Investigation of cationic Claisen-type electrophilic rearrangements of amides

Article abstract of DOI:10.1016/j.tet.2015.06.027

Abstract Herein we report an extension of the electrophilic rearrangement of amides to the preparation of α-prenyl-hydrocoumarins, indoles, isoquinolines and dihydro-isoquinolinones. An unusual competitive sulfonyl migration, uncovered upon attempted aza-

Full text of DOI:10.1016/j.tet.2015.06.027

Tetrahedron xxx (2015) 1e12
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Investigation of cationic Claisen-type electrophilic rearrangements
of amides
Mohan Padmanaban a, Luísa C.R. Carvalho b, Desislava Petkova a, Ji-Woong Lee c,
,
a,
*
A. Sofia Santos b, M. Manuel B. Marques b , Nuno Maulide
*
a
€
Institute of Organic Chemistry, University of Vienna, Wahringer Strasse 38, 1090, Vienna, Austria
b
^
LAQV@REQUIMTE, Departamento de Química, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516,
Caparica, Portugal
c Department of Chemistry, University of California, Berkeley, Berkeley, CA, 94720, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Herein we report an extension of the electrophilic rearrangement of amides to the preparation of a-
Received 3 May 2015
Received in revised form 4 June 2015
Accepted 8 June 2015
Available online xxx
prenyl-hydrocoumarins, indoles, isoquinolines and dihydro-isoquinolinones. An unusual competitive
sulfonyl migration, uncovered upon attempted aza-Claisen rearrangement, is also described.
Ó 2015 Elsevier Ltd. All rights reserved.
Dedicated with respect and admiration to
Professor Barry M. Trost on the occasion of
the Tetrahedron Prize for Creativity in Or-
ganic Chemistry 2014
Keywords:
oxa and aza-Claisen
Amides
Rearrangement
Hydrocoumarin
Isoquinolinone
1. Introduction
These results encouraged us to explore these reactions further
and, eventually, to develop an aza-Claisen variant, by replacing the
The Claisen and related rearrangements are well-established
tools in organic synthesis.1 Our group has reported a ‘Claisen-like’
intramolecular rearrangement of keteniminium salts, opening
a direct and stereoselective route towards challenging substituted
lactones.2 As depicted in Scheme 1a, this process converts simple
oxygen tethering element with a nitrogen atom. In particular, we
hoped that this might open a new platform to assemble hetero-
cyclic compounds (Scheme 1c), a valuable endeavour for synthesis,
medicinal chemistry and materials science.6,7
u
-allyloxy, -propargyloxy and benzyloxyamides into a-substituted
2. Results and discussion
lactones in the presence of triflic anhydride (Tf2O) and 2,4,6-
collidine.2a,3 The formation of the intermediate iminium ether 1a
(Scheme 1a) has been confirmed and lends support to the original
mechanistic proposal, involving an intramolecular cyclization fol-
lowed by a [3,3] sigmatropic rearrangement.4 Furthermore, in-
corporation of a phenyl ring within the alkyl tether restricted the
conformational freedom and facilitated the cyclization/rearrange-
ment of amide 2 (Scheme 1b).5
The recently reported methodology for the preparation of
a-
substituted lactones via a [3,3] sigmatropic rearrangement, in-
volving the formation of a keteniminium ion intermediate, presents
several advantages: high accessibility of starting materials; rela-
tively high yields; broad substrate scope and simple reaction con-
ditions. This procedure was applied for the preparation of a-prenyl
hydrocoumarin derivatives, useful as substrates in organocatalytic
transformations.8 Thus, in our initial studies, we attempted to
prepare five-membered ring substrates by applying the rear-
rangement conditions (Tf2O, collidine, 120 ꢀC, 5 min) to the readily
available o-allyl phenol 4. Indeed, the rearrangement intermediate
* Corresponding authors. Tel.: þ43 1 4277 51255 (N.M.); tel.: þ43 351 21
2948300x10983 (M.M.B.M.); e-mail addresses: msbm@fct.unl.pt (M.M.B. Marques),
nuno.maulide@univie.ac.at (N. Maulide).
http://dx.doi.org/10.1016/j.tet.2015.06.027
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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2
M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
We thus decided to probe this methodology for the synthesis of
-reverse prenylated hydrocoumarin derivatives (Scheme 3b). Re-
a
verse prenylation is typically a challenging transformation and [3,3]
sigmatropic rearrangement of a ‘normal’ prenyl substrate such as
10, whenever possible, offers a straightforward alternative.10 Under
the standard rearrangement conditions, 10 was completely con-
sumed to a new product after hydrolytic work-up. NMR analysis
revealed that this was in fact the ring-opened amide 11 (in a mix-
ture with collidine). After a survey of different conditions, we found
that exposure to boiling acetic acid led to the hydrocoumarin 12 in
81% yield.
It should be noted that, in our original study of this trans-
formation (Scheme 1a),1a reverse prenylation was not possible.
Thus, the success observed in the transformations of Scheme 3 is
worthy of note. As depicted in Scheme 4, it is likely that the pres-
ence of the aromatic ring in 13 facilitates the nucleophilic attack of
the oxygen atom, placing it in closer proximity to the keteniminium
ion when compared to the aliphatic chain A (represented in the
box) (Scheme 4). Furthermore, steric decompression during the
rearrangement event (compare 14 with B) might also account for
the reaction outcome.
Scheme 1. Preparation of lactones and ring-fused heterocycles by a Claisen-like re-
arrangement via formation of iminium ether intermediates.
5 was detected by NMR of the reaction mixture (Scheme 2). How-
ever, efforts to hydrolyse the intermediate 5 proved fruitless, as the
2-aminobenzofuran 6 resulted as the only observable product.
Scheme 4. Conformational and electronic comparison of rearrangements for acyclic
and aromatic substrates.
We then proceeded to examine the reaction scope for the
preparation of hydrocoumarins with a series of allyl and alkynyl
substrates (Scheme 5).
Scheme 2. Rearrangement of 4 to a benzofuran derivative 6.
In spite of the generally moderate yields, all the substrates
probed gave the corresponding hydrocoumarins. Substitution at
the aromatic ring did not influence the reaction outcome, as well as
substitution at the olefinic tether. Compound 16g was isolated in
a lower yield due to concomitant decomposition under the reaction
conditions. A propargylated substrate furnished the corresponding
hydrocoumarin 16h possessing an allene group. However, the re-
action did not proceed for substrates carrying a substituent at the
terminal carbon of the double bond. The observed lower reactivity
of these compounds might be due to the additional steric hindrance
during the rearrangement step.
Acknowledging that the aromaticity of benzofuran 6 was behind
our inability to hydrolise 6, we turned towards substrate 7, obtained
from commercially available a,b-unsaturated coumarin. It is worth
noting here that hydrocoumarins, also known as flavanoids, show
vast biological activity.9 Although a simple alkylation can provide
derivatization on
a-position, sterically hindered alkyl and aryl
substituents cannot readily be introduced via alkylation. Recog-
nizing the facile reactivity shown above, we presumed that
hydrocoumarin-derived substrates would be capable candidates for
the rearrangement reaction. After simple preparation of substrate 7,
subsequent rearrangement provided
a-allylated compound 9 upon
At this juncture, we became interested in investigating the aza-
variant of this transformation. In this apparently simple re-
placement of oxygen for nitrogen, substrate design was a concern
from the outset, as the reaction was expected to proceed according
to the mechanism2a,3 depicted in Scheme 6. In the aza-substrate an
additional substituent is required at the nitrogen atom. Impor-
tantly, this substituent must be capable of reducing the nucleo-
philicity of the N-atom while at the same time not competing with
the amide for the electrophilic Tf2O activator (thus excluding am-
ide, carbamatedand relateddgroups from consideration). The
tosyl (Ts) group covers these requirements and it was therefore the
substituent of choice.
hydrolysis in moderate yield (Scheme 3a).
Our preliminary studies focused on alicyclic amine substrates.
The starting materials were prepared in two simple steps. Having
Scheme 3. Rearrangement of substrates 7 and 10.
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M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
3
The surprising formation of compounds 23 indicates that, for
these substrates, the rearrangement conditions promote tosyl mi-
gration instead of the expected aza-Claisen rearrangement. The
allyl and benzyl-substituted derivatives 22a and 22b afforded
similar results. However, for the propargyl derivative 22c, an ad-
ditional cyclization event took place concurrently with tosyl mi-
gration. The unusual structure of 23b was confirmed by X-ray
analysis of a crystal obtained after anion exchange of triflate by the
tetrafluoroborate ion (Fig. 1).
Fig. 1. X-ray structure of 23b after anion exchange.
Sulfonamides typically rank amongst the most stable amine
protecting groups.11 Cleavage of the RO2SeN bond has been docu-
mented to occur under relatively harsh conditions, including dis-
solving metal reduction.12,13 It should be noted that a 1,2-N-to-C
tosyl rearrangement has been reported in specifically substituted
N-tosyl ynamides.13 The observed tosyl migration in the rear-
rangement of 22a,b to 23a,b allows speculation about either a di-
rect 1,3-rearrangement (which we believe is precluded by
geometric reasons) or the involvement of free-radical species. The
transient formation of sulfonyl radicals has been proposed under
reductive and photoinduced desulfonylation of indoles.14 As most
sulfur-based radicals, sulfonyl radicals are very stable, and a tosyl
migration may occur through homolytic dissociation of a key in-
termediate such as 23a (Scheme 8). The recombination of the two
species 26 may occur faster than their diffusion and it is possible
that this process is energetically more favourable than allyl
migration.
Scheme 5. Rearrangement of allyloxyamides 15aeg and propargylamide 15h to hy-
drocoumarins 16aeh.
Hydrolysis of the amidinium 23a turned out to be very difficult.
A control experiment established the acidity of the methine proton
of 23a, as shown by the observed deuteration under mild basic
conditions (such as either satd NaHCO3 or satd Na2CO3 in D2O,
Scheme 8 and confirmed by NMR). Upon treatment of 23a with
NaH, the formation of dihydropyrrole 28 was observed.
Based on these preliminary results employing tosyl protection,
we decided to explore the aza-Claisen rearrangement for the con-
struction of heterocyclic compounds adopting a different strategy.
The first experiments focused on the use of N-diallylated anilines as
rearrangement substrates aiming to obtain fused five- or six-
membered ring heterocycles. Thus, upon treatment of 29 with
Tf2O and 2,4,6-collidine, at room temperature or under microwave
conditions, a mixture was observed, wherein intermediate 30 was
detected (NMR analysis). After purification, 31 could be isolated in
45% yield (Scheme 9). The allyl chain in compound 31 is located at
the indolic C-7 position. The aza-Claisen rearrangement of N-
Scheme 6. Foreseen mechanism for the aza-Claisen rearrangement.
compounds 22aec in hands the rearrangement conditions were
applied and, surprisingly, instead of the expected
a-substituted
lactams 21, the amidinium derivatives 23aec were observed
(Scheme 7).
Scheme 7. Unexpected rearrangement of amides 22aec.
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4
M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
Scheme 8. Proposed mechanism for the observed tosyl migration upon rearrangement
of 22a.
allylanilines is a known transformation.15,16 The [3,3]-sigmatropic
rearrangement of N-allyl-N-arylamines usually requires high tem-
peratures affording the corresponding anilines along with un-
desired by-products.17 Due to the biological relevance of indole
derivatives,18 other substrates akin to 29 were then tested, in-
cluding N-benzyl and N-propargyl derivatives. However, the cor-
responding indoles were obtained in low yield as mixtures of
regioisomeric rearrangement products.19 The difficulty in hydro-
lysing 31 might be attributed to the aromaticity of the indole nu-
cleus, similarly to benzofuran 6 (Scheme 2).
Scheme 10. Reaction of anilines 32 under rearrangement conditions.
Scheme 9. Reaction of aniline 29 under rearrangement conditions with formation of
indole 31.
Despite the disappointing results obtained for the indoles, we
decided to investigate whether the same strategy could be applied
to the preparation of fused six-membered nitrogenated heterocy-
cles, such as isoquinolinones and hydroquinolinones. Experiments
carried with substrate 32a under the standard conditions led to the
formation of 33a in 39% yield (Scheme 10).
Substrates 32b and 32c also afforded the corresponding dihy-
droquinolinium triflates 33b and 33c with moderate yields. The
position of the substituents at the double bond, i.e., inner and outer
carbons, had a slight effect on the yield of the rearrangement
compounds 33b and 33c. The lower yield observed for 33c might be
due to a possible steric hindrance of the methyl substituent at the
outer olefinic carbon. The same was observed for compound 33d
that contains the allene moiety.
Furthermore, we investigated the possibility of achieving dihy-
droisoquinolones, and substrate 34 was prepared from the iso-
chromanone 35, via benzylamine 36 (Scheme 11). Pleasingly,
treatment of 34 under the rearrangement conditions afforded 37
that was successfully hydrolysed using a saturated NaHCO3 solution
into the corresponding isoquinolone 38 in 90% yield.
Scheme 11. Preparation of 2,4-diallyl-1,4-dihydroisoquinolin-3(2H)-one 38.
Similarly to the results obtained previously in the oxygenated
series,5 compound 34 underwent rearrangement under very mild
conditions and a high conversion. Following hydrolysis, the dihy-
droisoquinoline 38 was obtained in very high yield.
3. Conclusions
We have expanded the scope of the electrophilic Claisen rear-
rangement of conformationally restricted amides incorporating an
aromatic ring. This procedure was applied to oxygen-based sub-
strates, including the preparation of
a-reversed prenyl hydro-
coumarin derivatives, useful substrates for organocatalytic
reactions, in high yield. The strategy proved useful for the conver-
sion of diverse alkyl and alkynyl substrates into the corresponding
hydrocoumarins. We also investigated an aza-Claisen rearrange-
ment applying the same protocol. Surprisingly, it was observed that
the simplest nitrogen-containing derivatives do not undergo
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M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
5
rearrangement but rather tosyl migration. Conversely, conforma-
tionally restricted aromatic substrates led to smooth rearrange-
J¼8.20, 2.36 Hz, 1H), 5.47 (t, J¼6.59 Hz, 1H), 4.49 (d, J¼6.60 Hz, 2H),
3.78 (s, 3H), 3.46 (t, J¼6.76 Hz, 2H), 3.35 (t, J¼6.65 Hz, 2H), 2.89 (dd,
J¼9.15, 6.92 Hz, 2H), 2.45e2.64 (m, 2H), 1.80e1.93 (m, 4H), 1.78 (s,
ment, enabling the preparation of
quinolinones and isoquinolinones.
a variety of rearranged
3H), 1.73 (s, 3H); 13C NMR (125 MHz, CDCl3),
d 171.7, 159.3, 157.6,
137.4, 130.4, 122.4, 120.0, 103.8, 99.5, 64.8, 55.4, 46.6, 45.5, 35.5,
4. Experimental section
26.1, 26.0, 25.8, 24.5, 18.2. ESI-MS: calculated [MþNa]þ for
C
19H27O3NNa: 340.1889, found: 340.1886.
Unless otherwise stated, all glassware was flame-dried before
use and all reactions were performed under an atmosphere of ar-
gon. All solvents were distilled from appropriate drying agents
prior to use. All reagents were used as received from commercial
suppliers unless otherwise stated. Reaction progress was moni-
tored by thin layer chromatography (TLC) performed on aluminium
plates coated with silica gel F254 with 0.2 mm thickness. Chro-
matograms were visualized by fluorescence quenching with UV
light at 254 nm or by staining using potassium permanganate. Flash
column chromatography was performed using silica gel 60
(230e400 mesh, Merck and co.). Neat infra-red spectra were
recorded using a PerkineElmer Spectrum 100 FTIR spectrometer.
~
4.3. 3-(2-((2-(Chloromethyl)allyl)oxy)phenyl)-1-(pyrrolidin-
1-yl)propan-1-one (15a)
A mixture of dihydrocoumarin (0.74 g, 0.64 mL, 5.0 mmol,
1.0 equiv), pyrrolidine (0.72 g, 0.84 mL, 10 mmol, 2.0 equiv) and
triethylamine (1.52 g, 2.0 mL, 15 mmol, 3.0 equiv) was heated to
reflux at 90 ꢀC for 16 h. The mixture was evaporated to dryness
afforded the desired product as a yellow solid. The crude product
used further without any purification. To a solution of the crude
amide (1.1 g, 5.0 mmol, 1.0 equiv) in THF (10 mL) was added NaH
(0.4 g, 60% suspension in mineral oil, 10 mmol, 2.0 equiv) portion
wise at 0 ꢀC and brought to rt for 2 h. Then, 3-chloro-2-(chlor-
omethyl)prop-1-ene, (1.25 g, 1.2 mL, 10 mmol, 2.0 equiv) was added
drop wise through syringe in 10 min and let it stir 16 h. When the
reaction was done, water was added carefully (10 mL) and the
resulting mixture was extracted with ethyl acetate (50 mL). The
organic phase was washed with brine (3ꢂ25 mL) and dried over
Na2SO4. The solvent was removed in vacuum. Column chroma-
tography afforded 3-(2-((2-(chloromethyl)allyl)oxy)phenyl)-1-(pyr-
rolidin-1-yl)propan-1-one (15a) as a colourless oil (0.88 g, 57%); Rf
(EtOAc/heptane¼40/60): 0.11; 1H NMR (400 MHz, CDCl3)
Wavenumbers (
y
¼1/
l
) are reported in cmꢁ1. Mass spectra were
obtained using a Finnigan MAT 8200 or (70 eV) or an Agilent 5973
(70 eV) spectrometer, using electrospray ionization (ESI). All 1H
NMR and 13C NMR spectra were recorded using a Bruker AV-400 or
AV-600 spectrometer at 300 K. Chemical shifts were given in parts
per million (ppm,
d), referenced to the solvent peak of CDCl3, de-
fined at ¼77.16 (13C NMR). Coupling
d
¼7.26 ppm (1H NMR) and
d
constants are quoted in Hz (J). 1H NMR splitting patterns were
designated as singlet (s), doublet (d), triplet (t), quartet (q), pentet
(p). Splitting patterns that could not be interpreted or easily visu-
alized were designated as multiplet (m) or broad (br).
d
7.21e7.15 (m, 2H), 6.91e6.85 (m, 2H), 5.38e5.37 (m, 2H), 4.64 (br
s, 2H), 4.21 (br s, 2H), 3.45 (t, J¼6.6 Hz, 2H), 3.29 (t, J¼6.5 Hz, 2H),
4.1. 3-(2-(Allyloxy)phenyl)-1-(pyrrolidin-1-yl)propan-1-one
(7)
3.00 (t, J¼7.4 Hz, 2H), 2.55 (t, J¼7.5 Hz, 2H), 1.89e1.79 (m, 4H); 13
C
NMR (100 MHz, CDCl3) d 171.3, 156.3, 141.1, 130.5, 130.2, 127.5, 121.1,
117.3, 111.5, 68.0, 46.6, 45.7, 45.3, 35.2, 26.4, 26.2, 24.5; ATR-FTIR
(cmꢁ1): 2973, 2872, 1636, 1493, 1444, 1342, 1275, 1260, 1239,
1191, 1110, 1150, 1050, 763, 750, 633; ESI-MS: calculated [MþNa]þ
for C17H22ClO2NNa: 330.1231, found: 330.1227.
A mixture of dihydrocoumarin (0.37 g, 0.32 mL, 2.5 mmol,
1.0 equiv), pyrrolidine (0.36 g, 0.42 mL, 5 mmol, 2.0 equiv) and
triethylamine (0.76 g, 1.0 mL, 7.5 mmol, 3.0 equiv) was heated to
reflux at 90 ꢀC for 16 h. The mixture was evaporated to dryness
afforded the desired product as a yellow solid. The crude product
used further without any purification. To a solution of the crude
amide (0.548 g, 2.5 mmol, 1.0 equiv) in THF (5 mL) was added NaH
(0.2 g, 60 percent suspension in mineral oil, 5.0 mmol, 2.0 equiv)
portion wise at 0 ꢀC and brought to rt for 2 h. Then 3-bromoprop-1-
ene (0.60 g, 0.63 mL, 5.0 mmol, 2.0 equiv) was added drop wise
through syringe in 10 min and let it stir 16 h. When the reaction was
completed, water was added carefully (10 mL) and the resulting
mixture was extracted with ethyl acetate (50 mL). The organic
phase was washed with brine (3ꢂ25 mL) and dried over Na2SO4.
The solvent was removed in vacuum. Column chromatography
afforded 3-(2-(allyloxy)phenyl)-1-(pyrrolidin-1-yl)propan-1-one (7)
as a colourless oil (0.52 g, 80%); Rf (EtOAc/heptane¼40/60): 0.12; 1H
4.4. 2-((2-(3-oxo-3-(Pyrrolidin-1-yl)propyl)phenoxy)methyl)
allyl acetate (15b)
To a solution of 3-(2-((2-(chloromethyl)allyl)oxy)phenyl)-1-
(pyrrolidin-1-yl)propan-1-one (0.462 g, 1.5 mmol, 1.0 equiv) in
DMF (4 mL), was added KOAc (0.162 g, 1.65 mmol, 1.10 equiv), and
the solution was heated at 65 ꢀC for 18 h. After 18 h, cooled to room
temperature then H2O (5 mL) and Et2O (5 mL) were then added,
and the layers were separated. The organic layer was then washed
with H2O (3ꢂ10 mL), dried over Na2SO4, filtered and concentrated
under reduced pressure, to give 2-((2-(3-Oxo-3-(pyrrolidin-1-yl)
propyl)phenoxy)methyl)allyl acetate (15b) as colourless oil (0.35 g,
70%); Rf (EtOAc/heptane¼40/60): 0.08; 1H NMR (400 MHz, CDCl3)
NMR (400 MHz, CDCl3)
d
7.20e7.14 (m, 2H), 6.89e6.81 (m, 2H),
d 7.21e7.14 (m, 2H), 6.91e6.82 (m, 2H), 5.39 (br s, 1H), 5.32 (br s,
6.06e6.02 (m, 1H), 5.40 (dq, J¼17.2, 1.6 Hz, 1H), 5.25 (dq, J¼10.5,
1.6 Hz, 1H) 4.54 (dt, J¼5.0, 1.5 Hz, 2H), 3.45 (t, J¼6.7 Hz, 2H), 3.31 (t,
J¼6.7 Hz, 2H), 2.99 (t, J¼8.2 Hz, 2H), 2.55 (t, J¼8.2 Hz, 2H),1.89e1.79
1H), 4.69 (br s, 2H), 4.56 (br s, 2H), 3.45 (t, J¼6.8 Hz, 2H), 3.29 (t,
J¼6.8 Hz, 2H), 2.99 (t, J¼8.0 Hz, 2H), 2.54 (t, J¼7.9 Hz, 2H), 2.08 (s,
3H), 1.89e1.78 (m, 4H); 13C NMR (100 MHz, CDCl3)
d 171.3, 170.7,
(m, 4H); 13C NMR (100 MHz, CDCl3)
d
171.46, 156.56, 133.62, 130.44,
156.4, 139.8, 130.5, 130.2, 127.5, 121.1, 116.0, 111.4, 68.5, 64.8, 46.6,
45.7, 35.1, 26.4, 26.2, 24.5, 20.9; ATR-FTIR (cmꢁ1): 2977, 2874, 1740,
1639, 1493, 1451, 1372, 1343, 1276, 1260, 1239, 1191, 1110, 1027, 915,
764, 750, 633; ESI-MS: calculated [MþNa]þ for C19H25O4NNa:
354.1676, found: 354.1686.
130.17, 127.42, 120.81, 117.21, 111.58, 68.80, 46.66, 45.65, 35.19,
26.56, 26.16, 24.50 ATR-FTIR (cmꢁ1): 3445, 3063, 2970, 2870, 1632,
1432, 1343, 1239, 1191, 1165, 1047, 1020, 997, 868, 752, 638; ESI-MS:
calculated [MþNa]þ for C16H21O2NNa: 282.1465, found: 282.1460.
4.2. 3-(5-Methoxy-2-((3-methylbut-2-en-1-yl)oxy)phenyl)-1-
(pyrrolidin-1-yl)propan-1-one (10)
4.5. 3-(2-(Allyloxy)-5-methoxyphenyl)-1-(pyrrolidin-1-yl)
propan-1-one (15c)
Following the procedure described for 7: 1H NMR (500 MHz,
5-methoxy-indan-1-one (1.62 g, 10.0 mmol, 1.0 equiv) in 100 mL
of DCM cooled to 0 ꢀC was added NaHCO3 (1.7 g, 20 mmol,
CDCl3),
d
7.09 (d, J¼8.20 Hz, 1H), 6.44 (d, J¼2.29 Hz, 1H), 6.40 (dd,
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6
M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
2.0 equiv). To this, 3-chloro-perbenzoic acid (4.5 g, 20 mmol,
2.0 equiv) was added portion wise, and the reaction mixture was
stirred at 0 ꢀC for 2 h and at room temperature for 16 h. The pre-
cipitate was filtered off and washed with DCM. The filtrate was
washed with saturated solution of NaHCO3 and dried over Na2SO4.
After evaporation of the solvent under vacuum 6-methoxy-chro-
man-2-one was obtained as brown oil (1.5 g, 84%), which was used
(t, J¼8.0 Hz, 2H), 2.53 (t, J¼8.0 Hz, 2H), 2.31 (s, 3H), 1.90e1.84 (m,
4H); 13C NMR (100 MHz, CDCl3)
171.6, 156.5, 137.3, 133.8, 130.2,
d
127.2, 121.4, 117.2, 112.6, 68.8, 46.7, 45.7, 35.5, 26.2, 26.2, 24.6, 21.6;
ATR-FTIR (cmꢁ1): 2973, 2871, 1723, 1640, 1507, 1433, 1275, 1260,
1193, 1158, 1027, 930, 764, 750; ESI-MS: calculated [MþNa]þ for
C17H23O2NNa: 296.1621, found: 296.1617.
without further purification. To
a
mixture of crude dihy-
4.7. 3-(2-((2-Methylallyl)oxy)phenyl)-1-(pyrrolidin-1-yl)
propan-1-one (15e)
drocoumarin (1.5 g, 8.4 mmol, 1.0 equiv), pyrrolidine (1.2 g, 1.41 mL,
16.8 mmol, 2.0 equiv) and triethylamine (2.56 g, 3.5 mL, 25.3 mmol,
3.0 equiv) was heated to reflux at 90 ꢀC for 16 h. The mixture was
evaporated to dryness to afford the desired product as a pale brown
sticky liquid. The crude product used further without any purifi-
cation. To a solution of the crude amide (1 g, 4.0 mmol, 1.0 equiv) in
THF (10 mL) was added NaH (0.32 g, 60% suspension in mineral oil,
8.0 mmol, 2.0 equiv) portion wise at 0 ꢀC and brought to rt for 2 h.
Then, 3-bromoprop-1-ene (1.0 g, 0.7 mL, 8.0 mmol, 2.0 equiv) was
added drop wise through syringe in 10 min and let it stir 16 h at
room temperature. When the reaction was done, water was added
carefully (20 mL) and the resulting mixture was extracted with
ethyl acetate (100 mL). The organic phase was washed with brine
(3ꢂ50 mL) and dried over Na2SO4. The solvent was removed in
vacuo. Several column chromatography afforded 3-(2-(allyloxy)-5-
methoxyphenyl)-1-(pyrrolidin-1-yl)propan-1-one (15c) as a brown
sticky liquid (0.30 g, 26%); Rf (EtOAc/heptane¼40/60): 0.10; 1H NMR
Mixture of dihydrocoumarin (see SI) (0.37 g, 0.32 mL,
2.5 mmol, 1.0 equiv), pyrrolidine (0.36 g, 0.42 mL, 5 mmol,
2.0 equiv) and triethylamine (0.76 g, 1.0 mL, 7.5 mmol, 3.0 equiv)
was heated to reflux at 90 ꢀC for 16 h. The mixture was evaporated
to dryness to afford the desired product as a yellow solid. The
crude product used further without any purification. To a solution
of the crude amide (0.548 g, 2.5 mmol, 1.0 equiv) in THF (5 mL)
was added NaH (0.2 g, 60% suspension in mineral oil, 5.0 mmol,
2.0 equiv) portion wise at 0 ꢀC and brought to rt for 2 h. Then, 3-
bromo-2-methylpropene, (0.68 g, 0.5 mL, 5.0 mmol, 2.0 equiv) was
added drop wise through syringe in 10 min and let it stir 16 h.
When the reaction was done, water was added carefully (10 mL)
and the resulting mixture was extracted with ethyl acetate
(50 mL). The organic phase was washed with brine (3ꢂ25 mL) and
dried over Na2SO4. The solvent was removed in vacuum. Column
chromatography afforded 3-(2-((2-methylallyl)oxy)phenyl)-1-(pyr-
rolidin-1-yl)propan-1-one (15e) as a colourless oil (0.6 g, 87%); Rf
(EtOAc/heptane¼40/60): 0.18; 1H NMR (400 MHz, CDCl3)
(400 MHz, CDCl3)
d
6.79e6.75 (m, 2H), 6.67 (dd, J¼8.8, 3.0 Hz, 1H),
6.08e6.01 (m, 1H), 5.38 (dq, J¼17.2, 1.6 Hz, 1H), 5.24 (dq, J¼10.5,
1.4 Hz, 1H), 4.49 (dt, J¼5.1, 1.5 Hz, 2H), 3.75 (s, 3H), 3.46 (t, J¼6.7 Hz,
2H), 3.32 (t, J¼6.6 Hz, 2H), 2.96 (t, J¼8.0 Hz, 2H), 2.54 (t, J¼8.0 Hz,
d
7.21e7.13 (m, 2H), 6.89e6.81 (m, 2H), 5.09 (br s, 1H), 4.98 (br s,
2H), 1.90e1.80 (m, 4H). 13C NMR (100 MHz, CDCl3)
d
171.4, 153.8,
1H), 4.44 (s, 2H), 3.45 (t, J¼6.8 Hz, 2H), 3.30 (t, J¼6.7 Hz, 2H), 3.00
150.8, 133.9, 131.6, 117.2, 116.4, 112.9, 111.7, 69.7, 55.8, 46.7, 45.7,
35.3, 26.8, 26.2, 24.6; ATR-FTIR (cmꢁ1): 2971, 2872, 1638, 1499,
1432, 1276, 1260, 1042, 997, 930, 804, 764, 633; ESI-MS: calculated
[MþNa]þ for C17H23O3NNa: 312.1570, found: 312.1566.
(t, J¼6.4 Hz, 2H), 2.56 (t, J¼6.4 Hz, 2H), 1.89e1.81 (m, 7H); 13C NMR
(100 MHz, CDCl3)
d 171.5, 156.7, 141.2, 130.5, 130.1, 127.5, 120.8,
112.5, 111.5, 71.7, 46.7, 45.7, 35.2, 26.6, 26.2, 24.5, 19.7; ATR-FTIR
(cmꢁ1): 2971, 2870, 1640, 1492, 1435, 1343, 1294, 1238, 1191,
1164, 1110, 1055, 1016, 899, 752, 632; ESI-MS: calculated [MþH]þ
for C17H24O2N: 274.1802, found: 274.1801.
4.6. 3-(2-(Allyloxy)-4-methylphenyl)-1-(pyrrolidin-1-yl)
propan-1-one (15d)
4.8. Ethyl 2-((2-(3-oxo-3-(pyrrolidin-1-yl)propyl)phenoxy)
methyl)acrylate (15f)
To 6-methyl-indan-1-one (0.585 g, 4.0 mmol,1.0 equiv) in 40 mL
of DCM cooled to 0 ꢀC was added NaHCO3 (0.67 g, 8 mmol,
2.0 equiv). 3-Chloro-perbenzoic acid (1.8 g, 8 mmol, 2.0 equiv) was
added portion wise, and the reaction mixture was stirred at 0 ꢀC for
2 h and at room temperature for 16 h. The precipitate was filtered
off and washed with DCM. The filtrate was washed with NaHCO3
and dried over Na2SO4. After evaporation of the solvent under
vacuum, 7-methylchroman-2-one was obtained as brown oil,
which was used without further purification. A mixture of crude
dihydrocoumarin (0.4 g, 2.5 mmol, 1.0 equiv), pyrrolidine (0.35 g,
0.41 mL, 5.0 mmol, 2.0 equiv) and triethylamine (0.75 g, 1.0 mL,
7.5 mmol, 3.0 equiv) was heated to reflux at 90 ꢀC for 16 h. The
mixture was evaporated to dryness to afford the desired product as
a pale brown oil. The crude product used further without any pu-
rification. To a solution of the crude amide (0.6 g, 2.5 mmol,
1.0 equiv) in THF (5 mL) was added NaH (0.2 g, 60% suspension in
mineral oil, 5.0 mmol, 2.0 equiv) portion wise at 0 ꢀC and brought to
rt for 2 h. Then 3-bromoprop-1-ene (0.60 g, 0.63 mL, 5.0 mmol,
2.0 equiv) was added drop wise through syringe in 10 min and let it
stir 16 h. When the reaction was done, water was added carefully
(10 mL) and the resulting mixture was extracted with ethyl acetate
(50 mL). The organic phase was washed with brine (3ꢂ25 mL) and
dried over Na2SO4. Several column chromatography afforded 3-(2-
(allyloxy)-4-methylphenyl)-1-(pyrrolidin-1-yl)propan-1-one (15d) as
a brown oil (0.15 g, 22%); Rf (EtOAc/heptane¼40/60): 0.11; 1H NMR
A mixture of dihydrocoumarin (0.37 g, 0.32 mL, 2.5 mmol,
1.0 equiv), pyrrolidine (0.36 g, 0.42 mL, 5 mmol, 2.0 equiv) and
triethylamine (0.76 g, 1.0 mL, 7.5 mmol, 3.0 equiv) was heated to
reflux at 90 ꢀC for 16 h. The mixture was evaporated to dryness
afforded the desired product as a yellow solid. The crude product
used further without any purification. To a solution of the crude
amide (0.548 g, 2.5 mmol, 1.0 equiv) in THF (5 mL) was added NaH
(0.2 g, 60% suspension in mineral oil, 5.0 mmol, 2.0 equiv) portion
wise at 0 ꢀC and brought to rt for 2 h. Then, ethyl 2-(bromomethyl)
acrylate (1.0 g, 0.7 mL, 5.0 mmol, 2.0 equiv) was added drop wise
through syringe in 10 min and let it stir 16 h. When the reaction was
done, water was added carefully (10 mL) and the resulting mixture
was extracted with ethyl acetate (50 mL). The organic phase was
washed with brine (3ꢂ25 mL) and dried over Na2SO4. The solvent
was removed in vacuum. Column chromatography afforded ethyl 2-
((2-(3-oxo-3-(pyrrolidin-1-yl)propyl)phenoxy)methyl)acrylate (15f)
as a yellow oil (0.64 g, 77%); Rf (EtOAc/heptane¼40/60): 0.15; 1H
NMR (400 MHz, CDCl3) d 7.21e7.17 (m, 2H), 6.91e6.85 (m, 2H), 6.39
(q, J¼1.3 Hz,1H), 6.00 (q, J¼1.3 Hz, 1H), 4.76 (t, J¼1.6 Hz, 2H), 4.25 (t,
J¼7.1 Hz, 2H), 3.44 (t, J¼6.7 Hz, 2H), 3.28 (t, J¼6.7 Hz, 2H), 3.00 (t,
J¼8.0 Hz, 2H), 2.54 (t, J¼8.0 Hz, 2H), 1.88e1.79 (m, 4H), 1.32 (t,
J¼7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 171.3, 165.6, 156.3, 136.4,
130.5,130.2,127.5,126.2,121.2,111.6, 66.2, 61.0, 46.6, 45.7, 35.1, 26.5,
26.2, 24.5, 14.3; ATR-FTIR (cmꢁ1): 3462, 2974, 2873, 1717, 1639,
1493, 1437, 1274, 1243, 1175, 1156, 1110, 1053, 953, 891, 631; ESI-MS:
calculated [MþNa]þ for C19H25O4NNa: 354.1676, found: 354.1678.
(400 MHz, CDCl3)
d
7.07 (d, J¼7.5 Hz,1H), 6.69 (d, J¼7.5 Hz, 1H), 6.65
(s, 1H), 6.11e6.01 (m, 1H), 5.43e5.38 (m, 1H), 5.27e5.24 (m, 1H),
4.54e4.53 (m, 2H), 3.45 (t, J¼6.6 Hz, 2H), 3.32 (t, J¼6.5 Hz, 2H), 2.95
Please cite this article in press as: Padmanaban, M.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.027

M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
7
4.9. 3-(2-((2-Bromoallyl)oxy)phenyl)-1-(pyrrolidin-1-yl)
propan-1-one (15g)
temperatureuntil consumption of the starting material. The mixture
was washed consecutively with satd NH4Cl, brine, water and
extracted with EtOAc. The combined organic extracts were dried
(Na2SO4), filtered and concentrated in vacuum. The crude mixtures
were purified by silica gel column chromatography (Pentane/EtOAc,
gradient from 40 to 100%) to afford the desired products.
A mixture of dihydrocoumarin (0.37 g, 0.32 mL, 2.5 mmol,
1.0 equiv), pyrrolidine (0.36 g, 0.42 mL, 5 mmol, 2.0 equiv) and
triethylamine (0.76 g, 1.0 mL, 7.5 mmol, 3.0 equiv) was heated to
reflux at 90 ꢀC for 16 h. The mixture was evaporated to dryness
afforded the desired product as a yellow solid. The crude product
used further without any purification. To a solution of the crude
amide (0.548 g, 2.5 mmol, 1.0 equiv) in THF (5 mL) was added NaH
(0.2 g, 60% suspension in mineral oil, 5.0 mmol, 2.0 equiv) portion
wise at 0 ꢀC and brought to rt for 2 h. Then, 2,3-dibromopropene,
(1.0 g, 0.5 mL, 5.0 mmol, 2.0 equiv) was added drop wise through
syringe in 10 min and let it stir 16 h. When the reaction was done,
water was added carefully (10 mL) and the resulting mixture was
extracted with ethyl acetate (50 mL). The organic phase was washed
with brine (3ꢂ25 mL) and dried over Na2SO4. The solvent was re-
moved in vacuum. Column chromatography afforded 3-(2-((2-
bromoallyl)oxy)phenyl)-1-(pyrrolidin-1-yl)propan-1-one (15g) as
yellow oil (0.46 g, 54%); Rf (EtOAc/heptane¼40/60): 0.14; 1H NMR
4.12. N-allyl-4-methyl-N-(4-oxo-4-(pyrrolidin-1-yl)butyl)-
benzenesulfonamide (22a)
The general procedure for the preparation of substrates was
adapted using NaH (140.4 mg, 3.5 mmol, 3.0 equiv, 0.5 M in DMF), 4-
methyl-N-(4-oxo-4-(pyrrolidin-1-yl)butyl)benzene-sulfonamide
(362.9 mg, 1.2 mmol, 1.0 equiv, 0.08 M in DMF) and allyl bromide
(0.25 mL, 2.93 mmol,2.5 equiv), to give N-allyl-4-methyl-N-(4-oxo-4-
(pyrrolidin-1-yl)butyl)-benzenesulfon amide (22a) (331.6 mg, 81%);
1H NMR (500 MHz, CDCl3):
d
7.61 (d, J¼8.0 Hz, 2H), 7.22 (d, J¼8.0 Hz,
2H), 5.57e5.46 (m, 1H), 5.11 (dd, J¼17.0 Hz, 1.0 Hz, 1H), 5.04 (dd,
J¼10.0 Hz,1.0 Hz,1H), 3.73 (d, J¼6.5 Hz, 2H), 3.41e3.33 (m, 4H), 3.13
(t, J¼7.0 Hz, 2H), 2.35 (s, 3H), 2.25 (t, J¼7.0 Hz, 2H),1.92e1.74 (m, 6H);
13C NMR (125 MHz, CDCl3): 170.6, 143.2, 136.9, 132.9, 129.7, 127.1,
119.1, 50.6, 46.8, 46.5, 45.7, 31.2, 26.1, 24.4, 22.9, 21.5. IR (neat, cmꢁ1):
2972, 1634, 1435, 1331, 1153, 1090, 917, 731, 659; HRMS: calculated
[MþNa]þ for C18H26N6NaO3S: 373.1555, found: 373.1556.
(400 MHz, CDCl3)
d
7.23e7.14 (m, 2H), 6.91(td, J¼7.4, 0.6 Hz,1H), 6.78
(d, J¼8.1 Hz,1H), 6.01 (m,1H), 5.68e5.67 (m,1H), 4.64 (br s, 2H), 3.45
(t, J¼6.7 Hz, 2H), 3.32 (t, J¼6.7 Hz, 2H), 3.01 (t, J¼7.6 Hz, 2H), 2.57 (t,
J¼7.6 Hz, 2H), 1.90e1.80 (m, 4H); 13C NMR (100 MHz, CDCl3)
d 171.3,
155.7,130.7,130.3,127.5,127.5,121.6,118.2,111.6, 71.8, 46.7, 45.7, 35.2,
26.5, 26.2, 24.5; ATR-FTIR (cmꢁ1): 2971, 2871,1636,1492,1438,1343,
1275, 1260, 1190, 1164,1109, 1035, 763, 750, 633; ESI-MS: calculated
[MþNa]þ for C16H20BrO2NNa: 360.0570, found: 360.0566.
4.13. N-benzyl-4-methyl-N-(4-oxo-4-(pyrrolidin-1-yl)butyl)-
benzenesulfonamide (22b)
The general procedure for the preparation of substrates was
adapted using NaH (150.0 mg, 3.75 mmol, 3.0 equiv, 0.5 M in DMF), 4-
methyl-N-(4-oxo-4-(pyrrolidin-1-yl)butyl)benzene-sulfonamide
(388.01 mg,1.25 mmol,1.0 equiv, 0.08 M in DMF) and benzyl bromide
(0.37 mL 3.10 mmol, 2.5 equiv), to give N-benzyl-4-methyl-N-(4-oxo-
4-(pyrrolidin-1-yl)butyl)-benzene-sulfonamide (22b) (392.9 mg, 79%);
4.10. 3-(2-(But-2-yn-1-yloxy)phenyl)-1-(pyrrolidin-1-yl)
propan-1-one (15h)
A mixture of dihydrocoumarin (0.37 g, 0.32 mL, 2.5 mmol,
1.0 equiv), pyrrolidine (0.36 g, 0.42 mL, 5 mmol, 2.0 equiv) and
triethylamine (0.76 g, 1.0 mL, 7.5 mmol, 3.0 equiv) was heated to
reflux at 90 ꢀC for 16 h. The mixture was evaporated to dryness to
afford the desired product as a yellow solid. The crude product used
further without any purification. To a solution of the crude amide
(0.548 g, 2.5 mmol, 1.0 equiv) in THF (5 mL) was added NaH (0.2 g,
60% suspension in mineral oil, 5.0 mmol, 2.0 equiv) portion wise at
1H NMR (500 MHz, CDCl3):
d
7.71 (d, J¼8.0 Hz, 2H), 7.34e7.23 (m, 7H),
4.29 (s, 2H), 3.38 (t, J¼7.0 Hz, 2H), 3.24 (t, J¼7.0 Hz, 2H), 3.18 (t,
J¼7.0 Hz, 2H), 2.43 (s, 3H), 2.08 (t, J¼7.5 Hz, 2H),1.89 (quint., J¼7.0 Hz,
2H), 1.80 (quint., J¼7.0 Hz, 2H), 1.69 (quint., J¼7.0 Hz, 2H); 13C NMR
(125 MHz, CDCl3): 170.4, 143.2, 136.7, 136.5, 129.7, 128.6, 128.5,127.7,
127.2, 52.4, 48.1, 46.4, 45.5, 31.2, 26.0, 24.3, 23.0, 21.5. IR (neat, cmꢁ1):
2873, 1633, 1437, 1333, 1154, 1001, 923, 815, 727, 697; HRMS: calcu-
lated [MþNa]þ for C22H28N2NaO3S: 423.1716, found: 423.1713.
0
ꢀC and brought to rt for 2 h. Then, 1-bromo-2-butyne (0.67 g,
0.5 mL, 5.0 mmol, 2.0 equiv) was added drop wise through syringe
in 10 min and let it stir 16 h. When the reaction was done, water
was added carefully (10 mL) and the resulting mixture was
extracted with ethyl acetate (50 mL). The organic phase was
washed with brine (3ꢂ25 mL) and dried over Na2SO4. The solvent
was removed in vacuum. Column chromatography afforded 3-(2-
(but-2-yn-1-yloxy)phenyl)-1-(pyrrolidin-1-yl)propan-1-one (15h) as
a colourless oil (0.5 g, 74%); Rf (EtOAc/heptane¼40/60): 0.15; 1H
4.14. N-(but-2-yn-1-yl)-4-methyl-N-(4-oxo-4-(pyrrolidin-1-yl)
butyl)benzene-sulfonamide (22c)
The general procedure for the preparation of substrates was
adapted using NaH (186.0 mg, 4.65 mmol, 3.0 equiv, 0.5 M in DMF),
4-methyl-N-(4-oxo-4-(pyrrolidin-1-yl)butyl)benzene-sulfonamide
(480.3 mg, 1.55 mmol, 1.0 equiv, 0.08 M in DMF) and propargyl
bromide (0.34 mL, 3.90 mmol, 2.5 equiv), to give N-(but-2-yn-1-yl)-
4-methyl-N-(4-oxo-4-(pyrrolidin-1-yl)butyl)benzene-sulfonamide
NMR (400 MHz, CDCl3) d 7.20e7.16 (m, 2H), 6.95e6.88 (m, 2H), 4.66
(q, J¼2.3 Hz, 2H), 3.45 (t, J¼6.8 Hz, 2H), 3.35 (t, J¼6.7 Hz, 2H), 2.97 (t,
J¼6.4 Hz, 2H), 2.55 (t, J¼6.4 Hz, 2H), 1.89e1.80 (m, 7H); 13C NMR
(100 MHz, CDCl3)
d
171.6, 155.9, 130.6, 130.4, 127.4, 121.3, 111.9, 83.4,
(22c) (488.1 mg, 87%); 1H NMR (500 MHz, CDCl3):
d 7.89 (d,
74.5, 56.6, 46.7, 45.7, 35.3, 26.7, 26.3, 24.6, 3.8; ATR-FTIR (cmꢁ1):
2949, 2870, 1633, 1492, 1437, 1343, 1293, 1222, 1189, 1166, 1141,
1048, 1006, 868, 753, 632; ESI-MS: calculated [MþNa]þ for
J¼7.0 Hz, 2H), 7.29 (d, J¼8.0 Hz, 2H), 4.06 (s, 2H), 3.51e3.43 (m, 4H),
3.24 (t, J¼7.0 Hz, 2H), 2.42 (s, 3H), 2.38 (t, J¼7.5 Hz, 2H), 2.00e1.90
(m, 4H), 1.87 (quint., J¼7.0 Hz, 2H), 1.52 (s, 3H); 13C NMR (125 MHz,
CDCl3): 170.8, 143.2, 135.9, 129.2, 127.9, 81.6, 71.6, 46.7, 45.8, 36.6,
31.1, 26.1, 24.4, 22.2, 21.4, 3.3. IR (neat, cmꢁ1): 2874, 1631, 1438,
1329, 1156, 1088, 1004, 908, 814, 726, 653; HRMS: calculated
[MþNa]þ for C19H26N2NaO3S: 385.1555, found: 385.1556.
C
17H21O2NNa: 294.1465, found: 294.1465.
4.11. General procedure for N-alkylated tosyl amides
NaH (60% suspension in mineral oil, 3.0 equiv) was suspended in
DMF (0.5 M) and cooled to 0 ꢀC. A DMF solution (0.08 M) of methyl-
N-(4-oxo-4-(pyrrolidin-1-yl)butyl) benzenesulfonamide (1.0 equiv)
was added slowly to the above mixture. The reaction mixture was
stirred at room temperature for 35 min. The alkyl bromide
(2.5 equiv) was added dropwise and the mixture was stirred at room
4.15. 2-(2-(Diallylamino)phenyl)-1-(pyrrolidin-1-yl)ethanone
(29)
2-(2-Aminophenyl)-1-(pyrrolidin-1-yl)ethanone (see SI) (210 mg,
1.07 mmol)wasdissolvedinDMF(10mL). Na2CO3 (171mg, 3.2mmol)
Please cite this article in press as: Padmanaban, M.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.027

8
M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
and allyl bromide (0.37 mL, 3.2 mmol) were added and the mixture
was stirred at 100 ꢀC overnight. The reaction was quenched with
water, extracted with EtOAc, washed with water and brine, dried over
Na2SO4 and evaporated to dryness. Purification by flash column
chromatography using a gradient system from hexane to hex-
ane:ethyl acetate (2:3), afforded the product 2-(2-(Diallylamino)
phenyl)-1-(pyrrolidin-1-yl)ethanone (29) as colourless oil (170 mg,
16 h. The mixture was diluted with ethyl acetate (10 mL) and
washed with water (3ꢂ25 mL). The organic phase was dried over
Na2SO4 and evaporated to dryness. Column chromatography
(EtOAc/hexane: 10/40 to 20/30) afforded 3-(2-(bis(2-methylallyl)
amino)phenyl)-1-(pyrrolidin-1-yl)propan-1-one (32c) as a yellow oil
(0.24 g, 84%); Rf (EtOAc): 0.7; 1H NMR (400 MHz, CDCl3)
d 7.20e6.99
(m, 4H), 5.54e5.38 (m, 4H), 3.49e3.44 (m, 6H), 3.30e3.28 (m, 2H),
3.04e3.02 (m, 2H), 2.58e2.54 (m, 2H), 1.89e1.81 (m, 4H), 1.62 (d,
J¼6.3 Hz, 6H); 13C NMR (100 MHz, CDCl3): 171.7, 150.4, 138.2, 130.0,
128.2, 128.1, 126.5, 123.9, 123.3, 55.9 (2C), 46.6, 45.7, 36.0, 27.3, 26.2,
24.5, 17.9 (2C); FTIR (cmꢁ1): 3380, 2933, 1645, 1434; ESI-MS: cal-
culated [MþNa]þ for C21H30N2ONa: 349.2256, found: 349.2244.
65%); Rf (hexane/EtOAc¼3/2): 0.3; 1H NMR (500 MHz, CDCl3)
d:
7.23e7.10 (m, 2H), 7.08e7.03 (m, 2H), 5.75 (ddt, J¼16.5, 10.2, 6.2 Hz,
2H), 5.17e5.08 (m, 4H), 3.75 (s, 2H), 3.60e3.43 (m, 6H), 3.29 (t,
J¼6.5 Hz, 2H),1.81e1.79 (m, 4H); 13C NMR (126 MHz, CDCl3)
d: 170.6,
149.8, 135.1 (2C), 131.9, 130.1, 127.1, 124.2, 122.8, 117.5 (2C), 56.5 (2C),
46.8, 45.9, 37.8, 26.2, 24.5; IR (neat, cmꢁ1): 2974, 2876, 1623, 1420;
HRMS: calculated for
307.1781.
C
18H24N2O [MþNa]þ: 307.1778, found:
4.19. 3-(2-(Dibut-2-ynylamino)phenyl)-1-(pyrrolidin-1-yl)
propan-1-one (32d)
4.16. 3-(2-(Diallylamino)phenyl)-1-(pyrrolidin-1-yl)propan-1-
one (32a)
To a 3-(2-aminophenyl)-1-(pyrrolidin-1-yl)propan-1-one (0.2 g,
0.92 mmol, 1.0 equiv) solution in DMF (4 mL) was added K2CO3
(0.38 g, 2.75 mmol, 3.0 equiv) and 3-bromo-2-methylpropene
(0.24 mL, 2.75 mmol, 3.0 equiv) at 0 ꢀC. The mixture was stirred
at 50 ꢀC for 16 h. The mixture was diluted with ethyl acetate (10 mL)
and washed with water (3ꢂ25 mL). The organic phase was dried
over Na2SO4 and evaporated to dryness. Column chromatography
(EtOAc/hexane: 10/40 to 20/30) afforded 3-(2-(bis(2-methylallyl)
amino)phenyl)-1-(pyrrolidin-1-yl)propan-1-one (32d) as a white
solid (0.23 g, 78%); Rf: 0.7 (EtOAc); mp: 72e75 ꢀC; 1H NMR
To a 3-(2-aminophenyl)-1-(pyrrolidin-1-yl)propan-1-one (see
SI) (0.13 g, 0.6 mmol, 1.0 equiv) solution in DMF (2.5 mL) was added
K2CO3 (0.33 g, 2.38 mmol, 4.0 equiv) and allyl bromide (0.21 mL,
2.38 mmol, 4.0 equiv) at 0 ꢀC. The mixture was stirred at 50 ꢀC for
16 h. The mixture was diluted with ethyl acetate (10 mL) and
washed with water (3ꢂ25 mL). The organic phase was dried over
Na2SO4 and evaporated to dryness. Column chromatography
(EtOAc/hexane: 10/40 to 20/30) afforded 3-(2-(diallylamino)phe-
nyl)-1-(pyrrolidin-1-yl)propan-1-one (32a) as a white oil (0.13 g,
(400 MHz, CDCl3)
d 7.26e7.15 (m, 3H), 7.08e7.05 (m, 1H), 3.77 (s,
4H), 3.49e3.45 (m, 2H), 3.41e3.37 (m, 2H), 3.41e3.37 (m, 2H),
3.00e2.94 (m, 2H), 1.91e1.79 (m, 10H);
73%); Rf (EtOAc): 0.6; 1H NMR (400 MHz, CDCl3)
d 7.21e6.99 (m,
4H), 5.79 (ddt, J¼16.6, 10.2, 6.3 Hz, 2H), 5.16e5.06 (m, 4H), 3.55 (d,
J¼6.3 Hz, 4H), 3.48 (t, J¼6.7 Hz, 2H), 3.31 (t, J¼6.6 Hz, 2H),
3.07e3.05 (m, 2H), 2.60e2.55 (m, 2H), 1.91e1.81 (m, 4H); 13C NMR
13C NMR (101 MHz, CDCl3)
d 171.6,149.1,138.1,130.1,126.7,125.2,
123.2, 80.3 (2C), 75.0 (2C), 46.7, 45.7, 43.2 (2C), 36.3, 27.5, 26.3, 24.6,
3.7 (2C); FTIR (neat, cm-1): 3376, 2923, 1643, 1436; ESI-MS: cal-
culated [MþNa]þ for C21H26N2ONa: 345.1943, found: 345.1930.
(100 MHz, CDCl3) d 171.5, 149.9, 138.2 (2C), 135.3, 130.1, 126.6, 124.3,
123.3, 117.4 (2C), 56.9 (2C), 46.6, 45.7, 35.9, 27.0, 26.2, 24.5; FTIR
(neat, cmꢁ1): 3376, 1643, 1432; ESI-MS: calculated [MþNa]þ for
4.20. 2-(2-((Diallylamino)methyl)phenyl)-1-(pyrrolidin-1-yl)
ethanone (34)
C
19H26N2ONa: 321.1943, found: 321.1924.
4.17. 3-(2-((2-Methylallyl)oxy)phenyl)-1-(pyrrolidin-1-yl)
propan-1-one (32b)
3-Isochromanone (35) (0.50 g, 3.37 mmol) was refluxed in
pyrrolidine (0.55 mL, 6.75 mmol) and triethylamine (1.4 mL,
10.1 mmol) until total consumption of starting material, Rf¼0.3
EtOAc. The mixture was evaporated to dryness and the product was
To a 3-(2-aminophenyl)-1-(pyrrolidin-1-yl)propan-1-one (see
SI) (0.17 g, 0.78 mmol, 1.0 equiv) solution in DMF (3 mL) was added
K2CO3 (0.32 g, 2.34 mmol, 3.0 equiv) and 3-bromo-2-
methylpropene (0.24 mL, 2.34 mmol, 3.0 equiv) at 0 ꢀC. The mix-
ture was stirred at 50 ꢀC for 16 h. The mixture was diluted with
ethyl acetate (10 mL) and washed with water (3ꢂ25 mL). The or-
ganic phase was dried over Na2SO4 and evaporated to dryness.
Column chromatography (EtOAc/hexane: 10/40 to 20/30) afforded
3-(2-(bis(2-methylallyl)amino)phenyl)-1-(pyrrolidin-1-yl)propan-1-
one (32b) as a yellow oil (0.19 g, 75%); Rf (EtOAc): 0.75; 1H NMR
used without further purification; 1H NMR (500 MHz, CDCl3)
d 7.41
(dd, J¼7.1, 1.8 Hz, 1H), 7.27e7.24 (m, 2H), 7.15 (dd, J¼7.2, 1.6 Hz, 1H),
4.60 (s, 2H), 3.77 (s, 2H), 3.65 (t, J¼6.8 Hz, 2H), 3.47 (t, J¼6.9 Hz, 2H),
2.04e1.98 (m, 2H), 1.91e1.85 (m, 2H) (OH fast exchangednot ob-
served); 13C NMR (126 MHz, CDCl3)
d: 170.4, 140.6, 133.9, 130.9,
130.6, 128.3, 127.8, 63.8, 47.5, 46.4, 39.0, 26.3, 24.4; IR (cmꢁ1): 3357,
2971, 2874, 1614, 1440, 1015, 747; HRMS: calculated for C13H17NO2
[MþNa]þ: 242.1152, found: 242.1151.
2-(2-(Hydroxymethyl)phenyl)-1-(pyrrolidin-1-yl)ethanone
(200 mg, 0.92 mmol) was dissolved in THF (6 mL) and the flask was
placed in an ice bath. Diphenyl phosphoryl azide (0.25 mL,
1.19 mmol) was then added followed by DBU (0.18 mL, 1.19 mmol)
and the mixture was allowed to reach room temperature and stir-
red overnight. The mixture was dissolved with EtOAc, washed with
water and brine, dried over Na2SO4 and evaporated to dryness. The
crude product was used without further purification (Rf¼0.5
EtOAc). The crude product was dissolved in toluene (4.5 mL) and
10% Pd/C (97 mg, 10 mol %) was added. The mixture was stirred
under H2 atmosphere for 5 h until total consumption of starting
material (Rf¼0.1 EtOAc). The mixture was filtered through a Celite
pad and evaporated to dryness. The crude product 36 was dissolved
in THF (6 mL) and K2CO3 (633 mg, 4.58 mmol) and allyl bromide
(0.2 mL, 2.29 mmol) were added and the mixture was stirred at
50 ꢀC overnight. The reaction was filtrated through a Celite pad and
evaporated to dryness. The crude product was purified by flash
(400 MHz, CDCl3) d 7.21e7.19 (m, 1H), 7.14e7.07 (m, 2H), 7.05e6.96
(m, 1H), 4.91 (s, 2H), 4.82 (s, 2H), 3.50e3.44 (m, 6H), 3.34e3.31 (m,
2H), 3.16e3.12 (m, 2H), 2.60e2.56 (m, 2H), 1.92e1.82 (m, 4H), 1.71
(s, 6H). 13C NMR (100 MHz, CDCl3): 171.3, 150.2, 142.9, 137.32, 129.7,
126.3 (2C), 123.8, 122.3, 113.3 (2C), 60.7 (2C), 46.6, 45.7, 35.7, 26.2,
25.8, 24.5, 21.1 (2C); FTIR (neat, cmꢁ1): 3380, 2971, 1645, 1434; ESI-
MS: calculated [MþNa]þ for C21H30N2ONa: 349,2256, found:
349,2246.
4.18. 3-(2-(Di(E)-but-2-enylamino)phenyl)-1-(pyrrolidin-1-yl)
propan-1-one (32c)
To a 3-(2-aminophenyl)-1-(pyrrolidin-1-yl)propan-1-one (see
SI) (0.2 g, 0.92 mmol, 1.0 equiv) solution in DMF (4 mL) was added
K2CO3 (0.51 g, 3.66 mmol, 4.0 equiv) and crotyl bromide (0.38 mL,
3.66 mmol, 4.0 equiv) at 0 ꢀC. The mixture was stirred at 50 ꢀC for
Please cite this article in press as: Padmanaban, M.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.027

M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
9
column chromatography using a gradient system from hexane to
(77 mg, 0.25 mmol, 1.0 equiv) and triflic anhydride (44
0.263 mmol, 1.05 equiv) with 2,4,6-collidine (40
m
L,
hexane: ethyl acetate (1:5). The product 2-(2-((diallylamino)methyl)
phenyl)-1-(pyrrolidin-1-yl)ethanone (34) was obtained as an yellow
oil (80 mg, 29% over 4 steps); Rf¼0.2, hexane:EtOAc (1:1); 1H NMR
m
L, 0.30 mmol,
1.2 equiv) in DCM (3 mL) was heated at 120 ꢀC for 5 min in a mi-
crowave reactor. After cooled to room temperature 1 M AcOH
(5 mL) was added and stirred at room temperature for 24 h.
Aqueous work followed by flash column chromatography afforded
3-(2-(chloromethyl)allyl)chroman-2-one (16a) as a colourless liquid
(25 mg, 42%); Rf (EtOAc/heptane¼10/90): 0.33; 1H NMR (400 MHz,
(300 MHz, CDCl3)
d
: 7.21e7.16 (m, 4H), 5.83 (ddt, J¼13.1, 10.1, 6.5 Hz,
2H), 5.18e5.11 (m, 4H), 3.85 (s, 2H), 3.55e3.49 (m, 4H), 3.38 (t,
J¼6.5 Hz, 2H), 3.03 (d, J¼5.8 Hz, 4H), 1.93e1.83 (m, 4H); 13C NMR
(126 MHz, CDCl3) d: 170.2, 135.7 (2C), 135.1, 130.8, 129.4, 127.5,
126.5, 126.3, 117.7 (2C), 56.6, 46.9, 46.0, 39.3, 26.3 (2C), 24.6 (2C); IR
(neat, cmꢁ1): 3372, 2974, 2874, 1639, 1417, 915, 748; HRMS: calcu-
lated for C19H26N2O [MþNa]þ: 321.1939 found: 321.1937.
CDCl3) d 7.28e7.17 (m, 2H), 7.12e7.04 (m, 2H), 5.31 (br s, 1H), 5.05
(br s, 1H), 4.09 (app d, J¼2.2 Hz, 2H), 3.05 (dd, J¼14.8, 5.4 Hz, 1H),
3.03e2.87 (m, 2H), 2.80 (dd, J¼15.1, 4.9 Hz, 1H), 2.38 (dd, J¼14.2,
5.8 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 170.3, 151.7, 141.5, 128.5,
4.21. Rearrangementsegeneral procedure
128.3, 124.6, 122.3, 117.8, 116.7, 47.9, 37.7, 33.8, 29.1; ATR-FTIR
(cmꢁ1): 2917, 2849, 1767, 1589, 1489, 1459, 1360, 1260, 1231, 1131,
918, 764; ESI-MS calculated [MþNa]þ for C13H13ClO2Na: 259.0496,
found: 259.0500.
To a flame-dried screw-capped microwave test tube equipped
with a magnetic stir bar was added the allyloxyamide derivative
(0.25 mmol, 1.0 equiv) followed by DCM (0.08 M) under Argon at-
mosphere. To this stirred solution, triflic anhydride (1.05 equiv) was
added dropwise and stirred at ambient temperature for 15 min.
After stirring for 15 min, 2,4,6-collidine (1.2 equiv) was added
dropwise and the reaction mixture was heated in a microwave
reactor at 120 ꢀC for 5 min. After compressed air cooling to room
temperature, 1 M AcOH (5 mL) was added and the biphasic mixture
was stirred at room temperature for 24 h. The aqueous phase was
separated and extracted with dichloromethane. The combined or-
ganic layers were washed with saturated brine and dried over
Na2SO4, filtered, and concentrated in vacuum. Pre-adsorbed on
silica gel and purified by flash column chromatography on silica gel
to yield the corresponding 3-allyl dihydrocoumarin derivatives.
4.25. 2-((2-Oxochroman-3-yl)methyl)allyl acetate (16b)
Following the general procedure, treatment of 2-((2-(3-oxo-3-
(pyrrolidin-1-yl)propyl)phenoxy)methyl)allyl acetate (15b) (83 mg,
0.25 mmol, 1.0 equiv) and triflic anhydride (44
mL, 0.26 mmol,
1.05 equiv) with 2,4,6-collidine (40 L, 0.3 mmol, 1.2 equiv) in DCM
m
(3 mL) was heated at 120 ꢀC for 5 min in a Microwave reactor. After
cooled to room temperature 1 M AcOH (5 mL) was added and
stirred at room temperature for 24 h. Aqueous work followed by
flash column chromatography afforded 2-((2-oxochroman-3-yl)
methyl)allyl acetate as a colourless liquid (25 mg, 38%); Rf (EtOAc/
heptane¼10/90): 0.13; 1H NMR (400 MHz, CDCl3)
d 7.28e7.24 (m,
2H), 7.18e7.04 (m, 2H), 5.22 (br s, 1H), 5.03 (br s, 1H), 4.55 (br s, 2H),
3.03 (dd, J¼15.2, 5.4 Hz, 1H), 2.94e2.74 (m, 3H), 2.26 (dd, J¼14.5,
4.22. 3-Allylchroman-2-one (9)
5.3 Hz, 1H), 2.07 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 170.7, 170.5,
Following the general procedure, treatment of 3-(2-(allyloxy)
phenyl)-1-(pyrrolidin-1-yl)propan-1-one (7) (65 mg, 0.25 mmol,
151.7, 140.1, 128.5, 128.3, 124.6, 122.4, 116.7, 116.3, 66.5, 37.6, 33.7,
28.8, 21.0; ATR-FTIR (cmꢁ1): 2163, 1767, 1741, 1655, 1616, 1589, 1489,
1459, 1372, 1232, 1162, 1132, 1030, 918, 764; ESI-MS: calculated
[MþNa]þ for C15H16O4Na: 283.0941, found: 283.0945.
1.0 equiv) and triflic anhydride (44
mL, 0.26 mmol, 1.05 equiv) with
2,4,6-collidine (40
m
L, 0.3 mmol,1.2 equiv) in DCM (3 mL) was heated
at 120 ꢀC for 5 min in a microwave reactor. After cooled to room
temperature 1 M AcOH (5 mL) was added and stirred at room tem-
perature for 24 h. Aqueous work followed by flash column chroma-
tography afforded 3-allylchroman-2-one (9) as a colourless liquid
4.26. 3-Allyl-6-methoxychroman-2-one (16c)
Following the general procedure, treatment of 3-(2-(allyloxy)-5-
methoxyphenyl)-1-(pyrrolidin-1-yl)propan-1-one (15c) (72 mg,
1
(27 mg, 57%); Rf (EtOAc/heptane¼10/90): 0.35; H NMR (400 MHz,
CDCl3)
d
7.26e7.23 (m, 1H), 7.18e7.16 (m, 1H), 7.11e7.03 (m, 2H),
0.25 mmol, 1.0 equiv) and triflic anhydride (44
mL, 0.26 mmol,
5.86e5.81 (m, 1H), 5.16e5.11 (m, 2H), 2.98 (dd, J¼14.6, 4.8 Hz, 1H),
1.05 equiv) with 2,4,6-collidine (40 L, 0.3 mmol, 1.20 equiv) in
m
2.85e2.68 (m, 3H), 2.36e2.33 (m, 1H); 13C NMR (100 MHz, CDCl3)
DCM (3 mL) was heated at 120 ꢀC for 5 min in a microwave reactor.
After cooled to room temperature 1 M AcOH (5 mL) was added and
stirred at room temperature for 24 h. Aqueous work followed by
flash column chromatography afforded 3-allyl-6-methoxychroman-
2-one (16c) as a colourless liquid (27 mg, 50%); Rf (EtOAc/
d
170.5, 151.8, 134.4, 128.4, 128.3, 124.5, 122.7, 118.3, 116.7, 38.9, 34.1,
28.8; ATR-FTIR (cmꢁ1): 3074, 2915,1766,1642,1616,1589,1489,1459,
1357, 1275, 1232, 1196, 1144, 998, 917, 753, 633; ESI-MS: calculated
[MþNa]þ for C12H12O2Na: 211.0730, found: 211.0723.
heptane¼10/90): 0.21; 1H NMR (400 MHz, CDCl3)
d 6.95 (d,
4.23. 6-methoxy-3-(2-methylbut-3-en-2-yl)chroman-2-one
(12)
J¼8.8 Hz, 1H), 6.75 (dd, J¼8.8, 2.8 Hz, 1H), 6.68 (d, J¼2.8 Hz, 1H),
5.88e5.78 (m, 1H), 5.15ꢁ5e11 (m, 2H), 3.78 (s, 3H), 2.94 (dd, J¼14.7,
4.7 Hz, 1H), 2.82e2.66 (m, 3H), 2.37e2.31 (m, 1H); 13C NMR
Following the general procedure: 1H NMR (500 MHz, CDCl3),
(100 MHz, CDCl3) d 170.6, 156.2, 145.67, 134.5, 123.6, 118.3, 117.4,
d
7.02 (d, J¼8.34 Hz, 1H), 6.62 (dd, J¼8.36, 2.54 Hz, 1H), 6.55 (d,
113.4, 113.3, 55.8, 38.8, 34.1, 29.0; ATR-FTIR (cmꢁ1): 2916, 2848,
1765, 1493, 1460, 1434, 1376, 1261, 1226, 1153, 1129, 1033, 750, 723,
617; ESI-MS: calculated [MþNa]þ for C13H14O3Na: 241.0835, found:
241.0839.
J¼2.50 Hz, 1H), 5.87 (dd, J¼17.34, 10.85 Hz, 1H), 5.02 (dd, J¼14.07,
6.11 Hz, 2H), 3.78 (s, 3H), 2.95 (dd, J¼15.92, 6.33 Hz, 1H), 2.84 (dd,
J¼15.92, 9.51 Hz, 1H), 2.57 (dd, J¼9.48, 6.35 Hz, 1H), 1.23 (s, 3H), 1.16
(s, 3H); 13C NMR (125 MHz, CDCl3),
d 168.6, 159.6, 152.3, 145.2,
128.2, 114.9, 112.6, 110.1, 101.9, 55.5, 48.3, 29.7, 26.3, 25.5, 23.5; ESI-
MS: calculated [MþNa]þ for C15H18O3Na: 269.1148, found:
269.1148.
4.27. 3-Allyl-7-methylchroman-2-one (16d)
Following the general procedure, treatment of 3-(2-(allyloxy)-4-
methylphenyl)-1-(pyrrolidin-1-yl)propan-1-one (15d) (68 mg,
4.24. 3-(2-(Chloromethyl)allyl)chroman-2-one (16a)
0.25 mmol, 1.0 equiv) and triflic anhydride (44
mL, 0.26 mmol,
1.05 equiv) with 2,4,6-collidine (40
mL, 0.3 mmol, 1.2 equiv) in DCM
Following the general procedure, treatment of 3-(2-((2-(chlor-
omethyl)allyl)oxy)phenyl)-1-(pyrrolidin-1-yl)propan-1-one (15a)
(3 mL) was heated at 120 ꢀC for 5 min in a microwave reactor. After
cooled to room temperature 1 M AcOH (5 mL) was added and
Please cite this article in press as: Padmanaban, M.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.027

10
M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
stirred at room temperature for 24 h. Aqueous work-up followed by
flash column chromatography afforded 3-allyl-7-methylchroman-2-
3-(2-bromoallyl)chroman-2-one (16g) as a colourless liquid (25 mg,
37%); Rf (EtOAc/heptane¼10/90): 0.36; 1H NMR (400 MHz, CDCl3)
one (16d) as
a
colourless liquid (28 mg, 55%); Rf (EtOAc/
d 7.29e7.19 (m, 2H), 7.13e7.05 (m, 2H), 5.73 (br s,1H), 5.58 (br s,1H),
heptane¼10/90): 0.43; 1H NMR (400 MHz, CDCl3)
d
7.03 (d,
3.20 (dd, J¼14.3, 3.8 Hz, 1H), 3.13e3.00 (m, 2H), 2.74 (dd, J¼15.1,
J¼7.6 Hz, 1H), 6.89 (app d, J¼7.8 Hz, 1H), 6.85 (app s, 1H), 5.89e5.79
(m, 1H), 5.15e5.11 (m, 2H), 2.94 (dd, J¼14.2, 3.2 Hz, 1H), 2.80e2.67
3.3 Hz, 1H), 2.59 (dd, J¼14.5, 5.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
169.9, 151.7, 130.2, 128.6, 128.4, 124.6,122.3,120.3, 116.8, 41.6, 37.6,
(m, 3H), 2.36e2.30 (m, 4H); 13C NMR (100 MHz, CDCl3)
d
170.7,
28.3; ATR-FTIR (cmꢁ1): 1765, 1631, 1458, 1358, 1275, 1232, 1148,
1037, 918, 754, 661; ESI-MS: calculated [MþNa]þ for C12H11BrO2Na:
290.9814, found: 290.9820.
151.6, 138.6, 134.5, 127.9, 125.2, 119.5, 118.3, 117.1, 39.1, 34.1, 28.4,
21.2; ATR-FTIR (cmꢁ1): 2978, 2922, 1767, 1626, 1588, 1509, 1440,
1417, 1356, 1253, 1214, 1142, 1120, 918, 813, 765, 633; ESI-MS: cal-
culated [MþNa]þ for C13H14O2Na: 225.0886, found: 225.0890.
4.31. 3-(Buta-2,3-dien-2-yl)chroman-2-one (16h)
4.28. 3-(2-Methylallyl)chroman-2-one (16e)
Following the general procedure, treatment of 3-(2-(but-2-yn-
1-yloxy)phenyl)-1-(pyrrolidin-1-yl)propan-1-one (15h) (68 mg,
Following
methylallyl)oxy)phenyl)-1-(pyrrolidin-1-yl)propan-1-one
(68 mg, 0.25 mmol, 1.0 equiv) and triflic anhydride (44
0.26 mmol, 1.05 equiv) with 2,4,6-collidine (40 L, 0.3 mmol,
a
general procedure, treatment of 3-(2-((2-
(15e)
L,
0.25 mmol, 1.0 equiv) and triflic anhydride (44
mL, 0.26 mmol,
1.05 equiv) with 2,4,6-collidine (40 L, 0.3 mmol, 1.2 equiv) in DCM
m
m
(3 mL) was heated at 120 ꢀC for 5 min in a Microwave reactor. After
cooled to room temperature 1 M AcOH (5 mL) was added and
stirred at room temperature for 24 h. Aqueous work followed by
flash column chromatography afforded 3-(Buta-2,3-dien-2-yl)
chroman-2-one (16h) as a colourless liquid using pentane and Et2O
as a eluent mixture (18 mg, 36%); Rf (EtOAc/heptane¼10/90): 0.33;
m
1.2 equiv) in DCM (3 mL) was heated at 120 ꢀC for 5 min in a mi-
crowave reactor. After cooled to room temperature 1 M AcOH
(5 mL) was added and stirred at room temperature for 24 h.
Aqueous work followed by flash column chromatography afforded
3-(2-methylallyl)chroman-2-one (16e) as a colourless liquid (22 mg,
44%). This product was obtained with 20% of the impurity, which
cannot be removed by chromatography; Rf (EtOAc/heptane¼10/
1H NMR (400 MHz, CDCl3)
d
7.26e7.21 (m, 1H), 7.16 (app d, J¼7.1 Hz,
1H), 7.07 (td, J¼7.6, 1.0 Hz, 1H), 7.01 (app d, J¼8.1 Hz, 1H), 4.72e4.63
(m, 2H), 3.32e3.27 (m, 1H), 3.09e3.07 (m, 2H), 1.83 (t, J¼3.1 Hz,
90): 0.40; 1H NMR (400 MHz, CDCl3)
d
7.28e7.16 (m, 2H), 7.11e7.04
3H); 13C NMR (100 MHz, CDCl3)
d 206.8, 168.5, 151.7, 128.5, 128.3,
(m, 2H), 4.89 (br s, 1H), 4.74 (br s, 1H), 3.00 (dd, J¼15.2, 5.5 Hz, 1H),
124.5, 122.4, 116.6, 95.3, 77.4, 43.3, 28.8, 17.4; ATR-FTIR (cmꢁ1):
2953, 2916, 2848, 1770, 1489, 1459, 1375, 1263, 1230, 1186, 1128,
981, 915, 749, 633; ESI-MS: calculated [MþNa]þ for C13H12O2Na:
223.0730, found: 225.0722.
2.90e2.83 (m, 1H), 2.77e2.70 (m, 2H), 2.20 (dd, J¼14.1, 4.8 Hz, 1H),
1.75 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 170.6, 151.8, 141.5, 128.4,
127.7, 124.5, 122.5, 116.7, 113.8, 37.9, 37.2, 28.5, 21.9; ATR-FTIR
(cmꢁ1): 3074, 2933, 1760, 1650, 1616, 1589, 1490, 1459, 1377, 1356,
1232, 1196, 1161, 1130, 1057, 998, 918, 755; ESI-MS: calculated
[MþNa]þ for C13H14O2Na: 225.0886, found: 225.0881.
4.32. 10-Allyl-30-tosyl-1,20-bipyrrolidine (23a)
Isolated in 94% yield. 1H NMR (600 MHz, CDCl3):
d 7.80e7.76
4.29. Ethyl 2-((2-oxochroman-3-yl)methyl)acrylate (16f)
(m, 2H), 7.45e7.41 (m, 2H), 5.95e5.87 (ddt, J¼17.2, 10.6, 6.5 Hz, 1H),
5.52 (dt, J¼17.0, 1.5, 1H), 5.43 (dt, J¼10.5, 1.5 Hz, 1H), 4.88
(d, J¼8.0 Hz, 1H), 4.51e4.44 (m, 1H), 4.42e4.36 (m, 1H), 4.29e4.23
(m, 1H), 4.18e4.04 (m, 3H), 4.18e4.13 (m, 1H), 4.12e4.04 (m, 2H),
3.87e3.81 (m, 1H), 3.65 (t, J¼10 Hz, 1H), 2.99e2.89 (m, 1H), 2.48
(s, 3H), 2.24e2.17 (m, 1H), 2.16e2.08 (m, 2H), 2.06e2.00 (m, 1H),
1.99e1.92 (m, 1H); 13C NMR (150 MHz, CDCl3): 158.5, 146.9, 134.1,
130.6, 130.5, 128.6, 119.8, 70.4, 55.5, 55.0, 51.9, 51.5, 25.9, 24.3, 23.8,
21.8.
Following the general procedure, treatment of ethyl 2-((2-(3-
oxo-3-(pyrrolidin-1-yl)propyl)phenoxy)methyl)acrylate
(83 mg, 0.25 mmol, 1.0 equiv) and triflic anhydride (44
0.26 mmol, 1.05 equiv) with 2,4,6-collidine (40 L, 0.3 mmol,
(15f)
mL,
m
1.2 equiv) in DCM (3 mL) was heated at 120 ꢀC for 5 min in a mi-
crowave reactor. After cooled to room temperature 1 M AcOH
(5 mL) was added and stirred at room temperature for 24 h.
Aqueous work followed by flash column chromatography afforded
ethyl 2-((2-oxochroman-3-yl)methyl)acrylate (16f) as a colourless
liquid (30 mg, 46%); Rf (EtOAc/heptane¼10/90): 0.19; 1H NMR
4.33. 1-(1-Benzyl-3-tosylpyrrolidin-2-ylidene)pyrrolidin-1-
ium (23b)
(400 MHz, CDCl3)
d
7.26e7.23 (m, 1H), 7.15 (app d, J¼7.2 Hz, 1H),
7.10e7.02 (m, 2H), 6.31 (s, 1H), 5.68 (s, 1H), 4.20 (q, J¼7.2 Hz, 2H),
3.11e2.94 (m, 3H), 2.80e2.73 (m, 1H), 2.48e2.43 (m, 1H), 1.29 (t,
Isolated 90% yield. 1H NMR (600 MHz, CDCl3):
d
7.78 (d, J¼8.0 Hz,
2H), 7.49e7.43 (m, 4H), 7.41e7.36 (m, 3H), 5.23 (d, J¼17.0 Hz, 1H),
4.91 (d, J¼8.5 Hz, 1H), 4.83 (d, J¼17.0 Hz, 1H), 4.50e4.42 (m, 1H),
4.25e4.15 (m, 2H), 4.08e3.99 (m, 1H), 3.81e3.73 (m, 1H), 3.62
(t, J¼9.0 Hz, 1H), 3.05e2.94 (m, 1H), 2.47 (s, 3H), 2.26e2.05 (m, 3H),
2.07e1.94 (m, 2H); 13C NMR (150 MHz, CDCl3): 158.7, 146.9, 133.5,
133.1, 130.6, 129.5, 128.6, 126.7, 70.5, 55.7, 55.1, 53.3, 51.7, 26.0, 24.2,
23.8, 21.8. Structure unambiguously determined by X-ray diffrac-
tion (see SI for details).
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 170.3, 166.6, 151.7, 137.2,
128.4 (for 2 carbons), 128.3, 124.4, 122.5, 116.7, 61.1, 38.3, 32.8, 29.0,
14.3; ATR-FTIR (cmꢁ1): 2982, 1765, 1711, 1630, 1589, 1489, 1459,
1368, 1305, 1275, 1231, 1200, 1149, 1127, 1026, 955, 919, 756, 689,
633; ESI-MS: calculated [MþNa]þ for C15H16O4Na: 283.0941, found:
283.0936.
4.30. 3-(2-Bromoallyl)chroman-2-one (16g)
4.34. 20-Methyl-80-tosyl-40,60,70,80-tetrahydrospiro[pyrroli-
Following the general procedure, treatment of 3-(2-((2-
dine-1,10-pyrro-lo[1,2-a]pyrimidine]-1,50-diium (23c)
bromoallyl)oxy)phenyl)-1-(pyrrolidin-1-yl)propan-1-one
(85 mg, 0.25 mmol, 1.0 equiv) and triflic anhydride (44
0.263 mmol, 1.05 equiv) with 2,4,6-collidine (40 L, 0.3 mmol,
(15g)
mL,
1H NMR (600 MHz, CDCl3):
d
8.01 (d, J¼8.0 Hz, 2H), 7.59 (d,
m
J¼8.0 Hz, 2H), 5.93 (d, J¼6.5 Hz, 1H), 5.24 (d, J¼8.5 Hz, 1H), 4.79 (dd,
J¼17.0, 6.0 Hz, 1H), 4.29e4.23 (m, 3H), 4.11 (dt, J¼11.4, 7.2 Hz, 1H),
4.03e4.01 (m, 1H), 3.72 (t, J¼10.3 Hz, 1H), 3.59 (dt, J¼10.3, 6.7 Hz,
1H), 2.72e2.70 (m, 1H), 2.50 (s, 3H), 2.42 (dd, J¼14.7, 5.7 Hz, 1H),
2.19 (s, 3H), 2.15e2.11 (m, 2H), 2.03e2.00 (m, 2H); 13C NMR
1.2 equiv) in DCM (3 mL) was heated at 120 ꢀC for 5 min in a mi-
crowave reactor. After cooled to room temperature 1 M AcOH
(5 mL) was added and stirred at room temperature for 24 h.
Aqueous work followed by flash column chromatography afforded
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M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
11
(150 MHz, CDCl3): 159.7, 149.3, 147.9, 134.3, 131.4, 130.1, 125.2, 123.1,
4.38. 1-(1,3-bis(2-methylallyl)-3,4-dihydroquinolin-2(1H)-yli-
dene)pyrrolidinium triflate (33b)
121.0, 118.8, 116.5, 70.5, 58.3, 54.9, 52.7, 45.5, 26.6, 24.9, 23.9, 21.6,
19.6. Note: the product was isolated as a mixture with the starting
material. HRMS: exact mass calculated for [M]2þ [OTf]-
([C19H26F3N2O2S]þ2 2[OTf]ꢁ Mw¼644; 495¼644- OTf): 495.1234,
found: 495.1230.
Purification by flash column chromatography (gradient DCM to
DCM:MeOH 5%) afforded 1-(1,3-bis(2-methylallyl)-3,4-dihydro-
quinolin-2(1H)-ylidene) pyrrolidinium triflate (32b) (30 mg,
0.07 mmol, 44%); Rf (DCM/methanol 2%): 0.2; 1H NMR (400 MHz,
4.35. 1,7-Diallyl-2-(pyrrolidin-1-yl)-1H-indole (31)
CDCl3) d 7.26e7.10 (m, 4H), 4.89 (s, 2H), 4.51 (s, 2H), 4.39e4.34 (m,
1H), 4.18e4.15 (m, 2H), 3.81e3.78 (m, 1H), 3.61e3.58 (m, 1H),
3.37e3.30 (m, 2H), 2.75 (dd, J¼16.1, 2.1 Hz, 1H), 2.16e1.90 (m, 6H),
To a flame-dried screw-capped microwave test tube equipped
with a magnetic stir bar was added the derivative 29 (20 mg,
0.07 mmol, 1.0 equiv) followed by DCM (0.1 M) under Argon at-
mosphere. To this stirred solution triflic anhydride (1.05 equiv)
was added dropwise and stirred at ambient temperature for
15 min. After stirring for 15 min, 2,4,6-collidine (1.20 equiv) was
added dropwise, the reaction mixture was heated in a microwave
reactor at 120 ꢀC for 5 min. After cooling to room temperature,
water was added and the biphasic mixture was stirred at room
temperature for 24 h. The aqueous phase was separated and
extracted with dichloromethane. The combined organic layers
were washed with brine and dried over Na2SO4, filtered, and
concentrated in vacuum. Compound was purified by flash column
chromatography (gradient hexane:EtOAc 1:1 to EtOAc:MeOH 10%)
to yield the product 31 as a white solid (8 mg, 43%); Rf (EtOAc/
1.80e1.74 (m, 7H); 13C NMR (101 MHz, CDCl3)
d 169.1, 141.9, 139.5,
138.8, 129.2, 127.9, 126.6, 125.7, 118.5, 115.5, 114.6, 57.9, 54.1, 53.5,
36.8, 35.5, 26.8, 26.5, 23.9, 21.7, 20.2; IR (NaCl, cmꢁ1) 1660, 1582;
ESI-MS: calculated for C21H29N2 [M]þ: 309.2325, found: 309.2320.
4.39. (E)-1-(1-(but-2-enyl)-3-(but-3-en-2-yl)-3,4-
dihydroquinolin-2(1H)-ylidene)pyrrolidinium triflate (33c)
Purification by flash column chromatography (gradient DCM to
DCM:MeOH 5%) afforded (E)-1-(1-(but-2-enyl)-3-(but-3-en-2-yl)-
3,4-dihydroquinolin-2(1H)-ylidene)pyrrolidinium
(25 mg, 0.05 mmol, 36%); Rf (DCM/methanol 2%): 0.2. 1H NMR
(400 MHz, CDCl3) 7.27e7.25 (m, 1H), 7.15e7.06 (m, 3H), 5.73 (dd,
triflate
(33c)
d
J¼15.7, 6.9 Hz, 1H), 5.58e5.56 (m, 1H), 5.35 (ddd, J¼16.9, 10.8,
8.3 Hz, 1H), 4.92 (d, J¼10.1 Hz, 1H), 4.82e4.61 (m, 3H), 4.25e4.22
(m, 1H), 4.03e3.86 (m, 3H), 3.0e3.20 (m, 2H), 2.91 (dd, J¼15.0,
4.7 Hz, 1H), 2.20e2.06 (m, 5H), 1.77e1.71 (m, 3H), 1.08e1.06 (m,
hexane¼1:1): 0.2; 1H NMR (500 MHz, CDCl3)
d: 7.28e7.16 (m, 1H),
6.92 (dd, J¼7.5, 0.8 Hz, 1H), 6.84 (d, J¼8.2 Hz, 1H), 6.03 (ddt, J¼17.2,
10.4, 5.2 Hz, 2H), 5.91 (s, 1H), 5.14e5.05 (m, 2H), 4.91e4.78 (m,
4H), 3.70e3.69 (m, 2H), 3.54e3.42 (m, 4H), 1.97e1.78 (m, 4H); 13C
3H); 13C NMR (100 MHz, CDCl3)
d 169.9, 138.9, 138.6, 131.3, 129.2,
NMR (126 MHz, CDCl3)
122.0, 119.8, 117.2, 115.6, 115.1, 86.4, 53.2 (2C), 46.5, 36.2, 24.8 (2C);
ESI-MS: calculated for
266.1783.
d
: 150.4, 138.8, 136.7, 133.7, 129.6, 122.6,
129.1, 127.9, 126.1, 125.8, 125.2, 124.9, 117.7, 117.1, 56.4, 56.2, 54.1,
53.9, 53.2, 49.9, 41.6, 41.5, 38.3, 38.2, 27.3, 26.4, 24.2, 18.9, 18.8, 18.0,
13.7; IR (NaCl, cmꢁ1) 1613, 1584; ESI-MS: calculated for C21H29N2
[M]þ: 309.2325, found: 309.2320.
C
18H22N2 [MþNa]þ: 266.1782, found:
4.36. General procedure for 3,4-dihydro-2(1H)-quinolinone-
4.40. 1-(1-(but-2-ynyl)-3-(buta-2,3-dien-2-yl)-3,4-
like scaffolds
dihydroquinolin-2(1H)-ylidene)pyrrolidinium triflate (33d)
To a flame-dried screw-capped sealed tube equipped with
a magnetic stir bar was added the derivative 32 (0.15 mmol,
1.0 equiv) followed by DCM (0.08 M) was added under the atmo-
sphere of Argon. To this stirred solution triflic anhydride
(1.05 equiv) was added dropwise and stirred at ambient tempera-
ture for 15 min. After stirring for 15 min, 2,4,6-collidine (1.20 equiv)
was added dropwise, the reaction mixture was heated at 120 ꢀC for
5 min. After cooling to room temperature, 1 M AcOH (5 mL) was
added and the biphasic mixture was stirred at room temperature
for 24 h. The aqueous phase was separated and extracted with
dichloromethane. The combined organic layers were washed with
water and brine, dried over Na2SO4, filtered, and concentrated in
vacuum.
The compound was purified by flash chromatography (DCM to
DCM:MeOH 5%) to yield the 1-(1,3-diallyl-3,4-dihydroquinolin-
2(1H)-ylidene)pyrrolidinium triflate (33d) (20 mg, 0.04 mmol, 29%);
Rf (DCM/methanol 2%): 0.2; 1H NMR (400 MHz, CDCl3)
d 7.79 (d,
J¼8.2 Hz, 1H), 7.30 (t, J¼7.9 Hz, 1H), 7.20e7.13 (m, 2H), 5.15e5.11 (m,
1H), 4.58e4.27 (m, 5H), 4.16 (td, J¼11.2, 5.9 Hz, 1H), 4.05 (d,
J¼4.9 Hz, 1H), 3.66e3.59 (m, 1H), 3.52 (dd, J¼15.9, 5.2 Hz, 1H), 2.81
(dd, J¼15.9, 2.0 Hz, 1H), 2.29e2.07 (m, 3H), 1.95 (s, 3H), 1.84e1.81
(m, 1H), 1.68 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 205.2, 167.9, 141.3,
128.4, 128.3, 126.8, 117.9, 93.6, 84.2, 76.5, 75.3, 55.1, 53.7, 45.3, 44.9,
27.3, 26.9, 24.0 (2C), 16.6, 3.9; IR (NaCl, cmꢁ1): 3383, 1662, 1560,
1431; ESI-MS: calculated for C21H25N2 [M]þ: 305.2012, found:
305.2009.
4.37. 1-(1,3-Diallyl-3,4-dihydroquinolin-2(1H)-ylidene)pyrro-
lidinium triflate (33a)
4.41. 2,4-Diallyl-1,2-dihydroisoquinolin-3(4H)-one (38)
To a flame-dried screw-capped microwave test tube equipped
with a magnetic stir bar was added the derivative 34 (25 mg,
0.083 mmol, 1.0 equiv) followed by DCM (0.1 M) was added under
the atmosphere of Argon. To this stirred solution triflic anhydride
(1.05 equiv) was added dropwise and stirred at ambient tempera-
ture for 15 min. After stirring for 15 min, 2,4,6-collidine (1.2 equiv)
was added dropwise, the reaction mixture was heated in a micro-
wave reactor at 120 ꢀC for 5 min. After cooling to room temperature,
the mixture was evaporated and dissolved in THF (0.5 mL). A sat-
urated solution of NaHCO3 (0.5 mL) was added and the mixture was
heated in the microwave reactor at 120 ꢀC for 5 min. The organic
layer was evaporated to dryness. Purification by flash column
chromatography afforded the corresponding derivative 38 as a light
Purification by flash column chromatography (gradient DCM to
DCM:MeOH 5%) afforded 1-(1,3-diallyl-3,4-dihydroquinolin-2(1H)-
ylidene) pyrrolidinium triflate (32a) (25 mg, 0.06 mmol, 39%); Rf
(DCM/methanol 2%): 0.15; 1H NMR (400 MHz, CDCl3)
d 7.26e7.15
(m, 4H), 5.95 (ddd, J¼15.5, 10.2, 4.6 Hz, 1H), 5.65 (ddd, J¼16.5, 8.5,
6.2 Hz, 1H), 5.38e5.27 (m, 2H), 5.12 (d, J¼10.0 Hz, 1H), 4.96e4.91
(m, 1H), 4.81e4.78 (m, 2H), 4.32e4.30 (m, 1H), 4.03e4.02 (m, 2H),
3.85e3.81 (m, 1H), 3.54e3.52 (m, 1H), 3.33 (dd, J¼16.0, 4.6 Hz, 1H),
2.78 (d, J¼15.0 Hz, 1H), 2.21e2.13 (m, 4H), 2.00e1.94 (m, 2H); 13C
NMR (101 MHz, CDCl3)
d 169.6, 138.3, 133.1, 132.8, 129.1, 128.0,
126.6, 126.3, 119.7, 119.6, 118.9, 55.3, 54.6, 53.7, 38.4, 32.1, 27.3, 26.6,
24.0; IR (NaCl, cmꢁ1): 3380, 1662, 1574, 1434, 1263; ESI-MS: cal-
culated for C19H25N2 [M]þ: 281.2012, found: 281.2005.
yellow oil (17 mg, 0.078 mmol, 90%); 1H NMR (500 MHz, CDCl3)
d:
Please cite this article in press as: Padmanaban, M.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.027

12
M. Padmanaban et al. / Tetrahedron xxx (2015) 1e12
3. (a) Valerio, V.; Madelaine, C.; Maulide, N. Chem.dEur. J. 2011, 17, 4742e4745 For
other references, see; (b) Peng, B.; Geerdink, G.; Fares, C.; Maulide, N. Angew.
7.34e7.20 (m, 2H), 7.15 (d, J¼7.5 Hz, 2H), 5.81e5.67 (m, 2H),
5.22e5.19 (m, 2H), 5.03e4.99 (m, 2H), 4.59 (d, J¼15.8 Hz, 1H),
4.28e4.08 (m, 3H), 3.65 (t, J¼6.5 Hz, 1H), 2.64e2.61 (m, 2H); 13C
ꢀ
Chem. 2014, 126, 5566e5570 Angew. Chem. Int. Ed. 2014, 53, 5462e5466.
4. For synthetic applications of iminium ethers, see: (a) Sheu, J.; Smith, M. B.;
Matsumoto, K. Synth. Commun. 1993, 23, 253e262; (b) Lambert, T. N.; Chitta-
muru, S.; Jacobs, H. K.; Gopalan, A. S. Tetrahedron Lett. 2002, 43, 7379e7383; (c)
Hedvati, L.; Nudelman, A.; Falb, E.; Kraiz, B.; Zhuk, R.; Sprecher, M. Eur. J. Med.
Chem. 2002, 37, 607e616; (d) Grassi, G.; Risitano, F.; Foti, F.; Cordaro, M.; Bruno,
G.; Nicol, F. Chem. Commun. 2003, 1868e1869; (e) Zhu, W.; Wu, P.; Liang, X.;
Dong, Y.; Zhang, J.; Yuan, H.; Qi, S.; Meng, X.; Wu, J.; Chen, F.; Wang, D. J. Agric.
Food Chem. 2008, 56, 6547e6553.
NMR (126 MHz, CDCl3) d: 171.1, 135.9, 134.4, 132.8, 131.2, 127.8,
127.6, 126.7, 125.3, 118.0, 117.9, 49.9, 49.5, 47.4, 38.6; IR (NaCl,
cmꢁ1): 2972, 2921, 1638, 915, 751; ESI-MS: calculated for
C
15H17NONa [MþNa]þ: 250.1203, found: 250.1202.
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~
^
The authors thank Fundac¸ ao para a Ciencia e Tecnologia for
a PhD fellowship to L.C. (SFRH/BD/63407/2009), the funding to
LAQV, REQUIMTE:UID/QUI/50006/2013 and access to spectrome-
ters from the National NMR Facility (RECI/BBB-BQB/0230/2012).
Generous support by the Deutsche Forschungsgemeinschaft
~
€
(Grants MA 4861/1-1 and 1-2), the Max-Planck-Institut fur Koh-
lenforschung (where parts of this research were carried out) and
the University of Vienna is gratefully acknowledged.
Supplementary data
Supplementary data (experimental procedures, characterization
data for new compounds and X-ray crystallographic data) related to
thisarticle can be foundathttp://dx.doi.org/10.1016/j.tet.2015.06.027.
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Please cite this article in press as: Padmanaban, M.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.027