Synthesis of 1-substituted benzo[c]isoxazol-3(1H)-imines via tandem nitroso-ene/intramolecular cyclizations of 2-nitrosobenzonitrile

Article abstract of DOI:10.1021/jo800055e

(Chemical Equation Presented) Instead of reacting via the expected coarctate cyclization pathway, 2-nitrosobenzonitrile undergoes a tandem nitrosoene/intramolecular cyclization to form benzo[c]isoxazol-3(1H)-imines in very good yields under neutral conditions and at moderate temperatures. Treatment of three of the imines with HBF₄ results in dimerization/condensation to furnish unusual, delocalized cationic systems.

Full text of DOI:10.1021/jo800055e

cal, transition metal or Lewis acid mediated cyclizations of
conjugated hetero-“ene-ene-yne” moieties (e.g., 1a-c, Scheme
1).7 Formation of the five-membered isoindazole rings (2a,b)
proceeds via carbene (carbenoid) intermediates (3a,b), which
may be trapped using typical methods. We recently expanded
the synthetic viability of this cyclization methodology to include
the nitrile functionality (1c).5d The conjugated azo-ene-nitrile
moiety reacts in a manner analogous to the aforementioned
cyclizations (e.g., 4) in very good to excellent overall yield,
with the resultant nitrogen-based functionality at the 3-position
of 5 permitting for additional synthetic manipulation.
Synthesis of 1-Substituted
Benzo[c]isoxazol-3(1H)-imines via Tandem
Nitroso-Ene/Intramolecular Cyclizations of
2-Nitrosobenzonitrile
Jenna L. Jeffrey, Sean P. McClintock, and
Michael M. Haley*
Department of Chemistry, UniVersity of Oregon,
Eugene, Oregon 97403-1253
haley@uoregon.edu
SCHEME 1. Cyclization of Conjugated Hetero-Ene-Ene-Yne
Systems
ReceiVed January 9, 2008
Instead of reacting via the expected coarctate cyclization
pathway, 2-nitrosobenzonitrile undergoes a tandem nitroso-
ene/intramolecular cyclization to form benzo[c]isoxazol-
3(1H)-imines in very good yields under neutral conditions
and at moderate temperatures. Treatment of three of the
imines with HBF4 results in dimerization/condensation to
furnish unusual, delocalized cationic systems.
These cyclizations are proposed to follow “coarctate” reaction
pathways. Coarctate reactions are characterized by simultaneous
formation of two bonds and breakage of two bonds in a single
reaction step at the coarctate atom.8 Incorporation of heteroatoms
into the ene-ene-yne skeleton provides the potential for lone
pair participation, giving rise to a “pseudocoarctate” reaction
pathway. The amount of lone pair participation is determined
computationally.9
Nitrogen-containing heterocycles have diverse applications,
from drugs used as antitumor agents and enzyme inhibitors1-3
to optical materials used in light-emitting diodes and conducting
polymers.4 Exploration of the properties of heterocyclic systems
requires efficient, facile, and high-yielding syntheses of these
molecules. Our group,5 among others,6 has explored novel
synthetic routes to heterocycles based on thermal, photochemi-
To further explore the applicability of the hetero-ene-ene-
yne cyclization methodology, we replaced the azo portion of
the conjugated system with a nitroso functionality (e.g., 6).
Density functional theory (DFT) calculations of the nitroso-
ene-nitrile cyclization (see Supporting Information) suggest that
the reaction has activation energies comparable to the azo-ene-
yne and azo-ene-nitrile cyclizations previously investigated in
our laboratory. Anisotropy of the current-induced density
(ACID)9 calculations reveal such a pathway to be a true coarctate
reaction with no lone pair participation. On the basis of our
previous studies, we envisioned that the coarctate cyclization
of 6 would proceed via a nitrene (nitrenium) intermediate,
reacting in a similar manner as the azo-ene-nitrile system.5d
Synthetic trials began with the preparation of cyclization
precursor 6. Oxidation of commercially available 2-aminoben-
zonitrile using oxone in a 1:4 mixture of CH2Cl2 and water
(1) Dell’Erba, C.; Novi, M.; Petrillo, G.; Tavani, C. Tetrahedron 1992,
48, 325-334.
(2) Iida, T.; Satoh, H.; Maeda, K.; Yamamoto, Y.; Asakawa, K.-i.;
Sawada, N.; Wada, T.; Kadowaki, C.; Itoh, T.; Mase, T.; Weissman, S. A.;
Tschaen, D.; Krska, S.; Volante, R. P. J. Org. Chem. 2005, 70, 9222-
9229.
(3) De Angelis, M.; Stossi, F.; Carlson, K. A.; Katzenellenbogen, B. S.;
Katzenellenbogen, J. A. J. Med. Chem. 2005, 48, 1132-1148.
(4) Cornil, J.; Beljonne, D.; Calbert, J.-P.; Bredas, J.-L. AdV. Mater. 2001,
13, 1053-1067.
(5) Recent contributions, inter alia: (a) Shirtcliff, L. D.; Weakley, T. J.
R.; Haley, M. M.; Kohler, F.; Herges, R. J. Org. Chem. 2004, 69, 6979-
6985. (b) Shirtcliff, L. D.; Rivers, J.; Haley, M. M. J. Org. Chem. 2006,
71, 6619-6622. (c) Shirtcliff, L. D.; Hayes, A. G.; Haley, M. M.; Kohler,
F.; Hess, K.; Herges, R. J. Am. Chem Soc. 2006, 128, 9711-9721. (d)
Shirtcliff, L. D.; Haley, M. M.; Herges, R. J. Org. Chem. 2007, 72, 2411-
2418.
(6) (a) Uemura, S.; Miki, K.; Washitake, Y.; Ohe, K. Angew. Chem.,
Int. Ed. 2004, 43, 1857-1860. (b) Uemura, S.; Nishino, F.; Miki, K.; Kato,
Y.; Ohe, K. Org. Lett. 2003, 5, 2615-2617. (c) Uemura, S.; Miki, K.; Yokoi,
T.; Nishino, F.; Ohe, K. J. Organomet. Chem. 2002, 645, 228-234. (d)
Nakatani, K.; Adachi, K.; Tanabe, K.; Saito, I. J. Am. Chem. Soc. 1999,
121, 8221-8228. (e) Maeyama, K.; Iwasawa, N. J. Org. Chem. 1999, 64,
1344-1346. (f) Jiang, D.; Herndon, J. W. Org. Lett. 2003, 5, 2043-2045.
(g) Sheridan, R. S.; Khasanova, T. J. Am. Chem. Soc. 2000, 122, 8585-
8586.
(7) Shirtcliff, L. D.; McClintock, S. P.; Haley, M. M. Chem. Soc. ReV.
2008, 37, 343-364.
(8) Herges, R. Angew. Chem., Int. Ed. Engl 1994, 33, 255-276.
(9) (a) Herges, R.; Geuenich, D. J. Phys. Chem. A 2001, 105, 3214-
3220. (b) Geuenich, D.; Hess, K.; Kohler, F.; Herges, R. Chem. ReV. 2005,
105, 3758-3772.
10.1021/jo800055e CCC: $40.75 © 2008 American Chemical Society
Published on Web 03/22/2008
3288
J. Org. Chem. 2008, 73, 3288-3291

SCHEME 2. Synthesis and Cyclization of Nitrile 6
FIGURE 1. Molecular structure of cation 9a; ellipsoids drawn at the
30% probability level. Selected bond lengths (Å): N2-O1 1.438, O1-
C1 1.352, C1-N1 1.313, N1-C8 1.337, C8-O2 1.357, O2-N3 1.413.
Repeated attempts to crystallize 7a were unsuccessful; thus,
we opted to protonate the compound with acid to hopefully
induce crystallization. Treating 7a with HBF4 in CH2Cl2 and
allowing the solution to stand in the dark for 24 h afforded pale
green needles. X-ray crystallographic analysis of the material
(Figure 1) confirmed formation of the benzisoxazole skeleton
but surprisingly showed the alkene trap attached to the ring
nitrogen and not to the exocyclic nitrogen as would be expected
for a coarctate cyclization. Even more surprising, the X-ray data
revealed that the green needles were an unusual U-shaped
cationic compound (9a) formed by the acid-catalyzed dimer-
ization/condensation of 7a.
TABLE 1. Reactions Conditions for Cyclization of 6a
solvent
Lewis acid (equiv)
temp (°C)
yield 7a (%)
DCEb
DCE
DCE
THF
Et2O
THF
THF
THF
THF
PhH
CuCl (10)
rt
rt
rt
rt
rt
100
rt
9
15
15
75
16
72
60
78
81
80
81
BF3‚OEt2 (1)
BF3‚OEt2 (10)
BF3‚OEt2 (10)
BF3‚OEt2 (10)
BF3‚OEt2 (10)
ZnCl2 (10)
p-TsOH‚H2O (10)
none
rt
rt
100
rt
none
none
Et2O
As shown in Figure 1, the cationic portion of 9a adopts a
U-shaped geometry that is essentially planar (mean deviation
of 2.1°). Bonds O1-C1 and O2-C8 are essentially identical
in length (1.352 and 1.357 Å, respectively). The C1-N1 and
N1-C8 bonds are also of similar length but slightly shorter
(1.313 and 1.337 Å, respectively). These data indicate a nearly
uniform distribution of charge across the five atoms. This
structural motif closely resembles the 1,3-dialkoxy-2-azapro-
penylium salts studied by Wu¨rthwein et al.11 These latter cationic
systems have been used in the synthesis of 2,6-disubstituted
4-aminopyridines11e and are proposed to occur in two geom-
etries: a linear, orthogonal 2-azaallenium form11a,b or a bent,
planar 2-azaallylium form.11c-e Electron-donating groups tend
to favor the bent, planar geometry, while the linear, orthogonal
structure is preferred in the presence of aliphatic and aromatic
substituents. The solid state conformation of 9a supports this
trend, as the benzisoxazole substituent functions as an electron
donor.
a 2,3-Dimethyl-2-butene (10 equiv) used as trapping agent. b 1,2-Dichlo-
roethane.
afforded 6 in 65% yield (Scheme 2).10 Nitrile 6 could be
synthesized in multigram quantities with only filtration over a
pad of silica gel necessary to obtain the desired product in pure
form.
Initial studies utilizing 2,3-dimethyl-2-butene (nitrene/nitre-
nium trap) and SnCl2‚2H2O, which was successful at inducing
cyclization of 1c, only resulted in reduction of the nitroso group
of 6, affording a complex mixture of products. Switching to
CuCl, which worked for 1a,b, furnished a cyclized product (7a,
9%) that incorporated the alkene trap (Table 1). Use of BF3‚
OEt2 at room temperature in DCE with excess 2,3-dimethyl-
2-butene also afforded 7a (15%). The yield could be increased
significantly (75%) using THF as solvent. A trial employing
p-TsOH‚H2O in place of a Lewis acid also resulted in cycliza-
tion. Surprisingly, when a control reaction was run in the
absence of any type of acid, cyclization also occurred and the
highest yield of product (81%) was attained. While the exact
structure of the cyclization product and the specific arrangement
of the nitrene trap were not readily obvious, 1D and 2D NMR
experiments implicated the basic benzisoxazole skeleton. Sub-
sequent experiments (vide infra) confirmed the cyclization
product to be benzo[c]isoxazol-3(1H)-imine 7a.
In contrast to the U-type structure of 9a, the Wu¨rthwein
systems typically adopt a W-type geometry. DFT calculations
confirm that, of the three possible conformations shown in
Figure 2, the planar U-shape of 9a is the lowest in relative
(11) (a) Wurthwein, E. U.; Kupfer, R.; Kaliba, C. Angew. Chem., Int.
Ed. Engl. 1983, 22, 252-253. (b) Al-Talib, M.; Jibril, I.; Wurthwein, E.
U.; Jochims, J. C.; Huttner, G. Chem. Ber. 1984, 117, 3365-3373. (c)
Kupfer, R.; Wurthwein, E. U.; Nagel, M.; Allmann, R. Chem. Ber. 1985,
118, 643-652. (d) Kupfer, R.; Wurthwein, E. U. Tetrahedron Lett. 1985,
26, 3547-3550. (e) Schleimer, R.; Wurthwein, E. U. Chem. Ber. 1994,
127, 1437-1440.
(10) Priewisch, B.; Ru¨ck-Braun, K. J. Org. Chem. 2005, 70, 2350-2352.
J. Org. Chem, Vol. 73, No. 8, 2008 3289

SCHEME 3. Tandem Nitroso-Ene/Cyclizations of 6 with
Tri- and Tetrasubstituted Alkenes
FIGURE 2. Possible conformations of 9a and calculated relative
energies (B3LYP/6-31G).
energy. Instead, the W-shaped geometry has the highest relative
energy (7.92 kcal mol-1) due to steric crowding of the aromatic
rings, which results in twisting of the cation by 66° (see
Supporting Information).
TABLE 2. Yields of Benzo[c]isoxazol-3(1H)-imines
The delocalized nature of the positive charge on 9a is
corroborated by the 1H NMR data. Only one signal is seen for
each of the four distinct aromatic hydrogen atoms, which give
rise to signals that are shifted downfield from those of 7a by as
much as 0.47 ppm for the hydrogen atoms nearest the cation:
(∆δ7af12a ) 0.47, 0.46, 0.44, 0.32 ppm for the aromatic
hydrogen atoms). The signals for the alkene and methyl
hydrogen atoms of 9a also are shifted downfield from those of
7a by 0.25 and 0.40 ppm, respectively. NMR signals of 9b,c
are similarly shifted downfield from their respective monomeric
units 7b,c (see Supporting Information).
The confirmed structure of 9a (and thus inferred structure of
7a) clearly shows that instead of reacting via the expected
coarctate reaction, precursor 6 preferentially undergoes a tandem
nitroso-ene/intramolecular cyclization to form cyclization prod-
uct 7a (Scheme 2). The nitroso functionality represents one of
many electrophilic enophiles capable of undergoing the het-
eroatom variant of the ene reaction.12 Due to the low energy of
their LUMO, nitroso compounds are among the most reactive
enophiles. Analogously, electron-rich alkenes (such as 2,3-
dimethyl-2-butene) represent the most reactive alkenes in the
nitroso-ene reaction; electron-deficient alkenes do not readily
participate in the analogous reaction. The resultant hydroxyl-
amine intermediate, while so far eluding detection, readily
cyclizes to furnish 7a. Although the calculated energy profile
(see Supporting Information) indicates that 6 could undergo a
coarctate cyclization, the tandem nitroso-ene/intramolecular
cyclization must represent a lower-energy, more favorable
reaction pathway.
Several attempts were made to determine the reactivity of
7a. KMnO4-mediated oxidation yielded multiple products, one
of which was identified as 2-nitrobenzonitrile. When stirred at
room temperature with p-TsOH‚H2O in THF, 7a converted into
a carbonyl-containing compound, which was later identified as
8 (Scheme 2).
Using the optimal conditions for cyclization of 6 with 2,3-
dimethyl-2-butene (Table 1), a variety of alkenes was tested
for reactivity in the tandem nitroso-ene/cyclization with 6
a Yield is approximate due to facile rearrangement of product.
(Scheme 3 and Table 2). Disubstituted alkenes (not shown)
required elevated temperatures (100 °C) and afforded poor yields
of cyclization products that proved to be unstable and/or
inseparable from multiple side products. In the case of trisub-
stituted alkenes, the initial cyclization product underwent an
irreversible rearrangement to yield the more stable imine upon
workup. For example, 7d readily afforded 10 when treated with
aqueous acid or base, with silica gel, or when left standing at
room temperature for 1 h. Only when tetra-substituted alkenes
were employed did the reaction proceeded in good yield under
neutral conditions at room temperature. Analogous to 7a,
subjecting 7b and 7c to HBF4 in CH2Cl2 afforded dimers 9b
and 9c in 49% and 53% yields, respectively.
In conclusion, our studies have shown that 6 reacts via an
unanticipated tandem nitroso-ene/intramolecular cyclization, as
opposed to a coarctate cyclization pathway. A novel route for
the selective cyclization of 6 in the presence of electron-rich,
tetra-substituted alkenes has been developed. HBF4-promoted
dimerization of cyclization products provides delocalized cat-
ionic salts. We are currently working on extending this new
methodology to the synthesis of novel heterocyclic compounds
and we continue to investigate the anion-binding ability of salts
9.
(12) Johannsen, M.; Jorgensen, K. A. Chem. ReV. 1998, 98, 1689-1708.
3290 J. Org. Chem., Vol. 73, No. 8, 2008

4.92 (d, J ) 12.6 Hz, 2H), 4.19 (m, 1H), 4.11 (m, 1H), 3.88 (m,
1H), 1.66 (m, 3H); 13C NMR (CDCl3) δ 154.1, 139.8, 133.5, 124.2,
124.1, 117.2, 112.0, 73.0, 61.2, 59.2, 25.9, 22.0; IR (NaCl) 3341,
2924, 1660, 1613, 1509, 1450, 1378, 1319, 1155, 1042, 914, 752,
629 cm-1. HRMS (EI) for C12H14N2O2: calcd 218.1055, found
218.1050.
General Dimerization Procedure. Imine (7a-c) (0.378 mmol)
was dissolved in CH2Cl2 (0.8 mL) and aqueous HBF4 (0.01 mL,
48-50% by weight) was added. The mixture was aged in the dark,
open to air for 48 h, allowing the dimer salt (9a-c) to crystallize
from the reaction mixture.
Experimental Section
General Methods. These are described in ref 5c.
General Cyclization Procedure. Nitrile 6 (50 mg, 0.38 mmol)
was dissolved in freshly distilled THF (15 mL, 0.03 M), and alkene
(2-10 equiv) was then added to the solution. The reaction was
stirred at room temperature until TLC indicated complete consump-
tion of the starting material (7-24 h). Removal of the solvent in
vacuo furnished the crude product. The material was dissolved in
CH2Cl2 (15 mL) and filtered through a pad of deactivated silica
gel (1:1 EtOAc/CH2Cl2). Removal of the solvent in vacuo furnished
the pure imines 7a-e.
Salt 9a. 65%; 1H NMR (CDCl3) δ 8.20 (d, J ) 9 Hz, 2H), 7.88
(m, 2H), 7.49 (m, 4H), 5.32 (d, J ) 9.3 Hz, 4H), 2.03 (s, 6H), 1.74
(s, 12H); 13C NMR (CDCl3) δ 152.2, 145.7, 139.2, 138.3, 126.3,
125.8, 116.1, 115.4, 112.3, 71.8, 25.0, 24.8, 19.3; IR (NaCl) 3501,
3094, 2987, 1755, 1643, 1611, 1515, 1462, 1379, 1332, 1151, 1074,
1017, 911 cm-1; UV (CH2Cl2) λmax (log ꢀ) 494 (3.33). Em λmax
229 (3.34). HRMS (EI) for C26H30N3O2 [M]+: calcd 416.2332,
found 416.2330.
Imine 7a. Nitrile 6 and 2,3-dimethyl-2-butene (0.23 mL, 1.89
mmol) were reacted for 7 h, affording 7a (65 mg, 81%) as a yellow
oil: 1H NMR (CDCl3) δ 7.74 (d, J ) 7.8 Hz, 1H), 7.41 (t, J ) 7.2
Hz, 1H), 7.17 (t, J ) 7.2 Hz, 1H), 7.05 (d, J ) 8.7 Hz, 1H), 5.06
(m, 2H), 2.02 (m, 3H), 1.32 (s, 6H); 13C NMR (CDCl3) δ 152.6,
148.5, 132.5, 124.0, 123.8, 113.7, 113.5, 104.1, 68.3, 29.7, 23.0,
19.4; IR (NaCl) 3302, 2924, 2854, 1688, 1666, 1462, 1148 cm-1
HRMS (EI) for C13H16N2O: calcd 216.1263, found 216.1261.
.
1
Salt 9b. 49%; H NMR (CDCl3) δ 8.20 (d, J ) 8.1 Hz, 2H),
Imine 7b. Nitrile 6 and (+)-pulegone (0.62 mL, 3.78 mmol)
were reacted for 8 h, affording 7b (84 mg, 78%) as a yellow oil:
1H NMR (CDCl3) δ 7.73 (d, J ) 7.5 Hz, 1H), 7.39 (t, J ) 7.2 Hz,
1H), 7.14 (m, 2H), 7.00 (d, J ) 8.1 Hz, 1H), 2.54 (m, 2H), 2.23
(m, 3H), 1.49 (s, 3H), 1.46 (s, 3H), 1.07 (d, J ) 6.7 Hz, 3H); 13C
NMR (CDCl3) δ 198.0, 146.9, 141.1, 132.5, 124.4, 124.2, 114.2,
67.4, 48.4, 34.8, 30.3, 23.9, 23.8, 21.2; IR (NaCl) 3297, 2955, 1677,
1461, 1364, 1312, 1234, 1153, 1023, 757 cm-1. HRMS (EI) for
C17H20N2O: calcd 284.1524, found 284.1524.
7.75 (t, J ) 7.5 Hz, 2H), 7.36 (t, J ) 7.8 Hz, 2H), 7.17 (m, 2H),
6.77 (s, 2H), 2.63 (m, 4H), 2.22 (t, J ) 11.1 Hz, 6H), 1.76 (s, 6H),
1.69 (s, 6H), 1.07 (d, J ) 5.4 Hz, 6H); 13C NMR (CDCl3) δ 198.2,
169.0, 151.8, 149.7, 149.5, 138.4, 138.3, 125.8, 112.2, 109.4, 69.1,
47.8, 34.6, 30.0, 25.6, 21.0; IR (NaCl) 3194, 2957, 2875, 1677,
1457, 1153, 1066, 1027, 755 cm-1; HRMS (ESI) for C34H38N3O4
[M]+: calcd 552.2857, found 552.2862.
1
Salt 9c. 53%; H NMR (CDCl3) δ 8.17 (d, J ) 8.7 Hz, 2H),
7.86 (t, J ) 2.4 Hz, 2H), 7.82 (m, 2H), 7.53 (d, J ) 8.7 Hz, 2H),
7.41 (t, J ) 7.8 Hz, 2H), 2.62 (m, 9H), 2.26 (m, 6H), 1.84 (m,
9H); 13C NMR (CDCl3) δ 169.6, 166.5, 152.9, 141.4, 138.2, 126.3,
125.5, 113.5, 110.4, 100.2, 75.7, 35.8, 35.5, 34.0, 33.9, 26.5, 22.7;
IR (NaCl) 3277, 3190, 2959, 2880, 1701, 1617, 1457, 1309, 1069,
756 cm-1. HRMS (ESI) for C34H36N3O4 [M]+: calcd 548.2544,
found 548.2549.
Imine 7c. Nitrile 6 and 2-cyclopentylidenecyclopentanone (0.057
mL, 3.78 mmol) were reacted for 9 h, affording 7c (59 mg, 55%)
as a yellow oil: 1H NMR (CDCl3) δ 7.65 (d, J ) 7.5 Hz, 1H),
7.51 (t, J ) 7.2 Hz, 1H), 7.43 (t, J ) 7.2 Hz, 1H), 7.15 (m, 2H),
2.76 (s, 1H), 2.44 (m, 3H), 2.28 (m, 2H), 2.19 (m, 2H), 1.86 (m,
2H), 1.68 (m, 4H); 13C NMR (CDCl3) δ 207.5, 163.5, 163.4, 152.9,
143.6, 132.7, 124.5, 123.8, 119.3, 114.6, 74.7, 40.0, 35.6, 34.4,
32.7, 29.7, 26.1, 25.4, 23.4; IR (NaCl) 2958, 2874, 1700, 1684,
1653, 1636, 1609, 1464, 1310, 1240, 1170, 1001, 758 cm-1. HRMS
(EI) for C17H18N2O2: calcd 282.1368, found 282.1376.
Imine 7d. Nitrile 6 and 2-methyl-2-butene (1.89 mL, 3.78 mmol,
2.0 M in THF) were reacted for 8 h, affording 7d (59 mg, 77%) as
a light yellow oil: 1H NMR (CDCl3) δ 7.78 (d, J ) 7.5 Hz, 1H),
7.56 (m, 1H), 7.15 (t, J ) 7.5 Hz, 1H), 6.96 (d, J ) 8.1 Hz, 1H),
5.08 (d, J ) 6.0 Hz, 1H), 5.00 (s, 1H), 4.25 (q, J ) 6.3 Hz, 1H),
1.07 (d, J ) 10.5 Hz, 3H), 1.30 (m, 3H); 13C NMR (CDCl3) δ
145.9, 133.8, 124.5, 124.1, 114.7, 113.2, 112.0, 113.6, 67.2, 66.1,
21.2, 14.1; IR (NaCl) 3301, 3210, 3091, 2978, 2941, 2920, 2877,
1678, 1611, 1597, 1467, 1310, 1238, 1151, 1101, 1029, 904, 756
cm-1. HRMS (EI) for C12H14N2O calcd 202.1106, found 202.1100.
Imine 7e. Nitrile 6 and 3-methyl-2-buten-1-ol (0.045 mL, 0.454
mmol) were reacted for 24 h, affording 7e (83 mg, 83%) as a yellow
solid: 1H NMR (CDCl3) δ 7.68 (d, J ) 7.8 Hz, 1H), 7.47 (t, J )
7.8 Hz, 1H), 7.11 (t, J ) 7.8 Hz, 1H), 6.98 (d, J ) 8.1 Hz, 1H),
Acknowledgment. We thank the National Science Founda-
tion (CHE-0718242) for financial support. S.P.M. acknowledges
the NSF for an IGERT fellowship (DGE-0549503). We thank
Dr. Lev Zakharov for obtaining the X-ray structure of 9a and
Prof. Rainer Herges for his continued interest and input on this
project.
Supporting Information Available: Experimental details for
6, 8, and 10; computed energy diagram for coarctate cyclization of
1
6; copies of H and 13C NMR spectra for 6, 7a-e, 8, 9a-c, 10;
X-ray structure of 9a in CIF format, structure refinement details,
tables of atomic coordinates, thermal parameters, bond lengths, and
bond angles. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO800055E
J. Org. Chem, Vol. 73, No. 8, 2008 3291