen bridge. On the other hand, b-
oriented hydroxyl in 70c tends to interact rather with the O-1
H
ꢁ
chromane atom (OH/O1 2.43 A) than with the ester alkoxy oxygen
ꢁ
(less stable)
(more stable)
B'
(OH/OeC]O 3.13 A), as seen from the respective calculated hy-
B
drogen bond lengths.
Despite the relatively low solubility of the aminochromane
products, we attempted to analyze the pure diastereomer 7c by
using chiral HPLC. The resulting chromatogram, however, surpris-
ingly contained four peaks evidently corresponding to two pairs of
enantiomers arising from the anomerization process during the
HPLC experiment. Chiral separation of the crude product 7c gave
essentially the same chromatographic profile. In addition to the
two smaller and slower eluting peaks, there were other two faster
and poorly resolved peaks with the second being the major one.
The variation of experimental conditions regarding the column
type, flow rate and mobile phase composition nevertheless did not
improve the separation. Quite gratifyingly, by manually collecting
fractions of the main component from two non-preparative anal-
yses, it was possible to gain a sufficient amount of the sample for
the electronic CD spectra recording. The obtained evaporation
residue was dissolved in MeCN and immediately subjected to the
chiroptical measurement. The experimental ECD curve is plotted in
Fig. 5a. The simulated spectra for the enantiomeric pair of 7c,
2R,3S,4S and 2S,3R,4R (Fig. 6), computed with the time-dependent
DFT at the CAM-B3LYP-SCFR(acetonitrile)/6-311þþG(d,p)//B3LYP/
6-31G(d,p) level of theory are displayed in Fig. 5b. As can be seen,
the calculated spectrum for the 2R,3S,4S isomer and the experi-
mental trace could be satisfactorily related to each other when
considering their overall shape. In particular, there is a predicted
strong electronic transition near 195 nm being similar in relative
intensity and sign with the observed positive Cotton effect. Even
though the two negative bands at higher wavelength of the theo-
retical spectrum appear somewhat weaker compared to the ex-
perimental pattern, they still reproduce acceptably the observed CD
profile.
O
Het
N
N
HO
Me
H
Si, Si approach
H
OR
HO
O
Fig. 4. Transition state structure of the Mannich reaction.
In order to gain a better understanding of the stereochemical
aspects of the studied reaction, some obtained chromanes were
subjected to isomer stability evaluation. Thus, NMR monitoring of
the pure diastereomer 7e in DMSO-d6 solution has shown that
equilibrium between epimers 7e and 70e was established within
about 16 h while the content of both forms corresponded approx-
imately to the composition found in the crude product. The
anomeric ratio at equilibrium remained almost unchanged al-
though some decomposition was observed. Accordingly, we con-
clude that the stereochemical outcome of the reaction is
determined by thermodynamic equilibration. This interconversion
process between both anomers takes place most probably through
the common open-chain form D (see Scheme 2). In support of such
a structure, an analogous hydroxyketone existing in a fast dynamic
equilibrium with 2-methylchroman-2,4-diol can be mentioned.19
Apparently, DFT quantum chemical calculations (B3LYP/6-
311þþG**) carried out on the compound 7c showed that the major
isomer represents the most stable form of the four theoretically
possible diastereomers originating from the presence of three
stereogenic centers in the molecule. The minor component 70c was
found to be approximately 2.6 kcal/mol higher in energy than the
Thus, the determined absolute stereostructure proves to be in
accord with the explanation based on the stereochemical model
given in Fig. 4. Moreover, following our findings resulting from the
circular dichroism investigation we may conclude that the pre-
diastereomer 7c. Moreover, as revealed by the computations, the
a
-
dominant enantiomer formed in the L-proline catalyzed three-
Fig. 5. (a) Experimental (left), and (b) calculated (right) CD spectra of 7c.
Please cite this article in press as: Svĕtlík, J.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.10.019

6
J. Svĕtlík et al. / Tetrahedron xxx (2016) 1e8
volume of aqueous ethanol and allowed to crystallize. The pure
diastereomers were obtained as white crystalline solids.
S
S
N
H
N
H
4.2.1. Methyl (2R*,3S*,4S*)-4-(benzothiazol-2-ylamino)-2-hydroxy-
HN
HN
2-methyl-3,4-dihydro-2H-chromene-3-carboxylate
yield 0.333 (45%), isomerization was not successful; mp
156e158 ꢂC (EtOH); Rf (EtOAc) 0.61; IR: nmax 3311, 1717, 1544, 1453,
1244,1227, 749 cmꢀ1; 1H NMR (DMSO-d6):
1.59 (s, 3H, Me-2), 3.05
(7a). Isolated
H
H
g
COOtertBu
OH
Me
COOtertBu
OH
Me
O
d
O
(d, 1H, J¼12 Hz, H-3), 3.62 (s, 3H, OMe), 5.60e5.70 (m, 1H, H-4),
6.79 (d, 1H, J¼7.8 Hz, H-8), 6.87 (t, 1H, J¼7.8 Hz, H-6), 7.05 (t, 1H,
J¼7.8 Hz, H-60), 7.17 (t, 1H, J¼7.8 Hz, H-7), 7.20 (br s, 1H, OH), 7.21 (d,
1H, J¼7.8 Hz, H-5), 7.25 (t, 1H, J¼7.8 Hz, H-50), 7.41 (d, 1H, J¼7.8 Hz,
H-40), 7.69 (d, 1H, J¼7.8 Hz, H-70), 8.42 (d, 1H, J¼9.0 Hz, NH); 1H
NMR (DMSO-d6, minor isomer 70a, only resolved resonances):
7c: 2S,3R,4R
7c: 2R,3S,4S
Fig. 6. Examined enantiomers of 7c.
component reaction is expected to be the chromane 7 having the
2R,3S,4S stereochemistry.
d
1.49 (s, 3H, Me-2), 3.20 (d, 1H, J¼9.6 Hz, H-3), 3.46 (s, 3H, OMe),
5.48e5.54 (m, 1H, H-4), 7.64 (d, 1H, J¼7.5 Hz, H-70), 8.49 (d, 1H,
J¼9.0 Hz, NH). Anal. Calcd for C19H18N2O4S (370.42): C, 61.61; H,
4.90; N, 7.56%. Found: C 61.32; H, 5.05; N, 7.34%.
3. Conclusion
In summary, the cyclization of salicylaldehydes with alkyl ace-
toacetates and 2-aminobenzothiazoles or 2-aminothiadiazole/thi-
azoles catalyzed with L-proline affords under mild conditions alkyl
4.2.2. Isopropyl (2R*,3S*,4S*)-4-(benzothiazol-2-ylamino)-2-
hydroxy-2-methyl-3,4-dihydro-2H-chromene-3-carboxylate
(7b). Isolated yield 0.565
g (71%), isomerization 90%; mp
4-hetarylamino-2-hydroxy-2-methyl-3,4-dihydro-2H-chromene-
3-carboxylates. The formation of these heterocycles is different
from the hetarylamino substituted 2,20-spirobischromanecarbox-
ylate derivatives produced by employing classical Biginelli protocol
(HCl catalyst). The three component process proceeds via tandem
Mannich/hemiketalization reaction sequence. Based on the CD
spectra and quantum chemical calculations, the absolute stereo-
chemistry of the major enantiomer was established as 2R,3S,4S.
146e148 ꢂC (EtOH); mp 145e146 ꢂC: Ref. 11; Rf (EtOAc) 0.62.
Spectral data and X-ray structure: Ref. 11.
4.2.3. tert-Butyl (2R*,3S*,4S*)-4-(benzothiazol-2-ylamino)-2-
hydroxy-2-methyl-3,4-dihydro-2H-chromene-3-carboxylate
(7c). Isolated yield 0.569
158e159 ꢂC (EtOH); Rf (EtOAc) 0.71; IR: nmax 3290, 1708, 1556, 1445,
1252, 1142, 1097, 928, 752 cmꢀ1; 1H NMR (DMSO-d6):
1.28 (s, 9H,
g (69%), isomerization 83%; mp
d
3Me), 1.59 (s, 3H, Me-2), 2.82 (d, 1H, J¼12 Hz, H-3), 5.65e5.75 (m,
1H, H-4), 6.77 (d, 1H, J¼7.8 Hz, H-8), 6.87 (t, 1H, J¼7.8 Hz, H-6), 7.02
(br s, 1H, OH), 7.04 (t, 1H, J¼7.8 Hz, H-60), 7.15 (t, 1H, J¼7.8 Hz, H-7),
7.21 (d, 1H, J¼7.8 Hz, H-5), 7.24 (t, 1H, J¼7.8 Hz, H-50), 7.41 (d, 1H,
J¼7.8 Hz, H-40), 7.69 (d, 1H, J¼7.8 Hz, H-70), 8.41 (d, 1H, J¼9.0 Hz,
NH). Anal. Calcd for C22H24N2O4S (412.50): C, 64.06; H, 5.86; N,
6.79%. Found: C 64.21; H, 6.01; N, 6.55%.
4. Experimental
4.1. General
The melting points (uncorrected) were determined with a Kofler
hot stage microscope. The IR (FT-ATR) spectra were recorded on
a Nicolet 6700 spectrophotometer. The NMR spectra were mea-
sured in DMSO-d6 on a Varian Unity-Inova 300 instruments using
TMS as internal standard. The MS (ESI-) spectrum was obtained on
an Agilent 6410 Triple Quadrupole mass spectrometer. Elemental
analyses were taken on a Carlo-Erba Elemental Analyzer 1012 ap-
4.2.4. Benzyl (2R*,3S*,4S*)-4-(benzothiazol-2-ylamino)-2-hydroxy-
2-methyl-3,4-dihydro-2H-chromene-3-carboxylate
(7d). Isolated
yield 0.446 g (50%), isomerization 81%; mp 137e139 ꢂC (EtOH); Rf
(EtOAc) 0.63; IR: nmax 3313, 1716, 1557, 1252, 1083, 1047, 920,
752 cmꢀ1 1H NMR (DMSO-d6):
; d 1.57 (s, 3H, Me-2), 3.08 (d, 1H,
paratus. Optical rotations were determined with a POLAR L-mP po-
larimeter (IBZ Messtechnik). Chiral phase HPLC analysis was done
on a Knauer instrument system using Daicel Chiralpak AS-H
(25ꢁ0.46 cm) column, n-hexane/isopropanol (92:8) as the eluent,
and a flow rate of 0.6 mL/min. CD spectra were measured in ace-
tonitrile on a Jasco J-815 spectropolarimeter with 2 mm path length.
J¼12 Hz, H-3), 5.13 (dd, 2H, J¼21.0, 12.6 Hz, OCH2), 5.74e5.83 (m,
1H, H-4), 6.79 (d, 1H, J¼7.8 Hz, H-8), 6.88 (t, 1H, J¼7.8 Hz, H-6), 7.07
(t, 1H, J¼7.8 Hz, H-60), 7.10e7.28 (m, 4H, H-5þH-7þH-50þOH), 7.42
(d, 1H, J¼7.8 Hz, H-40), 7.71 (d, 1H, J¼7.8 Hz, H-70), 8.48 (d, 1H,
J¼9.3 Hz, NH). Anal. Calcd for C25H22N2O4S (446.13): C, 67.25; H,
4.97; N, 6.27%. Found: C 67.38; H, 5.07; N, 6.19%.
4.2. General procedure for the synthesis of chromane de-
rivatives 7
4.2.5. tert-Butyl (2R*,3S*,4S*)-4-(6-methylbenzothiazol-2-ylamino)-
2-hydroxy-2-methyl-3,4-dihydro-2H-chromene-3-carboxylate
To a solution of amine 4 or 5 (2.0 mmol) in dry EtOH (15 mL)
were added alkyl acetoacetate 3 (2.1 mmol), aldehyde 2 (2.0 mmol)
(7e). Isolated yield 0.486
149e151 ꢂC (EtOH); Rf (EtOAc) 0.61; IR: nmax 3319, 1704, 1581, 1556,
1257, 1143, 930, 754 cmꢀ1; 1H NMR (DMSO-d6):
1.29 (s, 9H, 3Me),
g (57%), isomerization 76%; mp
and
L-proline (69 mg, 30 mol %). The mixture was stirred for
d
40e45 h at room temperature until the completion of reaction was
confirmed by TLC. While most of the compounds precipitated
during the reaction, the other products (7e, 7j, 7k) crystallized after
removal of the solvent and trituration of an oily residue with
a small volume of isoPrOHeH2O. Another crop of chromanes were
isolated from the filtrate upon standing. Obtained solids were
washed with water and diethylether.
1.60 (s, 3H, Me-2), 2.33 (s, 3H, Me-60), 2.81 (d, 1H, J¼12 Hz, H-3),
5.66e5.74 (m, 1H, H-4), 6.77 (d, 1H, J¼7.8 Hz, H-8), 6.86 (t, 1H,
J¼7.8 Hz, H-6), 6.98 (br s, 1H, OH), 7.05 (d,1H, J¼7.8 Hz, H-50), 7.15 (t,
1H, J¼7.8 Hz, H-7), 7.21 (d, 1H, J¼7.8 Hz, H-5), 7.29 (d, 1H, J¼7.8 Hz,
H-40), 7.49 (s, 1H, J¼7.8 Hz, H-70), 8.29 (d, 1H, J¼9.0 Hz, NH). Anal.
Calcd for C23H26N2O4S (426.53): C, 64.77; H, 6.14; N, 6.57%. Found: C
64.92; H, 6.01; N, 6.38%.
The crude products (1.0 mmol) were then dissolved in acetone
or methanol and isomerized by treatment of p-TosOH (48 mg,
25 mol %) at room temperature for 40 h. The solution was con-
centrated in vacuo, the resulting oil was dissolved in minimal
4.2.6. tert-Butyl (2R*,3S*,4S*)-4-(4-methylbenzothiazol-2-ylamino)-
2-hydroxy-2-methyl-3,4-dihydro-2H-chromene-3-carboxylate
(7f). Isolated yield 0.665
g (78%), isomerization 52%; mp
Please cite this article in press as: Svĕtlík, J.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.10.019

J. Svĕtlík et al. / Tetrahedron xxx (2016) 1e8
7
137e139 ꢂC (EtOH); Rf (EtOAc) 0.64; IR: nmax 3286, 1711, 1596, 1552,
1449,1366,1252,1145, 917, 756 cmꢀ1; 1H NMR (DMSO-d6):
1.30 (s,
carboxylate (7k). Isolated yield 0.619 g (63%), isomerization 68%;
mp 147e148 ꢂC (EtOH); Rf (EtOAc) 0.66; IR: nmax 3295, 1707, 1557,
d
9H, 3Me), 1.61 (s, 3H, Me-2), 2.43 (s, 3H, Me-40), 2.84 (d, 1H,
J¼12 Hz, H-3), 5.64e5.74 (m, 1H, H-4), 6.77 (d, 1H, J¼7.8 Hz, H-8),
6.87 (t, 1H, J¼7.8 Hz, H-6), 6.94 (t, 1H, J¼7.8 Hz, H-60), 7.00 (br s, 1H,
OH), 7.07 (d, 1H, J¼7.8 Hz, H-50), 7.15 (t, 1H, J¼7.8 Hz, H-7), 7.24 (d,
1H, J¼7.8, H-5), 7.51 (d, 1H, J¼7.8 Hz, H-70), 8.37 (d, 1H, J¼9.0 Hz,
NH). Anal. Calcd for C23H26N2O4S (426.53): C, 64.77; H, 6.14; N,
6.57%. Found: C 64.52; H, 6.31; N, 6.28%.
1449, 1254, 1143, 1103, 893, 750 cmꢀ1 1H NMR (DMSO-d6):
; d 1.28
(s, 9H, 3Me), 1.60 (s, 3H, Me-2), 2.83 (d, 1H, J¼12 Hz, H-3),
5.68e5.75 (m, 1H, H-4), 6.78 (d, 1H, J¼7.8 Hz, H-8), 7.07 (t, 1H,
J¼7.8 Hz, H-60), 7.18 (br s, 1H, OH), 7.26 (t, 1H, J¼7.8 Hz, H-50), 7.26
(overlapped s, 1H, H-5), 7.33 (d, 1H, J¼7.8 Hz, H-7), 7.44 (d, 1H,
J¼7.8 Hz, H-40), 7.71 (d, 1H, J¼7.8 Hz, H-70), 8.48 (d, 1H, J¼9.0 Hz,
NH). Anal. Calcd for C22H23BrN2O4S (491.40): C, 53.77; H, 4.72; N,
5.70%. Found: C, 53.98; H, 4.51; N, 5.64%.
4.2.7. tert-Butyl (2R*,3S*,4S*)-4-(6-methoxybenzothiazol-2-
ylamino)-2-hydroxy-2-methyl-3,4-dihydro-2H-chromene-3-
carboxylate (7g). Isolated yield 0.355 g (42%), isomerization 71%;
mp 155e156 ꢂC (EtOH); Rf (EtOAc) 0.64; IR: nmax 3486, 1722, 1606,
1581,1560,1477,1248,1230,1159,1031, 911, 835, 757 cmꢀ1; 1H NMR
4.2.12. tert-Butyl (2R*,3S*,4S*)-4-(benzothiazol-2-ylamino)-2-
hydroxy-8-methoxy-2-methyl-3,4-dihydro-2H-chromene-3-
carboxylate (7l). Isolated yield 0.513 g (58%), isomerization 71%;
mp 137e139 ꢂC (EtOH); Rf (EtOAc) 0.56; IR: nmax 3289, 1712, 1557,
(DMSO-d6):
d
1.30 (s, 9H, 3Me), 1.59 (s, 3H, Me-2), 2.81 (d, 1H,
1448, 1267, 1149, 1090, 924, 750 cmꢀ1 1H NMR (DMSO-d6):
; d 1.29
J¼12 Hz, H-3), 3.75 (s, 3H, MeO-60), 5.63e5.70 (m, 1H, H-4), 6.76 (d,
1H, J¼7.8 Hz, H-8), 6.85 (d, 1H, J¼7.8, H-50), 6.87 (t, 1H, J¼7.8 Hz, H-
6), 6.97 (br s, 1H, OH), 7.14 (t, 1H, J¼7.8 Hz, H-7), 7.21 (d, 1H,
J¼7.8 Hz, H-5), 7.31 (d, 1H, J¼7.8 Hz, H-40), 7.34 (d, 1H, J¼1.8 Hz, H-
70), 8.18 (d, 1H, J¼9.6 Hz, NH). Anal. Calcd for C23H26N2O5S (422.53):
C, 62.43; H, 5.92; N, 6.33%. Found: C 62.55; H, 6.04; N, 6.09%.
(s, 9H, 3Me), 1.61 (s, 3H, Me-2), 2.81 (d, 1H, J¼12 Hz, H-3), 3.73 (s,
3H, MeO-8), 5.67e5.74 (m, 1H, H-4), 6.78e6.86 (m, 3H, H-5þH-
6þH-7), 7.01 (br s, 1H, OH), 7.03 (t, 1H, J¼7.8 Hz, H-60), 7.24 (t, 1H,
J¼7.8 Hz, H-50), 7.40 (d, 1H, J¼7.8 Hz, H-40), 7.69 (d, 1H, J¼7.8 Hz, H-
70), 8.38 (d,1H, J¼9.6 Hz, NH). Anal. Calcd for C23H26N2O5S (442.53):
C, 62.43; H, 5.92; N, 6.33%. Found: C, 62.66; H, 6.12; N, 6.11%.
4.2.8. tert-Butyl (2R*,3S*,4S*)-4-(thiazol-2-ylamino)-2-hydroxy-2-
4.3. Preparation of 2-aminobenzothiazol-3-ium
(8)
L-prolinate
methyl-3,4-dihydro-2H-chromene-3-carboxylate
(7h). Isolated
yield 0.384 g (53%), isomerization 43%; mp 125e126 ꢂC (EtOH); Rf
(EtOAc) 0.57; IR: nmax 3311, 1709, 1557, 1253, 1144, 1099, 917,
To a solution of L-proline (115 mg, 1.0 mmol) in acetonitrile
(55 mL) was added amine 4a (0.155 g, 1.0 mmol) under stirring at
room temperature. After 20 h the separated solid was collected and
750 cmꢀ1; 1H NMR (DMSO-d6):
d 1.32 (s, 9H, 3Me),1.57 (s, 3H, Me-2),
2.85 (d, 1H, J¼12 Hz, H-3), 5.40e5.45 (m, 1H, H-4), 6.63 (d, 1H,
J¼3.9 Hz, H-50), 6.74 (d,1H, J¼7.8 Hz, H-8), 6.86 (t,1H, J¼7.8 Hz, H-6),
6.89 (br s,1H, OH), 7.01 (d,1H, J¼3.9 Hz, H-40), 7.13 (t,1H, J¼7.8 Hz, H-
7), 7.17 (d, 1H, J¼7.8 Hz, H-5), 7.93 (d, 1H, J¼9.0 Hz, NH); 13C NMR
washed with acetonitrile and ether. Compound 8 was obtained as
25
a white powder (0.229 g, 86%), mp 210e212 ꢂC; [
a
]
¼e36.9 (c¼1,
D
EtOH); IR: nmax 3388, 1640, 1606, 1536, 1444, 754 cmꢀ1
;
1H NMR
(DMSO-d6): d 27.0 (Me-2), 27.5 (Me ester), 50.1 (CH-4), 54.6 (CH-3),
(DMSO-d6): 1.65e1.70 (m, 1H, H-4b proline), 1.74e1.79 (m, 1H, H-
d
80.2 (OCq ester), 97.1 (C-2),106.1 (CH-50),116.4 (CH-8),120.5 (CH-6),
124.6 (C-4a), 126.8 (CH-5), 128.2 (CH-7), 138.6 (CH-40), 151.3 (C-8a),
168.7 (COO), 169.5 (C-20). Anal. Calcd for C18H22N2O4S (362.44): C,
59.65; H, 6.12; N, 7.73%. Found: C 59.90; H, 6.01; N, 7.55%.
4a),1.91e1.95 (m, 1H, H-3b), 1.97e2.03 (m, 1H, H-3a), 2.98e3.02 (m,
1H, H-5b), 3.18e3.36 (m, 1H, H-5a), 3.62e3.64 (m, 1H, H-2), 7.00 (t,
1H, J¼7.8 Hz, HAr-6), 7.19 (t, 1H, J¼7.8 Hz, HAr-5), 7.32 (d, 1H,
J¼7.8 Hz, HAr-4), 7.47 (s, 2H, NH), 7.64 (d, 1H, J¼7.8 Hz, HAr-7),
8.20e8.80 (br, 1H, NH); 13C NMR (DMSO-d6):
d 23.9 (CH2-4 proline),
4.2.9. tert-Butyl (2R*,3S*,4S*)-4-(5-methylthiazol-2-ylamino)-2-
hydroxy-2-methyl-3,4-dihydro-2H-chromene-3-carboxylate
28.9 (CH2-3), 45.2 (CH2-5), 60.7 (CH-2), 117.7 (CHAr-4), 120.7 (CHAr
-
6/CHAr-7), 120.8 (CHAr-7/CHAr-6), 125.4 (CHAr-5), 130.9 (CAr-7a),
152.8 (CAr-3a), 166.4 (CAr-2), 169.3 (COO); ESI MS (m/z) 342 [M-
HþDMSO]ꢀ. Anal. Calcd for C12H15N3O2S (265.33): C, 54.32; H, 5.70;
N, 15.84%. Found: C, 54.54; H, 5.51; N, 16.01%.
(7i). Isolated yield 0.527
137e138 ꢂC (EtOH); Rf (EtOAc) 0.55; IR: nmax 3295, 1708, 1557, 1363,
1251, 1141, 1087, 909, 759 cmꢀ1; 1H NMR (DMSO-d6):
1.32 (s, 9H,
g (70%), partial isomerization; mp
d
3Me), 1.56 (s, 3H, Me-2), 2.22 (s, 3H, Me-50), 2.83 (d, 1H, J¼12 Hz, H-
3), 5.33e5.39 (m, 1H, H-4), 6.66 (s, 1H, H-40), 6.73 (d, 1H, J¼7.8 Hz,
H-8), 6.85 (t, 1H, J¼7.8 Hz, H-6), 6.88 (br s, 1H, OH), 7.12 (t, 1H,
J¼7.8 Hz, H-7), 7.18 (d, 1H, J¼7.8 Hz, H-5), 7.69 (d, 1H, J¼9.0 Hz, NH);
1H NMR (DMSO-d6, minor isomer 70i, only resolved resonances):
Acknowledgements
This work was supported by the Grant Agency of the Slovak
Republic (VEGA 1/0371/16). The research was carried out with the
equipment purchased thanks to the financial support of the Euro-
pean Regional Development Fund in the framework of the Polish
Innovation Economy Operational Program (Contract No.
POIG.02.01.00-12-023/08).
d
1.11 (s, 9H, 3Me), 1.45 (s, 3H, Me-2), 2.15 (s, 3H, Me-50), 2.96 (d, 1H,
J¼10.2 Hz, H-3), 5.22e5.28 (m, 1H, H-4), 7.73 (d, 1H, J¼9.0 Hz, NH).
Anal. Calcd for C19H24N2O4S (376.47): C, 60.62; H, 6.43; N, 7.44%.
Found: C, 60.88; H, 6.29; N, 7.39%.
4.2.10. tert-Butyl (2R*,3S*,4S*)-4-(5-methyl-1,3,4-thiadiazol-2-
ylamino)-2-hydroxy-2-methyl-3,4-dihydro-2H-chromene-3-
carboxylate (7j). Isolated yield 0.377 g (50%), isomerization 34%; mp
125e127 ꢂC (EtOH); Rf (EtOAc) 0.40; IR: nmax 3282, 1709, 1548, 1363,
References and notes
1. (a) Spencer, J. P. E.; Crozier, A. Flavonoids and Related Compounds: Bioavailability
and Function; CRC Press: Boca Raton, 2012; (b) Anderson, O. M.; Markham, K. R.
Flavonoids: Chemistry, Biochemistry and Applications; CRC Press: Boca Raton,
2015.
2. Eicher, T.; Hauptmann, S. The Chemistry of Heterocycles. Structure, Reactions,
Syntheses and Applications, 2nd ed.; Wiley-VCH: Weinheim, 2003; p 269.
3. Ellis, G. P.; Lockhart, I. M. The Chemistry of Heterocyclic Compounds, Chromans
and Tocopherols; Wiley-Interscience: New York, 1981.
1251, 1145, 1125, 1091, 918, 766 cmꢀ1; 1H NMR (DMSO-d6):
d 1.34 (s,
9H, 3Me),1.58 (s, 3H, Me-2), 2.47 (s, 3H, Me-50), 2.87 (d,1H, J¼12 Hz,
H-3), 5.32e5.39 (m, 1H, H-4), 6.75 (d, 1H, J¼7.8 Hz, H-8), 6.87 (t, 1H,
J¼7.8 Hz, H-6), 6.94 (br s, 1H, OH), 7.12e7.18 (m, 2H, H-5þH-7), 8,00
(d,1H, J¼9.0 Hz, NH). Anal. Calcd for C18H23N3O4S (377.46): C, 57.28;
H, 6.14; N, 11.13%. Found: C, 57.15; H, 6.04; N, 11.27%.
4. Mannhold, R. Med. Res. Rev. 2004, 24, 213.
5. (a) Grover, G. J.; twal, K. S. Cardiovasc. Drug Rev. 2002, 20, 121; (b) Jahangir, A.;
Terzic, A. J. Mol. Cell. Cardiol. 2005, 39, 99; (c) Cecchetti, V.; Tabarrini, O.; Sa-
batini, S. Curr. Top. Med. Chem. 2006, 6, 1049; (d) Bano, M.; Barot, K. P.; Ahmed,
S. M.; Nikolova, S.; Ivanov, I.; Ghate, M. D. Mini-Rev. Med. Chem. 2013, 13, 1744.
4.2.11. tert-Butyl (2R*,3S*,4S*)-4-(benzothiazol-2-ylamino)-6-
bromo-2-hydroxy-2-methyl-3,4-dihydro-2H-chromene-3-
Please cite this article in press as: Svĕtlík, J.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.10.019

8
J. Svĕtlík et al. / Tetrahedron xxx (2016) 1e8
6. (a) Yadav, J. S.; Reddy, B. V. S.; Madhwi, C.; Sabitha, G.; Jagannadh, B.; Kumar, S.
13. (a) Yadav, J. S.; Kumar, S. P.; Kondaji, G.; Rao, R. S.; Nagaiah, K. Chem. Lett. 2004,
33, 11689; (b) Pandey, J.; Anand, N.; Tripathi, R. P. Tetrahedron 2009, 65, 9350;
(c) Samai, S.; Nandi, G. C.; Singh, P.; Singh, M. S. Tetrahedron 2009, 65, 10155; (d)
Jiang, H.; Mai, R.; Cao, H.; Zhu, Q.; Liu, X. Org. Biol. Chem. 2009, 7, 4943; (e)
Mecadon, H.; Rohman, R.; Kharbangar, I.; Badaker, M. L.; Kharkongor, I.; Raj-
bangshi, M.; Myrboh, B. Tetrahedron Lett. 2011, 52, 3228; (f) Dabiri, M.; Tisseh,
Z. N.; Nobahar, M.; Bazgir, A. Helv. Chim. Acta 2011, 94, 824; (g) Rao, L. C.;
Meshram, H. M.; Kumar, N. S.; Rao, N. N.; Babu, N. J. Tetrahedron Lett. 2014, 55,
1127; (h) Sarkar, R.; Mukhopadhyay, C. Tetrahedron Lett. 2014, 55, 2618; (i)
Kanani, M. B.; Patel, M. P. RSC Adv. 2014, 4, 28798; (j) Yang, X.; Zhang, C.; Wu, L.
RSC Adv. 2015, 5, 18945; (k) Rao, L. C.; Kumar, N. S.; Meshram, H. M. Helv. Chim.
Acta 2015, 98, 978; (l) Cai, H.; Xia, L.; Lee, Y. R.; Shim, J.-J.; Kim, S. H. Eur. J. Org.
Chem. 2015, 5212.
K.; Kunwar, A. C. Tetrahedron Lett. 2001, 42, 6381; (b) Anniyappan, M.; Mur-
alidharan, D.; Perumal, P. T. Tetrahedron 2002, 58, 10301; (c) Anniyappan, M.;
Perumal, P. T.; Vittal, J. J. Tetrahedron 2004, 60, 2965; (d) Yadav, J. S.; Reddy, B. V.
S.; Reddy, P. N. Chem. Lett. 2004, 33, 1436; (e) Wang, J.; Xu, F. X.; Lin, X. F.; Wang,
Y. G. Tetrahedron Lett. 2008, 49, 5208; (f) He, L.; Liu, H. B.; Zhao, L.; Wang, D. X.;
Wang, M. X. Tetrahedron 2015, 71, 523.
7. (a) Kumar, R. S.; Nagarajan, R.; Perumal, P. T. Synthesis 2004, 949; (b) Kumar, R.
S.; Nagarajan, R.; Vijay, K.; Perumal, P. T. Lett. Org. Chem. 2005, 2, 458.
8. Yadav, J. S.; Reddy, B. V. S.; Sekhar, K. C.; Geetha, V. Tetrahedron Lett. 2001, 42,
4405.
9. Kundu, K.; Nayak, S. K. RSC Adv. 2012, 2, 480.
10. (a) Rueping, M.; Lin, M. Y. Chem.dEur. J. 2010, 16, 4169; (b) Bernardi, L.; Comes-
Franchini, M.; Fochi, M.; Leo, V.; Mazzati, A.; Ricci, A. Adv. Synth. Catal. 2010,
352, 3399; (c) Zhang, Y.; Dong, S.; Liu, X.; Xie, M.; Zhu, Y.; Lin, L.; Feng, X. Chem.
dEur. J. 2011, 17, 13684; (d) Wang, X. F.; An, J.; Zhang, X. X.; Tan, F.; Chen, J. R.;
Xiao, W. J. Org. Lett. 2011, 13, 808; (e) Dong, S.; Liu, X.; Zhang, Y.; Lin, L.; Feng, X.
Org. Lett. 2011, 13, 5060; (f) Hou, W.; Zheng, B.; Chen, J.; Peng, Y. Org. Lett. 2012,
14, 2378.
14. Nagarajan, K.; Rao, V. R. Indian J. Chem. 1969, 7, 964.
15. Ilkimen, H.; Yenikaya, C.; San, M.; Bulbul, M.; Tunca, E.; Suzen, Y. Polyhedron
€
€
€
2013, 61, 56.
16. Huy, P.; Schmalz, H.-G. Synthesis 2011, 954.
17. Shekhtman, N. M.; Viktorova, E. A.; Karakkhanova, E. A.; Khvorostukhina, N. N.;
Zefirov, N. S. Dokl. Akad. Nauk SSSR 1971, 196, 367.
11. Svetlik, J.; Pronayova, N.; Svorc, L.; Frecer, V. Tetrahedron 2014, 70, 8354.
12. (a) Svetlík, J.; Veizerova, L.; Kettmann, V. Tetrahedron Lett. 2008, 49, 3520; (b)
Svetlík, J.; Kettmann, V. Tetrahedron Lett. 2011, 52, 1062; (c) Svetlík, J.; Veizer-
ova, L.; Mayer, T. U.; Catarinella, M. Bioorg. Med. Chem. Lett. 2010, 20, 4073.
18. (a) List, B.; Pojarliev, P.; Biller, W. T.; Martin, H. J. J. Am. Chem. Soc. 2002, 124,
827; (b) List, B. Tetrahedron 2002, 58, 5573.
19. Ramachary, D. B.; Sakthidevi, R. Chem.dEur. J. 2009, 15, 4516.
Please cite this article in press as: Svĕtlík, J.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.10.019