Verdazyl radicals as substrates for organic synthesis: The synthesis and characterization of [12]-, [13]-, and [21]-paraheteraphanes

Article abstract of DOI:10.1002/ejoc.201101754

A tandem intermolecular-intramolecular 1,3-dipolar cycloaddition sequence with the bis-azomethine imine derived from a para-aryl-substituted bis-verdazyl radical has been used to form a series of [n]-paraheteraphanes, which form exclusively by a [1+1] dou

Full text of DOI:10.1002/ejoc.201101754

FULL PAPER
DOI: 10.1002/ejoc.201101754
Verdazyl Radicals as Substrates for Organic Synthesis: The Synthesis and
Characterization of [12]-, [13]-, and [21]-Paraheteraphanes
Abbarna A. Cumaraswamy,[a] Gordon K. Hamer,[a] and Michael K. Georges*[a]
Keywords: Radicals / Cycloaddition / Azo compounds / Heteraphanes / Macrocycles
A tandem intermolecular–intramolecular 1,3-dipolar cycload-
dition sequence with the bis-azomethine imine derived from
a para-aryl-substituted bis-verdazyl radical has been used to
form a series of [n]-paraheteraphanes, which form exclu-
sively by a [1+1] double cycloaddition reaction, with no evi-
dence for the formation of the [2+2] quadruple cycloadduct
products. 1H NMR spectroscopic studies show that rotation
of the phenyl ring of these compounds is affected by the size
and structure of the [n]-paraheteraphane cavity.
lecular rearrangements to produce a second generation of
molecular scaffolds that would otherwise require laborious
multistep synthetic sequences.[6c]
Introduction
While the creative manipulation of chemical reactions by
synthetic chemists provides an ever increasing number of
innovative macrocycles of wide-ranging molecular architec-
tures, material scientists continue their pursuit to discover
new and diverse applications for these molecules. The last
step in the formation of macrocycles is typically a ring-clos-
ing reaction, which can be a single reaction or two or more
tandem reactions.[1–4] Of particular interest is the use of cy-
cloaddition reactions to achieve the ring closing because
they are efficient, occur under relatively mild conditions,
and result in the formation of a smaller ring structure which
adds a further interesting feature and complexity to the
macrocyclic structure.[2a–2i] Thus, for example, the [4+2]
Diels–Alder reaction leads to cyclohexene links, Cu-cata-
lyzed click chemistry give 1,2,3-triazoles,[3,4] and nitrile ox-
ides give dihydroisoxazoles.[5]
In the past few years our group has been interested in
using verdazyl radicals as substrates for organic synthe-
sis.[6a–6c] We recently reported that the 1,5-dimethyl-3-
phenyl-6-oxoverdazyl radical (1) can serve as a precursor to
azomethine imine 2 through a disproportionation reaction
between two molecules of 1.[6a] In the presence of electron-
poor dipolarophiles, for example, acrylates, methacrylates,
and acrylonitrile, as well as weakly electron-rich di-
polarophiles, such as styrene and its derivatives, 2 un-
dergoes a [3+2] dipolar cycloaddition reaction to give vari-
ous substituted tetrapyrazolotetrazinones 3 (Scheme 1).
One of the interesting features of these heterocyclic com-
pounds is their propensity to undergo single-step intramo-
Scheme 1. Disproportionation reaction between two verdazyl radi-
cals and a subsequent cycloaddition reaction.
Recently, Kim and co-workers[7a–7c] used tandem 1,3-di-
polar cycloaddition reactions between a nitrile oxide dipole
and ethylene glycol diacrylates of various lengths, in a pro-
cess they referred to as multiple cycloadditive macrocycliza-
tion, to provide a series of polyethylene oxide containing
macrocyclic structures.
In the case of their meta-aryl-substituted bifunctional di-
pole (m-terephthaldinitrile oxide), reaction with di- or tri-
ethylene glycol diacrylates gave [1+1] cycloadducts 4 as the
major products. However, the reactions of the correspond-
ing para-substituted bifunctional dipole with the same di-
polarophiles gave [2+2] cycloadducts 6 due to the inability
of the short acrylates to bridge the distance between the
[a] Chemical & Physical Sciences,
University of Toronto at Mississauga,
3359 Mississauga Rd, Mississauga, Ontario, L5L 1C6 Canada
Fax: +1-905-828-5425
E-mail: michael.georges@utoronto.ca
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101754.
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A. A. Cumaraswamy, G. K. Hamer, M. K. Georges
FULL PAPER
two nitrile oxide groups. The [1+1] addition product 5 was
obtained when the longer tetraethylene glycol acrylate was
used (Figure 1).
Figure 1. Macrocycles synthesized by Kim et al.[6] from diacrylate
dipolarophiles using a nitrile oxide dipole.
With this as a background, we became interested in see-
ing how azomethine imine 2 would perform under similar
conditions, although it is interesting to note that azometh-
ine imines have not been used to date to make macrocyclic
structures. Herein, we report the efficient use of a tandem
intermolecular–intramolecular 1,3-dipolar cycloaddition se-
quence with bis-azomethine imine 11 (Figure 2), derived
Scheme 2. Synthetic pathway to [n]-paraheteraphanes 10.
The formation of 9 was inferred indirectly by the color
of the reaction mixture going from white to reddish brown,
the typical color of 6-oxoverdazyl radicals, and the subse-
quent formation of [n]-paraheteraphanes 10. Targeted
[12]-, [13]-, and [21]-paraheteraphanes 10a–d (Figure 2)
were produced through tandem intermolecular–intramolec-
ular 1,3-dipolar cycloaddition (1,3-DC) reactions with the
appropriate bifunctional diacrylate or dimethacrylate di-
polarophiles. In all cases, the [n]-paraheteraphanes were iso-
from para-aryl-substituted bis-verdazyl radical
9
(Scheme 2), to provide a series of [n]-paraheteraphanes 10.
In contrast to the results of Kim et al., all the [n]-paraheter-
aphanes obtained from bis-azomethine imine 11 were the
[1+1] double cycloaddition reaction products, with no evi-
dence for the formation of the [2+2] quadruple cycloadduct
products even with the use of a monoethylene glycol diacryl-
ate dipolarophile. Clearly, the construct of our azomethine
imine intermediate is such that even the shortest ethylene
glycol diacrylate can reach both reacting centers confirming
the preference of the system to undergo the intramolecular
cycloaddition if the chain lengths permit, as evident in the
work of Kim et al.[7] The structural features and conforma-
tional biases of the ethylene glycol derived macrocycles, as
evidenced by 1H NMR spectroscopy and X-ray crystal-
lography, are highlighted herein.
Results and Discussion
Synthesis of [n]-Paraheteraphanes
The synthesis of 9 (Scheme 2) began by condensing
terephthaldicarboxaldehyde with N,NЈ-dimethylcarbono-
hydrazide (7, 2 equiv.)[6b,6c] to afford bis(2,4-dimethyl-6-
phenyl-1,2,4,5-tetrazinan-3-one) (8) in 40% yield.[8] The
oxidation of 8 was carried out in a suspension of NaIO4 in
water to give 9 in 96% yield.[8]
Figure 2. Formation of [12]-, [13]-, and [21]-paraheteraphanes 10a–
d via the intermediacy of azomethine imine 11.
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Verdazyl Radicals as Substrates for Organic Synthesis
lated as major products, in yields ranging from 10 to 20% the blue spectrum and the minor diastereomer by the red
with the exception of [21]-paraheteraphane 10d, which was spectrum. The diastereomer shown in red has two mul-
isolated in 6% yield. Although the products were isolated tiplets representing the eight methylene protons of the ethyl-
in low yield, in the context of macrocycle synthesis the ene glycol bridging unit, whereas the other diastereomer,
yields are typical. Although other products formed in the shown in blue, shows the presence of an additional mul-
reaction, in many cases probably oligomers, only the mono- tiplet where all three collectively integrate for the same eight
verdazyl cycloadduct was isolable in reasonable purity. Due methylene protons. The diastereomers for the other parah-
to the paramagnetic structure of the monoverdazyl cycload- eteraphanes were never isolated.
duct, the peaks in the 1H NMR spectrum were significantly
broadened, but the position and the integration of the
broad peaks were compatible with the structure.
It is assumed that the two cycloaddition reactions occur
in tandem, rather than simultaneously, due to the relatively
slow formation of the azomethine imine. So, whereas struc-
ture 11 is informative, it is unlikely that it actually ever ex-
ists.
Structural and Conformational Studies
Single-crystal X-ray diffraction studies of two of the four
[n]-paraheteraphanes, 10a and 10c, corroborate the 13C
NMR spectra data which revealed them to be symmetric
compounds. Both structures have two stereogenic centers,
C5 and C10 in 10a and C1 and C17 in 10c (Figure 3), and
the cycloadditions are seen to be diastereoselective with
only the R,S isomers forming.
Figure 4. 1H NMR spectrum at 296 K for two possible dia-
stereomers of 10d.
With the successful preparation of [n]-paraheteraphanes
10a–d, the size and flexibility of their cavities were investi-
1
gated through the rotation of the phenyl ring by using H
NMR spectroscopy (Figure 5). Not unexpectedly, the rota-
tion of the phenyl ring in [21]-paraheteraphane 10d, the
macrostructure with the largest cavity, is completely unre-
stricted. As a result, all the aromatic hydrogen atoms of
1
10d are equivalent and appear as a singlet in the H NMR
spectrum. Interestingly, shortening the linker to a single
ethylene glycol unit, as in 10c, still provides a cavity large
enough to allow complete rotation of the phenyl ring and
again all the aromatic hydrogen atoms show up as a singlet.
The use of a methacrylate linker, which adds two methyl
groups into the cavity, as illustrated in structure 10a, results
in complete restricted rotation of the phenyl ring. In this
case, the aromatic hydrogen atoms show up as two distinct
somewhat broad singlets. The aromatic protons can be
Figure 3. X-ray structures of 10a and 10c.
grouped into two enantiotopic pairs, HA/HAЈ and HB/HBЈ
and two diastereotopic pairs, HA/HB and HAЈ/HBЈ. Thus,
For 10d, the [21]-paraheteraphane, both diastereomers one diastereotopic pair, due to the restricted rotation, expe-
are evident in the 1H NMR spectrum in a ratio of 3:1 (Fig- riences one environment and the other diastereomeric pair
ure 4). The higher yielding diastereomer is represented by experiences a different environment.
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A. A. Cumaraswamy, G. K. Hamer, M. K. Georges
FULL PAPER
Conclusions
In order to scope out the synthetic utility of verdazyl
radicals for the synthesis of macrocycles, a study was initi-
ated to prepare a series of verdazyl-derived [n]-parahetera-
phanes, 10a–d. While it was initially anticipated, based on
the work of Kim, that the azomethine imine derived from
a bis-verdazyl radical would undergo [2+2] cycloaddition
reactions with various bis-acrylate and methacrylate linkers,
only [1+1] cycloaddition reactions actually occurred even
with the use of a monoethylene glycol diacrylate di-
polarophile. Single-crystal X-ray diffraction studies pro-
vided insight into the structural characteristics of para-
heteraphanes 10a and 10c showing them to be symmetric
molecules with mirror image S,R configurations at the two
stereogenic centers in the molecules and no deformation of
the phenyl ring, which is common for smaller parahetera-
phanes. The ease of rotation of the phenyl ring was shown
to be dependent on the macrocyclic cavity and, in the case
where a neopentyl glycol diacrylate was used as the linker,
there was evidence for a twisting of the macrocyclic ring to
alleviate steric interactions of the two methyl groups in the
linking unit.
Figure 5. 1H NMR spectra at 273 K: aromatic proton shifts for the
[12]-, [13]-, and [21]-paraheteraphanes.
Experimental Section
General Methods: All reagents and solvents were purchased from
Sigma-Aldrich or Fluka unless otherwise stated. Silica gel
chromatography was peformed with Silica Gel 60 (particle size 40–
63 µm) obtained from EMD. Thin layer chromatography (TLC)
plates were obtained from EMD. Verdazyl radical 9[8] was synthe-
sized according to a published procedure. NMR spectra were re-
corded with a Varian Unity INOVA spectrometer at 20 °C, op-
When a carbon with two methyl groups is inserted into
the middle of the ethylene glycol diacrylate linker, hetera-
phane 10b results. The 1H NMR spectrum of 10b now
shows a pair of doublet of doublets. One way of interpret-
ing this result is to view the molecule in a twisted conforma-
tion, as shown in Figure 5, where HA/HAЈ are enantiotopic,
as are the other two hydrogen atoms para to each other.
1
erating at 500 MHz for H NMR and 125 MHz for 13C NMR or
a Bruker Avance III spectrometer at 23 °C, operating at 400 MHz
When the temperature of the sample is raised from 0 to for 1H NMR and 100 MHz 13C NMR spectroscopy. Chemical
shifts (δ) are reported in parts per million (ppm) referenced to tet-
ramethylsilane (δ = 0 ppm) for H NMR spectra and CDCl3 (δ =
50 °C, the doublet of doublets collapses into two broad sin-
glets signifying slow rotation of the phenyl ring at the ele-
vated temperature (Figure 6).
1
77.0 ppm) for 13C NMR spectroscopy. Coupling constants (J) are
reported in Hertz (Hz). Mass spectrometry was performed with an
AB/Sciex QStar mass spectrometer with an ESI source, MS/MS
and accurate mass capabilities, associated with an Agilent 1100
capillary LC system. X-ray data were collected with a Bruker-Non-
ius Kappa-CCD diffractometer by using monochromated Mo-Kα
radiation, and measurements were made by using a combination
of ° and ω scans with κ offsets to fill the Ewald sphere. The
data were processed by using the Denzo-SMN package. Absorption
corrections were carried out by using SORTAV. The structure was
solved and refined by using SHELXTL V6.1 for full-matrix least-
squares refinement that was based on F2. All H atoms were in-
cluded in the calculated positions and allowed to refine in the ri-
ding-motion approximation with U isotied to the carrier atom.
CCDC-862210 (for 10a) and -862211 (for 10c) contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Synthesis of N,N-Dimethylcarbonohydrazide 7: The title compound
was synthesized according to a slightly modified procedure re-
ported in the literature.[9a] Precautions should be undertaken when
working with triphosgene or methyl hydrazine, as they are highly
toxic substances. Methyl hydrazine (18.6 g, 0.404 mol) was dis-
Figure 6. Variable-temperature 1H NMR spectroscopic experi-
ments for 10b.
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Verdazyl Radicals as Substrates for Organic Synthesis
solved in CH2Cl2 (200 mL) and added to a three-necked, round-
bottomed flask fitted with an overhead stirrer, an addition funnel,
and a gas inlet. The addition funnel was filled with a solution of
triphosgene (10.0 g, 0.034 mol) in dichloromethane (DCM,
150 mL). The reaction flask was immersed in a dry ice/2-propanol
(–78 °C) bath, and the reaction mixture was purged with N2 for
15 min while stirring. The triphosgene solution was added dropwise
over a 5 h period while the reaction temperature was maintained
at –78 °C. When the addition was complete, the reaction mixture
was brought up to room temperature and allowed to stir for 2 h.
The resulting hydrazine salts were filtered and washed with DCM
(3ϫ20 mL). The filtrate was concentrated under vacuum to a yel-
45.7 (CH2), 63.8 (CH2), 70.0 (Cquart), 128.9 (CH), 129.1 (CH),
134.0 (Cquart), 145.7 (Cquart), 155.0 (Cquart), 173.5 (Cquart) ppm. IR
(KBr): ν = 3447, 2989, 1738, 1682, 1602, 1365 cm–1. HRMS (EI):
˜
calcd. for C24H28N8O6 [M + H]+ 524.2132; found 524.2125.
Reaction of 9 in the Presence of Neopentyl Glycol Diacrylate (10b):
[13]-Paracyclophane 10b was synthesized according to the GP and
purified by flash chromatography (dichloromethane/ethyl acetate,
7:3) to yield the title compound (70 mg, 21%) as a yellow crystal-
line solid; m.p. 220–235 °C. 1H NMR (400 MHz, CDCl3): δ = 0.81
(s, 6 H), 1.96–2.09 (m, 2 H), 2.36–2.47 (m, 2 H), 3.32–3.39 (m, 2
H), 3.40 (s, 6 H), 3.41–3.49 (m, 4 H), 4.21–4.28 (t, J = 7.95 Hz, 2
H), 4.35–4.42 (m, 2 H), 7.55–7.63 (d, J = 8.47 Hz, 2 H), 7.72–7.80
(d, J = 8.47 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.5
(CH3), 30.8 (CH2), 33.1 (Cquart), 37.0 (CH3), 45.2 (CH2), 63.4
(CH2), 127.8 (CH), 128.4 (CH), 132.7 (Cquart), 145.0 (Cquart), 153.3
1
low oil (10.6 g, 88%). H NMR (400 MHz, CDCl3): δ = 4.16 (br.,
s, 4 H), 3.08 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.0
(Cquart), 42.0 (CH3) ppm. HRMS (ESI): calcd. for C3H10N4O [M
+ H]+ 119.0927; found 119.0931.
(Cquart), 171.4 (Cquart) ppm. IR (KBr): ν = 2922, 2852, 2361, 1741,
˜
1677, 1624, 1382 cm–1. HRMS (EI): calcd. for C25H30N8O6 [M +
H]+ 539.2361; found 539.2359.
Synthesis of Bis(2,4-Dimethyl-6-phenyl-1,2,4,5-tetrazinan-3-one) (8):
Compound 8 was synthesized according to a modified procedure
reported in the literature.[8] To a round-bottomed flask equipped
with an addition funnel and a stir bar was added 7 (3.52 g,
0.030 mol) in methanol (200 mL). The reaction flask was immersed
into an oil bath maintained at a temperature of 70 °C. Terephthald-
icarboxaldehyde (2.00 g, 0.015 mol) was dissolved in DCM (40 mL)
and methanol (100 mL). The solution was then added dropwise
over a period of 4 h while the reaction mixture was stirred vigor-
ously and maintained at 70 °C. During the addition, a white pre-
cipitate formed, which was filtered under vacuum. Once the ad-
dition was complete, the remaining precipitate was filtered and al-
lowed to dry. Product 8 was recrystallized from 2-propanol to yield
Reaction of 9 in the Presence of Ethylene Glycol Diacrylate (10c):
[12]-Paracyclophane 10c was synthesized according to the GP and
purified by flash chromatography (ethyl acetate/methanol, 95:5) to
yield the title compound (58 mg, 13%) as a yellow crystalline solid;
1
m.p. 210–230 °C. H NMR (400 MHz, CDCl3): δ = 1.98–2.09 (m,
2 H), 2.28–2.39 (m, 2 H), 3.39 (s, 6 H), 3.59–3.69 (m, 2 H), 3.80–
3.90 (m, 2 H), 3.95–4.06 (m, 2 H), 4.10–4.20 (m, 4 H), 7.67 (s, 4 H
ppm.) 13C NMR (100 MHz, CDCl3): δ = 30.8 (CH2), 37.1 (CH3),
45.5 (CH2), 63.1 (CH2), 63.5 (CH2), 128.3 (CH), 129.1 (CH), 132.9
(Cquart), 145.4 (Cquart), 153.4 (Cquart), 171.5 (Cquart) ppm. IR (KBr):
ν = 3439, 2959, 2361, 1741, 1687, 1625, 1363 cm–1. HRMS (EI):
˜
a
white powder (1.90 g, 40%); m.p. 228–236 °C. 1H NMR
calcd. for C22H24N8O6 [M + H]+ 497.1891; found 497.1871.
(400 MHz, [D6]DMSO): δ = 7.72 (s, 1 H), 7.48–7.36 (m, 3 H), 5.68
(d, 4 H), 4.90 (t, 2 H), 2.94 (s, 12 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 154.5 (Cquart), 136.8 (Cquart), 128.1 (Cquart), 126.5
(CH), 126.1 (CH), 68.6 (CH), 37.6 (CH3) ppm. HRMS (EI): calcd.
for C14H20N8O2 [M + H]+ 335.1940; found 335.1934.
Reaction of 9 in the Presence Tetraethylene Glycol Diacrylate (10d):
[21]-Paracyclophane 10d was synthesized according to the GP and
purified by flash chromatography (ethyl acetate/methanol, 95:5) to
yield the title compound (diastereomer 1; 6.0 mg, 6%) as a yellow
1
crystalline solid; m.p. 250–270 °C. H NMR (400 MHz, CDCl3): δ
Synthesis of Bis(1,5-dimethyl-3-phenyl-6-oxoverdazyl) Radical (9):
= 2.25–2.36 (m, 2 H), 2.38–2.50 (m, 2 H), 3.36 (s, 6 H), 3.51–3.64
(m, 14 H), 3.98–4.06 (m, 2 H), 4.11–4.22 (m, 4 H), 4.26–4.33 (m,
2 H), 7.72 (s, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 29.6
(CH2), 36.8 (CH3), 43.9 (CH2), 61.8 (CH2), 64.9 (CH2), 68.7
(Cquart), 70.4 (Cquart), 70.7 (Cquart), 127.7 (CH), 133.1 (Cquart), 144.9
Compound 9 was synthesized according to a slightly modified pro-
cedure reported in the literature.[8] Tetrazinone
8 (0.600 g,
0.002 mol) was added to a solution mixture of sodium metaperiod-
ate and water in a 500-mL round-bottomed flask equipped with a
stir bar. The reaction mixture was allowed to vigorously stir over
a 3 h period. A precipitate formed which was isolated by filtration
to yield title compound 9 (0.573 g, 96%) as a dark red powder;
m.p. 159–163 °C. HRMS (EI): calcd. for C14H16N8O2 [M]+
328.1390; found 328.1403.
(Cquart), 154.3 (Cquart), 170. 6 (Cquart) ppm. IR (KBr): ν = 3439,
˜
2945, 2358, 1741, 1687, 1625 cm–1. HRMS (EI): calcd. for
C28H36N8O9 [M + H]+ 629.2683; found 629.2655. Diastereomer 2
(2.5 mg, 2.5%) was obtained as a yellow crystalline solid; m.p. 230–
250 °C. 1H NMR (400 MHz, CDCl3): δ = 2.25–2.36 (m, 2 H), 2.38–
2.50 (m, 2 H), 3.36 (s, 6 H), 3.54–3.64 (m, 14 H), 4.07–4.13 (m, 4
H), 4.19–4.22 (m, 4 H), 7.72 (s, 4 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 29.6 (CH2), 36.8 (CH3), 43.9 (CH2), 61.8 (CH2), 64.9
(CH2), 68.7 (Cquart), 70.4 (Cquart), 70.7 (Cquart), 127.7 (CH), 133.1
(Cquart), 144.9 (Cquart), 154.3 (Cquart), 170. 6 (Cquart) ppm. IR
General Procedure (GP) for Cyclophane Formation: A solution of 9
(200 mg, 0.610 mmol) in DCM was added to a 25-mL round-bot-
tomed flask equipped with a stir bar, followed by the addition of
neat diacrylate (1 equiv.). The reaction mixture was stirred at room
temperature for 5–7 d. The excess amount of diacrylates was re-
moved under vacuum, and the desired products were purified by
flash silica gel chromatography. The products were then recrys-
tallized (DCM/hexane, 1:3) to yield the title compounds.
(KBr): ν = 3439, 2945, 2358, 1741, 1687, 1625 cm–1. HRMS (EI):
˜
calcd. for C28H36N8O9 [M + H]+ 629.2683; found 629.2655.
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra of compounds 10a, 10b, 10c and
10d.
Reaction of 9 in the Presence of Ethylene Glycol Dimethacrylate
10a: [12]-Paracyclophane 10a was synthesized according to the GP
and purified by flash chromatography (ethyl acetate/methanol,
95:5) on silica gel to yield the title compound (40 mg, 10%) as
a yellow crystalline solid; m.p. 234–260 °C. 1H NMR (400 MHz,
CDCl3): δ = 1.32 (s, 6 H), 1.80–1.94 (m, 2 H), 2.32–2.40 (m, 2 H),
3.39 (s, 6 H), 3.70–3.79 (m, 2 H), 3.97–4.05 (m, 2 H), 4.13–4.21 (m,
Acknowledgments
The authors gratefully acknowledge funding from the National Sci-
2 H), 4.31–4.39 (m, 2 H), 7.49 (s, 2 H), 7.77 (s, 2 H) ppm. 13C ence and Engineering Research Council of Canada and the Univer-
NMR (100 MHz, CDCl3): δ = 23.1 (CH3), 37.2 (CH3), 41.2 (CH2), sity of Toronto (UT) for a fellowship for A. A. C. The X-ray crystal
Eur. J. Org. Chem. 2012, 1717–1722
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Received: December 5, 2011
Published Online: February 13, 2012
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