Dicationic ring-opening reactions of trans -2- phenylcyclopropylamine·HCl: Electrophilic cleavage of the distal (C 2-C3) bond of cyclopropanes

Article abstract of DOI:10.1021/jo4016198

Electrophilic ring opening of trans-2-phenylcyclopropylamine·HCl occurs at the distal (C₂-C₃) bond. This is consistent with weakening of the distal bond by the σ-withdrawing ammonium group and charge-charge repulsive effects in the t

Full text of DOI:10.1021/jo4016198

Note
pubs.acs.org/joc
Dicationic Ring-Opening Reactions of trans-2-
Phenylcyclopropylamine·HCl: Electrophilic Cleavage of the Distal
(C2−C3) Bond of Cyclopropanes
Sten O. Nilsson Lill,‡ Rajasekhar Reddy Naredla,† Matthew E. Zielinski,† Larecia Knoecer,†
and Douglas A. Klumpp*,†
†Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, Illinois 60115, United States
‡Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden
S
* Supporting Information
ABSTRACT: Electrophilic ring opening of trans-2-phenyl-
cyclopropylamine·HCl occurs at the distal (C2−C3) bond.
This is consistent with weakening of the distal bond by the σ-
withdrawing ammonium group and charge−charge repulsive
effects in the transition state.
yclopropane ring-opening reactions have been the subject
of a vast number of synthetic, mechanistic, and biological
It has long been thought that donor−acceptor cyclopropane
ring-opening reactions involve electron donation into the π-
acceptor groups. Theoretical studies by Cruz-Cabeza and Allen
and by Clark and Schleyer have suggested that these processes
involve interaction of the 3e′ orbital of the cyclopropane ring
with the low-lying unoccupied orbital of the π-acceptor
substituent group(s).10 This interaction leads to weakening
and lengthening of the vicinal (C1−C2) bond of the
cyclopropane and can lead to bond heterolysis. Interestingly,
strong σ-acceptor groups are predicted to interact with the
cyclopropane 1e″ orbital, leading to lengthening (and
weakening) of the distal (C2−C3) bond of the cyclopropane.
This theoretical prediction has been confirmed by crystallo-
graphic data from cyclopropanes having strong σ-acceptor
groups. For example, 1,1-difluorocyclopropane has vicinal and
distal C−C bond lengths of 1.468 and 1.540 Å, respectively.11
The lengthened and weakened distal bond of 1,1-difluorocy-
clopropane is well-known for its tendency to undergo bond
homolysis reactions.12 In this note, we describe the ring-
opening reactions of trans-2-phenylcyclopropylamine·HCl in
superacid and trapping of the resulting ammonium−carbenium
dication with arene nucleophiles. This chemistry is a rare
example of distal bond cleavage accompanied by nucleophilic
and electrophilic reactions. The observed chemical reactions are
in accord with the theoretical predictions made by Clark and
Schleyer.10a
C
studies.1 Among the synthetic reactions, the ring-opening
reactions of donor−acceptor cyclopropanes have been
particularly useful.2−7 With ring opening by bond heterolysis,
the vicinal bond generally undergoes cleavage to form the
zwitterionic species wherein the charge centers are stabilized by
the appropriate substitutents (eq 1).8 This is often followed by
reactions with a nucleophile and an electrophile. Among recent
examples of this chemistry, Mattson and co-workers used a
boronate urea Lewis acid to promote ring opening of
nitrocyclopropane 1 (Scheme 1).9 Reaction of the zwitterionic
species 2 with 4-(trifluoromethoxy)aniline provides the
addition product 3 in good yield. Further synthetic steps
provide a CB-1 receptor inverse agonist drug from intermediate
3.
Scheme 1. Donor−Acceptor Ring Opening of Cyclopropane
1
Our studies began with the superacidic reaction of
cyclopropane 4 (tranylcypromine, a clinically useful anti-
depressant drug). We reasoned that both the amino group
and the cyclopropane ring would be protonated in the
Received: July 30, 2013
Published: August 13, 2013
© 2013 American Chemical Society
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Note
superacid, leading to the formation of a reactive dicationic
superelectrophile.13 When compound 4 was reacted with
benzene in the presence of the Brønsted superacid CF3SO3H
(triflic acid), ring opening occurred to provide the addition
product 6 in good yield (Scheme 2). The structure of the
Nevertheless, reaction in superacid led to the exclusive
formation of the 1,3-dication (i.e., 12) and subsequently gave
product 6 by Friedel−Crafts reaction with benzene (Scheme
3). The reaction course may be understood, however, by
considering the energies of the respective transition states (10
and 11). Transition state 10 leading to protolysis of the C1−C2
bond was found to be 28.7 kcal/mol above the starting
monocation 8, while transition state 11 leading to protolysis of
the distal (C2−C3) bond was found to be 22.2 kcal/mol above
monocation 8. Thus, transition state 11 is 6.5 kcal/mol more
stable than transition state 10. With the lower energy barrier
leading to dication 12, this becomes the kinetically preferred
reaction path. An examination of the transition-state structures
10 and 11 revealed that protolysis of the distal bond to give 11
provides a structure with a larger distance between the
ammonium charge and the developing carbocation charge. In
structure 11, the distance between the ammonium nitrogen and
the incoming proton (from triflic acid) was found to be 3.6 Å,
while in structure 10, the distance between the ammonium
nitrogen and the incoming proton was found to be 2.3 Å.16 In
order to rule out steric effects for the regioselectivity of
protonation, calculations were also done without the triflate
anion. Even without triflate, distal bond cleavage was preferred
over vicinal bond cleavage by about 5.0 kcal/mol.
Scheme 2. Superacid-Promoted Ring Opening of
Cyclopropane 4
product was verified by full characterization including DEPT
NMR analysis. This conversion may be explained by protolytic
ring opening of 4 to give 1,3-dication 5. Superelectrophile 5
then reacts with benzene to eventually provide compound 6.
The formation of product 6 involves regioselective protonation
at the distal (C2−C3) bond rather than the vicinal (C1−C2)
bond of the cyclopropane ring. Protolytic cleavage of the vicinal
bond would produce a more stable benzylic 1,4-dication (vide
infra), leading to product 7, but this was not observed.
In order to probe the regiochemistry of this cyclopropane
ring-opening reaction, we performed theoretical calculations
involving geometry optimizations at the M06/6-31+G(d,p)
level of theory using the Jaguar program suite14 followed by
single-point energy calculations at the M06/cc-pvtz(-f) level
(Figure 1). Energy values were calculated from the optimized
structures using the PBF solvent continuum model (triflic acid
solvent sphere) with a specific triflic acid as the protonating
agent. Protonation of the cyclopropane ring can give two
isomeric dications, 1,4-dication 9 and 1,3-dication 12. It has
been previously shown that increasing the charge separation
tends to stabilize dicationic species.15 As a result, 1,4-dication 9
was found to be 5.7 kcal/mol more stable than 1,3-dication 12.
As expected from previous theoretical calculations,10 the
distal (C2−C3) bond is lengthened prior to protonation relative
to the vicinal bonds. For cation 8, the length of the distal (C2−
C3) bond is estimated to be 1.510 Å, while the lengths of the
vicinal bonds are 1.502 Å (C1−C2) and 1.483 Å (C1−C3).
Clark and Schleyer previously noted that the longest cyclo-
propane bond is generally the bond most easily cleaved.10a To
further support this, we also calculated the natural atomic
orbital bond orders of 8, which were found to be 0.817 (C2−
C3), 0.828 (C1−C2), and 0.830 (C1−C3). Taken together, these
results suggest that the observed distal bond cleavage is the
result of two effects: lengthening and weakening of the (C2−
C3) bond by the σ-acceptor properties of the ammonium group
and the charge−charge repulsive effects in the transition states
leading to ring opening. Ring opening is of course initiated by
protonation.
Figure 1. Calculated relative free energies in solution for distal (8 → 11 → 12) and vicinal (8 → 10 → 9) ring-opening reactions involving
cyclopropane 8 and transition-state structures 10 and 11.
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Scheme 3. Superacid-Promoted Ring Opening of
Cyclopropane 13
Scheme 5. Superacid-Promoted Ring Opening of
Cyclopropane 21
A similar reaction was seen in the ring-opening chemistry of
an amide derivative of tranylcypromine. When compound 13
was reacted with benzene in superacid, compound 16 was
formed as the exclusive product (Scheme 3). This conversion
likely involves formation of ion 14 followed by protonation at
the distal C2−C3 bond to give dication 15. Electrophilic
reaction with benzene and deprotonation would then give the
final product 16. In contrast, the isomeric amide 17 derived
from 2-phenylcyclopropane carboxylic acid was ring-opened by
cleavage of the vicinal C1−C2 bond of the cyclopropane ring
(Scheme 4). This reaction also involves protonation of the
and 27) exhibit ring opening at the distal C2−C3 bond of the
cyclopropane ring (eqs 2 and 3). This leads to the respective
Friedel−Crafts products 26 and 28.
Scheme 4. Superacid-Promoted Ring Opening of
Cyclopropane 17
In summary, we have found unusual examples of distal bond
cleavage in several cyclopropane systems having a cationic σ-
acceptor group. The results are consistent with earlier
observations that σ-acceptor groups lengthen the distal bond
of cyclopropane rings. Theoretical calculations also indicate
that ring opening is a kinetically controlled process in which
charge−charge repulsive effects in the transition-state structures
may be important.
EXPERIMENTAL SECTION
■
General. All of the reactions were performed using oven-dried
glassware under an argon atmosphere. Trifluoromethanesulfonic acid
was freshly distilled prior to use. All commercially available
amide carbonyl bond, giving cation 18, although diprotonation
of the amide may also be possible in the superacidic medium.13
In either case, the resulting carboxonium ion should possess a
low-lying carbonyl LUMO, which should trigger the opening of
the vicinal C1−C2 bond and result in the formation of dication
19. The reaction with benzene then provides the final addition
product 20. Although amides 13 and 17 are similar in structure,
they undergo ring-opening reactions by two distinctly different
mechanisms.
Like other cyclopropanes having strong π-acceptor groups,
the amide group of 17 (and its carboxonium ion 18) interacts
with 3e′ orbital of the cyclopropane ring, leading to lengthening
and cleavage of the vicinal C1−C2 bond. Interestingly, the same
reaction with homologue 21 leads to cleavage of the distal C2−
C3 bond and formation of product 24 (Scheme 5). Thus, the
reaction with CF3SO3H leads to the formation of carboxonium
ion 22. Because the carboxonium group is no longer in
conjugation with the cyclopropane ring, the protonated amide
is not a π-acceptor group but rather is a cationic σ-acceptor
group. This leads to an interaction with the cyclopropane 1e″
orbital and lengthening of the distal C2−C3 bond with
electrophilic and nucleophilic reaction at this site. Following
protonation of the distal C2−C3 bond, superelectrophile 23 is
formed, and Friedel−Crafts reaction gives the final product 24.
In a similar respect, the amine and piperazine derivatives (25
compounds and solvents were used as received. H NMR and 13C
1
NMR spectra were obtained using a 300 MHz spectrometer; chemical
shifts were made in reference to NMR solvent signals. Low-resolution
mass spectra were obtained from a gas chromatography instrument
equipped with a mass-selective detector, while high-resolution mass
spectra were obtained from a commercial analytical laboratory
(electron impact ionization; sector instrument analyzer type).
1-Methyl-2,2-diphenylethylamine (6). In a vented flask or vial
(CAUTION: venting is necessary because the superacid protonates
the chloride, generating HCl gas and modest internal pressure), salt 4
(0.1 g, 0.59 mmol) was suspended in 1 mL of anhydrous benzene, to
which was added CF3SO3H (1.0 mL, 1.9 mmol). The mixture was
stirred at 25 °C for 4−6 h, after which the solution was poured over
several grams of ice. Chloroform (30 mL) was poured into the
mixture, and the aqueous phase was made basic (pH paper) by slow
addition of 10 M NaOH. Extraction and separation of the organic
phase was followed by a second chloroform extraction (30 mL) of the
aqueous phase. The combined chloroform extracts were washed with
H2O and then brine (twice). Following a drying step (Na2SO4),
filtration, and removal of solvent, compound 617 was isolated (oil,
0.096 g, 0.45 mmol).
N-(1,1-Diphenylpropan-2-yl)benzamide (16). Compound 4
(0.2 g, 1.18 mmol) was partitioned between dichloromethane (15
mL) and 1.0 M NaOH (15 mL) in a separatory funnel. Extraction of
the free amine was followed by drying of the organic solution with
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Na2SO4. The resulting solution was filtered directly into a reaction
flask, to which was added triethylamine (0.2 mL, 1.43 mmol) and
benzoyl chloride (0.14 mL, 1.18 mmol). The solution was stirred for 2
h and then washed with 1.0 M HCl, water, and brine (twice). Further
purification with silica gel chromatography (ether/hexanes) provided
known cyclopropylamide 13.18
vacuo. Silica gel column chromatography (2:1 hexanes/ethyl acetate)
provided a colorless solid (0.228 g, 91%). Mp: 80−81 °C. H NMR
1
(CDCl3, 300 MHz) δ: 0.97−1.03 (m, 1H), 1.08−1.14 (m, 1H), 1.44−
1.53 (m, 1H), 1.82−1.88 (m, 1H), 2.52 (dd, J = 5.2, 9.7 Hz, 1H), 3.36
(s, 1H), 7.11−7.14 (m, 2H), 7.18 (d, J = 7.3 Hz, 1H), 7.20−7.28 (m,
1H), 7.30−7.38 (m, 4H), 7.66 (d, J = 7.6 Hz, 2H), 8.73 (s, 1H). 13C
NMR (CDCl3, 75 MHz) δ: 15.8, 19.5, 23.1, 41.9, 120.3, 124.3, 125.8,
125.9, 128.5, 129.0, 138.3, 142.4, 171.1. Low-resolution MS (EI) m/z:
251 (M+), 193, 160, 117, 93, 91, 77. HRMS (EI) m/z: calcd for
C17H17NO, 251.13102; found, 251.13120.
Amide 13 (0.1 g, 0.42 mmol) was suspended in 1 mL of anhydrous
benzene, to which was added CF3SO3H (1.0 mL, 1.9 mmol). The
mixture was stirred at 25 °C for 4−6 h, after which the solution was
poured over several grams of ice. Chloroform (30 mL) was poured
into the mixture, and the aqueous phase was made basic (pH paper)
by slow addition of 10 M NaOH. Extraction and separation of the
organic phase was followed by a second chloroform extraction (30
mL) of the aqueous phase. The combined chloroform extracts were
washed with H2O and then brine (twice). Following a drying step
(Na2SO4), filtration, removal of solvent, and silica gel chromatography
(ether/hexanes), compound 1619 was isolated (0.114 g, 0.36 mmol) as
a light-yellow solid. Mp: 163−164 °C. 1H NMR (CDCl3, 500 MHz) δ:
1.27 (d, J = 6.5 Hz, 3H), 4.03 (d, J = 9.4 Hz, 1H), 5.07−5.13 (m, 1H),
7.18−7.25 (m, 2H), 7.31−7.39 (m, 8H), 7.45 (tt, J = 1.2, 7.4 Hz, 1H),
7.48−7.53 (m, 3H), 7.62 (tt, J = 1.8, 7.4 Hz, 1H)7.83−7.84 (m, 1H).
13C NMR (CDCl3, 125 MHz) δ: 20.4, 48.0, 58.1, 126.6, 126.8, 128.3,
128.5, 128.7, 130.1, 131.2, 132.4, 135.0, 137.6, 141.7, 142.1, 166.9.
Low-resolution MS (EI) m/z: 315 (M+), 194, 167, 165, 148, 105.
HRMS (EI) m/z: calcd for C22H21NO, 315.16232; found, 315.16253.
N-(3,3-Diphenylpropyl)benzamide (20). trans-2-Phenylcyclo-
propane-1-carbonyl chloride (0.2 g, 1.1 mmol) was dissolved in
anhydrous dichloromethane (10 mL), and the solution was cooled in
an ice bath. To this solution, aniline (0.25 mL in 5 mL
dichloromethane) was added slowly. The mixture was stirred for 2 h
and then washed with 1.0 M HCl, water, and brine (twice). Further
purification with silica gel chromatography (ether/hexanes) provided
known cyclopropylamide 17.20
Amide 17 (0.1 g, 0.42 mmol) was suspended in 1 mL of anhydrous
benzene, and CF3SO3H (1.0 mL, 1.9 mmol) was added. The mixture
was stirred at 25 °C for 4−6 h, after which the solution was poured
over several grams of ice. Chloroform (30 mL) was poured into the
mixture, and the aqueous phase was made basic (pH paper) by slow
addition of 10 M NaOH. Extraction and separation of the organic
phase was followed by a second chloroform extraction (30 mL) of the
aqueous phase. The combined chloroform extracts were washed with
H2O and then brine (twice). Following a drying step (Na2SO4),
filtration, removal of solvent, and silica gel chromatography (ether/
hexanes), compound 20 was isolated (0.13 g, 0.41 mmol) as an oil. 1H
NMR (CDCl3, 300 MHz) δ: 2.32 (t, J = 7.9 Hz, 2H), 2.48−2.55 (m,
2H), 3.99 (t, J = 7.8 Hz, 1H), 7.18−7.41 (m, 13H), 7.64 (d, J = 7.7 Hz,
2H), 8.27 (s, 1H). 13C NMR (CDCl3, 75 MHz) δ: 31.2, 35.9, 50.6,
120.3, 124.3, 126.5, 128.0, 128.7, 129.0, 138.3, 144.3, 171.8. Low-
resolution MS (EI) m/z: 315 (M+), 178, 167, 165, 152, 135, 105, 93,
92. HRMS (EI) m/z: calcd for C22H21NO, 315.16232; found,
315.16280.
N-Phenyl-2-(2-phenylcyclopropyl)acetamide (21). (E)-4-Phe-
nylbut-3-enoic acid (0.162 g, 1.0 mmol), aniline (0.09 mL,1 mmol),
EDCI (0.23 g, 1.2 mmol), and DMAP (0.05 g, 0.4 mmol) were
dissolved in anhydrous dichloromethane (20 mL). The solution was
stirred for 12 h at 25 °C, after which it was partitioned between cold
water and CHCl3. The organic layer was separated, washed with H2O
(twice) and brine (twice), and dried over anhydrous sodium sulfate.
The crude product was isolated, and further purification by column
chromatography (hexane/ethyl acetate) gave the known amide (E)-
N,4-diphenylbut-3-enamide.21
According to a published procedure, a stirred solution of (E)-N,4-
diphenylbut-3-enamide (0.237 g, 1.0 mmol) was prepared with
anhydrous dichloromethane (15 mL), and diethylzinc (1.0 M in
hexane, 2.5 mL, 2.5 mmol) was then added at −20 °C under an argon
atmosphere. After 10 min, diiodomethane (0.25 mL, 3 mmol) was
slowly added to the mixture. Stirring was continued for 10 h. A
saturated NH4Cl solution was then added to the mixture, and the
resulting solution was extracted with ethyl acetate. The organic extract
was washed with brine, dried over Na2SO4, and then concentrated in
3-Methyl-N,4,4-triphenylbutanamide (24). Compound 21
(0.251 g, 1.0 mmol) was dissolved in benzene (3 mL), and
CF3SO3H (3 mL, 34 mmol) was added slowly with stirring. The
reaction mixture was stirred overnight at room temperature and then
poured over several grams of ice. Chloroform (ca. 30 mL) was then
added, and the aqueous layer was made basic with 10 M NaOH.
Separation of the organic phase was followed by washing with water
and then saturated brine (twice). The organic solution was dried with
Na2SO4 and then concentrated in vacuo. Further purification with
silica gel column chromatography (2:1 hexanes/ethyl acetate) yielded
1
compound 24 as a colorless oil (0.26 g, 79%). H NMR (CDCl3, 300
MHz) δ: 1.02 (d, J = 6.6 Hz, 3H), 2.04 (dd, J = 4.5 Hz, 1H), 2.49 (dd,
J = 3, 14.5 Hz, 1H), 3.02−3.13 (m, 1H), 3.58 (d, J = 11.1 Hz, 1H),
7.15−7.40 (m, 13H), 7.62 (d, J = 7.8 Hz, 2H), 8.01 (s, 1H). 13C NMR
(CDCl3, 75 MHz) δ: 18.9, 34.3, 43.5, 58.8, 120.2, 124.3, 126.3, 126.5,
128.0, 128.6, 128.8, 129.0, 138.2, 143.7, 143.8, 171.5. Low-resolution
MS (EI) m/z: 329 (M+), 194, 167, 165, 135, 115, 92, 77. HRMS (EI)
m/z: calcd for C23H23NO, 329.17797; found, 329.17821.
N,N-Diethyl-2-methyl-3,3-diphenylpropan-1-amine (26).
Compound 25 was prepared using a published procedure.22 Amine
25 (0.1 g, 0.49 mmol) was suspended in 1 mL of anhydrous benzene,
to which was added CF3SO3H (1.0 mL, 1.9 mmol). The mixture was
stirred at 25 °C for 4−6 h, after which the solution was poured over
several grams of ice. Chloroform (30 mL) was poured into the
mixture, and the aqueous phase was made basic (pH paper) by slow
addition of 10 M NaOH. Extraction and separation of the organic
phase was followed by a second chloroform extraction (30 mL) of the
aqueous phase. The combined chloroform extracts were washed with
H2O and then brine (twice). Following a drying step (Na2SO4),
filtration, removal of solvent, and silica gel chromatography (ether/
hexanes), known compound 26 was isolated (0.090 g, 0.32 mmol) as
an oil.23
1-Methyl-4-(2-phenylcyclopropylmethyl)piperazine (27).
Compound 27 was prepared using a published synthetic method23
and isolated as an oil. 1H NMR (CDCl3, 500 MHz) δ: 0.76−0.80 (m,
1H), 0.90−0.94 (m, 1H), 1.19−1.23 (m, 1H), 1.63 (pent, J = 4.9 Hz,
1H), 2.24 (s, 3H), 2.31 (q, J = 6.6 Hz, 2H), 2.37−2.42 (m, 4H), 2.50
(q, J = 6 Hz, 4H), 6.99−7.01 (m, 2H), 7.07−7.11 (m, 1H), 7.20 (t, J =
7.6 Hz, 2H). 13C NMR (CDCl3, 125 MHz) δ: 15.0, 20.7, 22.7, 46.1,
53.1, 55.1, 63.0, 125.4, 125.6, 128.3, 142.8. Low-resolution MS (EI)
m/z: 230 (M+), 229, 215, 139, 91, 70. HRMS (EI) m/z: calcd for
C15H22N2, 230.17830; found, 230.17855.
1-Methyl-4-(2-methyl-3,3-diphenylpropyl)piperazine (28).
Amine 27 (0.102 g, 0.43 mmol) was suspended in 1 mL of anhydrous
benzene, to which was added CF3SO3H (1.0 mL, 1.9 mmol). The
mixture was stirred at 25 °C for 4−6 h, after which the solution was
poured over several grams of ice. Chloroform (30 mL) was poured
into the mixture, and the aqueous phase was made basic (pH paper)
by slow addition of 10 M NaOH. Extraction and separation of the
organic phase was followed by a second chloroform extraction (30
mL) of the aqueous phase. The combined chloroform extracts were
washed with H2O and then brine (twice). Following a drying step
(Na2SO4), filtration, removal of solvent, and silica gel chromatography
(ether/hexanes), compound 28 was isolated (0.123 g, 0.0004 mmol)
as a light-brown solid. Mp: 141−142 °C. 1H NMR (CDCl3, 500 MHz)
δ: 0.95 (d, J = 6.5 Hz, 3H), 2.13 (dd, J = 3.1, 10.8 Hz, 1H), 2.28 (dd, J
= 4.4, 12.4 Hz, 1H), 2.40−2.45 (m, 3H), 2.61−2.67 (m, 8H), 3.70 (d,
J = 9.6 Hz, 1H), 7.18−7.33 (m, 9H). 13C NMR (CDCl3, 125 MHz) δ:
17.4, 34.3, 45.4, 52.6, 54.9, 56.8, 63.2, 126.1, 126.1, 128.0, 128.4, 128.5,
143.9, 144.2. Low-resolution MS (EI) m/z: 308 (M+), 252, 193, 167,
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Note
165, 113, 70. HRMS (EI) m/z: calcd for C21H28N2, 308.22525, found
308.22471.
(20) Imamoto, T.; Yokoyama, H.; Yokoyama, M. Tetrahedron Lett.
1981, 22, 1803.
(21) Zhu, M.; Zheng, N. Synthesis 2011, 2223.
(22) Teotino, U. M.; Della Bella, D.; Gandini, A.; Benelli, G. J. Med.
Chem. 1967, 10, 1091.
ASSOCIATED CONTENT
■
S
* Supporting Information
(23) Li, A.; Kindelin, P. J.; Klumpp, D. A. Org. Lett. 2006, 8, 1233.
Experimental procedures, characterization data, H and 13C
1
NMR spectra, and computational procedures and results. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: dklumpp@niu.edu
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The financial support from the Åke Wiberg Foundation
(S.O.N.L.) and the NIH National Institute of General Medical
Sciences (GM085736-01A1 to D.A.K.) is gratefully acknowl-
edged. Prof. Thomas M. Gilbert is also thanked for helpful
discussions.
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For example, see: (a) Shi, M.; Lu, J.-M.; Wei, Y.; Wei, L.-X. Acc. Chem.
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DePuy, C. H.; Funfschilling, P. C.; Andrist, A. H.; Olson, J. M. J. Am.
̈
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